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Sobhy L, Mostafa M, Fathalla Z, Hussein AK. Ellagic acid-loaded chitosan nanoparticles as an approach for mitigating oxidative stress and liver damage in Poloxamer-407-induced hyperlipidemia in mice: Development and optimization through 3 level full factorial design. Int J Pharm 2025; 677:125659. [PMID: 40306446 DOI: 10.1016/j.ijpharm.2025.125659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Revised: 04/26/2025] [Accepted: 04/27/2025] [Indexed: 05/02/2025]
Abstract
The primary cause of atherosclerosis and cardiovascular disorders is hyperlipidemia. Ellagic Acid (EA) is a naturally occurring polyphenol found in fruits and nuts. This medication has garnered attention due to its possible therapeutic benefits, encompassing the treatment of hyperlipidemia. In this study, ellagic acid was incorporated into a nanocarrier system using chitosan, a biodegradable polymer, via an ionotropic gelation technique, aiming to enhance its solubility and bioavailability. The effects of ellagic acid-loaded chitosan nanoparticles (EA-CS-NPs) were evaluated in a hyperlipidemic mouse model induced by poloxamer 407 (PL-407). Administration of a single intraperitoneal dose of 300 mg/kg body weight of PL-407 resulted in the induction of hyperlipidemia. The mice were grouped into five groups: Control, PL-407, EA-free drug, blank CS-NPs, and EA-CS-NPs. Serum analysis included the measurement of liver function biomarkers, lipid profiles, and liver antioxidant capacity. Additionally, a histopathological evaluation of liver tissue was performed. This study showed that PL-407 treatment increased hepatic oxidative stress and serum lipid biomarkers, with significant liver tissue changes in hyperlipidemic mice. EA-CS-NPs exerted the most protective effects, improving hepatic antioxidant capacity, serum lipid profile, and hepatic histological changes, highlighting their potential as a therapeutic approach for hyperlipidemia.
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Affiliation(s)
- Lamiaa Sobhy
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
| | - Mahmoud Mostafa
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
| | - Zeinab Fathalla
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
| | - Amal K Hussein
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
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Pang B, Cao T. Hesperidin produces antidepressant effects by activating AMPA receptor: enhancing synaptic proteins to promote hippocampal neuronal activities. Behav Pharmacol 2025; 36:127-136. [PMID: 39611623 DOI: 10.1097/fbp.0000000000000801] [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: 11/30/2024]
Abstract
Hesperidin treatments reduce depressive symptoms in mouse models of depression, but the mechanism that mediates its antidepressant effects is unclear. This study shows that hesperidin exerts its antidepressant effects by activating α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor to promote synaptic and neuronal function in the hippocampus. The optimal dose of hesperidin (10 mg/kg) for the antidepressant potential was determined after 7 consecutive days of treatments, demonstrating decreased latency to eat and increased food consumption in novelty suppressed feeding, and decreased immobility time in tail suspension test (TST). Moreover, the optimal dose also reversed the depressive phenotypes of Institute of Cancer Research mice exposed to chronic unpredictable mild stress (CUMS), including reduced immobility time in the TST and increased sucrose preference in the sucrose preference test. In addition, hesperidin increased the expression of AMPA receptor protein (Glur1) and synaptic proteins (BDNF, PSD95, synapsin1) in the hippocampus of CUMS-exposed mice. Furthermore, inhibition of AMPA receptor activity by NBQX blocked the effect of hesperidin in reversing the depressive phenotypes, upregulated the expression of synaptic proteins (BDNF, PSD95, synapsin1) and cFOS-positive cells in the hippocampus, and increased the number of Ki67-positive cells in the dentate gyrus of the hippocampus of CUMS-exposed mice. These results help to further understand the antidepressant mechanism of hesperidin and provide new ideas for the future development of antidepressant drugs.
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Affiliation(s)
- Bo Pang
- The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Second Chinese Medicine Hospital, Faculty of Pharmacy, Nanjing, China
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Chilanti G, Branco CS, Touguinha LBA, Lodi KZ, Rech G, Jahn MP, Augusti PR, Salvador M, Flôres SH. Begonia cucullata Extracts Present Antidiabetic Potential by Protecting Human Endothelial Cells and Rats from Oxidative Damage Induced by Glucose Overload. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2025; 80:75. [PMID: 39985664 DOI: 10.1007/s11130-025-01312-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/04/2025] [Indexed: 02/24/2025]
Abstract
Diabetes mellitus (DM) is a disease characterized by issues in insulin metabolism and consequent hyperglycemia, associated with oxidative stress and endothelial dysfunction. Current pharmacotherapy for DM is not fully effective, as complications continue even after glycemic control. Thus, plants rich in bioactive compounds with antioxidant potential may be valuable in DM management. Begonia cucullata is a non-conventional edible plant rich in phenolic compounds and traditionally used in medicine as an anti-diabetic agent. However, pharmacological studies on this plant are scarce. This study evaluated the antidiabetic potential of B. cucullata flowers (BFE) and leaves (BLE) extracts in human endothelial cells and rats. Endothelial cells were cultivated in normal (25mM) or high (35mM) glucose and exposed to BFE or BLE (1-100 µg/mL) for 24 h. Healthy and streptozotocin-induced diabetic rats received BFE (200 mg/kg) orally for 4 weeks. HPLC analyses of extracts revealed gallic acid, catechin, epigallocatechin gallate, epicatechin, and epigallocatechin in BFE, whereas BLE exhibited epigallocatechin and myricetin. Both extracts displayed antioxidant activity in vitro and were able to protect cells against oxidative damage caused by glucose overload. BFE attenuated oxidative stress and decreased triglyceride levels in diabetic rats, besides being not hepatotoxic or nephrotoxic. The data suggests that B. cucullata extracts may be potential adjuncts in DM therapy by exerting antioxidant effects and improving triglyceride levels.
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Affiliation(s)
- Gabriela Chilanti
- Laboratory of Bioactive Compounds, Food Science and Technology Institute, Postgraduate Program in Food Science and Technology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Catia Santos Branco
- Laboratory of Oxidative Stress and Antioxidants, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, RS, Brazil.
| | | | - Karina Zanella Lodi
- Laboratory of Oxidative Stress and Antioxidants, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, RS, Brazil
| | - Giovana Rech
- Laboratory of Physiology, University of Caxias do Sul, Caxias do Sul, RS, Brazil
| | | | - Paula Rossini Augusti
- Laboratory of Food Bioactive and Toxic Compounds, Food Science and Technology Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Mirian Salvador
- Laboratory of Oxidative Stress and Antioxidants, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, RS, Brazil
| | - Simone Hickmann Flôres
- Laboratory of Bioactive Compounds, Food Science and Technology Institute, Postgraduate Program in Food Science and Technology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
- Laboratory of Food Bioactive and Toxic Compounds, Food Science and Technology Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
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Kamel EM, Othman SI, Rudayni HA, Allam AA, Lamsabhi AM. Multi-pronged molecular insights into flavonoid-mediated inhibition of squalene epoxidase: a pathway to novel therapeutics. RSC Adv 2025; 15:3829-3848. [PMID: 39917044 PMCID: PMC11799833 DOI: 10.1039/d4ra09076d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 01/29/2025] [Indexed: 02/09/2025] Open
Abstract
Squalene epoxidase (SQLE) is a crucial enzyme in the sterol biosynthesis pathway and a promising target for therapeutic intervention in hypercholesterolemia and fungal infections. This study evaluates the inhibitory potential of six flavonoids namely silibinin, baicalin, naringenin, chrysin, apigenin-7-O-glucoside, and isorhamnetin against SQLE using an integrative approach combining in silico and experimental methods. Molecular docking revealed that apigenin-7-O-glucoside, silibinin, and baicalin displayed the highest binding affinities (-10.7, -10.2, and -10.0 kcal mol-1, respectively) and robust interactions with the SQLE binding site. These findings were corroborated by 200 ns molecular dynamics (MD) simulations, which demonstrated stable binding trajectories, minimal structural fluctuations, a thermodynamically favored potential energy landscape (PEL) and favorable MM/PBSA binding free energies for three flavonoids. Experimental validation via in vitro inhibition assays confirmed the computational predictions, with apigenin-7-O-glucoside emerging as the most potent inhibitor (IC50 = 1.74 ± 0.05 μM), followed by silibinin (IC50 = 1.88 ± 0.28 μM) and baicalin (IC50 = 2.50 ± 0.46 μM). Enzyme kinetics studies revealed distinct mechanisms of action: apigenin-7-O-glucoside exhibited competitive inhibition, while silibinin and baicalin showed mixed inhibition. Furthermore, in silico ADMET analysis indicated favorable pharmacokinetic and pharmacodynamic profiles for these flavonoids, with silibinin demonstrating particularly high bioavailability and lipophilicity. This study highlights apigenin-7-O-glucoside, silibinin, and baicalin as potent SQLE inhibitors with promising therapeutic potential. The congruence between in silico predictions and experimental results underscores the reliability of computational approaches in drug discovery, paving the way for future preclinical development of these compounds as novel SQLE-targeted therapeutics.
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Affiliation(s)
- Emadeldin M Kamel
- Chemistry Department, Faculty of Science, Beni-Suef University Beni-Suef 62514 Egypt
| | - Sarah I Othman
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University P. O. BOX 84428 Riyadh 11671 Saudi Arabia
| | - Hassan A Rudayni
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University Riyadh 11623 Saudi Arabia
| | - Ahmed A Allam
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University Riyadh 11623 Saudi Arabia
- Department of Zoology, Faculty of Science, Beni-suef University Beni-suef 65211 Egypt
| | - Al Mokhtar Lamsabhi
- Departamento de Química, Módulo 13, Universidad Autónoma de Madrid, Campus de Excelencia UAM-CSIC Cantoblanco 28049 Madrid Spain
- Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid 28049 Madrid Spain
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Calabrese FM, Aloisio Caruso E, De Nunzio V, Celano G, Pinto G, Cofano M, Sallustio S, Iacobellis I, Apa CA, Santamaria M, Calasso M, Giannelli G, De Angelis M, Notarnicola M. Metataxonomics and Metabolomics Profiles in Metabolic Dysfunction-Associated Fatty Liver Disease Patients on a "Navelina" Orange-Enriched Diet. Nutrients 2024; 16:3543. [PMID: 39458536 PMCID: PMC11510614 DOI: 10.3390/nu16203543] [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: 09/19/2024] [Revised: 10/11/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the most common cause of chronic liver disease. Systemic inflammatory status and peripheral metabolic symptoms in the clinical picture have an impact on gut commensal bacteria. METHODS Our designed clinical trial was based on a cohort of patients with MAFLD whose diet included the daily consumption of 400 g of "Navelina" oranges for 28 days, compared with a control group of patients with the same pathologic conditions whose diet did not include the consumption of oranges and other foods containing similar nutrients/micronutrients. We used 16S metataxonomics and GC/MS analyses to identify taxa and urine/fecal VOCs, respectively. RESULTS A set of micronutrients from the diet were inspected, and some specific fatty acids were identified as the main contributors in terms of cluster sample separation. Metataxonomics and metabolomics profiles were obtained, and a stringent statistical approach allowed for the identification of significant taxa/VOCs, which emerged from pairwise group comparisons in both fecal and urine samples. CONCLUSIONS In conclusion, a set of taxa/VOCs can be directly referred to as a marker of dysbiosis status and other comorbidities that, together, make up the pathologic burden associated with MAFLD. The investigated variables can be a target of therapeutic strategies.
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Affiliation(s)
- Francesco Maria Calabrese
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Emanuela Aloisio Caruso
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (E.A.C.); (V.D.N.); (G.P.); (M.C.)
| | - Valentina De Nunzio
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (E.A.C.); (V.D.N.); (G.P.); (M.C.)
| | - Giuseppe Celano
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Giuliano Pinto
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (E.A.C.); (V.D.N.); (G.P.); (M.C.)
| | - Miriam Cofano
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (E.A.C.); (V.D.N.); (G.P.); (M.C.)
| | - Stefano Sallustio
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Ilaria Iacobellis
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Carmen Aurora Apa
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Monica Santamaria
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Maria Calasso
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy;
| | - Maria De Angelis
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, 70126 Bari, Italy; (G.C.); (S.S.); (I.I.); (C.A.A.); (M.S.); (M.C.); (M.D.A.)
| | - Maria Notarnicola
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, 70013 Castellana Grotte, Italy; (E.A.C.); (V.D.N.); (G.P.); (M.C.)
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Zou J, Song Q, Shaw PC, Wu Y, Zuo Z, Yu R. Tangerine Peel-Derived Exosome-Like Nanovesicles Alleviate Hepatic Steatosis Induced by Type 2 Diabetes: Evidenced by Regulating Lipid Metabolism and Intestinal Microflora. Int J Nanomedicine 2024; 19:10023-10043. [PMID: 39371479 PMCID: PMC11451394 DOI: 10.2147/ijn.s478589] [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: 05/17/2024] [Accepted: 09/25/2024] [Indexed: 10/08/2024] Open
Abstract
Purpose Non-alcoholic fatty liver disease (NAFLD) represents a significant global health burden, exhibiting a strong correlation with insulin resistance, obesity, and type 2 diabetes (T2DM). Despite the severity of hepatic steatosis in T2DM patients, no specific drugs have been approved for clinical treatment of the disease. Tangerine peel is one kind of popular functional food and reported to possess hypoglycemic and lipid-lowering potential. In this study, we investigated the effects of Tangerine-peel-derived exosome-like nanovesicles (TNVs) on hepatic lipotoxicity associated with T2DM. Methods The TNVs was prepared by differential centrifugation of the aqueous extract of Tangerine and chemical properties were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and LC-MS/MS. The hypoglycemic and lipid-lowering potential of TNVs were possessed by biochemical measurement, RT-PCR, 16S rRNA sequencing, GC/MS, UHPLC-MS/MS, in vivo small animal imaging assay and HE staining. Subsequently, effects of TNVs on lipid accumulation and glycolysis were investigated on 3T3-L1 and AML-12 cells. Results TNVs significantly inhibited insulin resistance, reduced hepatic lipid accumulation, facilitate intestinal mucosal repair, rescued gut microbiota dysbiosis, regulated colonic SCFA and liver bile acid metabolism in db/db mice. Furthermore, TNVs restored the expression of key genes in glucose and lipid metabolism (ACC, AMPK, CD36, LXRα, PPAR-γ, SREBP-1) while activating the expression of genes related to glycolysis (G6Pase, GLUT2, PCK1, PEPCK) in db/db mice. Further cell-based mechanistic studies revealed that TNVs reduced lipid accumulation in 3T3-L1 and AML-12 cells via regulation of glucose and lipid metabolism-related genes (UCP1, FGFR4, PRDM16, PGC-1α, Tmem26, Cpt1, Cpt2 and PPAR-α). Conclusion We for the first time demonstrated that TNVs could significantly improve glucose and lipid metabolism via activating the expression of genes related to fatty acid β-oxidation and glycolysis.
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Affiliation(s)
- Junju Zou
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
| | - Qianbo Song
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
| | - Pang Chui Shaw
- School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
| | - Yongjun Wu
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
- School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
| | - Zhong Zuo
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China
| | - Rong Yu
- School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
- Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China
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Notarnicola M, Tutino V, De Nunzio V, Cisternino AM, Cofano M, Donghia R, Giannuzzi V, Zappimbulso M, Milella RA, Giannelli G, Fontana L. Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial. Nutrients 2024; 16:3191. [PMID: 39339791 PMCID: PMC11435367 DOI: 10.3390/nu16183191] [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: 08/27/2024] [Revised: 09/16/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Background: Consumption of flavonoid-rich orange juice has been shown to reduce adiposity and liver steatosis in murine models of diet-induced obesity. However, little is known about the effects of whole orange intake, independent of body weight changes, on liver function and steatosis in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). The goal is to understand the direct impact of orange consumption on metabolic health. Methods: Sixty-two men and women aged 30-65 with MASLD (Controlled Attenuation Parameter, (CAP) > 275 dB/m) were randomly assigned to consume either 400 g of whole oranges or non-citrus fruits daily for 4 weeks. Baseline evaluations included medical assessments, blood tests, and body composition. Liver health was assessed using transient elastography (FibroScan®) for steatosis and fibrosis, conducted by blinded personnel. This clinical trial was registered at ClinicalTrials.gov (NCT05558592). Results: After 4 weeks of orange supplementation, liver steatosis decreased in the treatment group, with 70.9% showing steatosis compared to 100% in controls (p < 0.004), indicating a 30% reduction in liver disease prevalence. There were no significant changes in fibrosis or plasma liver enzymes, though plasma gamma glutaril transferase (GGT) levels decreased significantly. Body weight, waist circumference, body composition, lipid profile, fasting glucose, insulin, and C-reactive protein levels remained unchanged. Dietary analysis revealed no change in caloric intake, but vitamins C, A, thiamine, and riboflavin increased in the orange group. Conclusions: Our findings suggest that phytochemical-rich foods, especially whole fruits like oranges, may enhance liver function as an adjunct treatment for MASLD. The notable reduction in liver steatosis prevalence occurred independently of body weight changes. Further studies are needed to investigate the long-term effects of orange supplementation on steatosis and fibrosis progression and to identify the specific bioactive compounds and mechanisms involved.
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Affiliation(s)
- Maria Notarnicola
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.T.); (V.D.N.); (M.C.)
| | - Valeria Tutino
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.T.); (V.D.N.); (M.C.)
| | - Valentina De Nunzio
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.T.); (V.D.N.); (M.C.)
| | - Anna Maria Cisternino
- Ambulatory of Clinical Nutrition, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy;
| | - Miriam Cofano
- Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.T.); (V.D.N.); (M.C.)
| | - Rossella Donghia
- Data Science Unit, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy;
| | - Vito Giannuzzi
- Unit of Gastroenterology, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.G.); (M.Z.)
| | - Marianna Zappimbulso
- Unit of Gastroenterology, National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (V.G.); (M.Z.)
| | | | - Gianluigi Giannelli
- Scientific Direction National Institute of Gastroenterology—IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy;
| | - Luigi Fontana
- Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia;
- Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
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Cai T, Xu X, Dong L, Liang S, Xin M, Wang T, Li T, Wang X, Zheng W, Wang C, Xu Z, Wang M, Song X, Li L, Li J, Sun W. Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats. Heliyon 2024; 10:e29168. [PMID: 38617966 PMCID: PMC11015455 DOI: 10.1016/j.heliyon.2024.e29168] [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: 08/03/2023] [Revised: 03/30/2024] [Accepted: 04/02/2024] [Indexed: 04/16/2024] Open
Abstract
Background Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.
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Affiliation(s)
- Tianqi Cai
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Xiaoxue Xu
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Ling Dong
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Shufei Liang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Meiling Xin
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Tianqi Wang
- College of Life Science, Yangtze University, Jingzhou, Hubei, 434000, People's Republic of China
| | - Tianxing Li
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100000, People's Republic of China
| | - Xudong Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310000, People's Republic of China
| | - Weilong Zheng
- Institute of Biomass Resources, Taizhou University, Taizhou, Zhejiang, 317700, People's Republic of China
| | - Chao Wang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Zhengbao Xu
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Meng Wang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Xinhua Song
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
| | - Lingru Li
- National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100000, People's Republic of China
| | - Jingda Li
- College of Life Science, Yangtze University, Jingzhou, Hubei, 434000, People's Republic of China
| | - Wenlong Sun
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
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9
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Ran Q, Gan Q, Zhu Y, Song L, Shen L, Duan X, Zhu X, Huang W. Mechanism insights into the pleiotropic effects of nobiletin as a potential therapeutic agent on non-alcoholic fatty liver disease (NAFLD). Biomed Pharmacother 2024; 173:116322. [PMID: 38401524 DOI: 10.1016/j.biopha.2024.116322] [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: 12/03/2023] [Revised: 02/03/2024] [Accepted: 02/19/2024] [Indexed: 02/26/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is emerging as one of the fastest-growing causes of liver-related deaths worldwide. It is necessary to find strategies to effectively prevent and treat NAFLD, as no definitive drug has been approved. Nobiletin (NOB) is the critical active ingredient of Chinese herbal medicines such as Citrus aurantium and Citri Reticulatae Pericarpium, which have anti-inflammatory, antioxidant, lipid regulating, and insulin resistance regulating effects. Numerous studies have demonstrated that NOB can prevent and treat the onset and progression of NAFLD. In this review, the mechanisms of NOB for treating NAFLD have been summarized, hoping to provide a basis for subsequent studies of NOB and to provide a research ground for the development of therapeutic drugs for NAFLD.
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Affiliation(s)
- Qiqi Ran
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qianrong Gan
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Ye Zhu
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan 570102, China
| | - Li Song
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Longyu Shen
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xinyi Duan
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xinyun Zhu
- Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Wei Huang
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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10
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Song J, Kim DY, Lee HS, Rhee SY, Lim H. Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2024; 16:494. [PMID: 38398818 PMCID: PMC10892674 DOI: 10.3390/nu16040494] [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: 10/31/2023] [Revised: 01/28/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.
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Affiliation(s)
- Jungbin Song
- Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea;
| | - Do-Yeon Kim
- Research Institute of Medical Nutrition, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (D.-Y.K.); (H.S.L.)
| | - Han Songyi Lee
- Research Institute of Medical Nutrition, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (D.-Y.K.); (H.S.L.)
| | - Sang Youl Rhee
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Hyunjung Lim
- Research Institute of Medical Nutrition, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (D.-Y.K.); (H.S.L.)
- Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si 17104, Gyeonggi-do, Republic of Korea
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11
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Yang X, Zhuo S, Fang T. Interaction between dietary flavonoid intake and trouble sleeping on non-alcoholic fatty liver disease risk: a cross-sectional study. Eur J Gastroenterol Hepatol 2024; 36:210-219. [PMID: 38047726 DOI: 10.1097/meg.0000000000002687] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
OBJECTIVE The possible interaction of dietary flavonoid intake and sleep on non-alcoholic fatty liver disease (NAFLD) has not been well studied. This study investigated the interaction between dietary flavonoid intake and trouble sleeping on the risk of NAFLD. METHODS Three discrete National Health and Nutrition Examination Survey data cycles from 2007 to 2010 and 2017 to 2018 were used. NAFLD was diagnosed by a US Fatty Liver Index ≥30. A sleep questionnaire diagnosed trouble sleeping. Univariate and multivariate logistic regression, restricted cubic spline (RCS) and subgroup analyses were used to evaluate the association between dietary flavonoids, trouble sleeping and NAFLD. We employed the relative excess risk due to interaction, attributable proportion of interaction and synergy index to evaluate additive interactions. RESULTS Ultimately, 5056 participants were enrolled, and higher anthocyanidins and flavanones intake was negatively correlated with NAFLD. Conversely, trouble sleeping was positively associated with NAFLD. These correlations remained stable after adjusting for confounders, and there was a sex difference in this relationship. In the RCS model, anthocyanins were negatively non-linearly related to NAFLD, while flavanones showed a negative linear relationship. Moreover, there was a synergistic interplay between low dietary anthocyanin intake and trouble sleeping on the risk of NAFLD. A similar relationship existed for flavanone intake. CONCLUSION Anthocyanin and flavanone intake were negatively associated, whereas trouble sleeping was positively associated with NAFLD risk. There was a synergistic effect of low anthocyanin intake and trouble sleeping. The same relationship existed for low flavanone intake.
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Affiliation(s)
- Xinxia Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Shitu Zhuo
- Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Taiyong Fang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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12
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Fatima N, Ashique S, Upadhyay A, Kumar S, Kumar H, Kumar N, Kumar P. Current Landscape of Therapeutics for the Management of Hypertension - A Review. Curr Drug Deliv 2024; 21:662-682. [PMID: 37357524 DOI: 10.2174/1567201820666230623121433] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 03/16/2023] [Accepted: 03/22/2023] [Indexed: 06/27/2023]
Abstract
Hypertension is a critical health problem. It is also the primary reason for coronary heart disease, stroke, and renal vascular disease. The use of herbal drugs in the management of any disease is increasing. They are considered the best immune booster to fight against several types of diseases. To date, the demand for herbal drugs has been increasing because of their excellent properties. This review highlights antihypertensive drugs, polyphenols, and synbiotics for managing hypertension. Evidence is mounting in favour of more aggressive blood pressure control with reduced adverse effects, especially for specific patient populations. This review aimed to present contemporary viewpoints and novel treatment options, including cutting-edge technological applications and emerging interventional and pharmaceutical therapies, as well as key concerns arising from several years of research and epidemiological observations related to the management of hypertension.
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Affiliation(s)
- Neda Fatima
- Department of Pharmacology, Amity University, Lucknow Campus, Lucknow, Uttar Pradesh 226010, India
| | - Sumel Ashique
- Department of Pharmaceutics, Pandaveswar School of Pharmacy, Pandaveswar, West Bengal 713378, India
| | - Aakash Upadhyay
- Department of Pharmaceutics, Bharat Institute of Technology (BIT), School of Pharmacy, Meerut, Uttar Pradesh, 250103, India
| | - Shubneesh Kumar
- Department of Pharmaceutics, Bharat Institute of Technology (BIT), School of Pharmacy, Meerut, Uttar Pradesh, 250103, India
| | - Himanshu Kumar
- Department of Pharmaceutics, Bharat Institute of Technology (BIT), School of Pharmacy, Meerut, Uttar Pradesh, 250103, India
| | - Nitish Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh, 201204, India
| | - Prashant Kumar
- College of Pharmacy, Teerthanker Mahaveer University, Moradabad-244001, UP, India
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13
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Fan C, Ling-Hu A, Sun D, Gao W, Zhang C, Duan X, Li H, Tian W, Yu Q, Ke Z. Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:20105-20117. [PMID: 38073108 DOI: 10.1021/acs.jafc.3c06498] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2023]
Abstract
Nobiletin (NOB), a flavonoid with significant antioxidant potential, holds promise for treating nonalcoholic fatty liver disease (NAFLD). In this work, we aim to assess the effects and investigate the molecular mechanisms of NOB on NAFLD. After using a methionine choline-deficient diet to induce C57BL/6J mice, as well as oleic acid to induce HepG2 and L02 cells, we administered NOB as an intervention. The results indicated that the NOB significantly ameliorated lipid deposition, oxidative stress, and inflammation in NAFLD in both models. Its mechanism may involve the Nrf2, SREBP-1c, and NF-κB signaling pathways. Furthermore, Nrf2 is not only a direct target for NOB to improve oxidative damage but also indirectly involved in lipid-lowering and anti-inflammatory processes in NAFLD. By inhibiting Nrf2, we found that the regulatory role of Nrf2 in lipid metabolism is not related to SREBP-1c but is closely associated with NF-κB in terms of inflammation. Our results suggest that Nrf2 is one of the most critical targets for NOB against NAFLD in multiple aspects.
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Affiliation(s)
- Chaowen Fan
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Anli Ling-Hu
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Dali Sun
- Guizhou Medical University, Guiyang, Guizhou 550025, China
| | - Weiman Gao
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Chenfang Zhang
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Xueqing Duan
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Haiyang Li
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Weiyi Tian
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Qi Yu
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
| | - Zunli Ke
- Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China
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14
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Villar-López M, Soto-Becerra P, Chedraui P, Osorio-Manyari JD, Al-Kassab-Córdova A, Osorio-Manyari AA, Fernandez-Sosaya JL, Moya-Silvestre E, Rojas PA, Lugo-Martínez G, Mezones-Holguín E. Short-term effects and safety of a natural oral supplement containing glucosinolates, phytosterols, and citrus flavonoids compared with hormone treatment for the management of postmenopausal symptomatic women: a pilot single-center randomized phase 2 clinical trial. Menopause 2023; 30:1230-1240. [PMID: 37874969 DOI: 10.1097/gme.0000000000002268] [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: 10/26/2023]
Abstract
OBJECTIVE This study aimed to evaluate the short-term efficacy and safety of an oral herbal supplement containing glucosinolates, phytosterols, and citrus flavonoids for menopausal symptoms in comparison with estrogen plus progestogen therapy (EPT) among postmenopausal women. METHODS This was a pilot single-blinded, three-armed phase II randomized clinical trial, controlled with EPT. Sixty participants were randomly assigned to receive treatment for 3 months: (1) an oral herbal supplement of 1,500 mg/d (G1, n = 20), (2) an oral herbal supplement of 3,000 mg/d (G2, n = 20), or (3) conjugated equine estrogens 0.625 mg/d plus medroxyprogesterone acetate of 5 mg/d (EPT group, n = 20). The primary endpoint was the intensity of menopausal symptoms as measured using the Menopause-Specific Quality of Life Questionnaire (global and domain scores). The Menopause-Specific Quality of Life Questionnaire uses a 7-point scale to rate the symptom intensity, with higher scores indicating severity. The secondary endpoints were hormonal, lipid, and safety profiles. RESULTS Fifty-four participants (n = 54) completed the study. The mean, model-estimated, and global menopausal symptom scores at 3 months were 85.8 in the EPT group, 61.3 in G1, and 62.5 in G2. Participants treated with the herbal compound had lower global (13.7 [6.9-20.4], P < 0.001) and physical symptom scores (6.6 [1.6-11.5], P = 0.002) on the second month and lower psychosocial symptom scores (3.8 [1.3 to 6.3], P < 0.001) on the third month of follow-up, compared with EPT. Conversely, participants receiving EPT showed better outcomes on vasomotor symptoms since the first month of treatment (-6.1 [-8.3 to -4.0], P < 0.001). The EPT group exhibited higher values of estradiol and lower follicle-stimulating hormone and luteinizing hormone since the first month of follow-up. Also, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significantly higher in this group than in G2. CONCLUSIONS In this small single-blind exploratory trial, the oral herbal supplement was more efficacious in reducing global, physical, and psychosocial menopausal symptoms in the short term than EPT. However, further studies are needed to adequately assess the efficacy and safety of this herbal supplement in the treatment of menopausal symptoms.
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Affiliation(s)
| | | | - Peter Chedraui
- Escuela de Posgrado en Salud, Universidad Espíritu Santo, Samborondón, Ecuador
| | | | - Ali Al-Kassab-Córdova
- Centro de Excelencia en Investigaciones Económicas y Sociales en Salud, Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Perú
| | | | | | | | - Percy A Rojas
- Universidad Peruana Cayetano Heredia, Laboratorios de Investigación y Desarrollo, Unidad de Biotecnología Molecular, Lima, Perú
| | - Gabriela Lugo-Martínez
- Instituto Politécnico Nacional, Escuela Superior de Medicina, Sección de Estudios de Posgrado e Investigación, Ciudad de México, México
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15
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Zhu MZ, Yang MF, Song Y, Xu HM, Xu J, Yue NN, Zhang Y, Tian CM, Shi RY, Liang YJ, Yao J, Wang LS, Nie YQ, Li DF. Exploring the efficacy of herbal medicinal products as oral therapy for inflammatory bowel disease. Biomed Pharmacother 2023; 165:115266. [PMID: 37541177 DOI: 10.1016/j.biopha.2023.115266] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/30/2023] [Accepted: 07/31/2023] [Indexed: 08/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) encompasses a collection of idiopathic diseases characterized by chronic inflammation in the gastrointestinal (GI) tract. Patients diagnosed with IBD often experience necessitate long-term pharmacological interventions. Among the multitude of administration routes available for treating IBD, oral administration has gained significant popularity owing to its convenience and widespread utilization. In recent years, there has been extensive evaluation of the efficacy of orally administered herbal medicinal products and their extracts as a means of treating IBD. Consequently, substantial evidence has emerged, supporting their effectiveness in IBD treatment. This review aimed to provide a comprehensive summary of recent studies evaluating the effects of herbal medicinal products in the treatment of IBD. We delved into the regulatory role of these products in modulating immunity and maintaining the integrity of the intestinal epithelial barrier. Additionally, we examined their impact on antioxidant activity, anti-inflammatory properties, and the modulation of intestinal flora. By exploring these aspects, we aimed to emphasize the significant advantages associated with the use of oral herbal medicinal products in the treatment of IBD. Of particular note, this review introduced the concept of herbal plant-derived exosome-like nanoparticles (PDENs) as the active ingredient in herbal medicinal products for the treatment of IBD. The inclusion of PDENs offers distinct advantages, including enhanced tissue penetration and improved physical and chemical stability. These unique attributes not only demonstrate the potential of PDENs but also pave the way for the modernization of herbal medicinal products in IBD treatment.
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Affiliation(s)
- Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen 518020, Guangdong, China
| | - Yang Song
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China
| | - Ning-Ning Yue
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University), Shenzhen 518020, Guangdong, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou 516000, Guangdong, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Rui-Yue Shi
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen 518020, Guangdong, China.
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China.
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China.
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16
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Saad B. A Review of the Anti-Obesity Effects of Wild Edible Plants in the Mediterranean Diet and Their Active Compounds: From Traditional Uses to Action Mechanisms and Therapeutic Targets. Int J Mol Sci 2023; 24:12641. [PMID: 37628822 PMCID: PMC10454857 DOI: 10.3390/ijms241612641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 08/03/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases.
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Affiliation(s)
- Bashar Saad
- Qasemi Research Center, Al-Qasemi Academic College, P.O. Box 124, Baqa al-Gharbiyye 3010000, Israel;
- Department of Biochemistry, Faculty of Medicine, The Arab American University, Jenin P.O. Box 240, Palestine;
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17
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Xiong X, Kiperman T, Li W, Dhawan S, Lee J, Yechoor V, Ma K. The Clock-modulatory Activity of Nobiletin Suppresses Adipogenesis Via Wnt Signaling. Endocrinology 2023; 164:bqad096. [PMID: 37327385 PMCID: PMC10373950 DOI: 10.1210/endocr/bqad096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/18/2023]
Abstract
The circadian clock machinery exerts transcriptional control to modulate adipogenesis and its disruption leads to the development of obesity. Here, we report that Nobiletin, a circadian clock amplitude-enhancing molecule, displays antiadipogenic properties via activation of Wnt signaling pathway that is dependent on its clock modulation. Nobiletin augmented clock oscillatory amplitude with period lengthening in the adipogenic mesenchymal precursor cells and preadipocytes, accompanied by an induction of Bmal1 and clock components within the negative feedback arm. Consistent with its clock-modulatory activity, Nobiletin strongly inhibited the lineage commitment and terminal differentiation of adipogenic progenitors. Mechanistically, we show that Nobiletin induced the reactivation of Wnt signaling during adipogenesis via transcriptional up-regulation of key components within this pathway. Furthermore, Nobiletin administration in mice markedly reduced adipocyte hypertrophy, leading to a significant loss of fat mass and reduction of body weight. Last, Nobiletin inhibited the differentiation of primary preadipocytes, and this effect was dependent on a functional clock regulation. Collectively, our findings uncover a novel activity of Nobiletin in suppressing adipocyte development in a clock-dependent manner, implicating its potential application in countering obesity and associated metabolic consequences.
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Affiliation(s)
- Xuekai Xiong
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Tali Kiperman
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Weini Li
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Sangeeta Dhawan
- Department of Translational Research and Cellular Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
| | - Jeongkyung Lee
- Diabetes and Beta Cell Biology Center, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Vijay Yechoor
- Diabetes and Beta Cell Biology Center, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Ke Ma
- Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
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18
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Roy T, Boateng ST, Uddin MB, Banang-Mbeumi S, Yadav RK, Bock CR, Folahan JT, Siwe-Noundou X, Walker AL, King JA, Buerger C, Huang S, Chamcheu JC. The PI3K-Akt-mTOR and Associated Signaling Pathways as Molecular Drivers of Immune-Mediated Inflammatory Skin Diseases: Update on Therapeutic Strategy Using Natural and Synthetic Compounds. Cells 2023; 12:1671. [PMID: 37371141 PMCID: PMC10297376 DOI: 10.3390/cells12121671] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/10/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
The dysregulated phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway has been implicated in various immune-mediated inflammatory and hyperproliferative dermatoses such as acne, atopic dermatitis, alopecia, psoriasis, wounds, and vitiligo, and is associated with poor treatment outcomes. Improved comprehension of the consequences of the dysregulated PI3K/Akt/mTOR pathway in patients with inflammatory dermatoses has resulted in the development of novel therapeutic approaches. Nonetheless, more studies are necessary to validate the regulatory role of this pathway and to create more effective preventive and treatment methods for a wide range of inflammatory skin diseases. Several studies have revealed that certain natural products and synthetic compounds can obstruct the expression/activity of PI3K/Akt/mTOR, underscoring their potential in managing common and persistent skin inflammatory disorders. This review summarizes recent advances in understanding the role of the activated PI3K/Akt/mTOR pathway and associated components in immune-mediated inflammatory dermatoses and discusses the potential of bioactive natural products, synthetic scaffolds, and biologic agents in their prevention and treatment. However, further research is necessary to validate the regulatory role of this pathway and develop more effective therapies for inflammatory skin disorders.
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Affiliation(s)
- Tithi Roy
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Samuel T. Boateng
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Mohammad B. Uddin
- Department of Toxicology and Cancer Biology, Center for Research on Environmental Diseases, College of Medicine, University of Kentucky, Lexington, KY 40536, USA;
| | - Sergette Banang-Mbeumi
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
- Division for Research and Innovation, POHOFI Inc., Madison, WI 53744, USA
- School of Nursing and Allied Health Sciences, Louisiana Delta Community College, Monroe, LA 71203, USA
| | - Rajesh K. Yadav
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Chelsea R. Bock
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Joy T. Folahan
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Xavier Siwe-Noundou
- Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, P.O. Box 218, Pretoria 0208, South Africa;
| | - Anthony L. Walker
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
| | - Judy A. King
- Department of Pathology and Translational Pathobiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA;
- College of Medicine, Belmont University, 900 Belmont Boulevard, Nashville, TN 37212, USA
| | - Claudia Buerger
- Department of Dermatology, Venerology and Allergology, Clinic of the Goethe University, 60590 Frankfurt am Main, Germany;
| | - Shile Huang
- Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA;
- Department of Hematology and Oncology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA
- Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
| | - Jean Christopher Chamcheu
- School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209, USA; (T.R.); (S.T.B.); (S.B.-M.); (R.K.Y.); (C.R.B.); (J.T.F.); (A.L.W.)
- Department of Pathology and Translational Pathobiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA 71103, USA;
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Li L, Qin Y, Xin X, Wang S, Liu Z, Feng X. The great potential of flavonoids as candidate drugs for NAFLD. Biomed Pharmacother 2023; 164:114991. [PMID: 37302319 DOI: 10.1016/j.biopha.2023.114991] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/05/2023] [Accepted: 06/06/2023] [Indexed: 06/13/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of approximately 25 % and is associated with high morbidity and high mortality. NAFLD is a leading cause of cirrhosis and hepatocellular carcinoma. Its pathophysiology is complex and still poorly understood, and there are no drugs used in the clinic to specifically treat NAFLD. Its pathogenesis involves the accumulation of excess lipids in the liver, leading to lipid metabolism disorders and inflammation. Phytochemicals with the potential to prevent or treat excess lipid accumulation have recently received increasing attention, as they are potentially more suitable for long-term use than are traditional therapeutic compounds. In this review, we summarize the classification, biochemical properties, and biological functions of flavonoids and how they are used in the treatment of NAFLD. Highlighting the roles and pharmacological uses of these compounds will be of importance for enhancing the prevention and treatment of NAFLD.
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Affiliation(s)
- Liangge Li
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Yiming Qin
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Xijian Xin
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Shendong Wang
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Zhaojun Liu
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Xiujing Feng
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China.
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20
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Qiu M, Wei W, Zhang J, Wang H, Bai Y, Guo DA. A Scientometric Study to a Critical Review on Promising Anticancer and Neuroprotective Compounds: Citrus Flavonoids. Antioxidants (Basel) 2023; 12:antiox12030669. [PMID: 36978916 PMCID: PMC10045114 DOI: 10.3390/antiox12030669] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/20/2023] [Accepted: 02/23/2023] [Indexed: 03/12/2023] Open
Abstract
Flavonoids derived from citrus plants are favored by phytomedicinal researchers due to their wide range of biological activities, and relevant studies have been sustained for 67 years (since the first paper published in 1955). In terms of a scientometric and critical review, the scientometrics of related papers, chemical structures, and pharmacological action of citrus flavonoids were comprehensively summarized. The modern pharmacological effects of citrus flavonoids are primarily focused on their anticancer activities (such as breast cancer, gastric cancer, lung cancer, and liver cancer), neuroprotective effects (such as anti-Alzheimer’s disease, Parkinson’s disease), and metabolic diseases. Furthermore, the therapeutic mechanism of cancers (including inducing apoptosis, inhibiting cell proliferation, and inhibiting cancer metastasis), neuroprotective effects (including antioxidant and anti-inflammatory), and metabolic diseases (such as non-alcoholic fatty liver disease, type 2 diabetes mellitus) were summarized and discussed. We anticipate that this review could provide an essential reference for anti-cancer and neuroprotective research of citrus flavonoids and provide researchers with a comprehensive understanding of citrus flavonoids.
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Affiliation(s)
- Mingyang Qiu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Wenlong Wei
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Jianqing Zhang
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Hanze Wang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Yuxin Bai
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - De-an Guo
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Correspondence:
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21
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Xiong X, Kiperman T, Li W, Dhawan S, Lee J, Yechoor V, Ma K. The clock-modulatory activity of Nobiletin suppresses adipogenesis via Wnt signaling. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.02.07.527587. [PMID: 36798247 PMCID: PMC9934622 DOI: 10.1101/2023.02.07.527587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
The circadian clock machinery exerts transcriptional control to modulate adipogenesis and its disruption leads to the development of obesity. Here we report that Nobiletin, a clock amplitude-enhancing molecule, displays anti-adipogenic properties via activating a clock-controlled Wnt signaling pathway that suppresses adipocyte differentiation. Nobiletin augmented clock oscillation with period length shortening in the adipogenic mesenchymal precursor cells and preadipocytes, accompanied by an induction of Bmal1 and core clock components. Consistent with its circadian clock-modulatory activity, Nobiletin inhibited the lineage commitment and terminal differentiation of adipogenic progenitors. Mechanistically, we show that Nobiletin induced the re-activation of Wnt signaling during adipogenic differentiation via transcriptional up-regulation of key components of this pathway. Furthermore, Nobiletin administration in mice markedly reduced adipocyte hypertrophy, leading to a significant loss of fat mass and body weight reduction. Lastly, Nobiletin inhibited the maturation of primary preadipocytes and this effect was dependent on a functional clock regulation. Collectively, our findings uncover a novel activity of Nobiletin in suppressing adipocyte development, implicating its potential therapeutic application in countering obesity and its associated metabolic consequences.
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Liu S, Liu K, Wang Y, Wu C, Xiao Y, Liu S, Yu J, Ma Z, Liang H, Li X, Li Y, Zhou L. Hesperidin methyl chalcone ameliorates lipid metabolic disorders by activating lipase activity and increasing energy metabolism. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166620. [PMID: 36494040 DOI: 10.1016/j.bbadis.2022.166620] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/22/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022]
Abstract
Obesity has become an increasingly serious health issue with the continuous improvement in living standards. Its prevalence has become an economic burden on health care systems worldwide. Flavonoids have been shown to be beneficial in the prevention and treatment of obesity. Here, we evaluated the therapeutic potential of the flavonoid hesperidin methyl chalcone (HMC) on mice with high-fat diet (HFD)-induced hepatic steatosis in vivo and in vitro. Treatment with HMC reduced oleic and palmitic acid-induced increases in intracellular triglyceride accumulation in HepG2, AML12 and LMH cells. HMC also enhanced energy metabolism and lowered oxidative stress. We used Discovery studio to dock key proteins associated with lipid metabolism disorders to HMC, and found that HMC interacted with lipase. Furthermore, we demonstrated that HMC improved lipase activity and lipolysis. In addition, we found that HMC promoted glucose absorption, alleviated lipid metabolic disorders, improved HFD-induced liver injury, and regulated HFD-induced changes in energy metabolism. In conclusion, our study demonstrated that HMC ameliorated HFD-induced obesity and its complications by promoting lipase activity, and provides a novel approach for the prevention and treatment of obesity and related diseases.
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Affiliation(s)
- Songsong Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Kang Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Yuwei Wang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Chou Wu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Yang Xiao
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Siqi Liu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Jingsu Yu
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Zeqiang Ma
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Huanjie Liang
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Xiangling Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Yixing Li
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Lei Zhou
- State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China.
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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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Long S, Ji S, Xue P, Xie H, Ma Y, Zhu S. Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of shiliao decoction in the treatment of cancer-associated malnutrition. Front Nutr 2022; 9:985991. [PMID: 36091226 PMCID: PMC9452828 DOI: 10.3389/fnut.2022.985991] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
PurposeShiliao Decoction (SLD) was developed for treatment and prevention of cancer-associated malnutrition (CAM) in China. In this study, we aim to discover SLD’s active compounds and demonstrate the mechanisms of SLD that combat CAM through network pharmacology and molecular docking techniques.MethodsAll components of SLD were retrieved from the pharmacology database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). The GeneCards database and the Online Mendelian Inheritance in Man database (OMIM) were used to identify gene encoding target compounds, and Cytoscape was used to construct the drug compound–target network. The network of target protein-protein interactions (PPI) was constructed using the STRING database, while gene ontology (GO) functional terms and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways associated with potential targets were analyzed using a program in R language (version 4.2.0). Core genes linked with survival and the tumor microenvironment were analyzed using the Kaplan–Meier plotter and TIMER 2.0 databases, respectively. Protein expression and transcriptome expression levels of core gene were viewed using the Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA). A component-target-pathway (C-T-P) network was created using Cytoscape, and Autodock Vina software was used to verify the molecular docking of SLD components and key targets.ResultsThe assembled compound–target network primarily contained 134 compounds and 147 targets of the SLD associated with JUN, TP53, MAPK3, MAPK1, MAPK14, STAT3, AKT1, HSP90AA1, FOS, and MYC, which were identified as core targets by the PPI network. KEGG pathway analysis revealed pathways involved in lipid and atherosclerosis, the PI3K/Akt signaling pathway, and immune-related pathways among others. JUN is expressed at different levels in normal and cancerous tissues, it is closely associated with the recruitment of different immune cells and has been shown to have a significant impact on prognosis. The C-T-P network suggests that the active component of SLD is capable of regulating target genes affecting these related pathways. Finally, the reliability of the core targets was evaluated using molecular docking technology.ConclusionThis study revealed insights into SLD’s active components, potential targets, and possible molecular mechanisms, thereby demonstrating a potential method for examining the scientific basis and therapeutic mechanisms of TCM formulae.
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Affiliation(s)
- Sidan Long
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Medical Oncology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Shuangshuang Ji
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Peng Xue
- Medical Oncology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongting Xie
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yinjie Ma
- Medical Oncology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Yinjie Ma,
| | - Shijie Zhu
- Medical Oncology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, China
- Shijie Zhu,
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Xue M, Yao T, Xue M, Francis F, Qin Y, Jia M, Li J, Gu X. Mechanism Analysis of Metabolic Fatty Liver on Largemouth bass (Micropterus salmoides) Based on Integrated Lipidomics and Proteomics. Metabolites 2022; 12:metabo12080759. [PMID: 36005631 PMCID: PMC9415018 DOI: 10.3390/metabo12080759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/12/2022] [Accepted: 08/14/2022] [Indexed: 11/26/2022] Open
Abstract
Metabolic fatty liver disease caused by high-starch diet restricted the intensive and sustainable development of carnivorous fish such as largemouth bass. In this study, the combination liver proteomic and lipidomic approach was employed to investigate the key signaling pathways and identify the critical biomarkers of fatty liver in largemouth bass. Joint analysis of the correlated differential proteins and lipids revealed nine common metabolic pathways; it was determined that FABP1 were significantly up-regulated in terms of transporting more triglycerides into the liver, while ABCA1 and VDAC1 proteins were significantly down-regulated in terms of preventing the transport of lipids and cholesterol out of the liver, leading to triglyceride accumulation in hepatocyte, eventually resulting in metabolic fatty liver disease. The results indicate that FABP1, ABCA1 and VDAC1 could be potential biomarkers for treating metabolic fatty liver disease of largemouth bass.
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Affiliation(s)
- Moyong Xue
- Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, China
- Functional & Evolutionary Entomology, Agro-Bio-Tech Gembloux, University of Liege, 5030 Gembloux, Belgium
- Institute of Animal Science, Chinese Academy of Agriculture Sciences, Beijing 100193, China
| | - Ting Yao
- Beijing Institute of Feed Control, Beijing 110108, China
| | - Min Xue
- Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, China
| | - Frédéric Francis
- Functional & Evolutionary Entomology, Agro-Bio-Tech Gembloux, University of Liege, 5030 Gembloux, Belgium
| | - Yuchang Qin
- Institute of Animal Science, Chinese Academy of Agriculture Sciences, Beijing 100193, China
| | - Ming Jia
- Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, China
| | - Junguo Li
- Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, China
| | - Xu Gu
- Feed Research Institute, Chinese Academy of Agricultural Science, Beijing 100081, China
- Correspondence:
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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action. Int J Mol Sci 2022; 23:ijms23158344. [PMID: 35955475 PMCID: PMC9369232 DOI: 10.3390/ijms23158344] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/24/2022] [Accepted: 07/26/2022] [Indexed: 02/04/2023] Open
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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Guimarães JT, Almeida PP, Brito ML, Cruz BO, Costa NS, Almeida Ito RV, Mota JC, Bertolo MR, Morais ST, Neto RP, Tavares MIB, Souto F, Bogusz Junior S, Pimentel TC, Stockler-Pinto MB, Freitas MQ, Cruz AG. In vivo functional and health benefits of a prebiotic soursop whey beverage processed by high-intensity ultrasound: Study with healthy Wistar rats. Food Chem 2022; 380:132193. [DOI: 10.1016/j.foodchem.2022.132193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 12/21/2021] [Accepted: 01/16/2022] [Indexed: 12/31/2022]
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Liu M, Zhang Z, Qin C, Lv B, Mo S, Lan T, Gao B. Effects of 4-Week Tangeretin Supplementation on Cortisol Stress Response Induced by High-Intensity Resistance Exercise: A Randomized Controlled Trial. Front Physiol 2022; 13:886254. [PMID: 35665223 PMCID: PMC9160924 DOI: 10.3389/fphys.2022.886254] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/02/2022] [Indexed: 11/30/2022] Open
Abstract
Objective: This study aimed to investigate the effects of 4-week tangeretin supplementation on the cortisol stress response induced by high-intensity resistance exercise. Methods: A randomized controlled trial of twenty-four soccer players was conducted during the winter training season. The experimental group (EG) took the oral supplement with tangeretin (200 mg/day) and the control group (CG) took placebo for 4 weeks. Before and after the 4-week intervention, all players performed a high intensity bout of resistance exercise to stimulate their cortisol stress responses. Serum cortisol, adreno-corticotropic hormone (ACTH) and superoxide dismutase (SOD) were obtained by collecting blood samples before (PRE), immediately after (P0), and 10 (P10), 20 (P20) and 30 minutes (P30) after the exercise. Results: The serum cortisol level (PRE, p = 0.017; P10, p = 0.010; P20, p = 0.014; P30, p = 0.007) and ACTH (P10, p = 0.037; P30, p = 0.049) of experimental group significantly decreased after the 4-week intervention. Compared with control group, EG displayed a significantly lower level of the serum cortisol (PRE, p = 0.036; P10, p = 0.031) and ACTH (P30, p = 0.044). Additionally, EG presented significantly higher superoxide dismutase activity level compared with CG at P30 (p = 0.044). The white blood cell of EG decreased significantly (PRE, p = 0.037; P30, p = 0.046) and was significantly lower than CG at P20 (p = 0.01) and P30 (p = 0.003). Conclusion: Four-week tangeretin supplementation can reduce serum cortisol and ACTH, which may ameliorate the cortisol stress response in soccer players during high-intensity resistance exercise training. It can also enhance antioxidant capacity, accelerate the elimination of inflammation throughout the body, and shorten recovery time after high-intensity exercise.
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Affiliation(s)
- Meng Liu
- College of Physical Education and Training, Shanghai University of Sport, Shanghai, China
- Chongqing Institute of Sport Science, Chongqing, China
| | - Zheng Zhang
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Chunli Qin
- Chongqing Institute of Sport Science, Chongqing, China
| | - Bingqiang Lv
- Chongqing Institute of Sport Science, Chongqing, China
| | - Shiwei Mo
- School of Physical Education, Shenzhen University, Shenzhen, China
- *Correspondence: Shiwei Mo, ; Tao Lan, ; Binghong Gao,
| | - Tao Lan
- Sports and Art Department, Hebei Sport University, Shijiazhuang, China
- *Correspondence: Shiwei Mo, ; Tao Lan, ; Binghong Gao,
| | - Binghong Gao
- College of Physical Education and Training, Shanghai University of Sport, Shanghai, China
- *Correspondence: Shiwei Mo, ; Tao Lan, ; Binghong Gao,
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Antioxidative and Anti-Inflammatory Activities of Chrysin and Naringenin in a Drug-Induced Bone Loss Model in Rats. Int J Mol Sci 2022; 23:ijms23052872. [PMID: 35270014 PMCID: PMC8911302 DOI: 10.3390/ijms23052872] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 11/19/2022] Open
Abstract
Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP.
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Carvalho BMR, Nascimento LC, Nascimento JC, Gonçalves VSDS, Ziegelmann PK, Tavares DS, Guimarães AG. Citrus Extract as a Perspective for the Control of Dyslipidemia: A Systematic Review With Meta-Analysis From Animal Models to Human Studies. Front Pharmacol 2022; 13:822678. [PMID: 35237168 PMCID: PMC8884359 DOI: 10.3389/fphar.2022.822678] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 01/10/2022] [Indexed: 12/09/2022] Open
Abstract
This study aims to obtain scientific evidence on the use of Citrus to control dyslipidemia. The surveys were carried out in 2020 and updated in March 2021, in the PubMed, Scopus, LILACS, and SciELO databases, using the following descriptors: Citrus, dyslipidemias, hypercholesterolemia, hyperlipidemias, lipoproteins, and cholesterol. The risk of bias was assessed according to the Cochrane methodology for clinical trials and ARRIVE for preclinical trials. A meta-analysis was performed using the application of R software. A total of 958 articles were identified and 26 studies demonstrating the effectiveness of the Citrus genus in controlling dyslipidemia were selected, of which 25 were included in the meta-analysis. The effects of Citrus products on dyslipidemia appear consistently robust, acting to reduce total cholesterol, LDL, and triglycerides, in addition to increasing HDL. These effects are associated with the composition of the extracts, extremely rich in antioxidant, as flavonoids, and that act on biochemical targets involved in lipogenesis and beta-oxidation. The risk of bias over all of the included studies was considered critically low to moderate. The meta-analysis demonstrated results favorable to control dyslipidemia by Citrus products. On the other hand, high heterogeneity values were identified, weakening the evidence presented. From this study, one can suggest that Citrus species extracts are potential candidates for dyslipidemia control, but more studies are needed to increase the strength of this occurrence.
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Affiliation(s)
- Betina M R Carvalho
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde, Universidade Federal de Sergipe, Lagarto, Brazil
| | - Laranda C Nascimento
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde, Universidade Federal de Sergipe, Lagarto, Brazil
| | - Jessica C Nascimento
- Programa de Pós-Graduação em Ciências Aplicadas à Saúde, Universidade Federal de Sergipe, Lagarto, Brazil
| | | | - Patricia K Ziegelmann
- Departamento de Estatística, Programa de Pós-graduação em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Débora S Tavares
- Departamento de Educação em Saúde, Universidade Federal de Sergipe, Lagarto, Brazil
| | - Adriana G Guimarães
- Departamento de Farmácia, Universidade Federal de Sergipe, São Cristóvão, Brazil
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Network Pharmacology-Based Strategy for Predicting Therapy Targets of Citri Reticulatae Pericarpium on Myocardial Hypertrophy. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4293265. [PMID: 35281609 PMCID: PMC8906983 DOI: 10.1155/2022/4293265] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 02/12/2022] [Indexed: 11/24/2022]
Abstract
Objective Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. Methods Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. Results We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. Conclusion CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
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Jia Y, Zhang L, Liu Z, Mao C, Ma Z, Li W, Yu F, Wang Y, Huang Y, Zhang W, Zheng J, Wang X, Xu Q, Zhang J, Feng W, Yun C, Liu C, Sun J, Fu Y, Cui Q, Kong W. Targeting macrophage TFEB-14-3-3 epsilon Interface by naringenin inhibits abdominal aortic aneurysm. Cell Discov 2022; 8:21. [PMID: 35228523 PMCID: PMC8885854 DOI: 10.1038/s41421-021-00363-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 12/08/2021] [Indexed: 12/14/2022] Open
Abstract
Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there is no proven drug treatment for this condition. In this study, by using the Connectivity Map (CMap) approach, we explored naringenin, a naturally occurring citrus flavonoid, as a putative agent for inhibiting AAA. We then validated the prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice and angiotensin II-infused ApoE−/− mice. Naringenin effectively blocked the formation of AAAs and the progression of established AAAs. Transcription factor EB (TFEB) is the master regulator of lysosome biogenesis. Intriguingly, the protective role of naringenin on AAA was abolished by macrophage-specific TFEB depletion in mice. Unbiased interactomics, combined with isothermal titration calorimetry (ITC) and cellular thermal shift assays (CETSAs), further revealed that naringenin is directly bound to 14-3-3 epsilon blocked the TFEB-14-3-3 epsilon interaction, and therefore promoted TFEB nuclear translocation and activation. On one hand, naringenin activated lysosome-dependent inhibition of the NLRP3 inflammasome and repressed aneurysmal inflammation. On the other hand, naringenin induced TFEB-dependent transcriptional activation of GATA3, IRF4, and STAT6 and therefore promoted reparative M2 macrophage polarization. In summary, naturally derived naringenin or macrophage TFEB activation shows promising efficacy for the treatment of AAA.
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Affiliation(s)
- Yiting Jia
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Lu Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.,The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ziyi Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Chenfeng Mao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Zihan Ma
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Wenqiang Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Fang Yu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Yingbao Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Yaqian Huang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Weizhen Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Jingang Zheng
- Department of Cardiology, China-Japan Friendship Hospital, Beijing, China
| | - Xian Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Qingbo Xu
- Cardiovascular Division, Kings College London BHF Centre, London, SE5 9NU, UK
| | - Jian Zhang
- State Key Laboratory of Oncogenes and Related Genes, Medicinal Chemistry & Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Feng
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Caihong Yun
- Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Chuanju Liu
- Department of Orthopedic Surgery, New York University Medical Center, New York, NY, USA.,Department of Cell Biology, New York University School of Medicine, New York, NY, USA
| | - Jinpeng Sun
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Yi Fu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Qinghua Cui
- Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing, China.
| | - Wei Kong
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
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Ademosun AO, Oboh G, Ajeigbe OF. Influence of Moringa (Moringa oleifera) enriched ice creams on rats’ brain: Exploring the redox and cholinergic systems. Curr Res Food Sci 2022; 5:366-373. [PMID: 35198996 PMCID: PMC8850994 DOI: 10.1016/j.crfs.2022.01.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 01/26/2022] [Accepted: 01/26/2022] [Indexed: 11/18/2022] Open
Abstract
The broad application of Moringa oleifera leaves in the treatment of numerous diseases is prevalent globally where it extends to the management of diabetes, hypertension, inflammation, hypercholesterolemia and neurodegenerative diseases. This study provides findings on the role of Moringa oleifera leaves (MO) [MO leaves] formulated ice creams on brain cholinergic enzymes [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)], antioxidant enzymes, glycemic index and blood lipid profile of rats. Thirty (30) adult male rats acclimatized for 2 weeks were divided into five groups: Group 1 rats received commercial ice cream, Group 2 rats were received plain ice-cream, Group 3, 4 and 5 received 0.5 g, 1.0 g and 2.0 g of MO-formulated ice creams. Rats were fed on normal pellets and exposed to ice creams produced from whipping cream, skimmed milk and Moringa oleifera leaves for 30 consecutive days. Following administration, results from this study revealed that rats that received Moringa formulated ice-creams had reduced brain butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes activities, glycemic index (GI), total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels and significantly increased high-density lipoprotein-cholesterol (HDL-C) level in the plasma while revealing elevated brain antioxidant status (Superoxide dismutase (SOD) and Catalase (CAT)) when compared against rats consuming commercial ice creams. Therefore, results from this study attests to the intake of ice creams made from blends of Moringa leaves in the reduction of rats’ body weight, glycemic index and lipid profile (TC, TG, LDL-C), inhibition of brain cholinergic enzymes (AChE and BChE) while increasing brain antioxidant enzymes activities (SOD and CAT).
Ice creams enriched with Moringa leaves reduces rats' body weight gain and GI. Also, rats' brain antioxidant and cholinergic enzymes activities was modulated. This study shows the influence of Moringa ice creams on brain enzymes activities.
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Affiliation(s)
- Ayokunle Olubode Ademosun
- Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria
- Corresponding author.
| | - Ganiyu Oboh
- Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria
| | - Olufunke Florence Ajeigbe
- Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria
- Department of Physical and Chemical Sciences, Biochemistry Programme, Elizade University, P.M.B. 002, Ilara-Mokin, Ondo State, Nigeria
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Hamid SB, Hamid AFA. Roles of Nutraceuticals and Functional Food in Prevention of Cardiovascular Disease. RESEARCH ANTHOLOGY ON RECENT ADVANCEMENTS IN ETHNOPHARMACOLOGY AND NUTRACEUTICALS 2022:810-839. [DOI: 10.4018/978-1-6684-3546-5.ch041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
The chapter provides an overview of cardiovascular disease, a major cause of mortality worldwide. It relates economic and social impacts to the disease, especially in developing countries. One of the approaches to addressing this challenge is increasing awareness within society, through implementation of education programs. It is important for society to understand the types and roles of the risk factors leading to cardiovascular disease. Emphasis is on the role of functional food and nutraceuticals as dietary sources that could prevent development of cardiovascular disease. The chapter highlights roles of nutraceuticals and functional food sources from medical plants, seeds, berries, and tropical fruits in lowering risk factors. Key findings from trials conducted in Asia, China, Europe, and America provide supporting evidence for the importance of functional food to health, and its potential for modifying the level of risk factors related to cardiovascular diseases.
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Chen J, Li H, Yang C, He Y, Arai T, Huang Q, Liu X, Miao L. Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway. Int J Mol Sci 2021; 23:385. [PMID: 35008811 PMCID: PMC8745540 DOI: 10.3390/ijms23010385] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/22/2021] [Accepted: 12/27/2021] [Indexed: 11/24/2022] Open
Abstract
Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.
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Affiliation(s)
- Jie Chen
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China; (J.C.); (C.Y.); (T.A.); (Q.H.)
- School of Life Sciences, Peking University, Beijing 100871, China
| | - Hui Li
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; (H.L.); (Y.H.)
| | - Changming Yang
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China; (J.C.); (C.Y.); (T.A.); (Q.H.)
- School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Yinjia He
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; (H.L.); (Y.H.)
| | - Tatsuo Arai
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China; (J.C.); (C.Y.); (T.A.); (Q.H.)
- School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Qiang Huang
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China; (J.C.); (C.Y.); (T.A.); (Q.H.)
- School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China
| | - Xiaodong Liu
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; (H.L.); (Y.H.)
| | - Linqing Miao
- Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China; (J.C.); (C.Y.); (T.A.); (Q.H.)
- School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China
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Malhi M, Norris MJ, Duan W, Moraes TJ, Maynes JT. Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection. Commun Biol 2021; 4:1239. [PMID: 34716403 PMCID: PMC8556396 DOI: 10.1038/s42003-021-02754-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 10/06/2021] [Indexed: 11/28/2022] Open
Abstract
Respiratory syncytial virus (RSV) is a leading cause of severe respiratory tract infections in children. To uncover new antiviral therapies, we developed a live cell-based high content screening approach for rapid identification of RSV inhibitors and characterized five drug classes which inhibit the virus. Among the molecular targets for each hit, there was a strong functional enrichment in lipid metabolic pathways. Modulation of lipid metabolites by statins, a key hit from our screen, decreases the production of infectious virus through a combination of cholesterol and isoprenoid-mediated effects. Notably, RSV infection globally upregulates host protein prenylation, including the prenylation of Rho GTPases. Treatment by statins or perillyl alcohol, a geranylgeranyltransferase inhibitor, reduces infection in vitro. Of the Rho GTPases assayed in our study, a loss in Rac1 activity strongly inhibits the virus through a decrease in F protein surface expression. Our findings provide new insight into the importance of host lipid metabolism to RSV infection and highlight geranylgeranyltransferases as an antiviral target for therapeutic development.
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Affiliation(s)
- Manpreet Malhi
- Department of Biochemistry, University of Toronto, Toronto, ON, Canada
- Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Michael J Norris
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Wenming Duan
- Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Theo J Moraes
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
- Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Paediatrics, Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada
| | - Jason T Maynes
- Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
- Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
- Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
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Nandagopal P, Steven AN, Chan LW, Rahmat Z, Jamaluddin H, Mohd Noh NI. Bioactive Metabolites Produced by Cyanobacteria for Growth Adaptation and Their Pharmacological Properties. BIOLOGY 2021; 10:1061. [PMID: 34681158 PMCID: PMC8533319 DOI: 10.3390/biology10101061] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/10/2021] [Accepted: 10/14/2021] [Indexed: 02/08/2023]
Abstract
Cyanobacteria are the most abundant oxygenic photosynthetic organisms inhabiting various ecosystems on earth. As with all other photosynthetic organisms, cyanobacteria release oxygen as a byproduct during photosynthesis. In fact, some cyanobacterial species are involved in the global nitrogen cycles by fixing atmospheric nitrogen. Environmental factors influence the dynamic, physiological characteristics, and metabolic profiles of cyanobacteria, which results in their great adaptation ability to survive in diverse ecosystems. The evolution of these primitive bacteria resulted from the unique settings of photosynthetic machineries and the production of bioactive compounds. Specifically, bioactive compounds play roles as regulators to provide protection against extrinsic factors and act as intracellular signaling molecules to promote colonization. In addition to the roles of bioactive metabolites as indole alkaloids, terpenoids, mycosporine-like amino acids, non-ribosomal peptides, polyketides, ribosomal peptides, phenolic acid, flavonoids, vitamins, and antimetabolites for cyanobacterial survival in numerous habitats, which is the focus of this review, the bioactivities of these compounds for the treatment of various diseases are also discussed.
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Affiliation(s)
- Pavitra Nandagopal
- Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia; (P.N.); (L.-W.C.); (Z.R.); (H.J.)
| | - Anthony Nyangson Steven
- Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia;
| | - Liong-Wai Chan
- Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia; (P.N.); (L.-W.C.); (Z.R.); (H.J.)
| | - Zaidah Rahmat
- Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia; (P.N.); (L.-W.C.); (Z.R.); (H.J.)
- Institute of Bioproduct Development, Universiti Teknologi Malaysia, Skudai 81310, Malaysia
| | - Haryati Jamaluddin
- Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia; (P.N.); (L.-W.C.); (Z.R.); (H.J.)
| | - Nur Izzati Mohd Noh
- Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai 81310, Malaysia; (P.N.); (L.-W.C.); (Z.R.); (H.J.)
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Guo X, Cao X, Fang X, Guo A, Li E. Inhibitory effects of fermented Ougan ( Citrus reticulata cv. Suavissima) juice on high-fat diet-induced obesity associated with white adipose tissue browning and gut microbiota modulation in mice. Food Funct 2021; 12:9300-9314. [PMID: 34606525 DOI: 10.1039/d0fo03423a] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In this study, Ougan juice (OJ) and lactic acid bacteria fermented Ougan juice (FOJ) were investigated individually for their capability of preventing obesity in high-fat diet (HFD)-fed C57BL/6J mice. After being administered with OJ or FOJ for 10 weeks, the body weight gain, hyperlipidemia, and gut microbiota dysbiosis of HFD-fed mice were examined. The results showed that OJ or FOJ supplementation inhibited weight gain, lowered fat accumulation, reduced liver steatosis, improved glucose homeostasis and insulin sensitivity, increased brown adipose tissue (BAT) activity, and promoted white adipose tissue (WAT) browning. Both OJ and FOJ additions increased the diversity of gut microbiota. OJ reduced the relative abundance of phylum Erysipelatoclostridiaceae and genus Erysipelatoclostridium and remarkably increased SCFA-producing bacteria Blautia, while FOJ reduced the ratio of Firmicutes to Bacteroidetes and enhanced the relative abundance of family Lactobacillaceae. Spearman's correlation analysis revealed that Akkermansia, Dubosiella, and Muribaculaceae were significantly negatively correlated with obesity-related indexes. In general, FOJ exhibited a better inhibitory effect on obesity than OJ, and the possible inhibitory mechanism lies in promoting WAT browning and increasing intestinal probiotics. This study provides the guidance for developing fermented Ougan juice as an obesity-inhibiting functional food.
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Affiliation(s)
- Xiao Guo
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Xuedan Cao
- Zhejiang Citrus Research Institute, Zhejiang Academy of Agricultural Sciences, Taizhou 318020, China
| | - Xiugui Fang
- Zhejiang Citrus Research Institute, Zhejiang Academy of Agricultural Sciences, Taizhou 318020, China
| | - Ailing Guo
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China. .,Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, Hubei, China
| | - Erhu Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China. .,Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, Hubei, China
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Sun G, Liu F, Zhao R, Hu Y, Li B, Liu S, Li Y, Shah BR. Enhanced stability and bioaccessibility of nobiletin in whey protein/cinnamaldehyde-stabilized microcapsules and application in yogurt. FOOD STRUCTURE 2021. [DOI: 10.1016/j.foostr.2021.100217] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Satsu H, Shibata R, Suzuki H, Kimura S, Shimizu M. Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo. Nutrients 2021; 13:3382. [PMID: 34684383 PMCID: PMC8539283 DOI: 10.3390/nu13103382] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 01/19/2023] Open
Abstract
Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.
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Affiliation(s)
- Hideo Satsu
- Department of Biotechnology, Faculty of Engineering, Maebashi Institute of Technology, Gunma 371-0816, Japan; (H.S.); (S.K.)
| | - Ryosuke Shibata
- Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan;
| | - Hiroto Suzuki
- Department of Biotechnology, Faculty of Engineering, Maebashi Institute of Technology, Gunma 371-0816, Japan; (H.S.); (S.K.)
| | - Shimon Kimura
- Department of Biotechnology, Faculty of Engineering, Maebashi Institute of Technology, Gunma 371-0816, Japan; (H.S.); (S.K.)
| | - Makoto Shimizu
- Department of Nutritional Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan;
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Kumar R, Akhtar F, Rizvi SI. Protective effect of hesperidin in Poloxamer-407 induced hyperlipidemic experimental rats. Biol Futur 2021; 72:201-210. [PMID: 34554473 DOI: 10.1007/s42977-020-00053-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/23/2020] [Indexed: 11/28/2022]
Abstract
Hyperlipidemia is one of the leading causes of, atherosclerosis, and cardiovascular disease. In this study, we evaluated the protective role of hesperidin (HES) against lipidemic stress in a hyperlipidemic model of rats. We developed a hyperlipidemic model of the rat through an i.p dose of poloxamer-407, 0.5 g/kg body weight for 3 alternative days in a week for 30 days and rats were supplemented with HES orally (100 mg/kg body weight) once daily. Bodyweight, fasting glucose, insulin, HOMA-IR index, triglyceride, cholesterol, ROS, FRAP, GSH, PMRS, AGE, MDA, PCO, AOPP, PON-1, TNF-α and IL-6, SGPT and SGOT were estimated in blood and plasma, and histopathology was done in liver tissue. Our data show that oxidative stress, inflammatory markers were increased in the P-407 treated group. Liver tissue histology also changes in the hyperlipidemic groups of rats.HES supplementation protects against P-407 induced alterations and maintains the redox homeostasis. Our results provide evidence that HES protects against lipidemic stress and redox imbalance induced by P-407 in rats.
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Affiliation(s)
- Raushan Kumar
- Department of Biochemistry, University of Allahabad, Allahabad, 211002, India
| | - Farhan Akhtar
- Department of Biochemistry, University of Allahabad, Allahabad, 211002, India
| | - Syed Ibrahim Rizvi
- Department of Biochemistry, University of Allahabad, Allahabad, 211002, India.
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Cui YY, Tian ZM, Deng D, Liu ZC, Wang G, Chen WD, Ma XY. Effects of dietary citrus extract on growth performance, carcass characteristics and meat quality of pigs. J Anim Physiol Anim Nutr (Berl) 2021; 106:813-824. [PMID: 34448260 DOI: 10.1111/jpn.13623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 05/14/2021] [Accepted: 08/04/2021] [Indexed: 11/29/2022]
Abstract
This study investigated the effects of citrus extract on growth, carcass and meat quality of Duroc × Landrace × Large White pigs. One hundred and eight pigs (54 barrows, 54 females) were assigned to one of three dietary treatments for 138 days. The dietary treatments were (1) basic diet; (2) basic diet supplemented with 75 mg/kg chlortetracycline; and (3) basic diet supplemented with citrus extract (0.25 ml/kg during 56-112 days of age and 0.20 ml/kg during 113-194 days of age). No significant differences among treatments were found for growth performance, carcass characteristics, meat quality and free amino acids (p > 0.05). Feeding citrus extract tended to increase intramuscular fat (p = 0.052). Citrus extract and chlortetracycline increased C15:0 concentration (p = 0.016) and superoxide dismutase activity (p = 0.004). The pigs that received chlortetracycline exhibited the lowest (p = 0.033) muscle malondialdehyde concentration. Overall, citrus extract ameliorated some meat quality indicators without adverse effects on pig growth or carcass performance.
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Affiliation(s)
- Yi-Yan Cui
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhi-Mei Tian
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Dun Deng
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Zhi-Chang Liu
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Gang Wang
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Wei-Dong Chen
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China
| | - Xian-Yong Ma
- State Key Laboratory of Livestock and Poultry Breeding, The Key Laboratory of Animal Nutrition and Feed Science in South China, Ministry of Agriculture, Guangdong Provincial Key Laboratory of Animal Breeding and Nutrition, Guangdong Engineering Technology Research Center of Animal Meat Quality and Safety Control and Evaluation, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou, China.,Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, China
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43
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Li Q, Gao B, Siqin B, He Q, Zhang R, Meng X, Zhang N, Zhang N, Li M. Gut Microbiota: A Novel Regulator of Cardiovascular Disease and Key Factor in the Therapeutic Effects of Flavonoids. Front Pharmacol 2021; 12:651926. [PMID: 34220497 PMCID: PMC8241904 DOI: 10.3389/fphar.2021.651926] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 04/23/2021] [Indexed: 01/30/2023] Open
Abstract
Cardiovascular disease is the main cause of death worldwide, and traditional cardiovascular risk factors cannot fully explain the occurrence of the disease. In recent years, the relationship between gut microbiota and its metabolites and cardiovascular disease has been a hot study topic. The changes in gut microbiota and its metabolites are related to the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. The mechanisms by which gut microbiota and its metabolites influence cardiovascular disease have been reported, although not comprehensively. Additionally, following ingestion, flavonoids are decomposed into phenolic acids that are more easily absorbed by the body after being processed by enzymes produced by intestinal microorganisms, which increases flavonoid bioavailability and activity, consequently affecting the onset of cardiovascular disease. However, flavonoids can also inhibit the growth of harmful microorganisms, promote the proliferation of beneficial microorganisms, and maintain the balance of gut microbiota. Hence, it is important to study the relationship between gut microbiota and flavonoids to elucidate the protective effects of flavonoids in cardiovascular diseases. This article will review the role and mechanism of gut microbiota and its metabolites in the occurrence and development of atherosclerosis, myocardial infarction, heart failure, and hypertension. It also discusses the potential value of flavonoids in the prevention and treatment of cardiovascular disease following their transformation through gut microbiota metabolism.
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Affiliation(s)
- Qinyu Li
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Bing Gao
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Bateer Siqin
- Xilinguole Meng Mongolian General Hospital, Xilinhaote, China
| | - Qian He
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Ru Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Xiangxi Meng
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Naiheng Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Na Zhang
- Department of Pharmacy, Baotou Medical College, Baotou, China
| | - Minhui Li
- Department of Pharmacy, Baotou Medical College, Baotou, China
- Pharmaceutical Laboratory, Inner Mongolia Institute of Traditional Chinese Medicine, Hohhot, China
- Inner Mongolia Key Laboratory of Characteristic Geoherbs Resources and Utilization, Baotou Medical College, Baotou, China
- Office of Academic Research, Qiqihar Medical University, Qiqihar, China
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44
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Ademosun AO, Oboh G, Ajeigbe OF. Antioxidant activities and glycemic indices of ice creams enriched with orange (Citrus sinensis) and shaddock (Citrus maxima) peels and effects on rat lipid profiles. J Food Biochem 2021; 45:e13813. [PMID: 34096081 DOI: 10.1111/jfbc.13813] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 04/22/2021] [Accepted: 05/20/2021] [Indexed: 11/29/2022]
Abstract
This study evaluated the effects of ice creams produced from blends of orange (Citrus sinensis) and shaddock (Citrus maxima) peels on the blood lipid profile, glycemic index, and antioxidant indices in the liver and heart of rats. Formulated ice cream was produced at a different proportion of citrus (orange and shaddock) blends and fed to rats for 28 days. The result showed that the formulated ice cream enriched with citrus peels blends caused a significant increase in high-density lipoprotein-cholesterol level in the plasma and antioxidant status in the liver and heart homogenates, decreased the glycemic index, concentration of total cholesterol, triglycerides, and low-density lipoprotein in the plasma as against rats fed on plain and commercial ice creams. To conclude, the use of ice creams from blends of orange and shaddock peels could serve as a functional food for weight reduction, glycemic index, management of lipid-related diseases, and prevention of oxidative stress-related complications in the liver and heart. PRACTICAL APPLICATIONS: The consumption of ice creams has increased in many parts of the world. However, there have been limited efforts aimed at improving the medicinal properties of frozen dairy products. Hence, these ice creams could be produced on a large scale under regulated condition since they have improved medicinal properties which would be a good option for preventing/combating degenerative conditions and their related complications.
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Affiliation(s)
| | - Ganiyu Oboh
- Department of Biochemistry, Federal University of Technology, Akure, Nigeria
| | - Olufunke Florence Ajeigbe
- Department of Biochemistry, Federal University of Technology, Akure, Nigeria.,Department of Physical and Chemical Sciences, Elizade University, Ilara-Mokin, Nigeria
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45
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Djafari F, Shahavandi M, Amini MR, Sheikhhossein F, Shahinfar H, Payandeh N, Jafari A, Djafarian K, Clark CCT, Shab-Bidar S. The effects of hesperidin supplementation or orange juice consumption on anthropometric measures in adults: A meta-analysis of randomized controlled clinical trials. Clin Nutr ESPEN 2021; 43:148-157. [PMID: 34024506 DOI: 10.1016/j.clnesp.2021.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/12/2021] [Accepted: 03/29/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND The current evidence-base regarding the effect of hesperidin (a flavanone found in citrus fruits) on body composition is equivocal. OBJECTIVE We conducted a meta-analysis on the effect of orange juice and/or hesperidin supplementation on anthropometric measures in randomized controlled trials (RCTs). MATERIALS AND METHODS A systematic search of PubMed and Scopus was performed up to February 2020. The overall estimates and their 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS Eleven eligible RCTs, with 512 individuals, were included in this study. The meta-analysis showed that orange juice and/or hesperidin had no significant effect on body weight [weighted mean difference (WMD) = -0.31 kg; 95% CI, -1.44 to 0.82, P = 0.592], body mass index [WMD = 0.11 kg/m2; 95% CI, -0.33 to 0.56, P = 0.617], fat mass [WMD = 0.14 kg; 95% CI, -0.95 to 1.22, P = 0.807], percentage body fat [WMD = -0.70%; 95% CI, -2.58 to 1.18, P = 0.463] and waist circumference [WMD = 0.07 cm; 95% CI, -1.16 to 1.30, P = 0.588]. CONCLUSION The present study revealed that there is no significant beneficial effect of orange juice and/or hesperidin supplementation on anthropometric measures. The authors advocate that more high-quality clinical trials are needed to better discern the potential efficacy of orange juice and/or hesperidin.
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Affiliation(s)
- Farhang Djafari
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mahshid Shahavandi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Mohammad Reza Amini
- Department of Clinical Nutrition, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Sheikhhossein
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Hossein Shahinfar
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nastaran Payandeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Alireza Jafari
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Kurosh Djafarian
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Cain C T Clark
- Centre for Intelligent Healthcare, Coventry University, Coventry, CV15FB, UK
| | - Sakineh Shab-Bidar
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
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Liu J, Cao J, Li Y, Guo F. Beneficial Flavonoid in Foods and Anti-obesity Effect. FOOD REVIEWS INTERNATIONAL 2021. [DOI: 10.1080/87559129.2021.1923730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Jingwen Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jiaoxian Cao
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yiming Li
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Fujiang Guo
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Smith LM, Pitts CB, Friesen-Waldner LJ, Prabhu NH, Mathers KE, Sinclair KJ, Wade TP, Regnault TRH, McKenzie CA. In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1- 13 C]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption. J Magn Reson Imaging 2021; 54:1404-1414. [PMID: 33970520 DOI: 10.1002/jmri.27677] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE Prospective. ANIMAL MODEL Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). FIELD STRENGTH/SEQUENCE 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. STATISTICAL TESTS Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. LEVEL OF EVIDENCE 2 TECHNICAL EFFICACY STAGE: 1.
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Affiliation(s)
- Lauren M Smith
- Department of Medical Biophysics, Western University, London, Ontario, Canada
| | - Conrad B Pitts
- Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
| | | | - Neetin H Prabhu
- Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
| | - Katherine E Mathers
- Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
| | - Kevin J Sinclair
- Department of Medical Biophysics, Western University, London, Ontario, Canada
| | - Trevor P Wade
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,Robarts Research Institute, Western University, London, Ontario, Canada
| | - Timothy R H Regnault
- Department of Physiology and Pharmacology, Western University, London, Ontario, Canada.,Department of Obstetrics and Gynaecology, Western University, London, Ontario, Canada.,Division of Maternal, Fetal & Newborn Health, Children's Health Research Institute, Lawson Research Institution, London, Ontario, Canada
| | - Charles A McKenzie
- Department of Medical Biophysics, Western University, London, Ontario, Canada.,Robarts Research Institute, Western University, London, Ontario, Canada.,Division of Maternal, Fetal & Newborn Health, Children's Health Research Institute, Lawson Research Institution, London, Ontario, Canada
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Nery M, Ferreira PS, Gonçalves DR, Spolidorio LC, Manthey JA, Cesar TB. Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high-fat diet and analyses of the metabolites originating from these two polymethoxylated flavones. Food Sci Nutr 2021; 9:1997-2009. [PMID: 33841818 PMCID: PMC8020949 DOI: 10.1002/fsn3.2167] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 11/28/2020] [Accepted: 01/17/2021] [Indexed: 12/29/2022] Open
Abstract
Two compounds from citrus peel, tangeretin (TAN) and 3',4',3,5,6,7,8-heptamethoxyflavone (HMF), were investigated for their abilities to repair metabolic damages caused by an high-fat diet (HFD) in C57BL/6J mice. In the first 4 weeks, mice were fed either a standard diet (11% kcal from fat) for the control group, or a HFD (45% kcal from fat) to establish obesity in three experimental groups. In the following 4 weeks, two groups receiving the HFD were supplemented with either TAN or HMF at daily doses of 100 mg/kg body weight, while the two remaining groups continued to receive the standard healthy diet or the nonsupplemented HFD. Four weeks of supplementation with TAN and HMF resulted in intermediate levels of blood serum glucose, leptin, resistin, and insulin resistance compared with the healthy control and the nonsupplemented HFD groups. Blood serum peroxidation (TBARS) levels were significantly lower in the TAN and HMF groups compared with the nonsupplemented HFD group. Several differences occurred in the physiological effects of HMF versus TAN. TAN, but not HMF, reduced adipocyte size in the mice with pre-existent obesity, while HMF, but not TAN, decreased fat accumulation in the liver and also significantly increased the levels of an anti-inflammatory cytokine, IL-10. In an analysis of the metabolites of TAN and HMF, several main classes occurred, including a new set of methylglucuronide conjugates. It is suggested that contrasts between the observed physiological effects of TAN and HMF may be attributable to the differences in numbers and chemical structures of TAN and HMF metabolites.
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Affiliation(s)
- Marina Nery
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
| | - Paula S. Ferreira
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Danielle R. Gonçalves
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Luis C. Spolidorio
- Department of Physiology and PathologySchool of DentistrySão Paulo State University (UNESP)AraraquaraBrazil
| | - John A. Manthey
- U.S. Horticultural Research LaboratoryAgricultural Research ServiceUSDAFort PierceFLUSA
| | - Thais B. Cesar
- Department of Food and NutritionLaboratory of NutritionFaculty of Pharmaceutical SciencesSão Paulo State University (UNESP)AraraquaraBrazil
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Guerrero-Rubio MA, Hernández-García S, García-Carmona F, Gandía-Herrero F. Flavonoids' Effects on Caenorhabditis elegans' Longevity, Fat Accumulation, Stress Resistance and Gene Modulation Involve mTOR, SKN-1 and DAF-16. Antioxidants (Basel) 2021; 10:antiox10030438. [PMID: 33809299 PMCID: PMC8001597 DOI: 10.3390/antiox10030438] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 12/21/2022] Open
Abstract
Flavonoids are potential nutraceutical compounds present in diary food. They are considered health-promoting compounds and promising drugs for different diseases, such as neurological and inflammatory diseases, diabetes and cancer. Therefore, toxicological and mechanistic studies should be done to assert the biological effects and identify the molecular targets of these compounds. In this work we describe the effects of six structurally-related flavonoids—baicalein, chrysin, scutellarein, 6-hydroxyflavone, 6,7-dihydroxyflavone and 7,8-dihydroxyflavone—on Caenorhabditis elegans’ lifespan and stress resistance. The results showed that chrysin, 6-hydroxyflavone and baicalein prolonged C. elegans’ lifespan by up to 8.5%, 11.8% and 18.6%, respectively. The lifespan extensions caused by these flavonoids are dependent on different signaling pathways. The results suggested that chrysin’s effects are dependent on the insulin signaling pathway via DAF-16/FOXO. Baicalein and 6-hydroxyflavone’s effects are dependent on the SKN-1/Nfr2 pathway. In addition, microarray analysis showed that baicalein downregulates important age-related genes, such as mTOR and PARP.
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Ávila-Gálvez MÁ, Giménez-Bastida JA, González-Sarrías A, Espín JC. New Insights into the Metabolism of the Flavanones Eriocitrin and Hesperidin: A Comparative Human Pharmacokinetic Study. Antioxidants (Basel) 2021; 10:435. [PMID: 33799874 PMCID: PMC8000041 DOI: 10.3390/antiox10030435] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/06/2021] [Accepted: 03/09/2021] [Indexed: 12/17/2022] Open
Abstract
The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.
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Affiliation(s)
| | | | | | - Juan Carlos Espín
- Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Department Food Science and Technology, Campus de Espinardo, CEBAS-CSIC, P.O. Box 164, 30100 Murcia, Spain; (M.Á.Á.-G.); (J.A.G.-B.); (A.G.-S.)
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