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Watkins BA, Mitchell AE, Shin AC, Dehghani F, Shen CL. Dietary flavonoid actions on senescence, aging, and applications for health. J Nutr Biochem 2025; 139:109862. [PMID: 39929283 DOI: 10.1016/j.jnutbio.2025.109862] [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: 10/08/2024] [Revised: 01/04/2025] [Accepted: 02/06/2025] [Indexed: 03/18/2025]
Abstract
Fruits and vegetables contain biologically active phenolic compounds that show mitigating effects against free radical damage and inflammation. The unique properties of phenolic compounds are protection against oxidative stress, and inception and potentiating of inflammation in the body. Aging is manifest with changes in epigenetic modifications and as with living systems undergo entropy. The gradual decline of body functions and in many cases with aging the cellular processes of senescence are contributors to age-related diseases. Herein the focus is on phenolic compounds as a diet approach to delay the negative consequences of aging. The actions of phenolic compounds on the biology of aging and senescence are presented. The phenolic compounds called flavonoids which are found in many fruits are potential antisenescence factors that benefit health by reducing damage to DNA and the senescence-associated phenotypic cell changes in healthy cells during aging. Flavonoids are proposed to delay and palliate aging where senescence is involved. The dietary sources of natural phenolic compounds afford protection in the aging process and include as some examples naringenin, hesperidin, quercetin, kaempferol, luteolin, genistein, epigallocatechin gallate, and resveratrol. Many of these compounds possess antisenescence effects. The purpose of the review is to discuss where food flavonoids interact with the targets of senescence and how these compounds can attenuate aging-related events. The goal is to provide greater insight into dietary flavonoids and how they improve health and lower the consequences of aging. A novel aspect of this review is the application of flavonoids to neuroprotective effects in brain to reduce pain and improve health with aging.
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Affiliation(s)
- Bruce A Watkins
- Department of Nutrition, University of California, Davis, Davis CA.
| | - Alyson E Mitchell
- Department of Food Science and Technology, University of California, Davis, Davis CA
| | - Andrew C Shin
- Department of Nutritional Sciences, Neurobiology of Nutrition Laboratory, College of Health & Human Sciences, Texas Tech University, Lubbock, TX
| | - Fereshteh Dehghani
- Department of Nutritional Sciences, Neurobiology of Nutrition Laboratory, College of Health & Human Sciences, Texas Tech University, Lubbock, TX
| | - Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430; Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430
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Sun J, Shi L, Xu F, Sun H, Liu Y, Sun J, Zhou Q. Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway. J Microbiol Biotechnol 2025; 35:e2412029. [PMID: 40295196 DOI: 10.4014/jmb.2412.12029] [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: 12/17/2024] [Revised: 02/04/2025] [Accepted: 02/20/2025] [Indexed: 04/30/2025]
Abstract
Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.
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Affiliation(s)
- Jiahui Sun
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Luyao Shi
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Fan Xu
- Department of Medical oncology, Xianyang Central Hospital, Xianyang, Shanxi 712000, P.R. China
| | - Hanyan Sun
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Yitong Liu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Jiangyun Sun
- Department of acupuncture, 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
| | - Qingxin Zhou
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
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Palumbo M, Ugolotti M, Zimetti F, Adorni MP. Anti-atherosclerotic effects of natural compounds targeting lipid metabolism and inflammation: Focus on PPARs, LXRs, and PCSK9. ATHEROSCLEROSIS PLUS 2025; 59:39-53. [PMID: 39877131 PMCID: PMC11773090 DOI: 10.1016/j.athplu.2024.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 12/17/2024] [Accepted: 12/19/2024] [Indexed: 01/31/2025]
Abstract
A large body of evidence has shown that modulation of the nuclear receptors peroxisome proliferator-activated receptors (PPARs), the liver X receptors (LXRs), the proprotein convertase subtilisin/kexin type 9 (PCSK9) and inflammatory processes by natural compounds has hypolipidemic and anti-atherosclerotic effects. These beneficial outcomes are certainly related to the crucial function of these targets in maintaining cholesterol homeostasis and regulating systemic inflammation. Currently, the therapeutic scenario for cardiovascular diseases (CVD) offers a plethora of widely validated and functional pharmacological treatments to improve the health status of patients. However, patients are increasingly sceptical of pharmacological treatments which are often associated with moderate to severe side effects. The aim of our review is to provide a collection of the most recent scientific evidence on the most common phytochemicals, used for centuries in the Mediterranean diet and traditional chinese medicine that act on these key regulators of cholesterol homeostasis and systemic inflammation, which could constitute important tools for CVD management.
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Affiliation(s)
| | | | | | - Maria Pia Adorni
- Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Italy
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Kupikowska-Stobba B, Niu H, Klojdová I, Agregán R, Lorenzo JM, Kasprzak M. Controlled lipid digestion in the development of functional and personalized foods for a tailored delivery of dietary fats. Food Chem 2025; 466:142151. [PMID: 39615348 DOI: 10.1016/j.foodchem.2024.142151] [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: 07/10/2024] [Revised: 11/04/2024] [Accepted: 11/17/2024] [Indexed: 12/14/2024]
Abstract
In recent decades, obesity and its associated health issues have risen dramatically. The COVID-19 pandemic has further exacerbated this trend, underscoring the pressing need for new strategies to manage weight. Functional foods designed to modulate lipid digestion and absorption rates and thereby reduce the assimilation of dietary fats have gained increasing attention in food science as a potentially safer alternative to weight-loss medications. This review provides insights into controlled lipid digestion and customized delivery of fats. The first section introduces basic concepts of lipid digestion and absorption in the human gastrointestinal tract. The second section discusses factors regulating lipid digestion and absorption rates, as well as strategies for modulating lipid assimilation from food. The third section focuses on applications of controlled lipid digestion in developing personalized foods designed for specific consumer groups, with particular emphasis on two target populations: overweight individuals and infants.
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Affiliation(s)
- Barbara Kupikowska-Stobba
- Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106 Warsaw, Poland.
| | - Hui Niu
- SCUT-Zhuhai Institute of Modern Industrial Innovation, School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| | - Iveta Klojdová
- DRIFT-FOOD, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, 165 21 Prague, Czech Republic
| | - Ruben Agregán
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain
| | - Jose Manuel Lorenzo
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain; Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, Universidad de Vigo, Ourense, Spain
| | - Mirosław Kasprzak
- Department of Animal Product Technology, Faculty of Food Technology, University of Agriculture, Balicka 122, 30-149 Kraków, Poland
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Tang X, Zhong J, Luo H, Zhou F, Wang L, Lin S, Xiong J, Lv H, Zhou Z, Yu H, Cao K. Efficacy of Naringenin against aging and degeneration of nucleus pulposus cells through IGFBP3 inhibition. Sci Rep 2025; 15:6780. [PMID: 40000729 PMCID: PMC11861589 DOI: 10.1038/s41598-025-90909-0] [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: 02/17/2024] [Accepted: 02/17/2025] [Indexed: 02/27/2025] Open
Abstract
Naringenin (NAR), a natural flavonoid, exerts anti-inflammatory and antioxidant pharmacology. However, the pharmacological mechanisms through which NAR prevents and treats intervertebral disc degeneration (IDD) remain unclear. We utilized bioinformatics, machine learning, and network pharmacology to identify shared targets among NAR, senescence, and IDD. Subsequently, molecular docking was conducted to evaluate NAR's binding affinity to common target. Additionally, we used IL-1β to induce senescence and degeneration in nucleus pulposus cells (NPCs) and conducted a series of cellular assays, including immunoblotting, immunofluorescence, β-galactosidase staining, cell proliferation, cell cycle analysis, and measurement of reactive oxygen species levels, to investigate NAR's impact on IL-1β-induced senescence and degeneration of NPCs. Our study revealed that Insulin-like growth factor binding protein 3 (IGFBP3) was the only common target. IGFBP3 exhibited significant differences between the IDD and healthy groups and proved to be an effective diagnostic marker for IDD. Molecular docking confirmed the binding between NAR and IGFBP3. In vitro experiments, we observed that Igfbp3 expression increased in the senescence and degeneration groups. Igfbp3 knockdown and NAR attenuated IL-1β-induced senescence and degenerative phenotypes in NPCs. In contrast, the effect of NAR was attenuated by recombinant IGFBP3 protein. In conclusion, our findings suggest that NAR plays a preventive and therapeutic role in IDD, likely achieved through the inhibition of Igfbp3 expression.
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Affiliation(s)
- Xiaokai Tang
- Department of Orthopedics, People's Hospital of Deyang City, Deyang, China
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China
| | - Junlong Zhong
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
| | - Hao Luo
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China
| | - Faxin Zhou
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China
| | - Lixia Wang
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China
| | - Sijian Lin
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jiachao Xiong
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
| | - Hao Lv
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China
| | - Zhenhai Zhou
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China
| | - Honggui Yu
- Orthopedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, #1519 Dongyue Avenue, Nanchang, 330209, Jiangxi, China.
| | - Kai Cao
- The Key Laboratory of Spine and Spinal Cord Disease of Jiangxi Province, Nanchang, 330006, China.
- Department of Orthopedics, Affiliated Rehabilitation Hospital of Nanchang University, Nanchang, 330002, China.
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Heo YJ, Lee MK, Im JH, Kim BS, Lee HI. Anti-obesity effects of ethanol extract of green Citrus junos peel enriched in naringin and hesperidin in vitro and in vivo. Nutr Res Pract 2025; 19:1-13. [PMID: 39959742 PMCID: PMC11821779 DOI: 10.4162/nrp.2025.19.1.1] [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: 08/06/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND/OBJECTIVES Green Citrus junos (yuja) peel extract has higher naringin and hesperidin contents and antioxidant activity than yellow yuja peel extract, but its anti-obesity effects are unclear. This study examined the anti-obesity properties of green yuja peel ethanol extract (GYE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. MATERIALS/METHODS The effects of GYE on adipocyte differentiation were assessed by measuring Oil red O staining, mRNA and protein expression. The beneficial effects of GYE on HFD-induced obese mice were evaluated using the body weight, body composition, visceral fat size, and biochemical analysis. RESULTS GYE inhibited adipocyte differentiation and lipid accumulation compared to the control cells, as evidenced by Oil red O staining and the triglyceride level, respectively. GYE down-regulated the adipogenic genes CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), and lipogenic gene diacylglycerol O-acyltransferase 2 (DGAT2). GYE at 100 μg/mL downregulated the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), and their downstream targets PPARγ and sterol regulatory element-binding protein-1 (SREBP-1c) compared to the control group. In obese mice, GYE (100 mg/kg/day) reduced the body weight, body weight gain, and serum lipid level compared to the control group. Analysis using dual-energy X-ray absorptiometry showed that GYE decreased the fat percentage, fat in tissue, and abdominal circumference, while it increased the lean percentage compared to control group. Furthermore, GYE significantly reduced the visceral fat weight and size compared to the control group. CONCLUSION GYE suppressed adipocyte differentiation by inhibiting the PI3K-Akt pathway in vitro and reduced the body fat mass and visceral adiposity in HFD-induced obese mice. These findings suggest that GYE is a viable natural option for combating obesity.
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Affiliation(s)
- Yu-Jin Heo
- Department of Food and Nutrition, Sunchon National University, Suncheon 57922, Korea
| | - Mi-Kyung Lee
- Department of Food and Nutrition, Sunchon National University, Suncheon 57922, Korea
| | - Ju-Hye Im
- Department of Food and Nutrition, Sunchon National University, Suncheon 57922, Korea
| | - Bo Seop Kim
- Department of Research & Technical Support Team, Mokpo Marine Food-Industry Research Center, Mokpo 58621, Korea
| | - Hae-In Lee
- Department of Food and Nutrition, Sunchon National University, Suncheon 57922, Korea
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Solanki S, Vig H, Khatri N, Singh BP, Khan MS, Devgun M, Wal P, Wal A. Naringenin: A Promising Immunomodulator for Anti-inflammatory, Neuroprotective and Anti-cancer Applications. Antiinflamm Antiallergy Agents Med Chem 2025; 24:1-25. [PMID: 39076091 DOI: 10.2174/0118715230320007240708074939] [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: 03/29/2024] [Revised: 05/19/2024] [Accepted: 06/03/2024] [Indexed: 07/31/2024]
Abstract
BACKGROUND Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with intertwined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments. OBJECTIVES This review offers an encompassing exploration of naringenin's anti-inflammatory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations. METHODS Data for this review were amassed through the scrutiny of various published studies via search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced. RESULTS Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions. CONCLUSION Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of in vivo data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.
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Affiliation(s)
- Sarita Solanki
- Department of Pharmacy, University of Kota, Kota Rajasthan, India
| | - Himangi Vig
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), NH 19 Bhauti Kanpur, Uttar Pradesh, India
| | - Nidhi Khatri
- Department of Pharmacy, University of Kota, Kota Rajasthan, India
| | | | | | - Manish Devgun
- Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana, India
| | - Pranay Wal
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), NH 19 Bhauti Kanpur, Uttar Pradesh, India
| | - Ankita Wal
- PSIT-Pranveer Singh Institute of Technology (Pharmacy), NH 19 Bhauti Kanpur, Uttar Pradesh, India
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Sharma S, Mishra A, Ramniwas S, Pandey P. An Updated Review Summarizing the Anticancer Potential of Naringenin. Endocr Metab Immune Disord Drug Targets 2025; 25:364-376. [PMID: 39005120 DOI: 10.2174/0118715303308238240705061522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/15/2024] [Accepted: 05/23/2024] [Indexed: 07/16/2024]
Abstract
One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.
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Affiliation(s)
- Srishti Sharma
- Department of Biotechnology, GLA University, Mathura, India
| | - Anuja Mishra
- Department of Biotechnology, GLA University, Mathura, India
| | - Seema Ramniwas
- University Centre of Research and Development, University Institute of Biotechnology, Chandigarh University Gharuan, Mohali, Punjab, India
| | - Pratibha Pandey
- Centre of Research Impact and Outcome, Chitkara University, Rajpura, 140417, Punjab, India
- Chitkara Centre for Research and Development, Chitkara University, Himachal Pradesh, 174103 India
- Saveetha Institute of Medical and Technical Sciences, Chennai, India
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Xiao J, Sun T, Jiang S, Xiao Z, Shan Y, Li T, Pan Z, Li Q, Fu F. Antioxidant Effects and Potential Mechanisms of Citrus reticulata 'Chachi' Components: An Integrated Approach of Network Pharmacology and Metabolomics. Foods 2024; 13:4018. [PMID: 39766961 PMCID: PMC11675786 DOI: 10.3390/foods13244018] [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: 10/29/2024] [Revised: 12/05/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Citrus reticulata 'Chachi' (CRC), recognized for its considerable edible and medicinal significance, is a valuable source of metabolites beneficial to human health. This research investigates the metabolic distinctions and antioxidant properties across four different parts of CRC, using multivariate statistical analysis to interpret metabolomic data and network pharmacology to identify potential antioxidant targets and relevant signaling pathways. The results indicate considerable metabolic differences in different parts of the sample, with 1622 metabolites showing differential expression, including 816 secondary metabolites, primarily consisting of terpenoids (31.02%) and flavonoids (25.22%). The dried mature citrus peel (CP) section demonstrates the highest level of total phenolics (6.8 mg/g), followed by the pulp without seed (PU) (4.52 mg/g), pulp with seed (PWS) (4.26 mg/g), and the seed (SE) (2.16 mg/g). Interestingly, targeted high-performance liquid chromatography of flavonoids reveals the highest level of nobiletin and tangeretin in CP, whereas PU has the highest level of hesperidin, narirutin, and didymin. Furthermore, all four sections of CRC exhibit robust antioxidant properties in in vitro assessments (CP > PU > PWS > SE). Lastly, the network pharmacology uncovered potential antioxidant mechanisms in CRC. This research offers deeper insights into the development and utilization of byproducts in the CRC processing industry.
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Affiliation(s)
- Jiahao Xiao
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
| | - Tian Sun
- Zheng Gan Hui (Jiang Men Xin Hui) Dried Tangerine Peel, Ltd., Jiangmen 529100, China
| | - Shengyu Jiang
- Zheng Gan Hui (Jiang Men Xin Hui) Dried Tangerine Peel, Ltd., Jiangmen 529100, China
| | - Zhiqiang Xiao
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China
| | - Yang Shan
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China
| | - Tao Li
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
| | - Zhaoping Pan
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
| | - Qili Li
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
| | - Fuhua Fu
- Hunan Agriculture Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha 410125, China; (J.X.)
- Longping Branch, College of Biology, Hunan University, Changsha 410125, China
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Yan C, Gu J, Yin S, Wu H, Lei X, Geng F, Zhang N, Wu X. Design and preparation of naringenin loaded functional biomimetic nano-drug delivery system for Alzheimer's disease. J Drug Target 2024; 32:80-92. [PMID: 38044844 DOI: 10.1080/1061186x.2023.2290453] [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: 09/05/2023] [Accepted: 11/23/2023] [Indexed: 12/05/2023]
Abstract
Efficient brain drug delivery has been a challenge in the treatment of Alzheimer's Disease and other brain disorders as blood-brain barrier (BBB) impedes most drugs to reach brain. To overcome this obstacle, we developed a novel TGN decorated erythrocyte membrane-coated poly (lactic-co-glycolic acid) nanoparticle (TRNNs). The nanoparticle significantly boosted the penetration (7.3 times) in a U-118MG and HCMEC/D3 cell co-culture BBB model in vitro. Living image was performed to assess the TRNNs distribution in vivo. The fluorescence intensity in the isolated brain of TRDNs-treated mice was about 8 times that of the DNs-treated. In the novel object recognition test, the mice after administration of TRDNs showed higher recognition index (0.414 ± 0.016) than the model group (0.275 ± 0.019). A significant increase in the number of dendritic spines from TRNNs administrated mice hippocampi neurons was observed after Golgi stain. This improvement of neurons was also confirmed by the significant high expression of PSD95 protein level in hippocampi. We measured the OD values of Aβ25-35 induced PC12 cells that pre-treatment with different nanoparticles and concluded that TRNNs had a robust neuroprotection effect. Above all, functional biomimetic nanoparticles could increase the accumulation of naringenin into brain, thereby enable the drug to exert greater therapeutic effects.
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Affiliation(s)
- Chang Yan
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
| | - Jinlian Gu
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
| | - Shun Yin
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
| | - Hao Wu
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
| | - Xia Lei
- Jiangsu MC Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Fang Geng
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
| | - Ning Zhang
- Jiangsu MC Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
- College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaodan Wu
- School of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, China
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Wen Y, Li Y, Liu T, Huang L, Yao L, Deng D, Luo W, Cai W, Zhong S, Jin T, Yang X, Wang Q, Wang W, Xue J, Mukherjee R, Hong J, Phillips AR, Windsor JA, Sutton R, Li F, Sun X, Huang W, Xia Q. Chaiqin chengqi decoction treatment mitigates hypertriglyceridemia-associated acute pancreatitis by modulating liver-mediated glycerophospholipid metabolism. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 134:155968. [PMID: 39217651 DOI: 10.1016/j.phymed.2024.155968] [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: 12/25/2023] [Revised: 06/25/2024] [Accepted: 07/18/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 μg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.
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Affiliation(s)
- Yongjian Wen
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yuying Li
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tingting Liu
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lijia Huang
- West China Biobank, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Linbo Yao
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Dan Deng
- West China Biobank, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wenjuan Luo
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wenhao Cai
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Shaoqi Zhong
- West China Biobank, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tao Jin
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xinmin Yang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qiqi Wang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wen Wang
- Chinese Evidence-based Medicine Centre, and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jing Xue
- Laboratory of Oncogenes and Related Genes, Stem Cell Research Centre, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China
| | - Rajarshi Mukherjee
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpoo,l L69 3GE, UK
| | - Jiwon Hong
- Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Anthony R Phillips
- Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - John A Windsor
- Surgical and Translational Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1010, New Zealand
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpoo,l L69 3GE, UK
| | - Fei Li
- Department of Pharmacy, Laboratory of Metabolomics and Drug-Induced Liver Injury, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xin Sun
- Chinese Evidence-based Medicine Centre, and National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China; West China Biobank, West China Hospital, Sichuan University, Chengdu, 610041, China; Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Muli S, Blumenthal A, Conzen CA, Benz ME, Alexy U, Schmid M, Keski-Rahkonen P, Floegel A, Nöthlings U. Association of Ultraprocessed Foods Intake with Untargeted Metabolomics Profiles in Adolescents and Young Adults in the DONALD Cohort Study. J Nutr 2024; 154:3255-3265. [PMID: 39332770 PMCID: PMC11600117 DOI: 10.1016/j.tjnut.2024.09.023] [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: 08/02/2024] [Revised: 09/16/2024] [Accepted: 09/22/2024] [Indexed: 09/29/2024] Open
Abstract
BACKGROUND High consumption of ultraprocessed foods (UPFs) continues to draw significant public health interest because of the associated negative health outcomes. Metabolomics can contribute to the understanding of the biological mechanisms through which UPFs may influence health. OBJECTIVES To investigate urine and plasma metabolomic biomarkers of UPF intake in adolescents and young adults. METHODS We used data from the Dortmund Nutritional and Anthropometric Longitudinally Designed study to investigate cross-sectional associations of UPF intake with concentrations of urine metabolites in adolescents using 3d weighed dietary records (3d-WDR) and 24-h urine samples (n = 339), and associations of repeatedly assessed UPF intake with concentrations of circulating plasma metabolites in young adults with 3-6 3d-WDRs within 5 y preceding blood measurement (n = 195). Urine and plasma samples were analyzed using mass spectrometry-based metabolomics. Biosample-specific metabolite patterns (MPs) were determined using robust sparse principal components analysis. Multivariable linear regression models were applied to assess the associations of UPF consumption (as a percentage of total food intake in g/d) with concentrations of individual metabolites and MP scores. RESULTS The median proportion of UPF intake was 22.0% [interquartile range (IQR): 12.3, 32.9] in adolescents and 23.2% (IQR: 16.0, 31.6) in young adults. We identified 42 and 6 UPF intake-associated metabolites in urine and plasma samples, respectively. One urinary MP, "xenobiotics and amino acids" [β = 0.042, 95% confidence interval (CI): 0.014, 0.070] and 1 plasma MP, "lipids, xenobiotics, and amino acids" (β = 0.074, 95% CI: 0.031, 0.117) showed positive association with UPF intake. Both patterns shared 29 metabolites, mostly of xenobiotic metabolism. CONCLUSIONS We identified urine and plasma metabolites associated with UPF intake in adolescents and young adults, which may represent some of the biological mechanisms through which UPFs may influence metabolism and health.
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Affiliation(s)
- Samuel Muli
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Annika Blumenthal
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Christina-Alexandra Conzen
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Maike Elena Benz
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Ute Alexy
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany
| | - Matthias Schmid
- Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), University Hospital Bonn, Bonn, Germany
| | | | - Anna Floegel
- Section of Dietetics, Faculty of Agriculture and Food Sciences, Hochschule Neubrandenburg, Neubrandenburg, Germany
| | - Ute Nöthlings
- Unit of Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany.
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13
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Liang Z, Pi D, Zhen J, Yan H, Zheng C, Liang Chen J, Fan W, Song Q, Pan J, Liu D, Pan M, Yang Q, Zhang Y. The AMPK-mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis. Mediators Inflamm 2024; 2024:4777789. [PMID: 39502754 PMCID: PMC11535263 DOI: 10.1155/2024/4777789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 09/03/2024] [Accepted: 09/23/2024] [Indexed: 11/08/2024] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH.
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Affiliation(s)
| | - Dajin Pi
- Jinan University, Guang Zhou 510632, China
| | | | | | | | | | - Wen Fan
- Jinan University, Guang Zhou 510632, China
| | | | - Jinyue Pan
- Jinan University, Guang Zhou 510632, China
| | | | | | - Qinhe Yang
- Jinan University, Guang Zhou 510632, China
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14
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Santos APMD, Mateus ML, Aschner M. Oranges, potatoes and phytonutrients; why are they good for human health. PHYTONUTRIENTS (KARACHI, PAKISTAN) 2024; 3:120-135. [PMID: 39633848 PMCID: PMC11616452 DOI: 10.62368/pn.v3i.37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
Dietary chemoprevention has emerged as a cost-effective approach to control most prevalent chronic diseases including cancer. Changes in dietary patterns and lifestyle, such as increasing the consumption of fruits and vegetables and more balanced intakes of meat and plant foods, are a practical and effective strategy for reducing the incidence of chronic diseases. Phytonutrients (or phytochemicals) are found in eatable fruits and vegetables that, daily ingested, may exhibit a potential for modulating human metabolism in a manner favourable for the prevention of chronic and degenerative diseases. Carotenoids and flavonoids (anthocyanins, phenolic acids, polyphenols) are examples of phytonutrients. Consumption of total phytochemical intake has been consistently linked to protection from chronic diseases, including cardiovascular disease, cancer and neurodegenerative diseases. To highlight the beneficial health effects of phytonutrients in plants, we choose two interesting plants, the potato and the citrus fruits. They were chosen owing to their phytonutrient content, and low price, which makes them more easily acquired in low incoming populations, and consequently they are highly consumed not only in developing but also in developed countries. Due to its high nutrient and phytochemical content, the potato can lower oxidative stress, a key mechanism for cancer and cardiovascular disease prevention. Its phenolic compounds act as antioxidants and improve heart health. Furthermore, this review emphasizes the bioactive compounds in citrus which can reduce inflammatory mediators and reactive oxygen species generation, thus attenuating the risk of neurodegenerative diseases, cardiovascular disease, diabetes, and cancer. Besides important applications in the functional food sector, phytochemicals are also employed in the production of cosmetic and/or cosmeceutical products.
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Affiliation(s)
| | - Maria Luisa Mateus
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
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15
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Valle-Velázquez E, Zambrano-Vásquez OR, Cortés-Camacho F, Sánchez-Lozada LG, Guevara-Balcázar G, Osorio-Alonso H. Naringenin - a potential nephroprotective agent for diabetic kidney disease: A comprehensive review of scientific evidence. BIOMOLECULES & BIOMEDICINE 2024; 24:1441-1451. [PMID: 38907737 PMCID: PMC11496875 DOI: 10.17305/bb.2024.10511] [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: 03/25/2024] [Revised: 06/19/2024] [Accepted: 06/19/2024] [Indexed: 06/24/2024]
Abstract
Diabetes mellitus (DM) is a chronic disease characterized by persistent hyperglycemia, which is a major contributing factor to chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular-related deaths. There are several mechanisms leading to kidney injury, with hyperglycemia well known to stimulate oxidative stress, inflammation, tissue remodeling, and dysfunction in the vascular system and organs. Increased reactive oxygen species (ROS) decrease the bioavailability of vasodilators while increasing vasoconstrictors, resulting in an imbalance in vascular tone and the development of hypertension. Treatments for diabetes focus on controlling blood glucose levels, but due to the complexity of the disease, multiple drugs are often required to successfully delay the development of microvascular complications, including CKD. In this context, naringenin, a flavonoid found in citrus fruits, has demonstrated anti-inflammatory, anti-fibrotic, and antioxidant effects, suggesting its potential to protect the kidney from deleterious effects of diabetes. This review aims to summarize the scientific evidence of the effects of naringenin as a potential therapeutic option for diabetes-induced CKD.
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Affiliation(s)
- Estefania Valle-Velázquez
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Oscar René Zambrano-Vásquez
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | - Fernando Cortés-Camacho
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | - Gustavo Guevara-Balcázar
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Horacio Osorio-Alonso
- Departamento de Fisiopatología Cardio-Renal, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico
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Lu J, Chen J, Li SY, Pan GJ, Ou Y, Yuan LF, Jiang JP, Zeng LH, Zhao J. Naringin and Naringenin: Potential Multi-Target Agents for Alzheimer's Disease. Curr Med Sci 2024; 44:867-882. [PMID: 39347923 DOI: 10.1007/s11596-024-2921-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] [Received: 10/26/2023] [Accepted: 07/15/2024] [Indexed: 10/01/2024]
Abstract
Alzheimer's disease (AD) is one of the most common forms of neurodegenerative dementia. The etiology of AD is multifactorial, and its complex pathophysiology involves tau and amyloid-β deposition, increased oxidative stress, neuroinflammation, metabolic disorders, and massive neuronal loss. Due to its complex pathology, no effective cure for AD has been found to date. Therefore, there is an unmet clinical need for the development of new drugs against AD. Natural products are known to be good sources of compounds with pharmacological activity and have potential for the development of new therapeutic agents. Naringin, a naturally occurring flavanone glycoside, is predominantly found in citrus fruits and Chinese medicinal herbs. Mounting evidence shows that naringin and its aglycone, naringenin, have direct neuroprotective effects on AD, such as anti-amyloidogenic, antioxidant, anti-acetylcholinesterase, and anti-neuroinflammatory effects, as well as metal chelation. Furthermore, they are known to improve disordered glucose/lipid metabolism, which is a high risk factor for AD. In this review, we summarize the latest data on the impact of naringin and naringenin on the molecular mechanisms involved in AD pathophysiology. Additionally, we provide an overview of the current clinical applications of naringin and naringenin. The novel delivery systems for naringin and naringenin, which can address their widespread pharmacokinetic limitations, are also discussed. The literature indicates that naringin and naringenin could be multilevel, multitargeted, and multifaceted for preventing and treating AD.
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Affiliation(s)
- Jing Lu
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310015, China
| | - Jie Chen
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310015, China
| | - Shu-Yue Li
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
| | - Guang-Jie Pan
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
| | - Yi Ou
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
| | - Li-Fu Yuan
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China
| | - Jian-Ping Jiang
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.
- Affiliated Hospital, Hangzhou City University School of Medicine, Hangzhou, 310015, China.
| | - Ling-Hui Zeng
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.
| | - Jie Zhao
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.
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Reda FM, Alagawany M, Mahmoud HK, Aldawood N, Alkahtani AM, Alhasaniah AH, Mahmoud MA, El-Saadony MT, El-Kassas S. Application of naringenin as a natural feed additive for improving quail performance and health. J APPL POULTRY RES 2024; 33:100446. [DOI: 10.1016/j.japr.2024.100446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
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18
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Chu Y, Pang B, Yang M, Wang S, Meng Q, Gong H, Kong Y, Leng Y. Exploring the possible therapeutic mechanism of Danzhixiaoyao pills in depression and MAFLD based on "Homotherapy for heteropathy": A network pharmacology and molecular docking. Heliyon 2024; 10:e35309. [PMID: 39170292 PMCID: PMC11336640 DOI: 10.1016/j.heliyon.2024.e35309] [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: 04/05/2024] [Revised: 07/25/2024] [Accepted: 07/25/2024] [Indexed: 08/23/2024] Open
Abstract
Objective Danzhixiaoyao pills (DXP) is a traditional Chinese medicine formula that has been effectively used in clinical practice to treat depression and metabolic associated fatty liver disease (MAFLD), but its therapeutic mechanism is not yet clear. The purpose of this study is to explore the possible mechanisms of DXP in treating depression and MAFLD using network pharmacology and molecular docking techniques based on existing literature reports. Methods By combining TCMSP, Swiss ADME, Swiss TargetPrediction, and UniProt databases, the active ingredients and potential targets of DXP were screened and obtained. By searching for relevant disease targets through Gene Cards, OMIM, and TTD databases, intersection targets between drugs and diseases were obtained. The network of "Disease - Potential targets - Active ingredients - Traditional Chinese medicine - Prescriptions" was constructed using Cytoscape 3.9.1 software, and the PPI network was constructed using STRING 12.0 database. The core targets were obtained through topology analysis. GO function enrichment and KEGG pathway enrichment analysis were conducted based on DAVID. The above results were validated by molecular docking using PyMol 2.5 and AutoDock Tool 1.5.7 software, and their possible therapeutic mechanisms were discussed. Results Network pharmacology analysis obtained 130 main active ingredients of drugs, 173 intersection targets between drugs and diseases, and 37 core targets. Enrichment analysis obtained 1390 GO functional enrichment results, of which 922 were related to biological process, 107 were related to cellular component, 174 were related to molecular function, and obtained 180 KEGG pathways. Molecular docking has confirmed the good binding ability between relevant components and targets, and the literature discussion has preliminarily verified the above results. Conclusion DXP can act on targets such as TNF, AKT1, ALB, IL1B, TP53 through active ingredients such as kaempferol, quercetin, naringenin, isorhamnetin, glyuranolide, etc, and by regulating signaling pathways such as pathways in cancer, MAPK signaling pathway, lipid and atherosclerosis, to exert its effect of "homotherapy for heteropathy" on depression and MAFLD. In addition, glyuranolide showed the strongest affinity with TNF (-7.88 kcal/mol), suggesting that it may play a key role in the treatment process. The research results provide a theoretical basis for elucidating the scientific connotation and mechanism of action of traditional Chinese medicine compound DXP, and provide new directions for its clinical application.
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Affiliation(s)
- YunHang Chu
- College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, China
| | - BingYao Pang
- Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China
| | - Ming Yang
- Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China
| | - Song Wang
- Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China
| | - Qi Meng
- College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, China
| | - HongChi Gong
- College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, China
| | - YuDong Kong
- College of Traditional Chinese Medicine, Changchun University of Traditional Chinese Medicine, Changchun, China
| | - Yan Leng
- Department of Hepatology, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China
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Rocha-Velasco OA, Morales-Suárez-Varela M, Llopis-González A. Dietary Flavonoids: Mitigating Air Pollution's Cardiovascular Risks. Nutrients 2024; 16:2647. [PMID: 39203784 PMCID: PMC11356943 DOI: 10.3390/nu16162647] [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: 07/05/2024] [Revised: 08/05/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
Air pollution significantly impacts cardiovascular health, yet pollution reduction strategies in cardiovascular disease prevention remain limited. Dietary flavonoids show promise in protecting cardiovascular health, but their potential to mitigate air-pollution-induced risks is unexplored. This study investigates this research gap. Following PRISMA-ScR guidelines, literature from 2014-2024 was searched across MedLine/PubMed, ScienceDirect, and MDPI databases. Of 463 identified studies, 53 were eligible for analysis based on PICO criteria. Findings revealed significant impacts of air pollution on cardiovascular health, including increased disease risks and mortality. Flavonoid intake demonstrated protective effects against these risks. Flavonoid mechanisms include improved endothelial function, antioxidant and anti-inflammatory effects, blood pressure regulation, antiplatelet effects, cardioprotection, and enhanced lipid and glucose metabolism. Higher flavonoid intake was consistently associated with reduced cardiovascular risks. While reducing pollution remains crucial, promoting flavonoid-rich diets is a promising complementary strategy. Public health initiatives should raise awareness about these benefits. Further research on direct interactions between flavonoid intake and air pollution exposure is needed. Current evidence supports integrating dietary interventions into broader strategies to reduce air pollution's cardiovascular impacts.
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Affiliation(s)
- Oscar Andrés Rocha-Velasco
- Research Group in Social and Nutritional Epidemiology, Pharmacoepidemiology and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estelles s/n, 46100 Burjassot, Spain; (O.A.R.-V.); (A.L.-G.)
| | - María Morales-Suárez-Varela
- Research Group in Social and Nutritional Epidemiology, Pharmacoepidemiology and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estelles s/n, 46100 Burjassot, Spain; (O.A.R.-V.); (A.L.-G.)
- Biomedical Research Center in Epidemiology and Public Health Network (CIBERESP), Carlos III Health Institute, Av. Monforte de Lemos 3-5 Pabellón 11 Planta 0, 28029 Madrid, Spain
| | - Agustín Llopis-González
- Research Group in Social and Nutritional Epidemiology, Pharmacoepidemiology and Public Health, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, Faculty of Pharmacy and Food Sciences, Universitat de València, Av. Vicent Andrés Estelles s/n, 46100 Burjassot, Spain; (O.A.R.-V.); (A.L.-G.)
- Biomedical Research Center in Epidemiology and Public Health Network (CIBERESP), Carlos III Health Institute, Av. Monforte de Lemos 3-5 Pabellón 11 Planta 0, 28029 Madrid, Spain
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Bajgai B, Suri M, Singh H, Hanifa M, Bhatti JS, Randhawa PK, Bali A. Naringin: A flavanone with a multifaceted target against sepsis-associated organ injuries. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155707. [PMID: 38788393 DOI: 10.1016/j.phymed.2024.155707] [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: 01/31/2024] [Revised: 04/16/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Sepsis causes multiple organ dysfunctions and raises mortality and morbidity rates through a dysregulated host response to infection. Despite the growing research interest over the last few years, no satisfactory treatment exists. Naringin, a naturally occurring bioflavonoid with vast therapeutic potential in citrus fruits and Chinese herbs, has received much attention for treating sepsis-associated multiple organ dysfunctions. PURPOSE The review describes preclinical evidence of naringin from 2011 to 2024, particularly emphasizing the mechanism of action mediated by naringin against sepsis-associated specific injuries. The combination therapy, safety profile, drug interactions, recent advancements in formulation, and future perspectives of naringin are also discussed. METHODS In vivo and in vitro studies focusing on the potential role of naringin and its mechanism of action against sepsis-associated organ injuries were identified and summarised in the present manuscript, which includes contributions from 2011 to 2024. All the articles were extracted from the Medline database using PubMed, Science Direct, and Web of Science with relevant keywords. RESULTS Research findings revealed that naringin modulates many signaling cascades, such as Rho/ROCK and PPAR/STAT1, PIP3/AKT and KEAP1/Nrf2, and IkB/NF-kB and MAPK/Nrf2/HO-1, to potentially protect against sepsis-induced intestinal, cardiac, and lung injury, respectively. Furthermore, naringin treatment exhibits anti-inflammatory, anti-apoptotic, and antioxidant action against sepsis harm, highlighting naringin's promising effects in septic settings. Naringin could be employed as a treatment against sepsis, based on studies on combination therapy, synergistic effects, and toxicological investigation that show no reported severe side effects. CONCLUSION Naringin might be a promising therapeutic approach for preventing sepsis-induced multiple organ failure. Naringin should be used alongside other therapeutic therapies with caution despite its great therapeutic potential and lower toxicity. Nonetheless, clinical studies are required to comprehend the therapeutic benefits of naringin against sepsis.
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Affiliation(s)
- Bivek Bajgai
- Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India
| | - Manisha Suri
- Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India
| | - Harshita Singh
- Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India
| | - Mohd Hanifa
- Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India
| | - Jasvinder Singh Bhatti
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Ghudda, Bathinda, India
| | - Puneet Kaur Randhawa
- Department of Pharmaceutical Sciences, Amritsar Group of Colleges, Amritsar, Punjab, 143001, India; Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA
| | - Anjana Bali
- Laboratory of Neuroendocrinology, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India.
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21
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Saadh MJ, Mustafa MA, Malathi H, Ahluwalia G, Kaur S, Al-Dulaimi MAAH, Alubiady MHS, Zain Al-Abdeen SH, Shakier HG, Ali MS, Ahmad I, Abosaoda MK. Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations. Med Oncol 2024; 41:201. [PMID: 39001987 DOI: 10.1007/s12032-024-02443-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 06/27/2024] [Indexed: 07/15/2024]
Abstract
Pancreatic cancer remains a significant health issue with limited treatment options. The tumor stroma, a complex environment made up of different cells and proteins, plays a crucial role in tumor growth and chemoresistance. Targeting tumor stroma, consisting of diverse non-tumor cells such as fibroblasts, extracellular matrix (ECM), immune cells, and also pre-vascular cells is encouraging for remodeling solid cancers, such as pancreatic cancer. Remodeling the stroma of pancreas tumors can be suggested as a strategy for reducing resistance to chemo/immunotherapy. Several studies have shown that phytochemicals from plants can affect the tumor environment and have anti-cancer properties. By targeting key pathways involved in stromal activation, phytochemicals may disrupt communication between the tumor and stroma and make tumor cells more sensitive to different treatments. Additionally, phytochemicals have immunomodulatory and anti-angiogenic properties, all of which contribute to their potential in treating pancreatic cancer. This review will provide a detailed look at how phytochemicals impact the tumor stroma and their effects on pancreatic tumor growth, spread, and response to treatment. It will also explore the potential of combining phytochemicals with other treatment options like chemotherapy, immunotherapy, and radiation.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
| | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, University of Imam Jaafar AL-Sadiq, Baghdad, Iraq
| | - H Malathi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
| | - Gunveen Ahluwalia
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, 303012, Rajasthan, India
| | - Sumeet Kaur
- Department of Applied Sciences, Chandigarh Engineering Colleges, Chandigarh Group of Colleges, Jhanjeri, 140307, Mohali, Punjab, India
| | | | | | | | | | | | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia.
| | - Munther Kadhim Abosaoda
- College of Pharmacy, The Islamic University, Najaf, Iraq
- College of Pharmacy, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- College of Pharmacy, The Islamic University of Babylon, Babylon, Iraq
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22
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Gao H, Chen F, Wang S. Hesperidin reduces systolic blood pressure in diabetic patients and has no effect on blood pressure in healthy individuals: A systematic review and meta-analysis. Phytother Res 2024; 38:3706-3719. [PMID: 38772688 DOI: 10.1002/ptr.8231] [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: 05/26/2023] [Revised: 04/19/2024] [Accepted: 04/20/2024] [Indexed: 05/23/2024]
Abstract
In recent years, there have been a number of studies where hesperidin was administered to modify arterial blood pressure, but the conclusions of each study are contradictory. In order to investigate the effect of hesperidin on blood pressure, we searched the CNKI, Wanfang Database, the VIP database, Sinomed database, Pubmed, Embase and The Cochrane Library databases, and searched the literature on hesperidin and blood pressure published in Chinese and English journals, mainly focusing on patients' systolic blood pressure and diastolic blood pressure. The search time frame was from the inception of the databases until December 2023. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the overall quality and used Cohen's kappa coefficient (κ) to measure agreement. We did preliminary screening of the retrieved literature through Notexpress, 14 articles with a total of 656 patients were included. Cochrance data conversion tool was used for data conversion, and RevMan 5.3 was used for meta-analysis, and finally Stata was used to make the Egger's test for the included study. The results of total population blood pressure showed that hesperidin had no antihypertensive effect on the population, but the conclusions changed when the population was divided into groups. The results of different populations showed that hesperidin had no effect on systolic blood pressure (weighted mean difference [WMD] = -0.50, 95% CI: -3.25 ~ 2.26, Z = 0.35, p = 0.72) and diastolic blood pressure (WMD = -0.51, 95% CI: -2.53 ~ 1.51, Z = 0.50, p = 0.62) in healthy individuals. However, hesperidin reduced systolic blood pressure in patients with type 2 diabetes (WMD = -4.32, 95% CI: - 7.77 ~ - 0.87, Z = 2.45, p = 0.01), and had a tendency to reduce diastolic blood pressure in diabetic patients (WMD = -3.72, 95% CI: -7.63 ~ 0.18, Z = 1.87, p = 0.06). The results in patients with type 2 diabetes needed to be further supported by future research focusing on individuals with diabetes.
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Affiliation(s)
- Haifeng Gao
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong, China
| | - Fang Chen
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong, China
| | - Shuo Wang
- School of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong, China
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23
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Yaseen HS, Zubair HM, Jamal A, Farrukh M, Mikrani R, Shaukat B, Hill JW, Rana R, Nazir A, Naveed M, Malik S. Naringin: Cardioprotective properties and safety profile in diabetes treatment. Fitoterapia 2024; 176:106011. [PMID: 38740344 DOI: 10.1016/j.fitote.2024.106011] [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: 11/04/2023] [Revised: 04/19/2024] [Accepted: 05/11/2024] [Indexed: 05/16/2024]
Abstract
Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating β-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use.
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Affiliation(s)
| | - Hafiz Muhammad Zubair
- Post-Graduate Medical College, Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
| | - Adil Jamal
- Sciences and Research, College of Nursing, Umm Al Qura University, Makkah 715, Saudi Arabia
| | - Maryam Farrukh
- Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Pakistan
| | - Reyaj Mikrani
- Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Bushra Shaukat
- Sciences and Research, College of Nursing, Umm Al Qura University, Makkah 715, Saudi Arabia
| | - Jennifer W Hill
- Department of Pharmacology and Physiology, School of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
| | - Reemal Rana
- Sciences and Research, College of Nursing, Umm Al Qura University, Makkah 715, Saudi Arabia
| | - Ansa Nazir
- Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan
| | - Muhammad Naveed
- Department of Pharmacology and Physiology, School of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA
| | - Samiullah Malik
- Post-Graduate Medical College, Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
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24
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Niu W, Feng Y, Peng M, Cai J. A narrative review on the mechanism of natural flavonoids in improving glucolipid metabolism disorders. Phytother Res 2024. [PMID: 38924256 DOI: 10.1002/ptr.8276] [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: 02/26/2024] [Revised: 05/29/2024] [Accepted: 06/07/2024] [Indexed: 06/28/2024]
Abstract
Glucolipid metabolism disorder (GLMD) is a complex chronic disease characterized by glucose and lipid metabolism disorders with a complex and diverse etiology and rapidly increasing incidence. Many studies have identified the role of flavonoids in ameliorating GLMD, with mechanisms related to peroxisome proliferator-activated receptors, nuclear factor kappa-B, AMP-activated protein kinase, nuclear factor (erythroid-derived 2)-like 2, glucose transporter type 4, and phosphatidylinositol-3-kinase/protein kinase B pathway. However, a comprehensive summary of the flavonoid effects on GLMD is lacking. This study reviewed the roles and mechanisms of natural flavonoids with different structures in the treatment of GLMD reported globally in the past 5 years and provides a reference for developing flavonoids as drugs for treating GLMD.
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Affiliation(s)
- Wenjing Niu
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Yongshi Feng
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Minwen Peng
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
| | - Jinyan Cai
- Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial TCM Key Laboratory for Metabolic Diseases, Guangzhou, China
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25
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Elsori D, Pandey P, Ramniwas S, Kumar R, Lakhanpal S, Rab SO, Siddiqui S, Singh A, Saeed M, Khan F. Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics. Front Pharmacol 2024; 15:1406619. [PMID: 38957397 PMCID: PMC11217354 DOI: 10.3389/fphar.2024.1406619] [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: 03/25/2024] [Accepted: 05/29/2024] [Indexed: 07/04/2024] Open
Abstract
The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.
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Affiliation(s)
- Deena Elsori
- Faculty of Resilience, Rabdan Academy, Abu Dhabi, United Arab Emirates
| | - Pratibha Pandey
- Centre of Research Impact and Outcome, Chitkara University, Rajpura, India
| | - Seema Ramniwas
- University Centre of Research and Development, University Institute of Biotechnology, Chandigarh University Gharuan, Mohali, India
| | - Rahul Kumar
- Chitkara Centre for Research and Development, Chitkara University, Himachal Pradesh, India
| | - Sorabh Lakhanpal
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India
| | - Safia Obaidur Rab
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Samra Siddiqui
- Department of Health Service Management, College of Public Health and Health Informatics, University of Ha’il, Ha’il, Saudi Arabia
| | - Ajay Singh
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, India
| | - Mohd Saeed
- Department of Biology, College of Science, University of Hail, Ha’il, Saudi Arabia
| | - Fahad Khan
- Center for Global Health Research Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
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26
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Chen J, Qin X, Chen M, Chen T, Chen Z, He B. Biological activities, Molecular mechanisms, and Clinical application of Naringin in Metabolic syndrome. Pharmacol Res 2024; 202:107124. [PMID: 38428704 DOI: 10.1016/j.phrs.2024.107124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/16/2024] [Accepted: 02/27/2024] [Indexed: 03/03/2024]
Abstract
Metabolic syndrome has become major health problems in recent decades, and natural compounds receive considerable attention in the management of metabolic syndrome. Among them, naringin is abundant in citrus fruits and tomatoes. Many studies have investigated the therapeutic effects of naringin in metabolic syndrome. This review discusses in vitro and in vivo studies on naringin and implications for clinical trials on metabolic syndrome such as diabetes mellitus, obesity, nonalcoholic fatty liver disease, dyslipidemia, and hypertension over the past decades, overviews the molecular mechanisms by which naringin targets metabolic syndrome, and analyzes possible correlations between the different mechanisms. This review provides a theoretical basis for the further application of naringin in the treatment of metabolic syndrome.
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Affiliation(s)
- Jie Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Xiang Qin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Mengyao Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Tianzhu Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Zheng Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China.
| | - Beihui He
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China; School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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27
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Peng Y, Qu R, Xu S, Bi H, Guo D. Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders. Heliyon 2024; 10:e24619. [PMID: 38317884 PMCID: PMC10839891 DOI: 10.1016/j.heliyon.2024.e24619] [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: 08/04/2023] [Revised: 12/02/2023] [Accepted: 01/11/2024] [Indexed: 02/07/2024] Open
Abstract
Naringin is a natural flavonoid with therapeutic properties found in citrus fruits and an active natural product from herbal plants. Naringin has become a focus of attention in recent years because of its ability to actively participate in the body's immune response and maintain the integrity of the immune barrier. This review aims to elucidate the mechanism of action and therapeutic efficacy of naringin in various inflammatory diseases and to provide a valuable reference for further research in this field. The review provided the chemical structure, bioavailability, pharmacological properties, and pharmacokinetics of naringin and found that naringin has good therapeutic potential for inflammatory diseases, exerting anti-inflammatory, anti-apoptotic, anti-oxidative stress, anti-ulcerative and detoxifying effects in the disease. Moreover, we found that the great advantage of naringin treatment is that it is safe and can even alleviate the toxic side effects associated with some of the other drugs, which may become a highlight of naringin research. Naringin, an active natural product, plays a significant role in systemic diseases' anti-inflammatory and antioxidant regulation through various signaling pathways and molecular mechanisms.
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Affiliation(s)
- Yuan Peng
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Ruyi Qu
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Shuqin Xu
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Hongsheng Bi
- Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Dadong Guo
- Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
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28
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Guan L, Guo L, Zhang H, Liu H, Zhou W, Zhai Y, Yan X, Men X, Peng L. Naringin Protects against Non-Alcoholic Fatty Liver Disease by Promoting Autophagic Flux and Lipophagy. Mol Nutr Food Res 2024; 68:e2200812. [PMID: 38054638 DOI: 10.1002/mnfr.202200812] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 05/07/2023] [Indexed: 12/07/2023]
Abstract
The autophagic degradation of lipid droplets, termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. Identifying effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here the effects of naringin on NAFLD and the underlying mechanisms involved are investigated. Naringin treatment effectively relieves HFD-induced hepatic steatosis in mice and inhibits PA-induced lipid accumulation in hepatocytes. Increased p62 and LC3-II levels are observed with excess lipid support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restores TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogates naringin-induced lipophagy, eliminating its therapeutic effect on hepatic steatosis. These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating NAFLD.
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Affiliation(s)
- Lingling Guan
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063000, China
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
- The fifth affiliated hospital, Guangzhou Medical University, Guangzhou, 510000, China
| | - Lan Guo
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063000, China
| | - Heng Zhang
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063000, China
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
| | - Hao Liu
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
| | - Wenling Zhou
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
| | - Yuanyuan Zhai
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
| | - Xu Yan
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
| | - Xiuli Men
- School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063000, China
| | - Liang Peng
- Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Medical Science, China-Japan Friendship Hospital, Beijing, 100000, China
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Tobaruela EDC, Brasili E, Zeraik L, Milenkovic D, Hassimotto NMA, Lajolo FM. Plasma proteome profiling reveals molecular mechanisms underlying the effects of daily consumption of 'Bahia' and 'Cara Cara' orange juices. Food Funct 2024; 15:1031-1049. [PMID: 38193367 DOI: 10.1039/d3fo04091g] [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: 01/10/2024]
Abstract
Orange juice is an important food source of bioactive compounds, mainly the flavanones hesperidin and narirutin. This study aimed to investigate the underlying molecular mechanisms of action of orange juice's health properties by analyzing changes in the plasma proteome of healthy Brazilian volunteers after consuming juices made from 'Bahia' (BOJ-source of flavanones) and 'Cara Cara' (CCOJ-source of flavanones and carotenoids) oranges cultivated in Brazil. We used an untargeted proteomic approach, with a particular emphasis on the juices' effects on blood coagulant activity. We identified 247 differentially expressed proteins, of which 170 significantly increased or decreased after BOJ consumption and 145 after CCOJ. These proteins are involved in 105 processes that can significantly regulate cell adhesion, cell signaling, cell metabolism, inflammation, or others. Bioinformatic analysis evidenced proteins with major cellular regulatory capacity (e.g., FN1 and GAPDH) and predicted transcription factors (TFs) (e.g., SP1 and CEBPA) and miRNAs (e.g., miR-1-3p and miR-615-3p) that could be involved in the regulation of differentially expressed proteins. In-silico docking analyses between flavanone metabolites and TFs evidenced the higher binding capacity of narirutin phase II metabolites with akt1 and p38, interactions that suggest how the expression of genes of differentially expressed proteins were activated or inhibited. Moreover, the study shed light on proteins of coagulation cascade that presented expression modulated by both juices, proposing the modulation of blood coagulant activity as a potential benefit of OJ (mainly CCOJ) consumption. Taken together, this study revealed that BOJ and CCOJ consumption affected plasma proteome in healthy individuals, suggesting potential molecular targets and mechanisms of OJ bioactive compounds in humans.
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Affiliation(s)
- Eric de Castro Tobaruela
- Food Research Center (FoRC), Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
| | - Elisa Brasili
- Department of Environmental Biology, Sapienza University of Rome, Rome, Italy
| | - Laila Zeraik
- Food Research Center (FoRC), Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
| | - Dragan Milenkovic
- Department of Nutrition, University of California Davis, 95616 Davis, CA, USA
| | - Neuza Mariko Aymoto Hassimotto
- Food Research Center (FoRC), Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
| | - Franco Maria Lajolo
- Food Research Center (FoRC), Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
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Hashim M, Badruddeen, Akhtar J, Khan MI, Ahmad M, Islam A, Ahmad A. Diabetic Neuropathy: An Overview of Molecular Pathways and Protective Mechanisms of Phytobioactives. Endocr Metab Immune Disord Drug Targets 2024; 24:758-776. [PMID: 37867264 DOI: 10.2174/0118715303266444231008143430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/31/2023] [Accepted: 08/25/2023] [Indexed: 10/24/2023]
Abstract
Diabetic neuropathy (DN) is a common and debilitating complication of diabetes mellitus that affects the peripheral nerves and causes pain, numbness, and impaired function. The pathogenesis of DN involves multiple molecular mechanisms, such as oxidative stress, inflammation, and pathways of advanced glycation end products, polyol, hexosamine, and protein kinase C. Phytochemicals are natural compounds derived from plants that have various biological activities and therapeutic potential. Flavonoids, terpenes, alkaloids, stilbenes, and tannins are some of the phytochemicals that have been identified as having protective potential for diabetic neuropathy. These compounds can modulate various cellular pathways involved in the development and progression of neuropathy, including reducing oxidative stress and inflammation and promoting nerve growth and repair. In this review, the current evidence on the effects of phytochemicals on DN by focusing on five major classes, flavonoids, terpenes, alkaloids, stilbenes, and tannins, are summarized. This compilation also discusses the possible molecular targets of numerous pathways of DN that these phytochemicals modulate. These phytochemicals may offer a promising alternative or complementary approach to conventional drugs for DN management by modulating multiple pathological pathways and restoring nerve function.
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Affiliation(s)
- Mohd Hashim
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Badruddeen
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Juber Akhtar
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | | | - Mohammad Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Anas Islam
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
| | - Asad Ahmad
- Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India
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31
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Liao Y, Meng Q. Protection against cancer therapy-induced cardiovascular injury by planed-derived polyphenols and nanomaterials. ENVIRONMENTAL RESEARCH 2023; 238:116896. [PMID: 37586453 DOI: 10.1016/j.envres.2023.116896] [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: 06/27/2023] [Revised: 07/18/2023] [Accepted: 08/13/2023] [Indexed: 08/18/2023]
Abstract
Cancer therapy-induced heart injury is a significant concern for cancer patients undergoing chemotherapy, radiotherapy, immunotherapy, and also targeted molecular therapy. The use of these treatments can lead to oxidative stress and cardiomyocyte damage in the heart, which can result in heart failure and other cardiac complications. Experimental studies have revealed that chemotherapy drugs such as doxorubicin and cyclophosphamide can cause severe side effects such as cardiac fibrosis, electrophysiological remodeling, chronic oxidative stress and inflammation, etc., which may increase risk of cardiac disorders and attacks for patients that underwent chemotherapy. Similar consequences may also be observed for patients that undergo radiotherapy for left breast or lung malignancies. Polyphenols, a group of natural compounds with antioxidant and anti-inflammatory properties, have shown the potential in protecting against cancer therapy-induced heart injury. These compounds have been found to reduce oxidative stress, necrosis and apoptosis in the heart, thereby preserving cardiac function. In recent years, nanoparticles loaded with polyphenols have also provided for the delivery of these compounds and increasing their efficacy in different organs. These nanoparticles can improve the bioavailability and efficacy of polyphenols while minimizing their toxicity. This review article summarizes the current understanding of the protective effects of polyphenols and nanoparticles loaded with polyphenols against cancer therapy-induced heart injury. The article discusses the mechanisms by which polyphenols protect the heart, including antioxidant and anti-inflammation abilities. The article also highlights the potential benefits of using nanoparticles for the delivery of polyphenols.
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Affiliation(s)
- Yunshu Liao
- Department of Cardiac Surgery, The First Hospital Affiliated to the Army Medical University, Chongqing, 400038, China
| | - Qinghua Meng
- Department of Cardiac Surgery, The First Hospital Affiliated to the Army Medical University, Chongqing, 400038, China.
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Xu N, Liu S, Zhang Y, Chen Y, Zuo Y, Tan X, Liao B, Li P, Feng J. Oxidative stress signaling in the pathogenesis of diabetic cardiomyopathy and the potential therapeutic role of antioxidant naringenin. Redox Rep 2023; 28:2246720. [PMID: 37747066 PMCID: PMC10538464 DOI: 10.1080/13510002.2023.2246720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023] Open
Abstract
Diabetes mellitus (DM) is one of the most prevalent metabolic disorders that poses a global threat to human health. It can lead to complications in multiple organs and tissues, owing to its wide-ranging impact on the human body. Diabetic cardiomyopathy (DCM) is a specific cardiac manifestation of DM, which is characterized by heart failure in the absence of coronary heart disease, hypertension and valvular heart disease. Given that oxidative stress is a key factor in the pathogenesis of DCM, intervening to mitigate oxidative stress may serve as a therapeutic strategy for managing DCM. Naringenin is a natural product with anti-oxidative stress properties that can suppress oxidative damage by regulating various oxidative stress signaling pathways. In this review, we address the relationship between oxidative stress and its primary signaling pathways implicated in DCM, and explores the therapeutic potential of naringenin in DCM.
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Affiliation(s)
- Nan Xu
- Department of Cardiology, The First People's Hospital of Neijiang, Neijiang, People’s Republic of China
| | - Siqi Liu
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Yongqiang Zhang
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Yujing Chen
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Yumei Zuo
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Xiaoqiu Tan
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Bin Liao
- Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China
| | - Pengyun Li
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
| | - Jian Feng
- Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, People’s Republic of China
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Qin MC, Li JJ, Zheng YT, Li YJ, Zhang YX, Ou RX, He WY, Zhao JM, Liu ST, Liu MH, Lin HY, Gao L. Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration. Food Funct 2023; 14:10347-10361. [PMID: 37930368 DOI: 10.1039/d3fo03858k] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Abstract
Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.
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Affiliation(s)
- Meng-Chen Qin
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Jun-Jie Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yan-Tao Zheng
- Emergency Department, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
| | - Yun-Jia Li
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Yu-Xue Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Rou-Xuan Ou
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Wei-Yi He
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Jia-Min Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Su-Tong Liu
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
| | - Ming-Hao Liu
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.
| | - Hai-Yan Lin
- Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, China.
| | - Lei Gao
- Emergency Department, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
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Shangguan Y, Ni J, Jiang L, Hu Y, He C, Ma Y, Wu G, Xiong H. Response surface methodology-optimized extraction of flavonoids from pomelo peels and isolation of naringin with antioxidant activities by Sephadex LH20 gel chromatography. Curr Res Food Sci 2023; 7:100610. [PMID: 37860143 PMCID: PMC10582393 DOI: 10.1016/j.crfs.2023.100610] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/31/2023] [Accepted: 10/02/2023] [Indexed: 10/21/2023] Open
Abstract
In this study, flavonoids were extracted from pomelo peels and naringin was isolated from the flavonoid extract. The effects of extraction parameters, namely, ethanol concentration, solid-to-liquid ratio, and extraction time, on the yield of flavonoids extracted from pomelo peels were analyzed according to the Box-Behnken design of response surface methodology. The experimental conditions for flavonoid extraction were optimized, and naringin was separated from the extracted flavonoids using Sephadex LH-20 column chromatography. Experimental results showed that the influence of factors on the extraction rate of flavonoids from pomelo peels was in the order of ethanol concentration > solid-to-liquid ratio > extraction time, and the optimal extraction parameters were 85% ethanol concentration, 1:20 solid-to-liquid ratio, and 4-h extraction time for extracting flavonoids from pomelo peels. Under these conditions, the yield of flavonoids was 6.07 ± 0.06 mg/g. After three times of extraction, the flavonoid extraction rate reached 96.55%, and the residual naringin in the pomelo peels was 0.017 mg/g, at which point the bitterness in the pomelo peels disappeared. Two components, namely, PF1 and PF2, were separated from the crude flavonoid of pomelo peels through Sephadex LH20 column chromatography. PF2 was identified as naringin by high-performance liquid chromatography tandem mass spectrometry, with a purity of 95.7 ± 0.23%. Both flavonoids and PF2 exhibited good in vitro radicals scavenging activities on DPPH, ABTS, superoxide anion and hydroxyl.
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Affiliation(s)
- Yuchen Shangguan
- College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China
- Jiangle County Agricultural Products Quality and Safety Inspection Station, Sanming, 353300, China
| | - Jing Ni
- Fisheries College of Jimei University, Xiamen, 361021, China
| | - Lili Jiang
- Xiamen Municipal Southern Ocean Testing Co., L, Xiamen, 361021, China
| | - Yang Hu
- College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China
| | - Chuanbo He
- College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China
| | - Ying Ma
- Fisheries College of Jimei University, Xiamen, 361021, China
| | - Guohong Wu
- College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China
| | - Hejian Xiong
- College of Ocean Food and Biological Engineering, Fujian Provincial Engineering Technology Research Center of Marine Functional Food, Jimei University, Xiamen, 361021, China
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Pierdomenico M, Cicero AFG, Veronesi M, Fogacci F, Riccioni C, Benassi B. Effect of Citrus bergamia extract on lipid profile: A combined in vitro and human study. Phytother Res 2023; 37:4185-4195. [PMID: 37312672 DOI: 10.1002/ptr.7897] [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: 09/08/2022] [Revised: 02/28/2023] [Accepted: 05/09/2023] [Indexed: 06/15/2023]
Abstract
With the aim of characterising the hypo-lipidemic function of the Brumex™ ingredient obtained from the whole fruit of Citrus bergamia, a combined pre-clinical and clinical study was conducted. In the HepG2 experimental model, we first demonstrated that Brumex™ does not trigger any significant alteration in cell viability over the tested concentration range of 1-2000 μg/mL (4 and 24 h). By stimulating the phosphorylation of AMP-activated protein kinase (AMPK) at threonine 172, Brumex™ significantly reduces both cholesterol and triglyceride (TG) intracellular content of HepG2 cells and impairs the expression levels of lipid synthesis-related genes (namely, SREBF1c, SREBF2, ACACA, SCD1, HMGCR and FASN). In vitro data have been validated in a dedicated double-blind, placebo-controlled, randomised clinical trial performed in 50 healthy moderately hyper-cholesterolemic subjects, undergoing supplementation with either Brumex™ (400 mg) or placebo for 12 weeks. Clinical and blood laboratory data were evaluated at the baseline and at the end of the trial. Brumex™ positively impacted on both plasma lipid pattern and liver enzymes compared with the placebo, mainly in terms of significant reduction of total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein B100 (ApoB), fasting plasma glucose (FPG), glutamic-oxaloacetic transaminase (GOT), glutamate pyruvate transaminase (GPT) and gamma-glutamyl-transferase (gGT).
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Affiliation(s)
- Maria Pierdomenico
- Division of Health Protection Technologies, ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Rome, Italy
| | - Arrigo F G Cicero
- Hypertension and Cardiovascular Risk Factors Research Center, Medical and Surgical Sciences Deptartment, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Maddalena Veronesi
- Hypertension and Cardiovascular Risk Factors Research Center, Medical and Surgical Sciences Deptartment, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Federica Fogacci
- Hypertension and Cardiovascular Risk Factors Research Center, Medical and Surgical Sciences Deptartment, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | | | - Barbara Benassi
- Division of Health Protection Technologies, ENEA-Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Rome, Italy
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Ajtony Z, Sik B, Csuti A. Examining the Naringin Content and Sensory Characteristics of Functional Chocolate Fortified with Grapefruit Peel Extract. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2023; 78:533-538. [PMID: 37594558 PMCID: PMC10495487 DOI: 10.1007/s11130-023-01091-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/30/2023] [Indexed: 08/19/2023]
Abstract
Grapefruit peel contains a high concentration of naringin- a potent antioxidant with strong bioactive properties. In this study, a new type of functional chocolate fortified with grapefruit peel extract and different concentrations of aqueous methanol and ethanol were evaluated as extraction solvents. A new high-performance liquid chromatography (HPLC) method to analyze the naringin content of the fortified chocolates was developed with a recovery of 107% ± 3.1% and repeatability below 3.5%. A sensory evaluation was conducted to assess the preference for the chocolates among individuals who self-described a preference for bitter flavors. No significant preference was observed in the cases of astringency and aftertaste while the increased bitterness proved to be favorable. However, taste, flavor and overall acceptability were regarded somewhat less favorably. While chocolate proved to be a satisfactory carrier for naringin and had several enjoyable characteristics, further research may focus on improving the organoleptic properties of chocolates fortified by naringin.
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Affiliation(s)
- Zsolt Ajtony
- Department of Food Science, Albert Casimir Faculty at Mosonmagyaróvár, Széchenyi István University, 15-17 Lucsony Street, Mosonmagyaróvár, 9200, Hungary
| | - Beatrix Sik
- Department of Food Science, Albert Casimir Faculty at Mosonmagyaróvár, Széchenyi István University, 15-17 Lucsony Street, Mosonmagyaróvár, 9200, Hungary.
| | - Aron Csuti
- Department of Food Science, Albert Casimir Faculty at Mosonmagyaróvár, Széchenyi István University, 15-17 Lucsony Street, Mosonmagyaróvár, 9200, Hungary
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37
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He J, Zhang HP. Research progress on the anti-tumor effect of Naringin. Front Pharmacol 2023; 14:1217001. [PMID: 37663256 PMCID: PMC10469811 DOI: 10.3389/fphar.2023.1217001] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 08/07/2023] [Indexed: 09/05/2023] Open
Abstract
Naringin is a kind of natural dihydro flavone, which mainly exists in citrus fruits of the Rutaceae family, as well as traditional Chinese medicines such as trifoliate orange, fingered citron, exocarpium citri grandis, and rhizoma dynamite. Modern pharmacological studies have shown that Naringin has excellent anti-tumor activity. Through reviewing the relevant literature at home and abroad in recent years, we summarized the pharmacological mechanism of Naringin to play an anti-cancer role in blocking tumor cell cycle, inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and metastasis, inducing tumor cell autophagy, reversing tumor cell drug resistance and enhancing chemotherapeutic drug sensitivity, as well as anti-inflammatory to prevent canceration, alleviate Adverse drug reaction of chemotherapy, activate and strengthen immunity, It provides theoretical basis and reference basis for further exploring the anticancer potential of Naringin and its further development and utilization.
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Affiliation(s)
- Jing He
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hui-Ping Zhang
- Oncology Department, Jinan Traditional Chinese Medicine Hospital, Jinan, China
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38
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Corrêa TAF, Tobaruela EDC, Capetini VC, Quintanilha BJ, Cortez RV, Taddei CR, Hassimotto NMA, Hoffmann C, Rogero MM, Lajolo FM. Blood orange juice intake changes specific bacteria of gut microbiota associated with cardiometabolic biomarkers. Front Microbiol 2023; 14:1199383. [PMID: 37469434 PMCID: PMC10352659 DOI: 10.3389/fmicb.2023.1199383] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/19/2023] [Indexed: 07/21/2023] Open
Abstract
Blood orange juice is an important source of flavanones and anthocyanins, mainly hesperidin, narirutin, and cyanidin-3-O-glucoside. The benefits of these bioactive compounds have been reported, but the mechanistic details behind their biological effects are not well established. This study investigated the effects of Moro orange (Citrus sinensis L. Osbeck) juice (MOJ) on gut microbiota composition and cardiometabolic biomarkers in overweight women. In this study, 12 overweight women (BMI from 25.0 to 29.9 kg/m2), aged 18-37 years, consumed 500 mL of MOJ every day for 4 weeks. We assessed the gut microbiota composition, levels of short-chain fatty acids (SCFAs), cardiometabolic biomarkers, and insulin resistance (HOMA-IR) at baseline and after 2 weeks and 4 weeks of MOJ intake. The results suggested that MOJ intake affected the abundance of specific operational taxonomic units (OTUs) of the gut microbiota but did not significantly alter the diversity and general composition of the gut microbiota. However, MOJ intake increased the production of SCFAs, especially propionic and isobutyric acids, and significantly improved cardiometabolic biomarkers such as blood pressure and plasma VCAM-1 levels in the overweight women. Additionally, we observed significant associations between gut microbiota OTUs belonging to the Bacteroidetes phyla and Prevotella 9 genera and the cardiometabolic biomarkers. Furthermore, MOJ reduced fasting glucose and insulin levels and HOMA-IR values, thereby enhancing insulin sensitivity in the insulin-resistant overweight women. Finally, we highlighted the importance of orange juice intake duration because some beneficial changes such as blood pressure improvements were evident at the 2-week time interval of the intervention, but other changes became significant only at the 4-week interval of MOJ intake. In conclusion, our study demonstrated that changes in specific OTUs of the gut microbiota in response to MOJ intake were associated with significant improvements in some cardiometabolic biomarkers and SCFA levels in overweight women with insulin resistance.
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Affiliation(s)
- Telma Angelina Faraldo Corrêa
- Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Food Research Center (FoRC), São Paulo, Brazil
| | - Eric de Castro Tobaruela
- Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Food Research Center (FoRC), São Paulo, Brazil
| | - Vinicius Cooper Capetini
- Food Research Center (FoRC), São Paulo, Brazil
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil
| | - Bruna Jardim Quintanilha
- Food Research Center (FoRC), São Paulo, Brazil
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil
| | - Ramon Vitor Cortez
- Department of Clinical Analyses and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Carla R. Taddei
- Department of Clinical Analyses and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
| | - Neuza Mariko Aymoto Hassimotto
- Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Food Research Center (FoRC), São Paulo, Brazil
| | - Christian Hoffmann
- Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Food Research Center (FoRC), São Paulo, Brazil
| | - Marcelo Macedo Rogero
- Food Research Center (FoRC), São Paulo, Brazil
- Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil
| | - Franco Maria Lajolo
- Department of Food and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Food Research Center (FoRC), São Paulo, Brazil
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Ma K, Liu W, Liu Q, Hu P, Bai L, Yu M, Yang Y. Naringenin facilitates M2 macrophage polarization after myocardial ischemia-reperfusion by promoting nuclear translocation of transcription factor EB and inhibiting the NLRP3 inflammasome pathway. ENVIRONMENTAL TOXICOLOGY 2023; 38:1405-1419. [PMID: 36988289 DOI: 10.1002/tox.23774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 02/22/2023] [Accepted: 02/25/2023] [Indexed: 05/18/2023]
Abstract
Myocardial ischemia-reperfusion injury (MIRI) remains an unsolved puzzle in medical circles. Naringenin (NAR) is a flavonoid with cardioprotective potential. The purpose of this article was to discuss the protective mechanism of NAR in MIRI by regulating macrophage polarization. The MIRI mouse model was established and perfused with NAR before surgery. In the in vitro experiment, macrophages RAW264.7 were treated with lipopolysaccharide to induce M1 polarization after pretreatment with NAR. Rescue experiments were carried out to validate the functions of transcription factor EB (TFEB), the NLR pyrin domain containing 3 (NLRP3) inflammasome, and autophagy in macrophage polarization. NAR reduced histopathological injury and infarction of myocardial tissues in MIRI mice, inhibited M1 polarization and promoted M2 polarization of macrophages, diminished levels of pro-inflammatory factors, and augmented levels of anti-inflammatory factors. NAR facilitated TFEB nuclear translocation and inhibited the NLRP3 inflammasome pathway. Silencing TFEB or Nigericin partly nullified the effect of NAR on macrophage polarization. NAR increased autophagosome formation, autophagy flux, and autophagy level. Autophagy inhibitor 3-methyladenine partly invalidated the inhibition of NAR on the NLRP3 inflammasome pathway. In animal experiments, NAR protected MIRI mice through the TFEB-autophagy-NLRP3 inflammasome pathway. Collectively, NAR inhibited NLRP3 inflammasome activation and facilitated M2 macrophage polarization by stimulating TFEB nuclear translocation, thus protecting against MIRI.
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Affiliation(s)
- Kuiying Ma
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Wenqing Liu
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Qi Liu
- Emergency Department, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Pengfei Hu
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Lingyu Bai
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Miao Yu
- Department of Cardiovascular Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
| | - Yan Yang
- Department of General Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao City, China
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40
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Zhu Y, Tao C, Goh C, Shrestha A. Innovative biomaterials for the treatment of periodontal disease. FRONTIERS IN DENTAL MEDICINE 2023; 4:1163562. [PMID: 39916927 PMCID: PMC11797777 DOI: 10.3389/fdmed.2023.1163562] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 05/03/2023] [Indexed: 02/09/2025] Open
Abstract
Periodontitis is a multifactorial disease that involves the destruction of hard and soft tissues surrounding the tooth. Routine periodontal treatment includes mechanical debridement (surgical and non-surgical) and the systemic administration of antibiotics. In contrast, severe and chronic periodontitis involves aggressive tissue destruction and bone resorption, and the damage is usually irreversible. In these severe cases, bone grafts, the delivery of growth hormones, and guided tissue regeneration can all be used to stimulate periodontal regeneration. However, these approaches do not result in consistent and predictable treatment outcomes. As a result, advanced biomaterials have evolved as an adjunctive approach to improve clinical performance. These novel biomaterials are designed to either prolong the release of antibacterial agents or osteogenic molecules, or to act as immunomodulators to promote healing. The first half of this review briefly summarizes the key immune cells and their underlying cellular pathways implicated in periodontitis. Advanced biomaterials designed to promote periodontal regeneration will be highlighted in the second half. Finally, the limitations of the current experimental design and the challenges of translational science will be discussed.
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Affiliation(s)
- Yi Zhu
- Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
| | - Chen Tao
- Stomatological Hospital of Chongqing, Key Laboratory of Oral Diseases and Biomaterial Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Cynthia Goh
- Department of Chemistry, University of Toronto, Toronto, ON, Canada
- Department of Materials Science and Engineering, University of Toronto, Toronto, ON, Canada
| | - Annie Shrestha
- Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- Department of Dentistry, Mt. Sinai Hospital, Toronto, ON, Canada
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Li J, Mao B, Tang X, Zhang Q, Zhao J, Zhang H, Cui S. Protective Effects of Naringenin and Apigenin in Ameliorating Skin Damage via Mediating the Nrf2 and NF-κB Pathways in Mice. Foods 2023; 12:foods12112120. [PMID: 37297362 DOI: 10.3390/foods12112120] [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: 04/23/2023] [Revised: 05/16/2023] [Accepted: 05/23/2023] [Indexed: 06/12/2023] Open
Abstract
Naringenin and apigenin are common flavonoids derived from edible plants with the potential to alleviate inflammation and improve skin antioxidation. This study aimed to evaluate the effects of naringenin and apigenin on oleic acid-induced skin damage in mice and compare their underlying mechanisms of action. Triglycerides and non-esterified fatty acids were significantly decreased by naringenin and apigenin, while apigenin intervention resulted in a better recovery of skin lesions. Naringenin and apigenin improved the antioxidative abilities of the skin by increasing catalase and total antioxidant capacity levels and decreasing malondialdehyde and lipid peroxide levels. The release of skin proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor α, was inhibited after naringenin and apigenin pretreatments, but naringenin only promoted the excretion of IL-10. Additionally, naringenin and apigenin regulated antioxidant defense and inflammatory response by activating nuclear factor erythroid-2 related factor 2-dependent mechanisms and suppressing the expression of nuclear factor-kappa B. In summary, naringenin and apigenin are prospective ingredients that contribute to the amelioration of skin damage by activating anti-inflammatory and antioxidative responses.
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Affiliation(s)
- Jie Li
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Bingyong Mao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xin Tang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Qiuxiang Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Shumao Cui
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
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Gan J, Deng X, Le Y, Lai J, Liao X. The Development of Naringin for Use against Bone and Cartilage Disorders. Molecules 2023; 28:3716. [PMID: 37175126 PMCID: PMC10180405 DOI: 10.3390/molecules28093716] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/17/2023] [Accepted: 04/24/2023] [Indexed: 05/15/2023] Open
Abstract
Bone and cartilage disorders are the leading causes of musculoskeletal disability. There is no absolute cure for all bone and cartilage disorders. The exploration of natural compounds for the potential therapeutic use against bone and cartilage disorders is proving promising. Among these natural chemicals, naringin, a flavanone glycoside, is a potential candidate due to its multifaceted pharmacological activities in bone and cartilage tissues. Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis in vivo and in vitro. Many signaling pathways, such as BMP-2, Wnt/β-catenin, and VEGF/VEGFR, participate in the biological actions of naringin in mediating the pathological development of osteoporosis. In addition, the anti-inflammatory, anti-oxidative stress, and anti-apoptosis abilities of naringin also demonstrate its beneficial effects against bone and cartilage disorders, including intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, bone and cartilage tumors, and tibial dyschondroplasia. Naringin exhibits protective effects against bone and cartilage disorders. However, more efforts are still needed due to, at least in part, the uncertainty of drug targets. Further biological and pharmacological evaluations of naringin and its applications in bone tissue engineering, particularly its therapeutic effects against osteoporosis, might result in developing potential drug candidates.
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Affiliation(s)
- Juwen Gan
- Department of Pulmonary and Critical Care Medicine, Ganzhou People’s Hospital, Ganzhou 341000, China
| | - Xiaolan Deng
- Department of Pharmacy, Haikou Affiliated Hospital, Xiangya School of Medicine, Central South University, Haikou 570208, China
| | - Yonghong Le
- Department of Pulmonary and Critical Care Medicine, Ganzhou People’s Hospital, Ganzhou 341000, China
| | - Jun Lai
- Department of Pharmacy, Ganzhou People’s Hospital, Ganzhou 341000, China
| | - Xiaofei Liao
- Department of Pharmacy, Ganzhou People’s Hospital, Ganzhou 341000, China
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Naringin: Nanotechnological Strategies for Potential Pharmaceutical Applications. Pharmaceutics 2023; 15:pharmaceutics15030863. [PMID: 36986723 PMCID: PMC10054771 DOI: 10.3390/pharmaceutics15030863] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 03/11/2023] Open
Abstract
Polyphenols comprise a number of natural substances, such as flavonoids, that show interesting biological effects. Among these substances is naringin, a naturally occurring flavanone glycoside found in citrus fruits and Chinese medicinal herbs. Several studies have shown that naringin has numerous biological properties, including cardioprotective, cholesterol-lowering, anti-Alzheimer’s, nephroprotective, antiageing, antihyperglycemic, antiosteoporotic and gastroprotective, anti-inflammatory, antioxidant, antiapoptotic, anticancer and antiulcer effects. Despite its multiple benefits, the clinical application of naringin is severely restricted due to its susceptibility to oxidation, poor water solubility, and dissolution rate. In addition, naringin shows instability at acidic pH, is enzymatically metabolized by β-glycosidase in the stomach and is degraded in the bloodstream when administered intravenously. These limitations, however, have been overcome thanks to the development of naringin nanoformulations. This review summarizes recent research carried out on strategies designed to improve naringin’s bioactivity for potential therapeutic applications.
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Capsicum baccatum Red Pepper Prevents Cardiometabolic Risk in Rats Fed with an Ultra-Processed Diet. Metabolites 2023; 13:metabo13030385. [PMID: 36984825 PMCID: PMC10052057 DOI: 10.3390/metabo13030385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Metabolic syndrome is a serious health condition reaching epidemic proportions worldwide and is closely linked to an increased risk of cardiovascular problems. The lack of appropriate treatment paves the way for developing new therapeutic agents as a high priority in the current research. In this study, we evaluated the protective effects of Capsicum baccatum red pepper on metabolic syndrome scenarios induced by an ultra-processed diet in rats. After four months, the ultra-processed diet increased central obesity, triglycerides, total cholesterol, LDL-cholesterol plasma levels, and impaired glucose tolerance. The oral administration of C. baccatum concomitantly with the ultra-processed diet avoided the accumulation of adipose tissue in the visceral region, reduced the total cholesterol and LDL fraction, and improved glucose homeostasis, factors commonly associated with metabolic syndrome. The data presented herein reveal an important preventive action of C. baccatum in developing metabolic disorders among animals fed a hypercaloric diet, significantly reducing their cardiometabolic risk. Allied with the absence of toxic effects after chronic use, our study suggests C. baccatum red pepper as a secure and enriched source of bioactive compounds promising to protect against pathological processes associated with metabolic syndrome.
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Luo D, Huang Z, Jia G, Zhao H, Liu G, Chen X. Naringin mitigates LPS-induced intestinal barrier injury in mice. Food Funct 2023; 14:1617-1626. [PMID: 36688440 DOI: 10.1039/d2fo03586c] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The aim of this study was to investigate the effect of naringin on lipopolysaccharide (LPS)-induced jejunal barrier function in mice. Forty-five 3-week-old healthy male Balb/c mice with similar body weights were randomly divided into control group, LPS group, LPS + naringin group, with 15 mice in each treatment group. The mice were intraperitoneally injected with the same dose of saline or LPS (10 mg per kg BW) at 43 d. The blood samples, liver and jejunal tissues were collected after 3 h of injection. The results showed that LPS significantly increased the serum diamine oxidase (DAO) activity, D-lactate (D-LA) concentration, and malondialdehyde (MDA) content in liver and jejunum, while decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (Gpx) and catalase (CAT) in liver and jejunum. The LPS treatment caused an increase in the crypt depth and a decrease in the villus height and the ratio of villus height to crypt depth (V/C) of the jejunum. In addition, the LPS treatment significantly increased the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, toll-like receptor 4 (TLR4), p38-mitogen-activated protein kinase (p38 MAPK), nuclear factor-κB (NF-κB) and kelch-like ECH-associated protein 1 (Keap1), while decreased mRNA expressions of zonula occludens 1 (ZO-1), occludin, claudin, mucin 2 (MUC2) and junctional adhesion molecule 2 (JAM2), Gpx, SOD1, GST, CAT and nuclear factor-erythroid 2-related factor 2 (Nrf2). However, the naringin treatment mitigated these effects induced by LPS. Taken together, our findings suggested that naringin attenuates LPS-induced intestinal barrier damage by inhibiting inflammatory factors and improving antioxidant function and intestinal tight junction, which might be mediated by activating the Nrf2 signaling and suppressing the TLR4/p38 MAPK/NF-κB signaling.
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Affiliation(s)
- Diaoyun Luo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
| | - Zhiqing Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
| | - Gang Jia
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
| | - Hua Zhao
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
| | - Guangmang Liu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
| | - Xiaoling Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.
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Kaci H, Bodnárová S, Fliszár-Nyúl E, Lemli B, Pelantová H, Valentová K, Bakos É, Özvegy-Laczka C, Poór M. Interaction of luteolin, naringenin, and their sulfate and glucuronide conjugates with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, and CYP3A4) enzymes and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. Biomed Pharmacother 2023; 157:114078. [PMID: 36481402 DOI: 10.1016/j.biopha.2022.114078] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/28/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Luteolin and naringenin are flavonoids found in various foods/beverages and present in certain dietary supplements. After a high intake of these flavonoids, their sulfate and glucuronide conjugates reach micromolar concentrations in the bloodstream. Some pharmacokinetic interactions of luteolin and naringenin have been investigated in previous studies; however, only limited data are available in regard to their metabolites. In this study, we aimed to investigate the interactions of the sulfate and glucuronic acid conjugates of luteolin and naringenin with human serum albumin, cytochrome P450 (CYP2C9, 2C19, and 3A4) enzymes, and organic anion transporting polypeptide (OATP1B1 and OATP2B1) transporters. Our main findings are as follows: (1) Sulfate conjugates formed more stable complexes with albumin than the parent flavonoids. (2) Luteolin and naringenin conjugates showed no or only weak inhibitory action on the CYP enzymes examined. (3) Certain conjugates of luteolin and naringenin are potent inhibitors of OATP1B1 and/or OATP2B1 enzymes. (4) Conjugated metabolites of luteolin and naringenin may play an important role in the pharmacokinetic interactions of these flavonoids.
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Affiliation(s)
- Hana Kaci
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2., H-1117 Budapest, Hungary; Doctoral School of Biology, Institute of Biology, Eötvös Loránd University, Pázmány P. stny. 1/C, H-1117 Budapest, Hungary
| | - Slávka Bodnárová
- Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary
| | - Eszter Fliszár-Nyúl
- Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
| | - Beáta Lemli
- Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary; Green Chemistry Research Group, János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary
| | - Helena Pelantová
- Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ-142 20 Prague, Czech Republic
| | - Kateřina Valentová
- Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, CZ-142 20 Prague, Czech Republic
| | - Éva Bakos
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2., H-1117 Budapest, Hungary
| | - Csilla Özvegy-Laczka
- Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Magyar tudósok krt. 2., H-1117 Budapest, Hungary
| | - Miklós Poór
- Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary; Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, H-7624 Pécs, Hungary.
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Orange juice intake and lipid profile: a systematic review and meta-analysis of randomised controlled trials. J Nutr Sci 2023; 12:e37. [PMID: 37008412 PMCID: PMC10052563 DOI: 10.1017/jns.2023.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 02/14/2023] [Accepted: 02/14/2023] [Indexed: 03/19/2023] Open
Abstract
Abstract
Dyslipidaemia is a metabolic anomaly which has been related to numerous morbidities. Orange juice (OJ) is a popular flavonoid-rich drink consumed worldwide. Due to the existing controversies regarding its impact on blood lipids, we decided to investigate the impact of OJ supplementation on lipid profile parameters. Major scientific databases (Cochrane library, Scopus, PubMed and Embase) were searched. Pooled effects sizes were reported as weighted mean difference (WMD) and 95 % confidence intervals (CIs). Out of 6334 articles retrieved by the initial search, 9 articles met our inclusion criteria. Overall, supplementation with OJ did not exert any significant effects on blood levels of TG (WMD −1·53 mg/dl, 95 % CI −6·39, 3·32, P = 0·536), TC (WMD −5·91 mg/dl, 95 % CI −13·26, 1·43, P = 0·114) or HDL-C (WMD 0·61 mg/ dl, 95 % CI −0·61, 1·82, P = 0·333). OJ consumption did reduce LDL-C levels significantly (WMD −8·35 mg/dl, 95 % CI −15·43, −1·26, P = 0·021). Overall, we showed that the consumption of OJ may not be beneficial in improving serum levels of TG, TC or HDL-C. Contrarily, we showed that daily intake of OJ, especially more than 500 ml/d, might be effective in reducing LDL-C levels. In the light of the existing inconsistencies, we propose that further high-quality interventions be conducted in order to make a solid conclusion.
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Bae J, Yang Y, Xu X, Flaherty J, Overby H, Hildreth K, Chen J, Wang S, Zhao L. Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma. Front Nutr 2022; 9:1036655. [PMID: 36438760 PMCID: PMC9686290 DOI: 10.3389/fnut.2022.1036655] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 10/19/2022] [Indexed: 11/11/2022] Open
Abstract
Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), functional BAT can increase energy expenditure and aid obesity treatment and prevention. Naringenin (NAR) is a flavanone primarily found in citrus fruits. NAR has been reported to decrease body weight, increase energy expenditure in treated mice, and promote browning in human adipocytes. Here, we examined the effects of NAR on 3T3-L1 adipocytes' browning and β-adrenergic agonist isoproterenol (ISO)-stimulated thermogenic activation and classical murine brown adipogenesis. In addition, we demonstrated the signaling pathways and involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in the process. We found that NAR did not increase Ucp1 mRNA expression at the basal (i.e., non-ISO stimulated) condition. Instead, it enhanced Ucp1 and Pgc-1α up-regulation and thermogenesis under ISO-stimulated conditions in 3T3-L1 adipocytes. NAR promoted protein kinase A (PKA) activation and phosphorylation of p38 MAPK downstream of ISO stimulation and activated PPARγ. Pharmacological inhibition of either PKA or p38 and PPARγ knockdown attenuated Ucp1 up-regulation by NAR. Moreover, NAR promoted brown adipogenesis by increasing lipid accumulation, brown marker expression, and thermogenesis in murine brown adipocytes, which was also attenuated by PPARγ knockdown. Together, our results suggest that NAR may promote the development of functional BAT in part through PPARγ activation. NAR's role in combating human obesity warrants further investigation.
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Affiliation(s)
- Jiyoung Bae
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Yang Yang
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Xinyun Xu
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Jamie Flaherty
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Haley Overby
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Kelsey Hildreth
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Jiangang Chen
- Department of Public Health, The University of Tennessee, Knoxville, Knoxville, TN, United States
| | - Shu Wang
- College of Health Solutions, Arizona State University, Phoenix, AZ, United States
| | - Ling Zhao
- Department of Nutrition, The University of Tennessee, Knoxville, Knoxville, TN, United States,*Correspondence: Ling Zhao,
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Hydroxyl-riched covalent organic framework for solid-phase microextraction of flavonoids aglycones or their metabolites in mice's plasma: Luteolin and quercetagetin as examples. J Chromatogr A 2022; 1681:463478. [PMID: 36099693 DOI: 10.1016/j.chroma.2022.463478] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/25/2022] [Accepted: 09/04/2022] [Indexed: 11/20/2022]
Abstract
Herein, a hydroxyl‑riched covalent organic framework (named COF-DES-1) was synthesized using 1,3,5-tris(4-aminophenyl)benzene and 2,5-dihydroxyterephthalaldehyde as building blocks and employed as a coating of solid-phase microextraction (SPME) fiber. Ascribed to the advantages (e.g. suitable pore size and rich functional group characteristics) of coating, the SPME fiber showed good adsorption capacities to flavonoids aglycones including luteolin and quercetagetin, and the maximum adsorption capacities for them were 145.31 µg and 84.75 µg, respectively. Due to the size exclusion property of COF-DES-1, SPME fiber showed good protein exclusion effects on seven selected proteins with high exclusion efficiencies (>93%). Accordingly, an attractive strategy of the combination of COF-DES-1 based SPME fiber and HPLC-MS/MS was proposed for the extraction and determination of luteolin, quercetagetin or their metabolites. The results revealed that the fiber can be effectively applied to extract luteolin and its metabolites, and quercetagetin from mice's palsma. Compared with the traditional protein precipitation methods, the extraction effects of SPME fiber based extraction method were much better, indicating the promising applicability of the fiber for the enrichment of flavonoids aglycones or their metabolites in biological samples.
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Capozzi A, Saucier C, Bisbal C, Lambert K. Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196594. [PMID: 36235130 PMCID: PMC9573747 DOI: 10.3390/molecules27196594] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/23/2022] [Accepted: 09/28/2022] [Indexed: 11/21/2022]
Abstract
Today, inactivity and high-calorie diets contribute to the development of obesity and premature aging. In addition, the population of elderly people is growing due to improvements in healthcare management. Obesity and aging are together key risk factors for non-communicable diseases associated with several co-morbidities and increased mortality, with a major impact on skeletal muscle defect and/or poor muscle mass quality. Skeletal muscles contribute to multiple body functions and play a vital role throughout the day, in all our activities. In our society, limiting skeletal muscle deterioration, frailty and dependence is not only a major public health challenge but also a major socio-economic issue. Specific diet supplementation with natural chemical compounds such as grape polyphenols had shown to play a relevant and direct role in regulating metabolic and molecular pathways involved in the prevention and treatment of obesity and aging and their related muscle comorbidities in cell culture and animal studies. However, clinical studies aiming to restore skeletal muscle mass and function with nutritional grape polyphenols supplementation are still very scarce. There is an urgent need for clinical studies to validate the very encouraging results observed in animal models.
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Affiliation(s)
- Adriana Capozzi
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- SPO, INRAE, Institute Agro, University of Montpellier, 34000 Montpellier, France
| | - Cédric Saucier
- SPO, INRAE, Institute Agro, University of Montpellier, 34000 Montpellier, France
| | - Catherine Bisbal
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- Correspondence: (C.B.); (K.L.); Tel.: +33-(0)4-1175-9891 (C.B. & K.L.)
| | - Karen Lambert
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- Correspondence: (C.B.); (K.L.); Tel.: +33-(0)4-1175-9891 (C.B. & K.L.)
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