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Zou Z, Chen X, Gao Y, Theppawong A, Liu Y, Sangsawad P, Bunyameen N, Deng S, Kraithong S, Gao J. Recent insights into functional, structural, and digestibility modifications of starch through complexation with polyphenols: A review. Food Chem 2025; 482:144162. [PMID: 40187309 DOI: 10.1016/j.foodchem.2025.144162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/07/2025] [Accepted: 03/30/2025] [Indexed: 04/07/2025]
Abstract
Starch-polyphenol complexes, formed through hydrogen bonding and hydrophobic interactions, significantly alter starch's functional, structural, and digestive properties. These complexes enhance thermal stability, reduce starch digestibility, and slow glucose release, offering potential benefits for glycemic control and functional food development. Polyphenols, including phenolic acids, flavonoids, tannins, lignans, and stilbenes, form inclusion and non-inclusion complexes with amylose, potentially increasing resistant starch (RS) content and lowering the glycemic index of foods, which may benefit individuals with diabetes. However, the effectiveness of these complexes depends on factors such as polyphenol structure, starch type, and processing conditions. In some cases, processing may degrade polyphenols, potentially enhancing starch digestibility. Future research should focus on understanding the underlying mechanisms, validating health benefits through in vivo studies, and optimizing processing techniques for functional foods targeting glycemic control. This will maximize the potential of starch-polyphenol complexes in developing healthier, more sustainable food solutions.
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Affiliation(s)
- Zimo Zou
- School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Xiaoe Chen
- School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Yuanpei Gao
- School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Atiruj Theppawong
- Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000, Ghent, Belgium
| | - Yonghong Liu
- CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China
| | - Papungkorn Sangsawad
- School of Animal Technology and Innovation, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Nasuha Bunyameen
- Department of Research and Development Halal product, Faculty of Science and Technology, Fatoni University, Pattani 94160, Thailand
| | - Shanggui Deng
- School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China
| | - Supaluck Kraithong
- Guangxi Key Laboratory of Marine Drugs, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
| | - Jingrong Gao
- School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, China.
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2
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Chagas MDSDS, Moragas Tellis CJ, Silva AR, Brito MADSM, Teodoro AJ, de Barros Elias M, Ferrarini SR, Behrens MD, Gonçalves-de-Albuquerque CF. Luteolin: A novel approach to fight bacterial infection. Microb Pathog 2025; 204:107519. [PMID: 40164399 DOI: 10.1016/j.micpath.2025.107519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/13/2025] [Accepted: 03/26/2025] [Indexed: 04/02/2025]
Abstract
Diseases caused by bacteria significantly impact public health, causing both acute and chronic issues, sequelae, and death. The problems get even more significant, considering the antimicrobial resistance. Bacterial resistance occurs when antibacterial drugs fail to kill the microbes, leading to the persistence of infection and pathogen spread in the host. Thus, the search for new molecules with antibacterial activity dramatically impacts human health. Natural products have proven to be a prosperous source of these agents. Among them, the flavonoids deserve to be highlighted. They are secondary metabolites, primarily involved in plant signaling and protection. Thus, they play an essential role in plant adaptation to the environment. Herein, we will focus on luteolin because it is commonly found in edible plants and has diverse pharmacological properties such as anti-inflammatory, anticancer, antioxidant, and antimicrobial. We will further explore the luteolin antibacterial activity, mechanisms of action, structure-activity relationship, and toxicity of luteolin. Thus, we have included reports of luteolin with antibacterial activity recently published, as well as focused on nanotechnology as a pivotal and helpful approach for the clinical use of luteolin. This review aims to foster future research on luteolin as a therapeutic agent for treating bacterial infection.
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Affiliation(s)
- Maria do Socorro Dos Santos Chagas
- Programa de Pós-graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, UFF, Brazil; Laboratório de Imunofarmacologia, Departamento de Ciências Fisiológicas, UNIRIO, Rio de Janeiro, RJ, Brazil; Laboratório de Imunofarmacologia, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil; Laboratório de Produtos Naturais para Saúde Pública, Farmanguinhos, FIOCRUZ, RJ, Brazil
| | | | - Adriana R Silva
- Laboratório de Imunofarmacologia, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil; Programa de Pós-Graduação em Neurociências, Instituto de Biologia, UFF, Niterói, Brazil
| | - Maria Alice Dos Santos Mascarenhas Brito
- Laboratório de Imunofarmacologia, Departamento de Ciências Fisiológicas, UNIRIO, Rio de Janeiro, RJ, Brazil; Laboratório de Imunofarmacologia, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil; Programa de Pós-Graduação em Neurociências, Instituto de Biologia, UFF, Niterói, Brazil
| | - Anderson Junger Teodoro
- Laboratório de Biologia Celular e Nutrição (LABCEN) Universidade Federal Fluminense, UFF, Niteroi, Brazil
| | - Monique de Barros Elias
- Laboratório de Biologia Celular e Nutrição (LABCEN) Universidade Federal Fluminense, UFF, Niteroi, Brazil
| | - Stela Regina Ferrarini
- Laboratório de Nanotecnologia Farmacêutica, Universidade Federal do mato Grosso Campus Sinop - UFMT, Cuiabá, Brazil
| | - Maria Dutra Behrens
- Laboratório de Produtos Naturais para Saúde Pública, Farmanguinhos, FIOCRUZ, RJ, Brazil.
| | - Cassiano F Gonçalves-de-Albuquerque
- Programa de Pós-graduação em Ciências e Biotecnologia (PPBI), Instituto de Biologia, UFF, Brazil; Laboratório de Imunofarmacologia, Departamento de Ciências Fisiológicas, UNIRIO, Rio de Janeiro, RJ, Brazil; Programa de Pós-Graduação em Biologia Molecular e Celular (PPGBMC), UNIRIO, RJ, Brazil; Laboratório de Imunofarmacologia, IOC, FIOCRUZ, Rio de Janeiro, RJ, Brazil; Programa de Pós-Graduação em Neurociências, Instituto de Biologia, UFF, Niterói, Brazil.
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3
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Jalševac F, Segú H, Balaguer F, Ocaña T, Moreira R, Abad-Jordà L, Gràcia-Sancho J, Fernández-Iglesias A, Andres-Lacueva C, Martínez-Huélamo M, Beltran-Debon R, Rodríguez-Gallego E, Terra X, Ardévol A, Pinent M. TAS2R5 and TAS2R38 are bitter taste receptors whose colonic expressions could play important roles in age-associated processes. J Nutr Biochem 2025; 140:109872. [PMID: 39986633 DOI: 10.1016/j.jnutbio.2025.109872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 10/09/2024] [Accepted: 02/13/2025] [Indexed: 02/24/2025]
Abstract
Ageing disrupts how our bodies process nutrients, leading to deregulation of nutrient-sensing and increased inflammation. Dietary interventions can promote healthy ageing, which demonstrates the importance of both metabolism and the gastrointestinal tract for our health. Bitter taste receptors (TAS2R) present in the intestine are key members of metabolic regulation. TAS2R are involved in controlling enterohormonal secretion, detect phenolic compounds in our diet, and potentially have a great impact on the ageing process. Here, we aimed to analyze the potential role of intestinal TAS2R on the ageing process and establish potential impact of these receptors on the biomarkers. Healthy subjects were divided into two age cohorts: young (38.9±6) and aged (63.6±6). TAS2R expression was analyzed in the colon. Analyses of metabolomics and of phenolic markers were performed in plasma. Best discriminatory parameters were obtained using three machine-learning methods. Finally, Spearman's rank correlation was performed. The best separators of the age cohorts were docosahexaenoic acid and multiple lipoprotein fractions. Two TAS2R were also identified: TAS2R5 and TAS2R38. TAS2R5 correlated with multiple lipoprotein-derived fractions, inflammatory marker IL-6 and polyunsaturated fatty acids. TAS2R38 was much more selective, correlating with a few parameters, including membrane lipid sphingomyelin, ketone body acetone, and omega acids. Both TAS2R5 and TAS2R38 correlated with β-hydroxybutyrate. The parameters that correlated with TAS2R have known effects on the ageing process. This suggests that TAS2R5 and TAS2R38 are the bitter receptors most likely to play a role in the development and progress of ageing.
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Affiliation(s)
- Florijan Jalševac
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain
| | - Helena Segú
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain
| | - Francesc Balaguer
- Gastroenterology department, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Teresa Ocaña
- Gastroenterology department, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Rebeca Moreira
- Gastroenterology department, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Laia Abad-Jordà
- Liver Vascular Biology, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Jordi Gràcia-Sancho
- Liver Vascular Biology, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Anabel Fernández-Iglesias
- Liver Vascular Biology, Hospital Clinic Barcelona, IDIBAPS (Institut d´Investigacions Biomédiques August Pi i Sunyer), Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Cristina Andres-Lacueva
- Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Nutrition and Food Safety Research Institute (INSA), Food Innovation Network (XIA), Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Miriam Martínez-Huélamo
- Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Nutrition and Food Safety Research Institute (INSA), Food Innovation Network (XIA), Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
| | - Raul Beltran-Debon
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain; IISPV, Hospital Joan XXIII, Tarragona, Spain
| | - Esther Rodríguez-Gallego
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain; IISPV, Hospital Joan XXIII, Tarragona, Spain
| | - Ximena Terra
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain; IISPV, Hospital Joan XXIII, Tarragona, Spain
| | - Anna Ardévol
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain; IISPV, Hospital Joan XXIII, Tarragona, Spain.
| | - Montserrat Pinent
- Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, MoBioFood Research Group, Tarragona, Spain; IISPV, Hospital Joan XXIII, Tarragona, Spain
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Bouafir Y, Bouhenna MM, Nebbak A, Belfarhi L, Aouzal B, Boufahja F, Bendif H, Bruno M. Algal bioactive compounds: A review on their characteristics and medicinal properties. Fitoterapia 2025; 183:106591. [PMID: 40339617 DOI: 10.1016/j.fitote.2025.106591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/22/2025] [Accepted: 05/02/2025] [Indexed: 05/10/2025]
Abstract
Bioactive compounds derived from marine algae drawn increasing interest in pharmaceuticals, nutraceuticals, and cosmetics due to their wide range of therapeutic properties. These natural molecules, which include polysaccharides, polyphenols, phlorotannins, carotenoids, and pigments, exhibit potent antioxidant, antimicrobial, anti-inflammatory, antiviral, and antitumor activities. Algal bioactives are safer and more sustainable options for drug discovery since they often have less negative effects than synthesized compounds. This review highlights the structural diversity of algal biomolecules and their mechanisms of action, with emphasis on validated bioactivities supported by recent studies. It also critically examines challenges such as the low bioavailability of high-molecular-weight compounds like fucoidans, variability in metabolite production linked to environmental factors, and limitations in scalable extraction processes. Recent advances in nano-encapsulation, metabolic engineering, and eco-friendly extraction methods are explored as promising strategies to enhance bioavailability and industrial applicability. By integrating traditional knowledge with biotechnological innovations, this review underscores the underexploited potential of macroalgae in addressing chronic diseases and the urgent need for standardized protocols to facilitate the clinical translation of algal-derived bioactives.
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Affiliation(s)
- Yesmine Bouafir
- Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), BP384, Bou-Ismail 42004, Tipaza, Algeria
| | - Mustapha Mounir Bouhenna
- Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), BP384, Bou-Ismail 42004, Tipaza, Algeria
| | - Amira Nebbak
- Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), BP384, Bou-Ismail 42004, Tipaza, Algeria
| | - Leila Belfarhi
- Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques (CRAPC), BP384, Bou-Ismail 42004, Tipaza, Algeria
| | - Badis Aouzal
- Research Laboratory of Interactions, Biodiversity, Ecosystems and Biotechnology (LIBEB), Department of Nature and Life Sciences, Faculty of Sciences, University 20 August 1955 Skikda, Skikda 21000, Algeria
| | - Fehmi Boufahja
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia
| | - Hamdi Bendif
- Biology Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
| | - Maurizio Bruno
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Uni-versità degli Studi di Palermo, Viale delle Scienze, Ed. 17, 90128 Palermo, Italy.
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5
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Nguyen P, Sanderson B, Makama M, Mills K, Ammerdorffer A, Gülmezoglu AM, Vogel JP, McDougall ARA. Polyphenols for the Prevention or Management of Preeclampsia: A Systematic Review and Meta-Analysis. BJOG 2025; 132:867-879. [PMID: 40025969 PMCID: PMC12051244 DOI: 10.1111/1471-0528.18106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 01/29/2025] [Accepted: 02/04/2025] [Indexed: 03/04/2025]
Abstract
OBJECTIVES To evaluate the effects of polyphenol-containing products during pregnancy on preeclampsia-related maternal and neonatal outcomes. DESIGN Systematic review and meta-analysis. SETTING Nine databases and one trial registry, from inception to August 11th, 2023. POPULATION/SAMPLE Randomised controlled trials where women received polyphenolic-containing products (as standardised extracts or dietary supplements) compared to placebo or standard care. METHODS All review stages were conducted by two independent reviewers. Random-effects meta-analysis with the Hartung-Knapp-Sidik-Jonkman method using a framework for studies with few events. MAIN OUTCOME MEASURES Clinical outcomes combining the core outcome set for preeclampsia and WHO's priority outcomes. RESULTS Fourteen trials investigating six candidates were included. In women with preeclampsia, the addition of epigallocatechin gallate (EGCG) to nifedipine may reduce the time needed to achieve blood pressure control (mean difference (MD) = -14.10 min, 95% CI -18.46 to -9.74) and increase the time to the next hypertensive crisis (MD = 3.10 h, 95% CI 2.35 to 3.85) compared to nifedipine alone (1 trial, 349 women; low certainty). Similarly, the addition of resveratrol to nifedipine may reduce the time needed to achieve blood pressure control (MD = -15.50 min, 95% CI -19.83 to -11.17) and increase the time to the next hypertensive crisis (MD = 2.50 h, 95% CI 2.09 to 2.91) (1 trial, 349 women; low certainty). No differences were observed for other outcomes or candidates (Salvia miltiorrhiza, Bryophyllum pinnatum , raspberry and cranberry extracts). CONCLUSIONS ECGC and resveratrol supplements have been investigated for potential effects in managing clinical signs and symptoms of preeclampsia; however, evidence on the clinical and adverse effects of polyphenols is limited and uncertain.
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Affiliation(s)
- Phi‐Yen Nguyen
- Maternal, Child and Adolescent Health ProgramBurnet InstituteMelbourneAustralia
| | - Ben Sanderson
- Maternal, Child and Adolescent Health ProgramBurnet InstituteMelbourneAustralia
| | - Maureen Makama
- Maternal, Child and Adolescent Health ProgramBurnet InstituteMelbourneAustralia
| | - Kate Mills
- Maternal, Child and Adolescent Health ProgramBurnet InstituteMelbourneAustralia
| | | | | | - Joshua P. Vogel
- Maternal, Child and Adolescent Health ProgramBurnet InstituteMelbourneAustralia
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6
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Zu R, Lu H, Liu W, Shao S, Zheng J, Ying X, Zhou Y, Li Z, Wang W, Li D, Peng Q, Ma H, Zhang Z, Sun Y. Research Progress in the Molecular Mechanism of NLRP3 Inflammasome in Alzheimer's Disease and Regulation by Natural Plant Products. Mol Neurobiol 2025; 62:7296-7312. [PMID: 39875780 DOI: 10.1007/s12035-025-04715-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/19/2025] [Indexed: 01/30/2025]
Abstract
Alzheimer's disease (AD) is a prominent neurodegenerative disorder affecting the central nervous system in the elderly. Current understanding of AD primarily centers on the gradual decline in cognitive and memory functions, believed to be influenced by factors including mitochondrial dysfunction, β-amyloid aggregation, and neuroinflammation. Emerging research indicates that neuroinflammation plays a significant role in the development of AD, with the inflammasome potentially mediating inflammatory responses that contribute to neurodegeneration. Recent studies in AD pathology have identified a novel form of inflammasome referred to as NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Pathological alterations closely associated with NLRP3 inflammasome activation have been observed in the brain tissues of AD patients, transgenic mice, and in vitro neurocyte models. Numerous studies have demonstrated the potent neuroprotective properties of natural plant products (NPPs) against NLRP3 inflammasome-mediated AD pathology. This review provides a comprehensive examination of the NLRP3 inflammasome, its involvement in AD pathology, and the mechanisms underlying the therapeutic effects of NPP targeting the NLRP3 inflammasome.
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Affiliation(s)
- Runru Zu
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Hao Lu
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Wanting Liu
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Simai Shao
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Jiayao Zheng
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Xiran Ying
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Yangang Zhou
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Zhonghua Li
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China
| | - Wang Wang
- School of Basic Medicine, Nanchang Medical College, Nanchang, 330052, Jiangxi, PR China
| | - Dejuan Li
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China
| | - Quekun Peng
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
| | - Huifen Ma
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Zhenqiang Zhang
- Henan Engineering Research Center for Prevention and Treatment of Major Chronic Diseases With Chinese Medicine, Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
| | - Yiran Sun
- School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
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7
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Adedara IA, Weis GCC, Monteiro CS, Soares FAA, Rocha JBT, Schetinger MRC, Emanuelli T, Aschner M. Versatility of Caenorhabditis elegans as a Model Organism for Evaluating Foodborne Neurotoxins and Food Bioactive Compounds in Nutritional Neuroscience. Mol Neurobiol 2025; 62:7205-7229. [PMID: 39863742 DOI: 10.1007/s12035-025-04705-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
Epidemiological evidence has shown that the regular ingestion of vegetables and fruits is associated with reduced risk of developing chronic diseases. The introduction of the 3Rs (replacement, reduction, and refinement) principle into animal experiments has led to the use of valid, cost-effective, and efficient alternative and complementary invertebrate animal models which are simpler and lower in the phylogenetic hierarchy. Caenorhabditis elegans (C. elegans), a nematode with a much simpler anatomy and physiology compared to mammals, share similarities with humans at the cellular and molecular levels, thus making it a valid model organism in neurotoxicology. This review explores the versatility of C. elegans in elucidating the neuroprotective mechanisms elicited by food bioactive compounds against neurotoxic effects of food- and environmental-related contaminants. Several signaling pathways linked to the molecular basis of neuroprotection exerted by bioactive compounds in chemically induced or transgenic C. elegans models of neurodegenerative diseases are also discussed. Specifically, the modulatory effects of bioactive compounds on the DAF-16/FoxO and SKN-1/Nrf2 signaling pathways, stress resistance- and autophagy-related genes, and antioxidant defense enzyme activities were highlighted. Altogether, C. elegans represent a valuable model in nutritional neuroscience for the identification of promising neuroprotective agents and neurotherapeutic targets which could help in overcoming the limitations of current therapeutic agents for neurotoxicity and neurodegenerative diseases.
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Affiliation(s)
- Isaac A Adedara
- Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil.
| | - Grazielle C C Weis
- Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil
| | - Camila S Monteiro
- Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil
| | - Felix A A Soares
- Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Camobi, Santa Maria, 97105-900, Brazil
| | - Joao B T Rocha
- Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Camobi, Santa Maria, 97105-900, Brazil
| | - Maria R C Schetinger
- Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Camobi, Santa Maria, 97105-900, Brazil
| | - Tatiana Emanuelli
- Department of Food Technology and Science, Center of Rural Sciences, Federal University of Santa Maria, Camobi, Santa Maria, RS, 97105-900, Brazil
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
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8
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Tariq M, Qi H, Zakirullah, Zakareya, Liang H. Nano-encapsulation of Glabridin using enzymatically hydrolyzed sodium caseinate for improved bioavailability and functional applications. Int J Biol Macromol 2025; 315:144541. [PMID: 40409632 DOI: 10.1016/j.ijbiomac.2025.144541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 05/19/2025] [Accepted: 05/20/2025] [Indexed: 05/25/2025]
Abstract
Glabridin (Gla), a pyranoisoflavan, has diverse health benefits and significant applications in skincare due to its antioxidant, anti-inflammatory, anti-ageing, and UV-protective properties. This study aimed to enhance the entrapment efficiency of Gla by encapsulating it within enzymatically hydrolyzed sodium caseinate (Eh SC), showing 96.34 ± 0.24 % encapsulation efficiency. The successful incorporation of Gla into Eh SC@Gla nanoparticles was confirmed through FT-IR, XRD, and fluorescence spectroscopy. At the same time, the physical characterization by TEM, DLS, and PDI revealed uniformly spherical nanoparticles with an average diameter of about 120 nm. The enzymatically hydrolyzed Eh SC@Gla nanoparticles showed potent tyrosinase inhibitory activity and robust free radical scavenging abilities against DPPH and ABTS. At 32 μg/ml, they achieved 65 % DPPH and 99 % ABTS radical scavenging, outperforming free Gla (34 % and 17 %). Furthermore, Eh SC@Gla reduced B16 cell viability to 27.25 % while showing no toxicity to 3 T3 cells. It improved 3 T3 viability to 82.33 % under oxidative stress and lowered ROS levels by 1.69-fold. These nanoparticles showed selective cytotoxicity, strong intracellular antioxidant activity, and good biocompatibility. The current findings provide valuable insights for the development of advanced delivery systems and innovative formulations, and maximize the therapeutic and nutritional benefits of Gla across the skin care and cosmetics.
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Affiliation(s)
- Muhammad Tariq
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Haole Qi
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Zakirullah
- College of Life Sciences and Technology Beijing University of Chemical Technology, Beijing 100029, China
| | - Zakareya
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
| | - Hao Liang
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
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9
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Rębas E. Role of Flavonoids in Protecting Against Neurodegenerative Diseases-Possible Mechanisms of Action. Int J Mol Sci 2025; 26:4763. [PMID: 40429904 PMCID: PMC12112047 DOI: 10.3390/ijms26104763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2025] [Revised: 05/10/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
Neurodegenerative and mood disorders represent growing medical and social problems, many of which are produced by oxidative stress, neuroinflammation, disruption in the metabolism of various neurotransmitters, and some disturbances in lipid/carbohydrate homeostasis. Biologically active plant compounds, including flavonoids, have been shown to exert a positive impact on central nervous system function. This review assesses the studies of naturally occurring flavonoids belonging to various polyphenol subclasses and their mechanisms of neuroprotective action, especially against neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Most of the studied phytochemicals possess anti-oxidative, anti-inflammatory, and neuroprotective properties. These phytochemicals have been considered as compounds that reduce the risk of developing Alzheimer's and Parkinson's diseases and can be used in the treatment of neurological diseases. The neuroprotective actions of some flavonoids may entail mechanisms that regulate reactive oxygen species generation and modify inflammatory pathways, and they should be considered as therapeutic agents.
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Affiliation(s)
- Elżbieta Rębas
- Department of Molecular Neurochemistry, Medical University of Lodz, 90-419 Lodz, Poland
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10
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Ávila-Gálvez MÁ, Vico-Padilla A, Schneider C, Espín JC, González-Sarrías A, Giménez-Bastida JA. Angiogenesis as a Therapeutic Target of (Poly)phenols: Tackling Cancer and Vascular-Related Complications. Mol Nutr Food Res 2025:e70110. [PMID: 40370203 DOI: 10.1002/mnfr.70110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Revised: 04/01/2025] [Accepted: 04/29/2025] [Indexed: 05/16/2025]
Abstract
Targeting angiogenesis as a strategy for treating cancer or vascular-associated complications is an inspiring field for many investigators. An active area within this discipline is the search for agents capable of modulating angiogenesis in order to ameliorate its structural and functional abnormalities associated with these diseases. (Poly)phenols are a broad group of molecules, many of which fall within the category of natural compounds with therapeutic potential. These potential medicinal effects have launched a considerable number of studies investigating the pro- and(or) anti-angiogenic properties of (poly)phenols in different (patho)physiological settings. The purpose of this review is to summarize the current evidence of the role of (poly)phenols in modulating angiogenesis. This review will guide the reader through preclinical and human investigations describing the pro- and anti-angiogenic effects of these compounds in different pathophysiological context, the cellular and molecular mechanisms associated, the key points in the design and evaluation of the effects described, and suggest new approaches to be considered in future studies to overcome the current limitations.
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Affiliation(s)
- María Ángeles Ávila-Gálvez
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Antonio Vico-Padilla
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Claus Schneider
- Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Juan Carlos Espín
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Antonio González-Sarrías
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
| | - Juan Antonio Giménez-Bastida
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, Murcia, Spain
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11
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Klanrit P, Kitwetcharoen H, Vichitphan K, Vichitphan S, Thanonkeo S, Yamada M, Thanonkeo P. Enhancing the Bioactive Properties of Sugarcane Vinegar Through Caesalpinia sappan Extract Supplementation: A Novel Approach for Functional Beverage Development. Antioxidants (Basel) 2025; 14:590. [PMID: 40427473 PMCID: PMC12108335 DOI: 10.3390/antiox14050590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 05/07/2025] [Accepted: 05/12/2025] [Indexed: 05/29/2025] Open
Abstract
Functional vinegars have been produced from various ingredients worldwide, yet there remains a notable gap in utilizing herbal plants as complementary ingredients to sugar-based materials. This study investigates the innovative combination of Caesalpinia sappan extract with sugarcane juice for functional vinegar production. The results demonstrate that C. sappan-supplemented vinegars exhibited significantly enhanced quality parameters compared to control vinegar made from sugarcane juice alone. Specifically, the supplemented vinegars showed increased total acidity and total phenolic content (TPC), with the improvement directly proportional to the concentration of plant extract used. Gas chromatography-mass spectrometry (GC-MS) analysis revealed unique volatile organic compounds (VOCs) that were present exclusively in the C. sappan-supplemented vinegars but absent in the control. Most notably, the supplementation of C. sappan extract at concentrations of 2 and 4 g/L substantially enhanced both the antioxidant capacity and antimicrobial activity of the resulting vinegars. These biochemical improvements highlight the synergistic potential of combining sugarcane juice with C. sappan extract for developing novel functional vinegar beverages with enhanced bioactive properties. Our findings open new possibilities for creating value-added products that leverage traditional medicinal plants in modern functional beverages, potentially offering consumers additional health benefits beyond conventional vinegars.
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Affiliation(s)
- Preekamol Klanrit
- Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen 40002, Thailand; (P.K.); (K.V.); (S.V.)
- Fermentation Research Center for Value Added Agricultural Products (FerVAAPs), Khon Kaen University, Khon Kaen 40002, Thailand
| | - Haruthairat Kitwetcharoen
- Walai Rukhavej Botanical Research Institute (WRBRI), Mahasarakham University, Maha Sarakham 44150, Thailand; (H.K.); (S.T.)
| | - Kanit Vichitphan
- Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen 40002, Thailand; (P.K.); (K.V.); (S.V.)
- Fermentation Research Center for Value Added Agricultural Products (FerVAAPs), Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sukanda Vichitphan
- Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen 40002, Thailand; (P.K.); (K.V.); (S.V.)
- Fermentation Research Center for Value Added Agricultural Products (FerVAAPs), Khon Kaen University, Khon Kaen 40002, Thailand
| | - Sudarat Thanonkeo
- Walai Rukhavej Botanical Research Institute (WRBRI), Mahasarakham University, Maha Sarakham 44150, Thailand; (H.K.); (S.T.)
| | - Mamoru Yamada
- Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan;
- Research Center for Thermotolerant Microbial Resources, Yamaguchi University, Yamaguchi 753-8515, Japan
| | - Pornthap Thanonkeo
- Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen 40002, Thailand; (P.K.); (K.V.); (S.V.)
- Fermentation Research Center for Value Added Agricultural Products (FerVAAPs), Khon Kaen University, Khon Kaen 40002, Thailand
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12
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Patel J, Roy H, Chintamaneni PK, Patel R, Bohara R. Advanced Strategies in Enhancing the Hepatoprotective Efficacy of Natural Products: Integrating Nanotechnology, Genomics, and Mechanistic Insights. ACS Biomater Sci Eng 2025; 11:2528-2549. [PMID: 40211874 PMCID: PMC12076289 DOI: 10.1021/acsbiomaterials.5c00004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 03/13/2025] [Accepted: 03/17/2025] [Indexed: 05/13/2025]
Abstract
Liver disorders like hepatitis, cirrhosis, and hepatocellular carcinoma present a significant global health challenge, with high morbidity and mortality rates. Key factors contributing to liver disorders include inflammation, oxidative stress, and apoptosis. Due to their multifaceted action, natural compounds are promising candidates for mitigating liver-related disorders. Research studies revealed the antioxidant, anti-inflammatory, and detoxifying properties of natural compounds like curcumin, glycyrrhizin, and silymarin and their potential for liver detoxification and protection. With advancements in nanotechnology in drug delivery, natural compounds have improved stability and targetability, thereby enhancing their bioavailability and therapeutic efficiency. Further, recent advancements in genomics and an increased understanding of genetic factors influencing liver disorders and the hepatoprotective effects of natural agents made way for personalized medicine. Moreover, combinatorial therapy with natural products, synthetic drugs, or other natural agents has improved therapeutic outcomes. Even though clinical trials have confirmed the efficiency of natural compounds as hepatoprotective agents, several challenges remain unanswered in their translation to clinical practice. Therefore, it is logical to integrate natural compounds with nanotechnology and genomics to further advance hepatoprotection. This review gives an overview of the substantial progress made in the field of hepatoprotection, with specific emphasis on natural compounds and their integration with nanotechnology and genomics. This provides valuable insights for future research and innovations in developing therapeutic strategies for liver disorders.
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Affiliation(s)
- Jitendra Patel
- Datta
Meghe College of Pharmacy, Datta Meghe Institute
of Higher Education (Deemed to be University), Sawangi (Meghe), Wardha 442001, Maharashtra, India
| | - Harekrishna Roy
- Department
of Pharmaceutics, Nirmala College of Pharmacy, Mangalagiri 522503, Andhra Pradesh, India
| | - Pavan Kuma Chintamaneni
- Department
of Pharmaceutics, GITAM School of Pharmacy, GITAM Deemed to be University, Hyerabad 502329, Telangana, India
| | - Rukmani Patel
- Department
of Chemistry, Bharati University Durg, Durg 491001, Chhattisgarh, India
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13
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Pinto D, Santos I, Teixeira F, Sut S, Vieira M, Salazar M, Delerue-Matos C, Dall'Acqua S, Rodrigues F. Unraveling the nutraceutical potential of Salicornia ramosissima by-product - impact of gastrointestinal digestion and intestinal permeability on in vitro bioactivity. Food Chem 2025; 486:144665. [PMID: 40345033 DOI: 10.1016/j.foodchem.2025.144665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 04/06/2025] [Accepted: 05/05/2025] [Indexed: 05/11/2025]
Abstract
Salicornia ramosissima by-product (SP) is an underexploited antioxidant-rich by-product. This study explored the phytochemical profile, bioaccessibility, and biological activity of SP before and after extraction (SBE and SAE, respectively) upon gastrointestinal simulated digestion and intestinal permeability. The phenolic and flavonoid concentrations increased during digestion, reaching bioaccessibility rates above 95 % for both SBE and SAE. Promising antioxidant/antiradical properties and neuroprotective effects were attested upon digestion. Regarding the phytochemical profile, 17 compounds were identified, including (di)caffeoylquinic acids, gallocatechin, and triterpenoid saponins. The intestinal absorption of bioactive compounds from SAE and SBE intestinal digests was proven through a Caco-2/HT29-MTX cells co-culture model, with 4-caffeoylquinic acid (34.84 %) and 4,5-dicaffeoylquinic acid (26.73 %) reaching the highest permeation rates after 4 h, respectively, for SAE and SBE. These findings support the harnessing of SP as a promising functional and nutraceutical ingredient rich in pro-healthy compounds with proven bioactivity upon in vitro digestion and intestinal permeation.
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Affiliation(s)
- Diana Pinto
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal
| | - Inês Santos
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal
| | - Filipa Teixeira
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal
| | - Stefania Sut
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35121 Padova, Italy
| | - Mónica Vieira
- RISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), CQB, ESS, Polytechnic of Porto, R. Dr. António Bernardino de Almeida, 400, 4200-072 Porto, Portugal
| | - Miguel Salazar
- Agro-On/RiaFresh - Verduras da Ria Formosa, Sítio do Besouro, 8005-421 Faro, Portugal
| | - Cristina Delerue-Matos
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal
| | - Stefano Dall'Acqua
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35121 Padova, Italy.
| | - Francisca Rodrigues
- REQUIMTE/LAQV, ISEP, Polytechnic of Porto, Rua Dr. António Bernardino de Almeida, 4249-015 Porto, Portugal.
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14
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Kruszka J, Martyński J, Szewczyk-Golec K, Woźniak A, Nuszkiewicz J. The Role of Selected Flavonoids in Modulating Neuroinflammation in Alzheimer's Disease: Mechanisms and Therapeutic Potential. Brain Sci 2025; 15:485. [PMID: 40426656 PMCID: PMC12109823 DOI: 10.3390/brainsci15050485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2025] [Revised: 04/29/2025] [Accepted: 05/01/2025] [Indexed: 05/29/2025] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, amyloid-β (Aβ) deposition, tau hyperphosphorylation, oxidative stress, and chronic neuroinflammation. Growing evidence highlights neuroinflammation-driven by microglial activation and pro-inflammatory cytokine release-as a key contributor to AD pathogenesis and progression. In the absence of effective disease-modifying therapies, attention has turned to natural compounds with multi-target potential. Flavonoids, a diverse class of plant-derived polyphenols, have demonstrated neuroprotective properties through antioxidant activity, modulation of neuroinflammatory pathways, and interference with both Aβ aggregation and tau pathology. This narrative review provides an integrative overview of current findings on the mechanisms of action of key flavonoids-such as quercetin, luteolin, and apigenin-in both preclinical and clinical models. Emphasis is placed on their effects on microglial polarization, oxidative stress reduction, mitochondrial support, and synaptic function enhancement. Moreover, flavonoids show synergistic potential when combined with standard pharmacotherapies, such as acetylcholinesterase inhibitors, and may offer broader cognitive benefits in patients with mild cognitive impairment (MCI). Despite these promising findings, significant challenges persist, including poor bioavailability, inter-individual variability, and limited long-term clinical data. This review identifies critical gaps in knowledge and outlines future directions, including targeted drug delivery systems, biomarker-guided personalization, and long-duration trials. Flavonoids thus emerge not only as promising neuroprotective agents but also as complementary candidates in the development of future multi-modal strategies for AD treatment.
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Affiliation(s)
- Joanna Kruszka
- Student Research Club of Medical Biology and Biochemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland;
| | - Jakub Martyński
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland; (J.M.); (K.S.-G.); (J.N.)
| | - Karolina Szewczyk-Golec
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland; (J.M.); (K.S.-G.); (J.N.)
| | - Alina Woźniak
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland; (J.M.); (K.S.-G.); (J.N.)
| | - Jarosław Nuszkiewicz
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland; (J.M.); (K.S.-G.); (J.N.)
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15
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Kishino M, Kanehara R, Mori N, Ishihara J, Takachi R, Yamaji T, Iwasaki M, Tsugane S, Sawada N. Dietary Polyphenol Intake and Risk of Overall and Site-Specific Cancers: the Japan Public Health Center-based Prospective Study. J Nutr 2025:S0022-3166(25)00273-1. [PMID: 40324528 DOI: 10.1016/j.tjnut.2025.04.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/14/2025] [Accepted: 04/27/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Polyphenols may play a protective role in carcinogenesis through a wide range of properties, including antioxidant and anti-inflammatory. However, evidence for the association between total dietary polyphenol intake and cancer risk in Asian populations is limited. OBJECTIVE This population-based prospective study aimed to investigate the association between polyphenol intake and risk of overall and site-specific cancer among Japanese. METHODS Participants were 41,907 men and 48,268 women aged 45-74 y with no previous cancer diagnosis in the Japan Public Health Center-based Prospective Study. Dietary polyphenol intake was estimated by a 147-item food frequency questionnaire administered in 1995-1998. Participants were divided into quintiles (Q) according to intakes of total polyphenol and polyphenol from foods, not including high-polyphenolic beverages (tea, coffee, and alcoholic beverages). Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazard regression models adjusted for potential confounders. RESULTS During a median of 15.8 y of follow-up, 12,970 incident cancer cases (7999 men and 4971 women) were identified. We did not observe associations of lower risk of overall cancer with polyphenol intake. For site-specific cancers, compared with the lowest quintile (Q1), higher total polyphenol intake was associated with a lower risk of liver cancer in men (HRQ4: 0.67; 95% CI: 0.51, 0.89, HRQ5: 0.66; 95% CI: 0.48, 0.89; P-trend = 0.003) and women (HRQ5: 0.63; 95% CI: 0.39, 1.02; P-trend = 0.003), whereas higher polyphenol intake from foods not including tea, coffee, and alcoholic beverages was associated with a lower risk of colon cancer in men (HRQ4: 0.73; 95% CI: 0.58, 0.92, HRQ5: 0.72; 95% CI: 0.54, 0.96; P-trend = 0.07). CONCLUSIONS The results of the present study do not support a substantial role for dietary polyphenols in overall cancer prevention. Total polyphenol may reduce the risk of liver cancer, and polyphenol from foods, not including tea, coffee, and alcoholic beverages, may reduce the risk of colon cancer.
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Affiliation(s)
- Madoka Kishino
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Rieko Kanehara
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
| | - Nagisa Mori
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan; Stony Brook Cancer Center, Stony Brook University, NY, United States
| | - Junko Ishihara
- School of Life and Environmental Science, Department of Food and Life Science, Azabu University, Kanagawa, Japan
| | - Ribeka Takachi
- Department of Food Science and Nutrition, Faculty of Human Life and Environment, Nara Women's University, Nara, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Motoki Iwasaki
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan; Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan; International University of Health and Welfare Graduate School of Public Health, Tokyo, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
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16
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Meng X, Luo S, Yu Z, He F, Xu H, Jin X, Ke L, Zhou J, Gu H, Rao P, Wall P. Formation of polyphenol-based nanoparticles in dried hawthorn with enhanced cellular absorption over free polyphenols. Int J Biol Macromol 2025; 310:143274. [PMID: 40253047 DOI: 10.1016/j.ijbiomac.2025.143274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/05/2025] [Accepted: 04/16/2025] [Indexed: 04/21/2025]
Abstract
Plant-derived nanoparticles are gaining attention for enhancing the delivery and bioavailability of bioactive compounds, though the mechanisms remain unclear. This study aims to investigate dried hawthorn-derived nanoparticles (DHNPs), focusing on their composition, molecular interactions and impact on polyphenol absorption. The results showed that DHNPs, averaging 275.7 nm, were primarily composed of polysaccharides and high content of polyphenolic compounds (∼25%), with covalent and non-covalent interactions forming between them. Saponification increased the polyphenol release, and metabolomics identified 252 polyphenolic compounds, with 195 showing a relative increase post-treatment, including caffeic acid and (-)-catechin. An in vitro intestinal absorption test using Caco-2 cell monolayer model demonstrated that DHNPs-bound polyphenols exhibited significantly higher permeability (27.90%) compared to free polyphenols (12.38%), indicating that endocytosis may serve as a potential pathway through which DHNPs enhance polyphenol absorption. This study provides new insights into the role of plant-derived nanoparticles contributing to bioactive compound delivery and bioavailability.
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Affiliation(s)
- Xiangyu Meng
- UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland
| | - Sihao Luo
- SIBS-Zhejiang Gongshang University Joint Centre for Food and Nutrition Sciences, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Zhaoshuo Yu
- UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland; National Nutrition Surveillance Centre, University College Dublin, Dublin, Ireland; Food for Health Ireland, UCD Institute of Food and Health, University College Dublin, Belfield, Dublin 4, Ireland.
| | - Fangzhou He
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK
| | - Hanlin Xu
- UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland
| | - Xuanlu Jin
- SIBS-Zhejiang Gongshang University Joint Centre for Food and Nutrition Sciences, Zhejiang Gongshang University, Hangzhou 310012, China
| | - Lijing Ke
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK
| | - Jianwu Zhou
- College of Food and Bioengineering, Fujian Polytechnic Normal University, Fuqing, Fujian, China
| | - Huaiyu Gu
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Pingfan Rao
- International Union of Food Science and Technology (IUFoST), Guelph, ON, Canada.; College of Food and Bioengineering, Fujian Polytechnic Normal University, Fuqing, Fujian, China
| | - Patrick Wall
- National Nutrition Surveillance Centre, University College Dublin, Dublin, Ireland; Food for Health Ireland, UCD Institute of Food and Health, University College Dublin, Belfield, Dublin 4, Ireland
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17
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Haider L, Blank-Landeshammer B, Reiter N, Heckmann M, Iken M, Weghuber J, Röhrl C. Enhanced in-vitro bioavailability of curcumin, lutein and isoflavones through interaction with spearmint (Mentha spicata) via its bioactive component (R)-(-)-carvone. J Nutr Biochem 2025; 139:109868. [PMID: 39984059 DOI: 10.1016/j.jnutbio.2025.109868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/12/2025] [Accepted: 02/13/2025] [Indexed: 02/23/2025]
Abstract
Numerous dietary phytochemicals such as curcumin, lutein and isoflavones are associated with health beneficial activities, however their application is often limited by their low bioavailability. Therefore, bioenhancers represent a feasible approach to increase the absorption efficiency of bioactive compounds. Here, we combined uptake and transport studies in differentiated Caco-2 cells with high resolution analytics and fractionation to evaluate the impact of spearmint (Mentha spicata) on the cellular uptake of curcumin. Additionally, we utilized mechanistic studies in native and overexpressing cell systems to assess P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporter activity as well as in-silico molecular docking simulations. We found significantly elevated intracellular curcuminoid levels mediated by spearmint. Fractionation and functional assays identified (R)-(-)-carvone as a putative candidate for the biologically active compound mediating increased curcumin uptake via BCRP inhibition. Inhibition of P-gp-mediated efflux might additionally be involved. Molecular docking simulations suggest a common binding site of curcumin and (R)-(-)-carvone in BCRP. Further, spearmint significantly increased cellular uptake of lutein and transintestinal transport of isoflavones in-vitro. In summary, spearmint was identified as a novel bioenhancer for curcumin, lutein and isoflavones. Our findings suggest that spearmint increases bioavailability of a wide range of nutrients and drugs at least partially due to interference with BCRP via its active compound (R)-(-)-carvone.
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Affiliation(s)
- Lisa Haider
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Wels, Austria
| | - Bernhard Blank-Landeshammer
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Wels, Austria; Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria
| | - Nadine Reiter
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria
| | - Mara Heckmann
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria
| | - Marcus Iken
- PM International AG, 5445, Schengen, Luxembourg
| | - Julian Weghuber
- FFoQSI GmbH-Austrian Competence Centre for Feed and Food Quality, Safety and Innovation, Wels, Austria; Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria.
| | - Clemens Röhrl
- Center of Excellence Food Technology and Nutrition, University of Applied Sciences Upper Austria, Wels, Austria.
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18
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Islam MR, Al-Imran MIK, Zehravi M, Sweilam SH, Mortuza MR, Gupta JK, Shanmugarajan TS, Devi K, Tummala T, Alshehri MA, Rajagopal K, Asiri M, Ahmad I, Emran TB. Targeting signaling pathways in neurodegenerative diseases: Quercetin's cellular and molecular mechanisms for neuroprotection. Animal Model Exp Med 2025; 8:798-818. [PMID: 39843406 DOI: 10.1002/ame2.12551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 12/15/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Neurodegenerative diseases (NDs), including Alzheimer's disease, Parkinson's disease, and Huntington's disease, are complex and challenging due to their intricate pathophysiology and limited treatment options. METHODS This review systematically sourced articles related to neurodegenerative diseases, neurodegeneration, quercetin, and clinical studies from primary medical databases, including Scopus, PubMed, and Web of Science. RESULTS Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration. Quercetin, a flavonoid abundant in vegetables and fruits, is gaining attention for its antioxidant, anti-inflammatory, and antiapoptotic properties. It regulates signaling pathways such as nuclear factor-κB (NF-κB), sirtuins, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt). These pathways are essential for cellular survival, inflammation regulation, and apoptosis. Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models, indicating promising outcomes. CONCLUSIONS The study explores the potential of incorporating laboratory research into practical medical treatment, focusing on quercetin's neuroprotective effects on NDs and its optimal dosage.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Daffodil Smart City, Bangladesh
| | - Md Ibrahim Khalil Al-Imran
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Daffodil Smart City, Bangladesh
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy, College of Dentistry and Pharmacy, Buraydah Private Colleges, Buraydah, Saudi Arabia
| | - Sherouk Hussein Sweilam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
- Department of Pharmacognosy, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
| | | | - Jeetendra Kumar Gupta
- Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Thukani Sathanantham Shanmugarajan
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Chennai, India
| | - Kadirvel Devi
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Chennai, India
| | - Tanuja Tummala
- Department of Polymer Chemistry, Pittsburg State University, Pittsburg, Kansas, USA
| | | | - Kalirajan Rajagopal
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, India
| | - Mohammed Asiri
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Health and Life Sciences, Daffodil International University, Daffodil Smart City, Bangladesh
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19
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Liang W, Lu J, Yu P, Cai M, Xie D, Chen X, Zhang X, Tian L, Yan L, Lan W, Liu Z, Zhou X, Tang L. Evaluation of pharmacokinetics and metabolism of three marine-derived piericidins for guiding drug lead selection. Chin J Nat Med 2025; 23:614-629. [PMID: 40383617 DOI: 10.1016/s1875-5364(25)60866-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/25/2024] [Accepted: 12/30/2024] [Indexed: 05/20/2025]
Abstract
This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
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Affiliation(s)
- Weimin Liang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Jindi Lu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Ping Yu
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Meiqun Cai
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Danni Xie
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Xini Chen
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Xi Zhang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Lingmin Tian
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Liyan Yan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Wenxun Lan
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China
| | - Zhongqiu Liu
- International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
| | - Xuefeng Zhou
- CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
| | - Lan Tang
- NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 China.
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20
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Wang L, Wei C, Jing J, Shao M, Wang Z, Wen B, Lu M, Jia Z, Zhang Y. The Effects of Polyphenols on Doxorubicin-Induced Nephrotoxicity by Modulating Inflammatory Cytokines, Apoptosis, Oxidative Stress, and Oxidative DNA Damage. Phytother Res 2025; 39:2147-2164. [PMID: 40091446 DOI: 10.1002/ptr.8470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 12/10/2024] [Accepted: 02/20/2025] [Indexed: 03/19/2025]
Abstract
Doxorubicin (DOX) is an anthracyclic antibiotic with anti-neoplastic activity that has been found to be a highly effective and commonly used chemotherapeutic agent in the treatment of a variety of solid and hematologic malignancies. However, its effectiveness has been limited by the occurrence of dose-related renal, myocardial, and bone marrow toxicities. The clinical use of DOX is associated with nephrotic syndrome characterized by heavy proteinuria, hypoalbuminemia, and hyperlipidemia. DOX-induced changes in the renal tissue of rats include increased glomerular capillary permeability and tubular atrophy. Several lines of evidence suggest that reactive oxygen species and oxidative stress have been associated with DOX-induced renal damage. The mechanism of DOX-induced nephrotoxicity is believed to be mediated through free radical formation, iron-dependent oxidative damage of biological macromolecules, and membrane lipid peroxidation. Polyphenols are present in high concentration in fruits and vegetables. They have been shown to have potent antioxidant and cytoprotective effects in preventing endothelial apoptosis caused by oxidants. Treatment with polyphenols has been shown to prevent liver damage and suppress overexpression of inducible nitric oxide synthase, which is induced by various inflammatory stimuli. In addition, epidemiological studies have suggested that the intake of polyphenols may be associated with a reduced risk of DOX-induced nephrotoxicity by modulating inflammatory cytokines, apoptosis, oxidative stress, and oxidative DNA damage. Therefore, in the present review, we examined the influence of polyphenols on DOX-induced nephrotoxicity.
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Affiliation(s)
- Lang Wang
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
| | - Can Wei
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
| | - Junfeng Jing
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
| | - Mingmin Shao
- College of Humanities and Social Sciences, Shanxi Medical University, Taiyuan, China
| | - Zhen Wang
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
| | - Bo Wen
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
| | - Mingming Lu
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
| | - Zhenzhen Jia
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
| | - Yanbin Zhang
- Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, China
- The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, China
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21
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Gómez-Rocal S, Cruz-Carrión Á, Morales D, García-Ruiz A, Suárez M, Arola-Arnal A. Foodomics approaches: New insights in phenolic compounds analysis. Food Res Int 2025; 208:116168. [PMID: 40263832 DOI: 10.1016/j.foodres.2025.116168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 02/27/2025] [Accepted: 03/09/2025] [Indexed: 04/24/2025]
Abstract
Fruits, vegetables, and plant-based foods contain several bioactive substances such as phenolic compounds (PCs), that are plant secondary metabolites with attributed health properties. The study of the metabolic pathways of PCs, including those related with their synthesis, transport, accumulation, and degradation are essential to advance in this field of research. In this regard, omics tools such as foodomics are gaining relevance due to their versatility and their tremendous potential to generate significant advances in PC research. In this review, we present a comprehensive overview of the applications of omics technologies in PC analysis, including transcriptomics, micromics, proteomics and metabolomics, highlighting their role in metabolic pathways, current limitations, and emerging insights. Omics techniques as well as data analyses are continuously progressing, emerging new opportunities with onset of artificial intelligence and machine learning. However, significant limitations and challenges still remain. The immense diversity of PC chemical structures and their variability across plant species, varieties, and impact of agronomic factors complicate the analyses and limit the extrapolation of findings. Additionally, high data dimensionality, strong correlations among measured variables, and general lack of standardization in the different omics techniques can impact in the results. Addressing these limitations requires integrating multi-omics approaches and developing standardized protocols to enhance comparability and interpretation in PC research. In summary, foodomics approaches arise as essential for the complete mapping of PC biosynthesis.
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Affiliation(s)
- Saioa Gómez-Rocal
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona 43007, Spain; Institute of Health Pere Virgili (IISPV), Reus, 43204, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TecnATox), Reus 43201, Spain
| | - Álvaro Cruz-Carrión
- Arkansas Children's Nutrition Center, Little Rock, AR 72202, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
| | - Diego Morales
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona 43007, Spain
| | - Almudena García-Ruiz
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona 43007, Spain; Institute of Health Pere Virgili (IISPV), Reus, 43204, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TecnATox), Reus 43201, Spain
| | - Manuel Suárez
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona 43007, Spain; Institute of Health Pere Virgili (IISPV), Reus, 43204, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TecnATox), Reus 43201, Spain.
| | - Anna Arola-Arnal
- Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Tarragona 43007, Spain; Institute of Health Pere Virgili (IISPV), Reus, 43204, Spain; Universitat Rovira i Virgili, Center of Environmental, Food and Toxicological Technology (TecnATox), Reus 43201, Spain
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22
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Froyen EB, Barrantes GP. A Review of the Effects of Flavonoids on NAD(P)H Quinone Oxidoreductase 1 Expression and Activity. J Med Food 2025; 28:407-422. [PMID: 40097203 DOI: 10.1089/jmf.2023.0132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025] Open
Abstract
Cancer is a significant cause of death worldwide. It has been suggested that the consumption of flavonoids decreases the risk for cancer by increasing phase II enzymes, such as Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NAD(P)H) quinone oxidoreductase 1 (NQO1), glutathione S-transferases, and Uridine 5'-diphospho- (UDP)-glucuronosyltransferases that assist in removing carcinogens from the human body. Flavonoids are bioactive compounds found in a variety of dietary sources, including fruits, vegetables, legumes, nuts, and teas. As such, it is important to investigate which flavonoids are involved in the metabolism of carcinogens to help reduce the risk of cancer. Therefore, the objective of this narrative review was to investigate the effects of commonly consumed flavonoids on NQO1 mRNA expression, protein, and activity in human cell and murine models. PubMed was used to search for peer-reviewed journal articles, which demonstrated that selected flavonoids (e.g., quercetin, apigenin, luteolin, genistein, and daidzein) increase NQO1, and therefore, increase the excretion of carcinogens. However, more research is needed regarding the mechanisms by which flavonoids induce NQO1. Furthermore, it is suggested that future efforts focus on providing precise flavonoid recommendations to decrease the risk factors for chronic diseases.
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Affiliation(s)
- Erik B Froyen
- Department of Nutrition and Food Science, Huntley College of Agriculture, California State Polytechnic University, Pomona, California, USA
| | - Gianluis Pimentel Barrantes
- Department of Nutrition and Food Science, Huntley College of Agriculture, California State Polytechnic University, Pomona, California, USA
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23
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Krupa-Kozak U, Płatosz N, Bączek N, Šimková K, Starowicz M. Increased content of bioactive compounds and health benefits of gluten-free sponge cakes resulting from enrichment with freeze-dried berry powders. Food Chem 2025; 472:142861. [PMID: 39967066 DOI: 10.1016/j.foodchem.2025.142861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/16/2024] [Accepted: 01/09/2025] [Indexed: 02/20/2025]
Abstract
Berries are not only appreciated for their distinctive taste and flavor, but they are also highly valued for their nutritional and health-promoting properties. This study aimed to develop appealing new gluten-free sponge cakes (GFS) enriched with bioactive phytochemicals using berry powders. Freeze-dried powders of raspberry (R), blackberry (B), and blueberry (L) were used to replace 2 % of the starch in the experimental GFS formulation. This study analyzed the profile and content of phenolic acids, flavonoids, and anthocyanins, and assessed the antiglycation activity using spectrophotometric methods. Additionally, the color and textural parameters, as well as consumer preferences for the GFS, were evaluated. The application of berry powders in the experimental formulation significantly increased (p < 0.05) the content of phenolic acids, flavonoids, and anthocyanins in all the berry-enriched sponge cakes, although the degree of increase varied, depending on the berry used. All the berry-enriched sponge cakes acquired a pleasant reddish tint, with the raspberry sponge cake (GFR) receiving the highest scores for sensory attractiveness. However, the textural parameters (hardness, gumminess, and chewiness) of all the berry-enriched sponge cakes were negatively affected compared to the control. These findings indicate that incorporating berry powders into GFS formulations can create a visually appealing and tasty option for health-conscious consumers, particularly those with dietary restrictions such as celiac disease.
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Affiliation(s)
- Urszula Krupa-Kozak
- Chemistry and Biodynamics of Food Team, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10 Tuwima Street, 10-748 Olsztyn, Poland.
| | - Natalia Płatosz
- Chemistry and Biodynamics of Food Team, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10 Tuwima Street, 10-748 Olsztyn, Poland.
| | - Natalia Bączek
- Chemistry and Biodynamics of Food Team, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10 Tuwima Street, 10-748 Olsztyn, Poland.
| | - Kristýna Šimková
- Chemistry and Biodynamics of Food Team, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10 Tuwima Street, 10-748 Olsztyn, Poland; University of Ljubljana, Biotechnology Faculty, Department of Agronomy, Jamnikarjeva 101, Ljubljana 1000, Slovenia.
| | - Małgorzata Starowicz
- Chemistry and Biodynamics of Food Team, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, 10 Tuwima Street, 10-748 Olsztyn, Poland.
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24
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Frumuzachi O, Mocan A, Rohn S, Gavrilaș L. Impact of a Chokeberry ( Aronia melanocarpa (Michx.) Elliott) Supplementation on Cardiometabolic Outcomes: A Critical Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 2025; 17:1488. [PMID: 40362797 PMCID: PMC12073822 DOI: 10.3390/nu17091488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/26/2025] [Accepted: 04/27/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Chokeberry (Aronia melanocarpa (Michx.) Elliott) is a (poly)phenol-rich fruit with purported cardiometabolic benefits. However, the evidence from randomized controlled trials (RCTs) remains inconclusive. This systematic review and meta-analysis aimed to assess the effects of chokeberry supplementation on cardiometabolic outcomes, including anthropometric parameters, glycemic control, lipid profile, and blood pressure in adults. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science through January 2025. RCTs investigating chokeberry supplementation (≥2 weeks) in adults (≥18 years) with or without cardiometabolic risk factors were included. A random effects model was used to pool effect sizes, expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, and risk of bias was evaluated with the Cochrane risk of bias 1 (RoB 1) tool. Trial sequential analysis (TSA) was performed to assess the conclusiveness of the evidence. Certainty of evidence was rated using GRADE. Results: Ten RCTs (n = 666 participants) met the inclusion criteria. Chokeberry supplementation had no significant effects on cardiometabolic outcomes under evaluation. Subgroup analysis suggested that a chokeberry supplementation could reduce total cholesterol and LDL-C in individuals with a baseline total plasma cholesterol <200 mg/dL, and systolic blood pressure with interventions, containing >50 mg/day anthocyanin, while increasing fasting blood glucose in individuals ≤50 years old. Risk of bias was unclear or high in several studies, TSA indicated inconclusive evidence for most outcomes, and the certainty of evidence was rated as very low across all cardiometabolic markers. Conclusions: Chokeberry supplementation did not significantly improve cardiometabolic outcomes in the general adult population. Limited evidence is given for potential lipid-lowering and blood pressure effects in specific subgroups. However, a high risk of bias accompanies these results. More robust RCTs with standardized interventions and dietary assessments are needed.
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Affiliation(s)
- Oleg Frumuzachi
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany;
- Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Andrei Mocan
- Department of Pharmaceutical Botany, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Sascha Rohn
- Department of Food Chemistry and Analysis, Institute of Food Technology and Food Chemistry, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany;
| | - Laura Gavrilaș
- Department 2, Faculty of Nursing and Health Sciences, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Gheorghe Marinescu Street, 400337 Cluj-Napoca, Romania;
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25
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Geertsema J, Juncker HG, Wilmes L, Burchell GL, de Rooij SR, van Goudoever JB, O'Riordan KJ, Clarke G, Cryan JF, Korosi A. Nutritional interventions to counteract the detrimental consequences of early-life stress. Mol Psychiatry 2025:10.1038/s41380-025-03020-1. [PMID: 40289212 DOI: 10.1038/s41380-025-03020-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 03/19/2025] [Accepted: 04/07/2025] [Indexed: 04/30/2025]
Abstract
Exposure to stress during sensitive developmental periods comes with long term consequences for neurobehavioral outcomes and increases vulnerability to psychopathology later in life. While we have advanced our understanding of the mechanisms underlying the programming effects of early-life stress (ES), these are not yet fully understood and often hard to target, making the development of effective interventions challenging. In recent years, we and others have suggested that nutrition might be instrumental in modulating and possibly combatting the ES-induced increased risk to psychopathologies and neurobehavioral impairments. Nutritional strategies are very promising as they might be relatively safe, cheap and easy to implement. Here, we set out to comprehensively review the existing literature on nutritional interventions aimed at counteracting the effects of ES on neurobehavioral outcomes in preclinical and clinical settings. We identified eighty six rodent and ten human studies investigating a nutritional intervention to ameliorate ES-induced impairments. The human evidence to date, is too few and heterogeneous in terms of interventions, thus not allowing hard conclusions, however the preclinical studies, despite their heterogeneity in terms of designs, interventions used, and outcomes measured, showed nutritional interventions to be promising in combatting ES-induced impairments. Furthermore, we discuss the possible mechanisms involved in the beneficial effects of nutrition on the brain after ES, including neuroinflammation, oxidative stress, hypothalamus-pituitary-adrenal axis regulation and the microbiome-gut-brain axis. Lastly, we highlight the critical gaps in our current knowledge and make recommendations for future research to move the field forward.
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Affiliation(s)
- Jorine Geertsema
- Brain Plasticity group, Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
| | - Hannah G Juncker
- Brain Plasticity group, Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Emma Children's Hospital, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
| | - Lars Wilmes
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - George L Burchell
- Medical Library, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
| | - Susanne R de Rooij
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
- Amsterdam UMC location University of Amsterdam, Department of Epidemiology and Data Science, Meibergdreef 9, Amsterdam, The Netherlands
- Amsterdam Public Health research institute, Aging and Later Life, Health Behaviors and Chronic Diseases, Amsterdam, The Netherlands
| | - J B van Goudoever
- Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Emma Children's Hospital, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development, Amsterdam, The Netherlands
| | | | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Aniko Korosi
- Brain Plasticity group, Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
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26
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Yeh TS, Blacker D, Willett WC. Dietary Factors and Cognitive Function: with a Focus on Subjective Cognitive Decline. Curr Nutr Rep 2025; 14:62. [PMID: 40285979 DOI: 10.1007/s13668-025-00638-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2025] [Indexed: 04/29/2025]
Abstract
PURPOSE OF THE REVIEW Age-related cognitive decline is an important global challenge. Substantial evidence suggests that diet may prevent or delay cognitive aging. This narrative review examines recent literature on how dietary factors influence cognitive function, with a focus on subjective cognitive decline (SCD). RECENT FINDINGS Higher intakes of flavonoids, carotenoids, and plant-based protein were associated with lower odds of SCD. Berries, citrus fruits and juices, carotenoid-rich and green leafy vegetables, and beans/legumes were among the foods with the strongest inverse associations with SCD. Healthy dietary patterns, such as the Mediterranean and MIND diet, may be beneficial for maintaining subjective cognitive function. Healthy choice of diet may play a role in lowering the risk of late-life SCD.
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Affiliation(s)
- Tian-Shin Yeh
- Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, No.250, Wuxing St, Taipei, 11031, Taiwan.
- Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, New Taipei, 23561, Taiwan.
- Department of Physical Medicine and Rehabilitation, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
- Department of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
- Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK.
| | - Deborah Blacker
- Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Walter C Willett
- Department of Nutrition and Epidemiology, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA
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Thongbai B, Sukboonyasatit D, Banlue K, Inchuen S, Chuenta W, Siriamornpun S, Suwannarong S. Cascara Kombucha: The Role of Fermentation and Particle Size in Enhancing Antioxidant and Bioactive Properties. Molecules 2025; 30:1934. [PMID: 40363742 PMCID: PMC12073165 DOI: 10.3390/molecules30091934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025] Open
Abstract
This study aims to evaluate the effects of different cascara particle sizes and variations in the kombucha fermentation process on the bioactive compounds and antioxidant properties of cascara (Coffea arabica L.) kombucha. Cascara tea (CT), cascara tea with sugar (CS), and cascara kombucha (CK) were prepared using whole, coarsely ground, and finely ground cascara. A finer particle size enhanced color intensity and improved the extraction of bioactive compounds. CK prepared with finely ground cascara demonstrated the highest total phenolic content (TPC), total flavonoid content (TFC), and ferric reducing antioxidant power (FRAP). Fermentation influenced the profile of phenolic acids, leading to a decline in most compounds, except for vanillic acid in all CK samples, which increased during fermentation. Interestingly, apigenin levels increased, while quercetin levels decreased throughout fermentation. These findings highlight the role of fermentation, sugar addition, and particle size reduction in enhancing phenolic extraction and antioxidant potential in cascara-based beverages, particularly cascara kombucha.
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Affiliation(s)
- Bussagon Thongbai
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
| | - Duljira Sukboonyasatit
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
| | - Kriangsak Banlue
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
- Research Unit of Thai Food Innovation (TFI), Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand
| | - Sudathip Inchuen
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
| | - Wanida Chuenta
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
- Research Unit of Thai Food Innovation (TFI), Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand
| | - Sirithon Siriamornpun
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
- Research Unit of Thai Food Innovation (TFI), Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand
| | - Sarinthorn Suwannarong
- Department of Food Technology and Nutrition, Faculty of Technology, Mahasarakham University, Kantarawichai, Maha Sarakham 44150, Thailand; (B.T.); (D.S.); (K.B.); (S.I.); (W.C.); (S.S.)
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28
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Khan G, Hussain MS, Sultana A, Khan Y, Fatima R, Maqbool M, Bisht AS. Unveiling the Therapeutic Potential of Rumex abyssinicus: Phytochemical Insights and Pharmacological Applications. CURRENT PHARMACOLOGY REPORTS 2025; 11:32. [DOI: 10.1007/s40495-025-00411-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/10/2025] [Indexed: 05/04/2025]
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29
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Muscolo A, Maffia A, Marra F, Battaglia S, Oliva M, Mallamaci C, Russo M. Unlocking the Health Secrets of Onions: Investigating the Phytochemical Power and Beneficial Properties of Different Varieties and Their Parts. Molecules 2025; 30:1758. [PMID: 40333741 PMCID: PMC12029492 DOI: 10.3390/molecules30081758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/11/2025] [Accepted: 04/11/2025] [Indexed: 05/09/2025] Open
Abstract
Onions (Allium cepa L.) are widely consumed worldwide and are recognized for their high content of bioactive compounds with potential health benefits. This study investigates the nutritional and phytochemical properties of three onion varieties-Tropea red onion, red onion, and yellow onion-analyzed in their whole form as well as in their peel and pulp. An innovative drying system was employed to assess its impact on the retention of bioactive compounds. The results highlight significant differences in nutrient composition among varieties and onion parts. The peel exhibited the highest concentrations of proteins, phenolic compounds, flavonoids, and antioxidants, followed by the whole onion and pulp. Tropea red onion stood out for its superior antioxidant capacity, vitamin C content, and phenolic acid levels, reinforcing its potential for functional food applications. This study also revealed that mineral content, particularly calcium, potassium, and sulfates, varied across onion varieties, influencing their nutritional and health-promoting properties. These findings support the valorization of onion byproducts for their bioactive potential and sustainability in the food industry. The data emphasize the need for further research on innovative processing techniques that enhance the bioavailability and effectiveness of onion-derived health-promoting compounds.
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Affiliation(s)
- Adele Muscolo
- Department of Agraria, Mediterranea University, Feo di Vito, 89122 Reggio Calabria, Italy; (A.M.); (F.M.); (S.B.); (M.O.); (C.M.); (M.R.)
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30
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Cano-Lou J, Millán-Laleona A, Candrea R, Les F, Pina A, Caprioli G, López V. Apple peels as an edible source of phenolic bioactive compounds with antidiabetic and antiglycation properties. Food Funct 2025; 16:2947-2958. [PMID: 40065740 DOI: 10.1039/d4fo05241b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/15/2025]
Abstract
Apples (Malus domestica Borkh.) are one of the most consumed fruits around the world with a high production of peels as wastes and by-products. In this work, peels from different commercial and local apple samples are explored as a source of phenolic bioactive compounds that could be directly related to the prevention of type 2 diabetes. Six different cultivars from local and commercial apple samples were processed to obtain the phenolic compounds by ultrasonication of the peels using methanol as the solvent. The phenolic content was explored using the Folin-Ciocalteu assay and the quantification of 37 individual phenolic compounds was carried out by high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS/MS). Cellular viability was determined by performing the MTT assay in Caco-2 cell cultures exposed to the phenolic extracts. Subsequently, the capacity to inhibit α-glucosidase, α-amylase and pancreatic lipase enzymes, as well as antiglycation and antioxidant activities, was evaluated. These apple peel samples were considered a source of phenolic compounds with hyperoside, delphinidin 3,5-diglucoside, chlorogenic acid, phlorizin, epicatechin and procyanidin B2 as the main constituents. All samples neutralized the production of advanced glycation end-products and exhibited antiradical activities in a dose-dependent manner; four samples (Amarilla de Octubre, Manzana Helada, Verde Doncella and Pinova) inhibited α-glucosidase but only the sample known as "Amarilla de Octubre" was successful in inhibiting pancreatic α-amylase. Cytotoxicity was discarded in Caco-2 cell cultures at physiological concentrations considering these extracts as a source of phenolic compounds with antidiabetic, antiglycation and antioxidant properties.
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Affiliation(s)
- Javier Cano-Lou
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830, Zaragoza, Spain.
- Institute of Agri-food Research of Aragón, IA2, Zaragoza University-CITA, 50013, Zaragoza, Spain
| | - Adrián Millán-Laleona
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830, Zaragoza, Spain.
- Institute of Agri-food Research of Aragón, IA2, Zaragoza University-CITA, 50013, Zaragoza, Spain
| | - Rares Candrea
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830, Zaragoza, Spain.
| | - Francisco Les
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830, Zaragoza, Spain.
- Institute of Agri-food Research of Aragón, IA2, Zaragoza University-CITA, 50013, Zaragoza, Spain
| | - Ana Pina
- Unidad de Hortofruticultura, Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA), Av Montañana 930, 50059, Zaragoza, Spain
| | - Giovanni Caprioli
- Chemistry Interdisciplinary Project (ChIP), School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032, Camerino, Italy
| | - Víctor López
- Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830, Zaragoza, Spain.
- Institute of Agri-food Research of Aragón, IA2, Zaragoza University-CITA, 50013, Zaragoza, Spain
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Hernández-Fuentes GA, Sanchez-Ramirez CA, Cortes-Alvarez SI, Rodriguez-Hernández A, Cabrera-Medina AO, Moy-López NA, Guzman-Muñiz J, Garza-Veloz I, Rodriguez-Sanchez IP, Martinez-Fierro ML, Álvarez-Barajas JJ, Cortes-Alvarez NY, Ceballos-Magaña SG, Meza-Robles C, Delgado-Enciso I. Moringa oleifera Leaf Infusion as a Functional Beverage: Polyphenol Content, Antioxidant Capacity, and Its Potential Role in the Prevention of Metabolopathies. Life (Basel) 2025; 15:636. [PMID: 40283190 PMCID: PMC12028896 DOI: 10.3390/life15040636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/29/2025] Open
Abstract
Moringa oleifera (MO) leaf infusion has gained attention for its potential therapeutic effects, particularly in metabolic health, due to its rich content of bioactive compounds, including polyphenols. The study evaluates the antioxidant properties and metabolic effects of the prophylactic administration of MO infusion in a high-fat diet (HFD)-induced murine model. First, polyphenol content (0.45 mg/g) and antioxidant activity (45.39%) were determined using Folin-Ciocalteu, DPPH, phosphomolybdenum, ferrocyanide, and anti-browning assays. In the in vivo phase, BALB/c mice were divided into three groups: a balanced diet group, a negative control group, and an HFD group supplemented with MO infusion. Over eight months, biochemical analyses, psychomotor tests, glucose tolerance assessments, and liver histopathology were conducted. MO infusion significantly reduced food intake, weight gain, lipid profiles, and liver inflammation compared to the negative control group, while promoting a metabolic profile similar to that of the balanced diet group. Additionally, it positively influenced psychomotor performance, reinforcing its neuroactive potential. These findings suggest that MO leaf infusion may serve as a functional beverage with protective effects against metabolic disorders, offering a promising natural strategy for managing obesity-related health issues.
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Affiliation(s)
- Gustavo A. Hernández-Fuentes
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
- Colima State Institute of Cancerology, IMSS-Bienestar, Colima 28085, Mexico;
- Faculty of Chemical Sciences, University of Colima, Coquimatlan 28400, Mexico;
| | - Carmen A. Sanchez-Ramirez
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
| | - Salma I. Cortes-Alvarez
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
- Colima State Institute of Cancerology, IMSS-Bienestar, Colima 28085, Mexico;
| | - Alejandrina Rodriguez-Hernández
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
| | - Ana O. Cabrera-Medina
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
| | - Norma A. Moy-López
- Laboratory of Neuroscience, School of Psychology, University of Colima, Colima 28040, Mexico; (N.A.M.-L.); (J.G.-M.); (N.Y.C.-A.)
| | - Jorge Guzman-Muñiz
- Laboratory of Neuroscience, School of Psychology, University of Colima, Colima 28040, Mexico; (N.A.M.-L.); (J.G.-M.); (N.Y.C.-A.)
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico; (I.G.-V.); (M.L.M.-F.)
| | - Iram P. Rodriguez-Sanchez
- Molecular and Structural Physiology Laboratory, School of Biological Sciences, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66455, Mexico;
| | - Margarita L. Martinez-Fierro
- Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas 98160, Mexico; (I.G.-V.); (M.L.M.-F.)
| | | | - Nadia Y. Cortes-Alvarez
- Laboratory of Neuroscience, School of Psychology, University of Colima, Colima 28040, Mexico; (N.A.M.-L.); (J.G.-M.); (N.Y.C.-A.)
- Department of Nursing and Midwifery, Division of Natural and Exact Sciences, University of Guanajuato, Guanajuato 36259, Mexico
| | | | - Carmen Meza-Robles
- Colima State Institute of Cancerology, IMSS-Bienestar, Colima 28085, Mexico;
| | - Iván Delgado-Enciso
- Department of Molecular Medicine, School of Medicine, University of Colima, Colima 28040, Mexico; (G.A.H.-F.); (S.I.C.-A.); (A.R.-H.); (A.O.C.-M.)
- Colima State Institute of Cancerology, IMSS-Bienestar, Colima 28085, Mexico;
- Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA
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32
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Rosic N. Unveiling the Anti-Aging Potential of Marine Natural Bioproducts. Mar Drugs 2025; 23:165. [PMID: 40278286 PMCID: PMC12028505 DOI: 10.3390/md23040165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world's aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications.
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Affiliation(s)
- Nedeljka Rosic
- Faculty of Health, Southern Cross University, Gold Coast, QLD 4225, Australia;
- Marine Ecology Research Centre, Southern Cross University, Lismore, NSW 2480, Australia
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Nicolaescu OE, Ionescu C, Samide A, Tigae C, Spînu CI, Oprea B. Advancements in Cyclodextrin Complexes with Bioactive Secondary Metabolites and Their Pharmaceutical Applications. Pharmaceutics 2025; 17:506. [PMID: 40284503 PMCID: PMC12030412 DOI: 10.3390/pharmaceutics17040506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 04/09/2025] [Accepted: 04/09/2025] [Indexed: 04/29/2025] Open
Abstract
Cyclodextrins (CDs) have largely been investigated during the last decades for their outstanding properties, such as biocompatibility and biodegradability, with wide applications in the pharmaceutical field, among which the formation of inclusion complexes (ICs) with natural or synthetic lipophilic compounds. This review prioritizes the research of recent years (2022-2025), being focused on (1) systematization of the research of ICs based on the structure of the secondary metabolite, namely (i) polyphenols (PPs), (ii) terpenes and terpenoids (TTs), and (iii) alkaloids (Alks); (2) for each type of inclusion complex, the following aspects have been discussed: benefits of complexation, composite materials, and in vitro/in vivo and theoretical studies; and (3) pharmacokinetics and pharmacodynamics, risks, limitations, and perspectives of cyclodextrin inclusion complexes with secondary metabolites.
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Affiliation(s)
- Oana Elena Nicolaescu
- Department of Pharmaceutical Technique, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareş, 200349 Craiova, Dolj, Romania;
| | - Cătălina Ionescu
- Department of Chemistry, Faculty of Sciences, University of Craiova, 107i Calea București, 200144 Craiova, Dolj, Romania; (A.S.); (C.T.); (C.I.S.)
| | - Adriana Samide
- Department of Chemistry, Faculty of Sciences, University of Craiova, 107i Calea București, 200144 Craiova, Dolj, Romania; (A.S.); (C.T.); (C.I.S.)
| | - Cristian Tigae
- Department of Chemistry, Faculty of Sciences, University of Craiova, 107i Calea București, 200144 Craiova, Dolj, Romania; (A.S.); (C.T.); (C.I.S.)
| | - Cezar Ionuţ Spînu
- Department of Chemistry, Faculty of Sciences, University of Craiova, 107i Calea București, 200144 Craiova, Dolj, Romania; (A.S.); (C.T.); (C.I.S.)
| | - Bogdan Oprea
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 2 Petru Rares, 200349 Craiova, Dolj, Romania;
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Lešnik S, Jukić M, Bren U. Unveiling polyphenol-protein interactions: a comprehensive computational analysis. J Cheminform 2025; 17:50. [PMID: 40211304 PMCID: PMC11983793 DOI: 10.1186/s13321-025-00997-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 03/25/2025] [Indexed: 04/14/2025] Open
Abstract
Our study investigates polyphenol-protein interactions, analyzing their structural diversity and dynamic behavior. Analysis of the entire Protein Data Bank reveals diverse polyphenolic structures, engaging in various noncovalent interactions with proteins. Interactions observed across crystal structures among diverse polyphenolic classes reveal similarities, underscoring consistent patterns across a spectrum of structural motifs. On the other hand, molecular dynamics (MD) simulations of polyphenol-protein complexes unveil dynamic binding patterns, highlighting the influx of water molecules into the binding site and underscoring limitations of static crystal structures. Water-mediated interactions emerge as crucial in polyphenol-protein binding, leading to variable binding patterns observed in MD simulations. Comparison of high- and low-resolution crystal structures as starting points for MD simulations demonstrates their robustness, exhibiting consistent dynamics regardless of the quality of the initial structural data. Additionally, the impact of glycosylation on polyphenol binding is explored, revealing its role in modulating interactions with proteins. In contrast to synthetic drugs, polyphenol binding seems to exhibit heightened flexibility, driven by dynamic water-mediated interactions, which may also facilitate their promiscuous binding. Comprehensive dynamic studies are, therefore essential to understand polyphenol-protein recognition mechanisms. Overall, our study provides novel insights into polyphenol-protein interactions, informing future research for harnessing polyphenolic therapeutic potential through rational drug design.Scientific contribution: In this study, we present an analysis of (natural) polyphenol-protein binding conformations, leveraging the entirety of the Protein Data Bank structural data on polyphenols, while extending the binding conformation sampling through molecular dynamics simulations. For the first time, we introduce experimentally supported large-scale systematization of polyphenol binding patterns. Moreover, our insight into the significance of explicit water molecules and hydrogen-bond bridging rationalizes the polyphenol promiscuity paradigm, advocating for a deeper understanding of polyphenol recognition mechanisms crucial for informed natural compound-based drug design.
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Affiliation(s)
- Samo Lešnik
- Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000, Maribor, Slovenia
- IOS, Institute of Environmental Protection and Sensors, Beloruska 7, 2000, Maribor, Slovenia
| | - Marko Jukić
- Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000, Maribor, Slovenia
- Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000, Koper, Slovenia
| | - Urban Bren
- Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova 17, 2000, Maribor, Slovenia.
- IOS, Institute of Environmental Protection and Sensors, Beloruska 7, 2000, Maribor, Slovenia.
- Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000, Koper, Slovenia.
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Tillman L, Margalef Rieres J, Ahjem E, Bishop-Guest F, McGrath M, Hatrick H, Pranjol MZI. Thinking Outside the Therapeutic Box: The Potential of Polyphenols in Preventing Chemotherapy-Induced Endothelial Dysfunction. Cells 2025; 14:566. [PMID: 40277892 PMCID: PMC12026109 DOI: 10.3390/cells14080566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
The numerous side effects and adverse health implications associated with chemotherapies have long plagued the field of cancer care. Whilst in some cases a curative measure, this highly toxic intervention consistently scores poorly on quantitative measures of tolerability and safety. Of these side effects, cardiac and microvascular defects pose the greatest health risk and are the leading cause of death amongst cancer survivors who do not succumb to relapse. In fact, in many low-grade cancers, the risk of recurrence is far outweighed by the cardiovascular risk of morbidity. As such, there is a pressing need to improve outcomes within these populations. Polyphenols are a group of naturally occurring metabolites that have shown potential vasoprotective effects. Studies suggest they possess antioxidant and anti-inflammatory activities, in addition to directly modulating vascular signalling pathways and gene expression. Leveraging these properties may help counteract the vascular toxicity induced by chemotherapy. In this review, we outline the main mechanisms by which the endothelium is damaged by chemotherapeutic agents and discuss the ability of polyphenols to counteract such side effects. We suggest future considerations that may help overcome some of the published limitations of these compounds that have stalled their clinical success. Finally, we briefly explore their pharmacological properties and how novel approaches could enhance their efficacy while minimising treatment-related side effects.
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Affiliation(s)
- Luke Tillman
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
| | - Jaume Margalef Rieres
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
| | - Elena Ahjem
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
| | - Fynn Bishop-Guest
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
| | - Meghan McGrath
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
| | - Helena Hatrick
- School of Clinical Medicine, University of Cambridge, Cambridge CB2 0SP, UK; (L.T.); (J.M.R.); (M.M.); (H.H.)
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36
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Gao S, Zhang H, Li N, Zhang L, Zhu Z, Xu C. Pterostilbene: A natural neuroprotective stilbene with anti-Alzheimer's disease properties. J Pharm Anal 2025; 15:101043. [PMID: 40291020 PMCID: PMC12032911 DOI: 10.1016/j.jpha.2024.101043] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Revised: 07/01/2024] [Accepted: 07/12/2024] [Indexed: 04/30/2025] Open
Abstract
Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.
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Affiliation(s)
- Songlan Gao
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Honglei Zhang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Na Li
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Lijuan Zhang
- Departments of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Zhe Zhu
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110000, China
| | - Changlu Xu
- Departments of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110000, China
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Giampaoli O, Messi M, Merlet T, Sciubba F, Canepari S, Spagnoli M, Astolfi ML. Landfill fire impact on bee health: beneficial effect of dietary supplementation with medicinal plants and probiotics in reducing oxidative stress and metal accumulation. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2025; 32:10331-10347. [PMID: 38158534 DOI: 10.1007/s11356-023-31561-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 12/11/2023] [Indexed: 01/03/2024]
Abstract
The honey bee is an important pollinator insect susceptible to environmental contaminants. We investigated the effects of a waste fire event on elemental content, oxidative stress, and metabolic response in bees fed different nutrients (probiotics, Quassia amara, and placebo). The level of the elements was also investigated in honey and beeswax. Our data show a general increase in elemental concentrations in all bee groups after the event; however, the administration of probiotics and Quassia amara help fight oxidative stress in bees. Significantly lower concentrations of Ni, S, and U for honey in the probiotic group and a general and significant decrease in elemental concentrations for beeswax in the probiotic group and Li in the Quassia amara group were observed after the fire waste event. The comparison of the metabolic profiles through pre- and post-event PCA analyses showed that bees treated with different feeds react differently to the environmental event. The greatest differences in metabolic profiles are observed between the placebo-fed bees compared to the others. This study can help to understand how some stress factors can affect the health of bees and to take measures to protect these precious insects.
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Affiliation(s)
- Ottavia Giampaoli
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy
- NMR-Based Metabolomics Laboratory (NMLab), Sapienza University of Rome, 00185, Rome, Italy
| | - Marcello Messi
- Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy
| | - Thomas Merlet
- Department of Chemistry, Toulouse INP - ENSIACET, 4 Allée Emile Monso, 31030, Toulouse, France
| | - Fabio Sciubba
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy
- NMR-Based Metabolomics Laboratory (NMLab), Sapienza University of Rome, 00185, Rome, Italy
| | - Silvia Canepari
- Department of Environmental Biology, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy
- C.N.R. Institute of Atmospheric Pollution Research, Via Salaria, Km 29,300, Monterotondo St, 00015, Rome, Italy
| | - Mariangela Spagnoli
- Department of Medicine, Epidemiology, Environmental and Occupational Hygiene, INAIL, via Fontana Candida 1, 00078, Monte Porzio Catone, Italy
| | - Maria Luisa Astolfi
- Department of Chemistry, Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
- Research Center for Applied Sciences to the Safeguard of Environment and Cultural Heritage (CIABC), Sapienza University of Rome, P.le Aldo Moro 5, 00185, Rome, Italy.
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38
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Bilginoğlu E, Kızıl HE, Öğütcü H, Ağar G, Bağcı Y. Pharmacological Potential and Bioactive Components of Wild Anatolian Sage ( Salvia aethiopis L.). Food Sci Nutr 2025; 13:e70118. [PMID: 40144556 PMCID: PMC11936837 DOI: 10.1002/fsn3.70118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Salvia aethiopis L., a member of the Lamiaceae family, has gained attention due to its bioactive compounds with potential therapeutic applications. This study investigated the chemical composition and biological activities of S. aethiopis ethanol extract collected from Karaman province, Türkiye. The phenolic profile of the plant was characterized using LC-MS/MS analysis, which revealed substantial amounts of rosmarinic acid, ferulic acid, caffeic acid, and p-coumaric acid. The antimicrobial activity of the extracts was evaluated against various Gram-positive and Gram-negative bacteria, as well as fungal strains, using the agar well diffusion method. The results demonstrated potent antibacterial effects, particularly against Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. Furthermore, the cytotoxic potential of S. aethiopis was assessed on H-460 non-small cell lung cancer cells. The extract exhibited a dose-dependent cytotoxic effect, with a significant reduction in cell viability after 24 and 48 h of treatment, yielding IC50 values of 80.08 and 56.19 μg/mL, respectively. These findings suggest that S. aethiopis possesses promising antimicrobial and anticancer properties, which could contribute to the development of novel therapeutic agents.
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Affiliation(s)
- Emine Bilginoğlu
- Department of Field Corps, Faculty of AgricultureKırsehir Ahi Evran UniversityKırsehirTürkiye
| | - Hamit Emre Kızıl
- Department of Medical Services and Techniques, Vocational School of Health ServicesBayburt UniversityBayburtTürkiye
| | - Hatice Öğütcü
- Department of Field Corps, Faculty of AgricultureKırsehir Ahi Evran UniversityKırsehirTürkiye
- Department of Biology, Polatlı Faculty of Science and LetterAnkara Hacı Bayram Veli UniversityAnkaraTürkiye
| | - Güleray Ağar
- Department of Biology, Faculty of ScienceAtaturk UniversityErzurumTürkiye
| | - Yavuz Bağcı
- Department of Pharmaceutical Botany, Faculty of PharmacySelcuk UniversityKonyaTürkiye
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39
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Romanelli MA, Guerrero TN, Brito E, Albernaz L, Brand ALM, Gomes DS, Muzi-Filho H. Plant-derived secondary metabolites against Bothrops envenomation: A review. Toxicon 2025; 258:108340. [PMID: 40185249 DOI: 10.1016/j.toxicon.2025.108340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/18/2025] [Accepted: 04/01/2025] [Indexed: 04/07/2025]
Abstract
Snakebites from the Bothrops genus are a public health issue in Brazil, particularly in the most affected rural areas. Traditional medicinal plants offer potential complementary therapies for mitigating the damages caused by Bothrops envenomation. This review summarizes current research on the antiophidic potential in medicinal plants and its secondary metabolites to neutralize Bothrops venom effects. A comprehensive literature search was conducted to identify studies detailing the biochemical mechanisms and pharmacological effects of plant-based secondary metabolites, including polyphenols, saponins, quinones, sulfated polysaccharides, steroids, coumarins, alkaloids, and coumestans, on venom-induced pathologies. Polyphenols, particularly flavonoids, exhibit significant inhibitory activity against the proteolytic, hemorrhagic, and myotoxic effects of Bothrops venom by binding to active sites of metalloproteinases and phospholipase A2 (PLA2) Saponins and quinones demonstrated anti-inflammatory and anti-myotoxic effects through protein precipitation and ion chelation. Sulfated polysaccharides from marine algae showed anticoagulant and anti-edematous properties. Additionally, plant-derived steroids and coumarins inhibited venom-induced coagulation and tissue necrosis. Alkaloids and coumestans, such as wedelolactone, effectively reduced hemorrhagic and neurotoxic damage. Medicinal plants and their secondary metabolites have substantial potential to neutralize the biological responses of bothropic venom. Further research and clinical validation are needed to establish safety, efficacy, and standardized use in snakebite management protocols.
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Affiliation(s)
- Mayara A Romanelli
- Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Taissa N Guerrero
- Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ellen Brito
- Institute of Biodiversity and Sustainability-NUPEM, Federal University of Rio de Janeiro, Macaé, Brazil
| | - Lucas Albernaz
- Institute of Biodiversity and Sustainability-NUPEM, Federal University of Rio de Janeiro, Macaé, Brazil
| | - Ana Laura M Brand
- Institute of Chemistry, Center for Mathematical and Natural Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Dayene S Gomes
- Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Humberto Muzi-Filho
- Center for Research in Precision Medicine, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; National Center of Structural Biology and Bioimaging/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
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40
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Williamson G. Bioavailability of Food Polyphenols: Current State of Knowledge. Annu Rev Food Sci Technol 2025; 16:315-332. [PMID: 39899845 DOI: 10.1146/annurev-food-060721-023817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2025]
Abstract
(Poly)phenols, including flavonoids, phenolic acids, and tannins, are a diverse class of compounds found in plant-based foods and beverages. Their bioavailability has been extensively described and detailed metabolic pathways elucidated. Although some parent (poly)phenols are absorbed intact in the small intestine, most pass to the colon where they are extensively catabolized and their microbial products absorbed into the circulation. The sum of the metabolites absorbed can reach almost 100% in some cases and in some individuals. In recent years, there have been three major areas of advancement: (a) comprehensive and systematic reviews have brought together bioavailability data, including detailed metabolic pathways in humans, and quantitative estimates of absorption and excretion; (b) the action and importance of the gut microbiota in (poly)phenol metabolism have been better defined and our understanding of the important role of the microbiota in intra- and interindividual variation has greatly expanded; and (c) strategies to improve (poly)phenol bioavailability such as encapsulation employing various nanoformulations or cyclodextrins have been developed.
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Affiliation(s)
- Gary Williamson
- Department of Nutrition, Dietetics and Food, Victorian Heart Institute, Monash University, Clayton, Victoria, Australia;
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41
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Chaurasia PK, Bharati SL. Coriander: A holistic outlook on its chemistry and pharmacology. Food Chem 2025; 469:142444. [PMID: 39719783 DOI: 10.1016/j.foodchem.2024.142444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 11/23/2024] [Accepted: 12/09/2024] [Indexed: 12/26/2024]
Abstract
Coriander (Coriandrum sativum L.) is a nutraceutically renowned annual herb from Apiaceae family and used in cuisines in different countries in different ways to enhance the tastes, flavour and nutritional values of foods. Fruit (seed) has several medicinally valuable chemical components viz. Linalool, Geranyl acetate, Limonene, Camphor, Geraniol, and other while leaves are rich in (E)-2-Decenal, (E)-2-Dodecenal, Linalool, (E)-2-Undecenal, Decanol and other as the major constituents along with various noteworthy minor components. It has numerous traditional medicinal applications like useful in joint pain, rheumatoid arthritis, inflammation, digestive stimulant, carminative, anti-bilious, etc. Thus, this review has been prepared to comprehensively disclose its chemical constituents, chemical structures and main applications i.e. antioxidant, antibacterial, antifungal, anti-allergic, anti-aging, anticancer, anti-inflammatory, anti-hyperglycemic, anti-diabetic, anxiolytic effect, role in food preservation, skin sensitivity, natural alternative of antibiotics, and other miscellaneous applications. Toxicity of coriander has also been briefly described to present its safety profile.
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Affiliation(s)
- Pankaj Kumar Chaurasia
- Chemical, Biological and Environmental Laboratory, P.G. Department of Chemistry, L.S. College, B.R. Ambedkar Bihar University, Muzaffarpur 842001, Bihar, India.
| | - Shashi Lata Bharati
- Department of Chemistry, North Eastern Regional Institute of Science and Technology, Nirjuli, Itanagar, Arunachal Pradesh 791109, India.
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42
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Delgado-Andrade C, Olías R, Haro A, Marín-Manzano MC, Benavides L, Clemente A, Seiquer I. Analyses of Antioxidant Properties, Mineral Composition, and Fatty Acid Profiles of Soy-Based Beverages Before and After an In Vitro Digestion Process. Antioxidants (Basel) 2025; 14:411. [PMID: 40298690 PMCID: PMC12024155 DOI: 10.3390/antiox14040411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 03/25/2025] [Accepted: 03/26/2025] [Indexed: 04/30/2025] Open
Abstract
Soy beverages (SB) are the most popular beverage in the expanding market of plant-based drinks. They provide high-quality protein and polyphenols and are often Ca-fortified as a milk alternative. This work evaluated the antioxidant potential, the mineral content, and the fatty acid profiles found in SB, analysing as well the bioaccessibility of some nutrients after INFOGEST static digestion. Five types of SB available in the market, including Ca-fortified, high-protein, and low-fat drinks, were analysed. Ca supplementation and high protein content in the beverages significantly enhanced Ca bioaccessibility. The lipid profile demonstrated substantial changes during digestion, due to drastic reductions in saturated fatty acids and marked increases in polyunsaturated fatty acids in the bioaccessible fractions; these changes were mainly related to the content levels of Ca and polyphenols in the beverages. Significant increases in the antioxidant properties, as measured by ABTS and FRAP assays, were noticed after the digestive process. Additionally, ROS generation in Caco-2 cells after induced oxidative damage was prevented by the BF of digested SB. The digested low-fat drink, which also had a low level of protein content, showed the least antioxidant activity. In conclusion, composition of the soy drink considerably affected the bioaccessibility of nutritional components and the drink's antioxidant potential.
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Affiliation(s)
- Cristina Delgado-Andrade
- Departamento Nutrición y Producción Animal Sostenible, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas (CSIC), San Miguel 101, Armilla, 18100 Granada, Spain; (R.O.); (A.H.); (M.C.M.-M.); (L.B.); (A.C.)
| | | | | | | | | | | | - Isabel Seiquer
- Departamento Nutrición y Producción Animal Sostenible, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas (CSIC), San Miguel 101, Armilla, 18100 Granada, Spain; (R.O.); (A.H.); (M.C.M.-M.); (L.B.); (A.C.)
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43
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Jawad M, Talcott ST, Hillman AR, Brannan RG. A Comprehensive Polyphenolic Characterization of Five Montmorency Tart Cherry ( Prunus cerasus L.) Product Formulations. Foods 2025; 14:1154. [PMID: 40238295 PMCID: PMC11988622 DOI: 10.3390/foods14071154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Revised: 03/24/2025] [Accepted: 03/25/2025] [Indexed: 04/18/2025] Open
Abstract
The Montmorency tart cherry (Prunus cerasus L., MTC) polyphenols may contribute to reduced inflammation and oxidative stress biomarkers in the body. However, a comprehensive polyphenolic profile of MTC products is lacking. This study provides a comparative analysis of the polyphenolic distribution of individual anthocyanins, flavonols, flavanols, hydroxycinnamic acids, and hydroxybenzoic acids in five MTC products (frozen raw fruit, freeze-dried powder, sweet dried fruit, unsweetened dried fruit, juice concentrate). Twenty-three polyphenols were detected, and 21 were positively identified. Results from three replicates indicate that frozen raw MTC has the most total polyphenolics. Juice concentrate, unsweetened dried MTC, freeze-dried MTC powder, and sweet dried MTC contained 26%, 40%, 60%, and 77% fewer total polyphenolics than frozen raw MTC. Hydroxycinnamic acids, flavonols, and anthocyanins predominated, accounting for 87-99% of total polyphenols in MTC products. Chlorogenic acid, rutin, cyanidin-3-sophoroside, feruloquinic acid, ferulic acid, and coumaric acid isomers were noteworthy polyphenolics. Hydroxycinnamic acids predominated in sweet dried (82%), unsweetened dried (74%), juice concentrate (66%), and frozen-raw (54%) MTC. Flavonols predominated in freeze-dried MTC powder (52%). Anthocyanins, particularly cyanidin glycosides, were important polyphenolics in frozen-raw cherries (18%) but less so in other MTC products. These findings highlight the variability in polyphenols in MTC products and emphasize the importance of selecting appropriate MTC products for specific health benefits.
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Affiliation(s)
- Muhammad Jawad
- Department of Translational Biomedical Sciences, Ohio University, Athens, OH 45701, USA;
| | - Stephen T. Talcott
- Department of Food Science & Technology, Texas A&M University, College Station, TX 77845, USA;
| | - Angela R. Hillman
- Department of Exercise Physiology, Ohio University, Athens, OH 45701, USA;
| | - Robert G. Brannan
- Department of Food and Nutrition Sciences, Ohio University, Athens, OH 45701, USA
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44
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Marques-Magalhães Â, Moreira-Silva F, Graça I, Dias PC, Correia MP, Alzamora MA, Henrique R, Lopez M, Arimondo PB, Miranda-Gonçalves V, Jerónimo C. Combination of MLo-1508 with sunitinib for the experimental treatment of papillary renal cell carcinoma. Front Oncol 2025; 15:1399956. [PMID: 40196736 PMCID: PMC11973455 DOI: 10.3389/fonc.2025.1399956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 03/03/2025] [Indexed: 04/09/2025] Open
Abstract
Renal cell carcinoma (RCC) is the 14th most incident cancer worldwide, and no curative therapeutic options are available for advanced and metastatic disease. Hence, new treatment alternatives are urgently needed to tackle disease management and drug resistance. Herein, we explored the use of MLo-1508 as an anti-tumoral agent in RCC and further assessed its combination with sunitinib for the treatment of papillary RCC. For that, different RCC cell lines were treated with both drugs, alone or in combination, and different phenotypic assays were performed. Moreover, global DNA methylation levels and specific DNMT3a activity were measured, and gene-specific CpG methylation and transcript levels were quantified after treatment. Finally, the combinatory potential of MLo-1508 and sunitinib were asses both in vitro and in vivo using the ACHN cell line. We found that MLo-1508 significantly decreased RCC cell viability while inducing apoptosis in a dose-dependent manner without cytotoxicity for non-malignant cells. Moreover, the treatment induced morphometric alterations and DNA damage in all RCC cell lines. MLo-1508 decreased DNMT1 and DNMT3A transcript levels in 786-O and ACHN cells, inhibited DNMT3A activity, and reduced the global DNA methylation content of ACHN cells. When combined with sunitinib, a reduction in ACHN cell viability, as well as cell cycle arrest at G2/M was observed. Importantly, MLo-1508 decreased the sunitinib effective anti-tumoral concentration against ACHN cell viability. In an in vivo ACHN CAM model, the combination induced cell necrosis. Thus, MLo-1508 might improve sensitivity to sunitinib treatment by decreasing the required concentration and delaying resistance acquisition.
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Affiliation(s)
- Ângela Marques-Magalhães
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Filipa Moreira-Silva
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Inês Graça
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Paula C. Dias
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Margareta P. Correia
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Maria Ana Alzamora
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
| | - Rui Henrique
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences of the University of Porto (ICBAS-UP), Porto, Portugal
| | - Marie Lopez
- Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université de Montpellier-ENSCM, Montpellier, France
| | - Paola B. Arimondo
- Epigenetic Chemical Biology, Institut Pasteur, UMR 3523CNRS, Paris, France
| | - Vera Miranda-Gonçalves
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
| | - Carmen Jerónimo
- Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences of the University of Porto (ICBAS-UP), Porto, Portugal
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45
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Alhyari D, Qinna NA, Sheldrake HM, Kantamneni S, Ghanem BY, Paluch KJ. Antioxidant, Anti-Inflammatory, and Oral Bioavailability of Novel Sulfonamide Derivatives of Gallic Acid. Antioxidants (Basel) 2025; 14:374. [PMID: 40298632 PMCID: PMC12024234 DOI: 10.3390/antiox14040374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 04/30/2025] Open
Abstract
Gallic acid (GA) is known for its antioxidant and anti-inflammatory properties, yet its clinical potential is hindered due to poor oral bioavailability. This study investigates novel GA sulfonamide derivatives, 3,4,5-trimethoxybenzenesulfonamide (3,4,5-TMBS) and 3,4,5-trihydroxybenzenesulfonamide (3,4,5-THBS), and determines their antioxidant and anti-inflammatory activities and bioavailability. Antioxidant activity was evaluated using DPPH, FRAP, and ROS assays in human intestinal epithelial cells (HIEC-6). Protein denaturation and COX-2 inhibition were assayed to measure anti-inflammatory effects. 3,4,5-TMBS metabolism was assessed via CYP2D6, and pharmacokinetics were profiled in Sprague Dawley rats. GA and 3,4,5-THBS showed a three-fold increase in ROS scavenging activity at 1000 µM (96% for GA, 93% for 3,4,5-THBS). 3,4,5-TMBS and 3,4,5-THBS demonstrated significant anti-inflammatory activity when compared to ibuprofen at concentrations ≥100 nM (p < 0.05). 3,4,5-TMBS (50 µM) exhibited high COX-2 inhibition (p < 0.001) unlike GA (50 µM) which had a low COX-2 inhibition effect (p > 0.05), compared to ibuprofen. The percentage of 3,4,5-TMBS metabolism increased from 65% to 81% at 1500 µM (p < 0.05) when metabolized by CYP2D6. Pharmacokinetic studies revealed that 3,4,5-TMBS and 3,4,5-THBS had significantly higher Cmax and longer half-lives than GA, with 3,4,5-TMBS showing a half-life of 7.17 ± 1.62 h, compared to 3.60 ± 0.94 h for GA (p < 0.05). 3,4,5-TMBS and 3,4,5-THBS demonstrated superior antioxidant and anti-inflammatory effects in HIEC-6 compared to GA, with enhanced bioavailability. These findings support the potential of 3,4,5-TMBS and 3,4,5-THBS as effective alternatives to GA for clinical applications.
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Affiliation(s)
- Dania Alhyari
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Rd, Bradford BD7 1DP, UK; (D.A.); (K.J.P.)
- Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan
| | - Nidal A. Qinna
- Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan
| | - Helen M. Sheldrake
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Rd, Bradford BD7 1DP, UK; (D.A.); (K.J.P.)
| | - Sriharsha Kantamneni
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Rd, Bradford BD7 1DP, UK; (D.A.); (K.J.P.)
| | - Bayan Y. Ghanem
- Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan
| | - Krzysztof J. Paluch
- School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Richmond Rd, Bradford BD7 1DP, UK; (D.A.); (K.J.P.)
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46
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Zhao P, Li C, Zhou S, Wu T, Zhu Y, Liu Y, Wu X, Ouyang H, Mao H, He J. Comprehensive pharmacokinetic profiling of twelve compounds from Phellinus Igniarius extract in rats by UHPLC-MS/MS. J Pharm Biomed Anal 2025; 255:116645. [PMID: 39708480 DOI: 10.1016/j.jpba.2024.116645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 12/14/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
The medicinal fungus Phellinus Igniarius (P. igniarius) has been demonstrated to possess a variety of pharmacological effects, including anti-oxidant, anti-tumor, blood circulation promotion, anti-diarrheal and sedative properties, etc. In order to gain a deeper understanding of the components in P. igniarius extract and its dynamic process in vivo, an ultra-performance liquid chromatography-triple quadrupole mass spectrometry method was developed and validated for the simultaneous determination of 12 major components (nobiletin tangeretin, narirutin, 3,4-dihydroxybenzaldehyde, hesperidin, hispidin, caffeic acid, hispolon, osmundacetone, amygdalin, salvianolic acid B and protocatechuic acid) of P. igniarius extract in rat plasma. The analyses were conducted using an ACQUITY UPLC BEH C18 column with acetonitrile and 0.1 % formic acid (v/v) in aqueous solution as the mobile phases. The intra-day and inter-day precision was less than 12.61 % for all 12 experiments, with a precision range of -11.28-12.25 %. Extraction recovery exhibited a range of 74.03-114.33 %, while the matrix effect demonstrated a range of 83.95-119.28 %. The stability tests demonstrated that the analytes remained stable, with relative standard deviations below 11.65 %. The pharmacokinetic parameters of the 12 compounds in rat plasma after oral administration of P. igniarius extract were successfully determined by the established UPLC-MS/MS method. The findings presented a pivotal foundation for advancing future research on the in vivo processes and mechanisms underlying the effects of P. igniarius extracts.
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Affiliation(s)
- Peng Zhao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Caixia Li
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shuting Zhou
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Tiantian Wu
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yameng Zhu
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yang Liu
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Xiwei Wu
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Huizi Ouyang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300193, China.
| | - Haoping Mao
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Jun He
- State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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47
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Saraiva A, Raheem D, Roy PR, BinMowyna MN, Romão B, Alarifi SN, Albaridi NA, Alsharari ZD, Raposo A. Probiotics and Plant-Based Foods as Preventive Agents of Urinary Tract Infection: A Narrative Review of Possible Mechanisms Related to Health. Nutrients 2025; 17:986. [PMID: 40290034 PMCID: PMC11944753 DOI: 10.3390/nu17060986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/05/2025] [Accepted: 03/10/2025] [Indexed: 04/30/2025] Open
Abstract
Urinary tract infections (UTIs) are a prevalent global health issue, often requiring antibiotic treatment, which contributes to antimicrobial resistance. This narrative review explores the potential of probiotics and plant-based foods as alternative or complementary preventive strategies against UTIs. Fermented foods, such as yogurt, kefir, and kombucha, contain probiotic strains that can modulate the gut and urogenital microbiota, enhancing resistance to uropathogens. Likewise, plant-based foods, including cranberry, garlic, bearberry, juniper, and nettle, possess bioactive compounds with antimicrobial, anti-inflammatory, and diuretic properties. Laboratory and clinical studies suggest that these natural interventions may reduce the incidence of UTIs by inhibiting pathogen adhesion, modulating immune responses, and promoting urinary tract health. However, despite promising findings, inconsistencies in study methodologies, dosage standardization, and long-term efficacy warrant further investigation. Future research should focus on optimizing probiotic formulations, standardizing plant-based supplement dosages, and assessing potential food-drug interactions to establish evidence-based guidelines for UTI prevention.
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Affiliation(s)
- Ariana Saraiva
- Research in Veterinary Medicine (I-MVET), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal;
| | - Dele Raheem
- Global Change Research, Arctic Centre, University of Lapland, 96101 Rovaniemi, Finland;
| | - Poly Rani Roy
- Department of Chemistry, Jagannath University, Dhaka 1100, Bangladesh;
| | - Mona N. BinMowyna
- College of Education, Shaqra University, Shaqra 11911, Saudi Arabia;
| | - Bernardo Romão
- Faculty of Health Sciences, Department of Nutrition, University of Brasília, Brasília 70910-900, Brazil;
| | - Sehad N. Alarifi
- Department of Food and Nutrition Science, Al-Quwayiyah College of Sciences and Humanities, Shaqra University, Shaqraa 11971, Saudi Arabia;
| | - Najla A. Albaridi
- Department of Health Science, College of Health and Rehabilitation, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Zayed D. Alsharari
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi Arabia;
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
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48
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Hu L, Luo Y, Yang J, Cheng C. Botanical Flavonoids: Efficacy, Absorption, Metabolism and Advanced Pharmaceutical Technology for Improving Bioavailability. Molecules 2025; 30:1184. [PMID: 40076406 PMCID: PMC11902153 DOI: 10.3390/molecules30051184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/04/2025] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Flavonoids represent a class of natural plant secondary metabolites with multiple activities including antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. However, due to their structural characteristics, they often exhibit low bioavailability in vivo. In this review, we focus on the in vivo study of flavonoids, particularly the effects of gut microbiome on flavonoids, including common modifications such as methylation, acetylation, and dehydroxylation, etc. These modifications aim to change the structural characteristics of the original substances to enhance absorption and bioavailability. In order to improve the bioavailability of flavonoids, we discuss two feasible methods, namely dosage form modification and chemical modification, and hope that these approaches will offer new insights into the application of flavonoids for human health. In this article, we also introduce the types, plant sources, and efficacy of flavonoids. In conclusion, this is a comprehensive review on how to improve the bioavailability of flavonoids.
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Affiliation(s)
- Lei Hu
- Jiangxi Key Laboratory for Sustainable Utilization of Chinese Materia Medica Resources, Lushan Botanical Garden, Chinese Academy of Sciences, Jiujiang 332900, China; (L.H.); (Y.L.); (J.Y.)
- Lushan Xinglin Institute for Medicinal Plants, Jiujiang Xinglin Key Laboratory for Traditional Chinese Medicines, Jiujiang 332900, China
| | - Yiqing Luo
- Jiangxi Key Laboratory for Sustainable Utilization of Chinese Materia Medica Resources, Lushan Botanical Garden, Chinese Academy of Sciences, Jiujiang 332900, China; (L.H.); (Y.L.); (J.Y.)
- Lushan Xinglin Institute for Medicinal Plants, Jiujiang Xinglin Key Laboratory for Traditional Chinese Medicines, Jiujiang 332900, China
| | - Jiaxin Yang
- Jiangxi Key Laboratory for Sustainable Utilization of Chinese Materia Medica Resources, Lushan Botanical Garden, Chinese Academy of Sciences, Jiujiang 332900, China; (L.H.); (Y.L.); (J.Y.)
- Lushan Xinglin Institute for Medicinal Plants, Jiujiang Xinglin Key Laboratory for Traditional Chinese Medicines, Jiujiang 332900, China
| | - Chunsong Cheng
- Jiangxi Key Laboratory for Sustainable Utilization of Chinese Materia Medica Resources, Lushan Botanical Garden, Chinese Academy of Sciences, Jiujiang 332900, China; (L.H.); (Y.L.); (J.Y.)
- Lushan Xinglin Institute for Medicinal Plants, Jiujiang Xinglin Key Laboratory for Traditional Chinese Medicines, Jiujiang 332900, China
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49
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Alves Nobre T, de Sousa AA, Pereira IC, Carvalho Pedrosa-Santos ÁM, Lopes LDO, Debia N, El-Nashar HAS, El-Shazly M, Islam MT, Castro E Sousa JMD, Torres-Leal FL. Bromelain as a natural anti-inflammatory drug: a systematic review. Nat Prod Res 2025; 39:1258-1271. [PMID: 38676413 DOI: 10.1080/14786419.2024.2342553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/09/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024]
Abstract
Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.
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Affiliation(s)
- Taline Alves Nobre
- Toxicological Genetics Research Laboratory (LAPGENIC), Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Athanara Alves de Sousa
- Toxicological Genetics Research Laboratory (LAPGENIC), Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Irislene Costa Pereira
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Álina Mara Carvalho Pedrosa-Santos
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Luana de Oliveira Lopes
- Toxicological Genetics Research Laboratory (LAPGENIC), Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Nicole Debia
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Heba A S El-Nashar
- Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Mohamed El-Shazly
- Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Muhammad Torequl Islam
- Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
- BioLuster Research Center, Dhaka, Bangladesh
| | - João Marcelo de Castro E Sousa
- Toxicological Genetics Research Laboratory (LAPGENIC), Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Francisco Leonardo Torres-Leal
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
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50
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Parente Rocha SI, Fernandes VB, Barbosa da Silva WM, Frota LS, Garcia AR, Schulze Spíndola FF, Alexandre Roberto CH, Rodrigues de Souza VM, Antonio da Franca Rodrigues K, de Almeida Rodrigues I, Marinho ES, Marinho MM, Vila-Nova NS, Maia de Morais S. Antileishmanial activity of hesperetin on Leishmania donovani, in vitro and in silico inhibition of acetylcholinesterase and investigation of the targets sterol C-24 reductase and N-myristoyltransferase. Exp Parasitol 2025; 270:108903. [PMID: 39837406 DOI: 10.1016/j.exppara.2025.108903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 01/07/2025] [Accepted: 01/15/2025] [Indexed: 01/23/2025]
Abstract
The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilisation of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against Leishmania donovani, the causative agent of visceral leishmaniasis, was reported for the first time. Hesperetin was obtained through the hydrolysis of hesperidin and subsequently subjected to chemical characterisation via Infrared and NMR spectroscopy. The antileishmanial activity and cytotoxicity against RAW 264.7 macrophages were evaluated using the MTT colorimetric assay. In order to investigate the potential mechanisms of action, in vitro acetylcholinesterase inhibition assays and molecular docking analyses were conducted. Hesperetin showed an antipromastigote effect (IC50: 62.89 μM) with no evidence of cytotoxicity (CC50: 612.8 μM), with a selectivity index (SI) of 9.74, being 5.4 times more effective than trivalent antimony. In comparison, antimony showed an IC50 of 80.16 μM, a CC50 of 145.04 μM and a SI of 1.8, indicating a limited safety margin. The compound was observed to inhibit acetylcholinesterase (IC50 of 18.44 μg/mL), present in mitochondrial and plasma membrane of the parasite. Molecular docking and dynamic simulations indicated that hesperetin inhibit sterol C-24 reductase, essential for ergosterol biosynthesis and membrane integrity of L. donovani and shows activity against N-myristoyl transferase, responsible for parasite proliferation cycle. These findings open promising avenues for the development of effective antileishmanial therapies.
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Affiliation(s)
| | | | | | - Lucas Soares Frota
- Natural Products Chemistry Laboratory, State University of Ceará, Fortaleza, Brazil
| | - Andreza Raposo Garcia
- Bioactive Substances Research Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | | | - Igor de Almeida Rodrigues
- Bioactive Substances Research Laboratory, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Emmanuel Silva Marinho
- Natural Resources Bioprospecting and Monitoring Laboratory, State University of Ceará, Fortaleza, Brazil
| | - Márcia Machado Marinho
- Natural Resources Bioprospecting and Monitoring Laboratory, State University of Ceará, Fortaleza, Brazil
| | | | - Selene Maia de Morais
- Natural Products Chemistry Laboratory, State University of Ceará, Fortaleza, Brazil.
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