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Ouyang PW, Wu YN, Gu SS, Liu Q, Yi WZ, Xia LX, Chen JY, Cui YH, Meng J, Pan HW. Procyanidin B2 attenuates microvascular dysfunction in diabetic retinopathy via inhibition of caspase-1/GSDMD mediated pyroptosis. JOURNAL OF ETHNOPHARMACOLOGY 2025; 344:119528. [PMID: 39986358 DOI: 10.1016/j.jep.2025.119528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 02/13/2025] [Accepted: 02/19/2025] [Indexed: 02/24/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In traditional Chinese medicine (TCM), grape seeds (Vitis vinifera) are believed to nourish the liver and kidney and improve blood circulation, which aligns with the pathophysiological needs of conditions characterized by microvascular dysfunction. Procyanidin B2 (PB2), a major active compound in grape seeds, has shown potent anti-inflammatory and vascular-protective effects. However, the specific role of PB2 in diabetic retinal microvasculature and its underlying molecular mechanisms remain unexplored. AIMS OF THE STUDY This study aimed to evaluate the therapeutic potential of Procyanidin B2 (PB2) in alleviating microvascular damage in diabetic retinopathy and the possible mechanisms. MATERIALS AND METHODS Pyroptosis in endothelial cells was analyzed under high glucose conditions and in the retinas of diabetic mice. The effects of PB2 on pyroptosis and endothelial dysfunction were examined through in vitro assays evaluating cell proliferation, migration, and tube formation. In vivo experiments using diabetic mouse models were conducted to assess retinal vascular integrity, with a focus on PB2's impact on endothelial pyroptosis and its associated molecular mechanisms. RESULTS PB2 significantly suppressed pyroptosis in endothelial cells exposed to high glucose by inhibiting the caspase-1/GSDMD signaling pathway. This suppression enhanced endothelial cell proliferation, migration, and tube formation. In diabetic mice, PB2 treatment effectively alleviated retinal microvascular dysfunction by reducing pyroptosis and preserving retinal vascular integrity. CONCLUSION These findings provide a molecular basis for PB2's therapeutic potential in DR and support its further development as an intervention for diabetic vascular complications.
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Affiliation(s)
- Pei-Wen Ouyang
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Ya-Ni Wu
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Shuo-Shuo Gu
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Qi Liu
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Wan-Zhao Yi
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Ling-Xiao Xia
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Jian-Ying Chen
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Yu-Hong Cui
- Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China; Department of Histology and Embryology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Jing Meng
- Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China; The Affiliated Shunde Hospital of Jinan University, Foshan, China.
| | - Hong-Wei Pan
- Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital, Jinan University, Guangzhou, China.
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Wang X, Wang P, Li Y, Guo H, Wang R, Liu S, Qiu J, Wang X, Hao Y, Zhao Y, Liao H, Zou Z, Thinwa J, Liu R. Procyanidin C1 Modulates the Microbiome to Increase FOXO1 Signaling and Valeric Acid Levels to Protect the Mucosal Barrier in Inflammatory Bowel Disease. ENGINEERING 2024; 42:108-120. [DOI: 10.1016/j.eng.2023.10.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
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Zhao T, Liu D, Liu Y, Deng J, Yang H. Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice. Food Res Int 2024; 188:114508. [PMID: 38823847 DOI: 10.1016/j.foodres.2024.114508] [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: 01/13/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 06/03/2024]
Abstract
Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.
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Affiliation(s)
- Tong Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Dan Liu
- Department of Nutrition and Food Safety, College of Public Health, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yichen Liu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Jianjun Deng
- State Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Haixia Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
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Akagi R, Nanba F, Saito S, Maruo T, Toda T, Yamashita Y, Ashida H, Suzuki T. Black Soybean Seed Coat Extract Improves Endothelial Function and Upregulates Oxidative Stress Marker Expression in Healthy Volunteers by Stimulating Nitric Oxide Production in Endothelial Cells. J Med Food 2024; 27:134-144. [PMID: 38294791 DOI: 10.1089/jmf.2023.k.0149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2024] Open
Abstract
Black soybean seed coat extract (BE) contains multiple bioactive polyphenols, including flavan-3-ols and anthocyanins. BE improves endothelial function; however, it is unclear whether BE protects endothelial cells from senescence. In this study, we examined the effects of BE on endothelial cell senescence and vascular function in healthy individuals. High concentrations of glucose were used to induce senescence in bovine aortic endothelial cells incubated with BE. Senescence, vascular function, and oxidative stress markers were measured. Incubation with BE remarkably inhibited senescence-associated β-galactosidase and lactate dehydrogenase activities and dose dependently reduced intracellular reactive oxygen species levels in bovine aortic endothelial cells. BE treatment increased the levels of endothelial nitric oxide synthase (eNOS) mRNA and endothelial nitric oxide (NO) metabolites and increased the mRNA expression of klotho, a gene associated with an antiaging phenotype. To examine the effects of BE in humans, we conducted a clinical study using the second derivative of the fingertip photoplethysmogram to investigate vascular function and aging in 24 healthy volunteers. The participants consumed BE supplements (100 mg/day) or a placebo for 2 weeks. When compared with the placebo group, the BE group showed considerably improved vascular function, NO metabolite levels, and oxidative stress. These results suggest that BE supplementation improves endothelial function, possibly through antioxidant activity and NO production, and may consequently reduce the cardiovascular risk associated with aging. BE supplementation may be an effective and safe approach to reduce the risk of atherosclerosis and cardiovascular disease; however, additional studies investigating chronic vascular inflammation are needed.
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Affiliation(s)
- Ryota Akagi
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
| | - Fumio Nanba
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
| | - Shizuka Saito
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
| | - Toshinari Maruo
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
| | - Toshiya Toda
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
- Department of Innovative Food Sciences, School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya, Japan
| | - Yoko Yamashita
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Japan
| | - Hitoshi Ashida
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Japan
| | - Toshio Suzuki
- Research and Development Department, Fujicco Co. Ltd., Kobe, Japan
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Nishijima T, Yamashita Y, Ashida H. Black soybean seed coat polyphenols have different effects on glucose and lipid metabolism in growing and young adult mice. Food Funct 2024; 15:1004-1020. [PMID: 38180075 DOI: 10.1039/d3fo04269c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2024]
Abstract
Black soybean contains flavan-3-ols and cyanidin 3-O-glucoside in its seed coat. Polyphenol-rich black soybean seed coat extract (BE) possesses various health benefits, such as antioxidant, anti-obesity, and anti-hyperglycemic effects. However, these functions have been evaluated mainly in the growing stage of animals, and there is no comparison data for different life stages. In this present study, we compared the effect of BE in growing (5-week old) and young adult (22-week old) ICR male mice. These mice were given an AIN 93M diet containing 2.0% BE for 4 weeks. BE did not affect body weight gain in both growing and young adult mice, but it suppressed mesenteric and subcutaneous white adipose tissue weights and decreased the cell size. BE also significantly suppressed plasma free-fatty acid levels. The effect of both BE and life stages were observed in the protein expression of adipogenesis-related transcription factors; in particular, BE suppressed the expression of C/EBPα and PPARγ. No significant change was observed in lipolysis and lipogenesis factors in the white adipose tissue and liver. Alternatively, BE showed low glucose tolerance without affecting plasma insulin levels after glucose loading in young adult mice, as seen from the results of the oral glucose tolerance test. However, plasma glucose and insulin levels remained unchanged at the end of the experimental period. In conclusion, these results strongly suggest that the health-beneficial effects of BE may alter in mice at different life stages.
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Affiliation(s)
- Toshiki Nishijima
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan.
| | - Yoko Yamashita
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan.
| | - Hitoshi Ashida
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan.
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6
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Fan W, Zong H, Zhao T, Deng J, Yang H. Bioactivities and mechanisms of dietary proanthocyanidins on blood pressure lowering: A critical review of in vivo and clinical studies. Crit Rev Food Sci Nutr 2022; 64:3522-3538. [PMID: 36226711 DOI: 10.1080/10408398.2022.2132375] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Proanthocyanidins, widespread in natural plant sources, are bioactive substances that exhibit broad benefits to human health. Of note, proanthocyanidins have been reported to lower blood pressure and prevent hypertension, but a critical review of this is lacking. In this review, information on the basic structures and absorption of dietary proanthocyanidins as well as their bioactivities and related mechanisms on the lowering of blood pressure derived via in vivo and clinical studies are summarized. Clinical studies have shown that proanthocyanidins have a pronounced blood pressure-lowering effect, effectively preventing hypertension and reducing the occurrence of cardiovascular and cerebrovascular diseases. The potential mechanisms, which are herein reviewed in detail, involve the improvement of vascular function, reduction of oxidative stress and inflammation, and modulation of lipid metabolism. Taken together, this work provides information for a better understanding of the antihypertensive effects of proanthocyanidins, which may promote their use to reduce the risk of developing hypertension.
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Affiliation(s)
- Wendong Fan
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Houru Zong
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Tong Zhao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Jianjun Deng
- Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, China
- Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials and Fermentation Engineering, Biotech & Biomed Research Institute, School of Chemical Engineering, Northwest University, Xi'an, China
| | - Haixia Yang
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
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Yu Y, Chen P, Li X, Shen S, Li K. Persimmon Proanthocyanidins with Different Degrees of Polymerization Possess Distinct Activities in Models of High Fat Diet Induced Obesity. Nutrients 2022; 14:nu14183718. [PMID: 36145094 PMCID: PMC9505881 DOI: 10.3390/nu14183718] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 08/30/2022] [Accepted: 09/02/2022] [Indexed: 11/20/2022] Open
Abstract
Proanthocyanidins is a kind of polyphenol that had been found with strong prevention ability on high fat diet induced obesity. However, whether proanthocyanidins with different polymerization degree showed different anti-obesity ability is unclear. Therefore, in this study, the effects of persimmon proanthocyanidins (P-PCs) and persimmon oligo-proanthocyanidins (P-OPCs) on high-fat diet induced obesity were systematically investigated. The findings indicated that both of P-PCs and P-OPCs significantly reduced the body weight, and P-PCs showed stronger anti-obesity ability compared with P-OPCs, P-OPCs seemed with stronger ability on improvement of insulin resistance. Furthermore, gut microbiota results indicated that the composition of the gut microbiota was changed after P-PCs and P-OPCs intervention in C57BL/6J mice. In addition, P-PCs exhibited strong inhibitory on the digestion of starch and fat. Above all, this study indicated that P-PCs showed stronger anti-obesity ability compared with P-OPCs.
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Affiliation(s)
- Ying Yu
- College of Food Science and Technology, Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Wuhan 430070, China
| | - Ping Chen
- College of Food Science and Technology, Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiaofang Li
- College of Food Science and Technology, Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Wuhan 430070, China
| | - Shanshan Shen
- Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430016, China
- Correspondence: author: (S.S.); (K.L.)
| | - Kaikai Li
- College of Food Science and Technology, Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Wuhan 430070, China
- Correspondence: author: (S.S.); (K.L.)
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8
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Malek MA, Dasiman R, Khan NAMN, Mohamed-Akhlak S, Mahmud MH. The protective effects of Procyanidin C-1 on bisphenol a-induced testicular dysfunction in aged mice. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2022.03.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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9
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Marcińczyk N, Gromotowicz-Popławska A, Tomczyk M, Chabielska E. Tannins as Hemostasis Modulators. Front Pharmacol 2022; 12:806891. [PMID: 35095516 PMCID: PMC8793672 DOI: 10.3389/fphar.2021.806891] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 12/23/2021] [Indexed: 12/17/2022] Open
Abstract
The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention. This paper describes the hemostasis-modifying ability of three groups of tannins, namely ellagitannins, gallotannins, and procyanidins. The review highlights the desirable as well as undesirable influence of tannins on specific components of hemostasis, namely platelets, coagulation system, fibrinolysis system, and endothelium, and the multidirectional effect of these compounds on the thrombotic process. Studies performed under normal and pathological conditions such as diabetes or hypercoagulation are described, and the pathophysiology-dependent action of tannins is also highlighted. Most of the studies presented in the paper were performed in vitro, and due to the low bioavailability of tannins more studies should be conducted in the future to understand their actual activity in vivo.
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Affiliation(s)
- Natalia Marcińczyk
- Department of Biopharmacy, Medical University of Białystok, Białystok, Poland
| | | | - Michał Tomczyk
- Department of Pharmacognosy, Medical University of Białystok, Białystok, Poland
| | - Ewa Chabielska
- Department of Biopharmacy, Medical University of Białystok, Białystok, Poland
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Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP +-Induced Apoptosis in a Cell Culture Model of Parkinson's Disease. Molecules 2021; 26:molecules26216422. [PMID: 34770830 PMCID: PMC8587825 DOI: 10.3390/molecules26216422] [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: 09/25/2021] [Revised: 10/20/2021] [Accepted: 10/20/2021] [Indexed: 11/17/2022] Open
Abstract
Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP+)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP+. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP+. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP+ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.
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11
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Hügel HM, de Silva NH, Siddiqui A, Blanch E, Lingham A. Natural spirocyclic alkaloids and polyphenols as multi target dementia leads. Bioorg Med Chem 2021; 43:116270. [PMID: 34153839 DOI: 10.1016/j.bmc.2021.116270] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/25/2021] [Accepted: 06/04/2021] [Indexed: 01/03/2023]
Abstract
The U rhynchophylla, U tomentosa, Isatis indigotica Fortune, Voacanga Africana, herbal constituents, fungal extracts from Aspergillus duricaulis culture media, include spirooxindoles, polyphenols or bridged spirocyclic alkaloids. Their constituents exhibit specific and synergistic multiple neuroprotective properties including inhibiting of Aβ fibril induced cytotoxicity, NMDA receptor inhibition in mice models of Alzheimer's disease (AD). The pioneering research from Woodward to Waldmann has advanced the synthesis of spirocyclic alkaloids. Furthermore, the elucidation of the genetic analysis, biochemical pathways that links strictosidine to the alkaloids akuammicine, stemmadenine, tabersonine, catharanthine, will now enable the biotechnological generation, also stimulate synthesis of related bridged spirocyclic alkaloids for medicinal investigations. From the value of spirocyclic structures as multi target dementia leads, we hypothesise that simpler Lipinski-like natural/synthetic alkaloid analogues may likewise be discovered that provide neurocognitive enhancing activities against dementia and AD.
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Affiliation(s)
- Helmut M Hügel
- Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia.
| | - Nilamuni H de Silva
- Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia
| | - Aimen Siddiqui
- Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia
| | - Ewan Blanch
- Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia
| | - Anthony Lingham
- Applied Chemistry & Environmental Science, School of Science, RMIT University, GPO Box 2476, Melbourne, VIC 3001, Australia
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12
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Hiemori-Kondo M, Morikawa E, Fujikura M, Nagayasu A, Maekawa Y. Inhibitory effects of cyanidin-3-O-glucoside in black soybean hull extract on RBL-2H3 cells degranulation and passive cutaneous anaphylaxis reaction in mice. Int Immunopharmacol 2021; 94:107394. [PMID: 33582590 DOI: 10.1016/j.intimp.2021.107394] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 12/28/2020] [Accepted: 01/11/2021] [Indexed: 11/20/2022]
Abstract
Black soybean hull extract (BSHE) exhibits a variety of biological activities. However, little is known about the effects of BSHE on immunoglobulin E (IgE)-mediated type I allergic reactions. The anti-allergic effect of BSHE was assessed with the degranulation assay using rat basophilic leukemia RBL-2H3 cells and the passive cutaneous anaphylaxis (PCA) reaction in mice. An active compound in BSHE was identified by ultra-performance liquid chromatography coupled to diode array detection and electrospray ionization tandem mass spectrometry analysis. BSHE inhibited the release of β-hexosaminidase and histamine in RBL-2H3 cells, and cyanidin-3-O-glucoside (C3G) was identified as one of its active compounds. Oral administering of 200 μmol/kg of C3G to IgE-sensitized mice prior to antigen injection suppressed the PCA reaction, as compared with control (p < 0.01). Intravenous administration of BSHE (C3G content, 5.4%) more strongly inhibited PCA responses at lower doses (100 mg/kg, p < 0.01) than oral administration (1,000 mg/kg, p = 0.059). Intravenous C3G also suppressed PCA response at a low dose (40 mg/kg, p < 0.05), showing the same trend as BSHE. This information can be useful to design appropriate formulations of anthocyanin-based drug products to suppress allergic reactions. This study provides evidence for the potential use of BSHE and C3G for the prevention or the treatment of type I allergies.
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Affiliation(s)
- Miki Hiemori-Kondo
- Department of Food Nutritional Science, Tokushima Bunri University, 180 Nishihama, Yamashiro, Tokushima 770-8514, Japan; Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
| | - Etsuko Morikawa
- Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan
| | - Michiko Fujikura
- Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan
| | - Ayuko Nagayasu
- Department of Nutritional Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan
| | - Yuuki Maekawa
- Department of Food Nutritional Science, Tokushima Bunri University, 180 Nishihama, Yamashiro, Tokushima 770-8514, Japan
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Yang H, Tuo X, Wang L, Tundis R, Portillo MP, Simal-Gandara J, Yu Y, Zou L, Xiao J, Deng J. Bioactive procyanidins from dietary sources: The relationship between bioactivity and polymerization degree. Trends Food Sci Technol 2021; 111:114-127. [DOI: 10.1016/j.tifs.2021.02.063] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Yamashita Y, Sakakibara H, Toda T, Ashida H. Insights into the potential benefits of black soybean ( Glycine max L.) polyphenols in lifestyle diseases. Food Funct 2020; 11:7321-7339. [PMID: 32852022 DOI: 10.1039/d0fo01092h] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Black soybean (Glycine max L.), a cultivar containing abundant polyphenols in its seed coat such as anthocyanins and flavan-3-ols, has been reported to possess various health benefits toward lifestyle diseases. In this review article, the safety evaluation of polyphenol-rich black soybean seed coat extract (BE) and absorption of BE polyphenols are summarized. Additionally, we describe the antioxidant activity of BE polyphenols and their ability to induce antioxidant enzymes. The health benefits of BE and its polyphenols, such as anti-obesity and anti-hyperglycemic activities through the activation of AMP-activated protein kinase and translocation of glucose transporter 4, respectively, are also discussed. Furthermore, we found that black soybean polyphenols were involved in the improvement of vascular function. These emerging data require further investigation in scientific studies and human trials to evaluate the prevention of lifestyle diseases using black soybean polyphenols.
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Affiliation(s)
- Yoko Yamashita
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
| | | | - Toshiya Toda
- Department of Innovative Food Sciences, School of Food Sciences and Nutrition, Mukogawa Women's University, Nishinomiya 663-8558, Japan
| | - Hitoshi Ashida
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
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Casanova LM, Rodrigues LM, de Aguiar PF, Tinoco LW. An NMR-Based Chemometric Strategy to Identify Leishmania donovani Nucleoside Hydrolase Inhibitors from the Brazilian Tree Ormosia arborea. JOURNAL OF NATURAL PRODUCTS 2020; 83:243-254. [PMID: 31985226 DOI: 10.1021/acs.jnatprod.9b00622] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Nucleoside hydrolases are a strategic target for the development of drugs to treat leishmaniasis, a neglected disease that affects 700 thousand to one million people annually. The present study aimed to identify Leishmania donovani nucleoside hydrolase (LdNH) inhibitors from the leaves of Ormosia arborea, a tree endemic to Brazilian ecosystems, through a strategy based on 1H NMR analyses and chemometrics. The aqueous EtOH extract of O. arborea leaves inhibited LdNH activity by 95%. The extract was fractionated in triplicate (13 in each step, making a total of 39 fractions). Partial least squares discriminant analysis (PLS-DA) was used to correlate the 1H NMR spectra of the fractions with their LdNH inhibitory activity and thus to identify the spectral regions associated with the bioactivity. The strategy aimed at isolating the probable bioactive substances and led to two new A-type proanthocyanidins, linked to a p-coumaroyl unit (1 and 2), which appeared as noncompetitive inhibitors of LdNH (IC50: 28.2 ± 3.0 μM and 25.6 ± 4.1 μM, respectively). This study confirms the usefulness of the NMR-based chemometric methods to accelerate the discovery of drugs from natural products.
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Affiliation(s)
- Livia Marques Casanova
- Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil
| | - Luanna Monteiro Rodrigues
- Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil
| | - Paula Fernandes de Aguiar
- Departamento de Química Analítica, Instituto de Química, Centro de Ciências Matemáticas e da Natureza, Cidade Universitária , Universidade Federal do Rio de Janeiro , 21941-909 Rio de Janeiro , RJ , Brazil
| | - Luzineide Wanderley Tinoco
- Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Sau'de, Cidade Universita'ria , Universidade Federal do Rio de Janeiro , 21941-902 Rio de Janeiro , RJ , Brazil
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16
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Domae C, Nanba F, Maruo T, Suzuki T, Ashida H, Yamashita Y. Black soybean seed coat polyphenols promote nitric oxide production in the aorta through glucagon-like peptide-1 secretion from the intestinal cells. Food Funct 2019; 10:7875-7882. [PMID: 31746899 DOI: 10.1039/c9fo02050k] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Black soybean seed coat polyphenols were reported to possess various bioregulatory functions. However, the effects of black soybean seed coat polyphenols on vascular functions are unknown. Vascular dysfunction caused by aging and vascular stiffness is associated with a risk of cardiovascular disease (CVD), and a reduction in nitric oxide (NO) levels can trigger the onset of CVD. In the present study, we investigated the effect of polyphenol-rich black soybean seed coat extract (BE) on vascular functions and the underlying mechanisms involved. The oral administration of BE at 50 mg per kg body weight to Wistar rats increased NO levels as determined by eNOS phosphorylation. The administration of BE also increased GLP-1 and cAMP levels. Furthermore, the effects of BE were inhibited in the presence of a GLP-1 receptor antagonist. This suggests that GLP-1 is strongly involved in the underlying mechanism of NO production in vivo. In conclusion, BE contributes to the improvement of vascular functions by promoting NO production. Regarding the putative underlying mechanism, GLP-1 secreted from intestinal cells by the polyphenols in BE activates eNOS in vascular endothelial cells.
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Affiliation(s)
- Chiaki Domae
- Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Nada-ku, Kobe, Hyogo 657-8501, Japan.
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Sun P, Li K, Wang T, Ji J, Wang Y, Chen KX, Jia Q, Li YM, Wang HY. Procyanidin C1, a Component of Cinnamon Extracts, Is a Potential Insulin Sensitizer That Targets Adipocytes. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:8839-8846. [PMID: 31334651 DOI: 10.1021/acs.jafc.9b02932] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Natural products are one of the main sources for discovering new lead compounds. We previously reported that cinnamon extract has a promising effect in regulating lipid tissue volume and insulin sensitivity in vivo. However, its effective component and the underlying mechanism are not known. In the present study, we analyzed the effect of different components of cinnamon on regulating insulin sensitivity in 3T3-L1 adipocytes. Functional assay revealed that, of the six major components of cinnamon extracts, the B-type procyanidin, procyanidin C1, improves the differentiation of 3T3-L1 cells (TG content: 1.10 ± 0.09 mM at a dosage of 25 μM vs 0.67 ± 0.02 mM in vehicle group, p < 0.001) and promotes insulin-induced glucose uptake (8.58 ± 1.43 at a dosage of 25 μM vs 3.05 ± 1.24 in vehicle group, p < 0.001). Mechanism studies further suggested that procyanidin C1 activates the AKT-eNOS pathway, thus up-regulating glucose uptake and enhancing insulin sensitivity in mature adipocytes. Taken together, our study identified B-type procyanidin C1, a component of cinnamon extract, that stimulates preadipocyte differentiation and acts as a potential insulin action enhancer through the AKT-eNOS pathway in mature adipocytes.
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Affiliation(s)
- Peng Sun
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China
- Key Laboratory of Human Functional Genomics of Jiangsu Province , Nanjing Medical University , Nanjing 211166 , China
| | - Kai Li
- Key Laboratory of Human Functional Genomics of Jiangsu Province , Nanjing Medical University , Nanjing 211166 , China
| | - Ting Wang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China
| | - Jun Ji
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China
| | - Yan Wang
- Key Laboratory of Human Functional Genomics of Jiangsu Province , Nanjing Medical University , Nanjing 211166 , China
| | - Kai-Xian Chen
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China
- School of Pharmacy , Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road , Shanghai 201203 , China
| | - Qi Jia
- School of Pharmacy , Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road , Shanghai 201203 , China
| | - Yi-Ming Li
- School of Pharmacy , Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road , Shanghai 201203 , China
| | - He-Yao Wang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road , Shanghai 201203 , China
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18
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Tian Y, Yang C, Yao Q, Qian L, Liu J, Xie X, Ma W, Nie X, Lai B, Xiao L, Wang N. Procyanidin B2 Activates PPARγ to Induce M2 Polarization in Mouse Macrophages. Front Immunol 2019; 10:1895. [PMID: 31440258 PMCID: PMC6693435 DOI: 10.3389/fimmu.2019.01895] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 07/26/2019] [Indexed: 11/13/2022] Open
Abstract
Procyanidins, a subclass of flavonoids found in commonly consumed foods, possess potential anti-inflammatory activity. Manipulation of M1/M2 macrophage homeostasis is an effective strategy for the treatment of metabolic inflammatory diseases. The objective of this study was to determine the effect of procyanidins on macrophage polarization. Procyanidin B2 (PCB2), the most widely distributed natural procyanidins, enhanced the expressions of M2 macrophage markers (Arg1, Ym1, and Fizz1). PCB2 activated peroxisome proliferator-activated receptor γ (PPARγ) activity and increased the expressions of PPARγ target genes (CD36 and ABCG1) in macrophages. Inhibition of PPARγ using siRNA or antagonist GW9662 attenuated the PCB2-induced expressions of M2 macrophage markers. In addition, we identified cognate PPAR-responsive elements (PPREs) within the 5'-flanking regions of the mouse Arg1, Ym1, and Fizz1 genes. Furthermore, macrophages isolated from db/db diabetic mice showed lower expressions of M2 markers. PCB2 effectively restored the Arg1, Ym1, and Fizz1 expressions in a PPARγ-dependent manner. These findings support the notion that PCB2 regulated macrophage M2 polarization via the activation of PPARγ. Our results provide a new mechanism by which procyanidins exert their beneficial anti-inflammatory effects.
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Affiliation(s)
- Ying Tian
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Chunmiao Yang
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Qinyu Yao
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Lei Qian
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Jia Liu
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Xinya Xie
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Wen Ma
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Xin Nie
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
| | - Baochang Lai
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Lei Xiao
- Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China
| | - Nanping Wang
- The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.,College of Basic Medical Sciences, Dalian Medical University, Dalian, China
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Peng J, Jia Y, Hu T, Du J, Wang Y, Cheng B, Li K. GC-(4→8)-GCG, A Proanthocyanidin Dimer from Camellia ptilophylla, Modulates Obesity and Adipose Tissue Inflammation in High-Fat Diet Induced Obese Mice. Mol Nutr Food Res 2019; 63:e1900082. [PMID: 30893514 DOI: 10.1002/mnfr.201900082] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 02/25/2019] [Indexed: 12/22/2022]
Abstract
SCOPE Excessive fat accumulation in adipose tissue leads to obesity and related chronic inflammation. This study aims to examine the effects of gallocatechin -(4→8)-gallocatechin-3-O-gallate (GC-(4→8)-GCG), a main proanthocyanidin dimer from Camellia ptilophylla (Cocoa tea), on adipocyte- and adipose-related inflammation in vivo and in vitro. METHODS AND RESULTS C57BL/6 mice are fed a high-fat diet (HFD) and GC-(4→8)-GCG (40 or 80 mg kg-1 d-1 ) for 8 weeks. The metabolic profiles, adipose tissue hypertrophy, macrophage infiltration, and inflammatory cytokine production are investigated. Additionally, 3T3-L1 preadipocytes are utilized to investigate the effect of GC-(4→8)-GCG on preadipocyte differentiation and the tumor necrosis factor (TNF)-α-stimulated inflammatory response in vitro. GC-(4→8)-GCG supplementation decreases HFD-induced epididymal white adipose tissue (eWAT) hypertrophy, suppresses proinflammatory cytokine production and macrophage infiltration in eWAT, and improves insulin sensitivity in HFD-induced obese mice. In vitro, GC-(4→8)-GCG shows a strong anti-adipogenic potential in 3T3-L1 preadipocyte by inhibiting the expression of key adipogenic transcription factors and decreasing the production of proinflammatory cytokines by inhibiting the activation of the nuclear factor (NF)-κB, Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT3) and mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSION GC-(4→8)-GCG can modulate obesity and improve obesity-related insulin resistance by inhibiting preadipocyte differentiation and the related proinflammatory responses.
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Affiliation(s)
- Jinming Peng
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yan Jia
- Beijing Key Lab of Plant Resource Research and Development, School of Science, Beijing Technology and Business University, Beijing, 100048, China
| | - Tianyong Hu
- Shenzhen Key Laboratory of ENT, Longgang ENT Hospital and Institute of ENT, Shenzhen, 518172, China
| | - Jing Du
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yue Wang
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Baohui Cheng
- Shenzhen Key Laboratory of ENT, Longgang ENT Hospital and Institute of ENT, Shenzhen, 518172, China
| | - Kaikai Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.,Key Laboratory of Environment Correlative Food Science (Huazhong Agricultural University), Ministry of Education, Wuhan, 430070, China
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Xing YW, Lei GT, Wu QH, Jiang Y, Huang MX. Procyanidin B2 protects against diet-induced obesity and non-alcoholic fatty liver disease via the modulation of the gut microbiota in rabbits. World J Gastroenterol 2019; 25:955-966. [PMID: 30833801 PMCID: PMC6397725 DOI: 10.3748/wjg.v25.i8.955] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/25/2019] [Accepted: 01/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity, but the mechanisms underlying these effects are unclear.
AIM To investigate the effects of procyanidin B2 (PB2) on non-alcoholic fatty liver disease and to explore the possible mechanism.
METHODS Thirty male New Zealand white rabbits were randomized into three groups. All of them were fed either a high-fat-cholesterol diet (HCD) or chow diet. HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk. Body weight and food intake were evaluated once a week. Serum biomarkers, such as total cholesterols, triglycerides, and aspartate transaminase, were detected. All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections. Moreover, several lipogenic genes and gut microbiota (by 16S rRNA sequencing) were investigated to explore the possible mechanism.
RESULTS The HCD group had higher body weight, liver index, serum lipid profile, insulin resistance, serum glucose, and hepatic steatosis compared to the CHOW group. PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver. PB2 also ameliorated low-grade inflammation, which was reflected by serum lipopolysaccharides and improved insulin resistance. In rabbit liver, PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase, compared to the HCD group. Moreover, HCD led to a decrease of Bacteroidetes in gut microbiota. PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.
CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.
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Affiliation(s)
- Ya-Wei Xing
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Guang-Tao Lei
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Qing-Hua Wu
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yu Jiang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Man-Xiang Huang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Cacao liquor procyanidins prevent postprandial hyperglycaemia by increasing glucagon-like peptide-1 activity and AMP-activated protein kinase in mice. J Nutr Sci 2019; 8:e2. [PMID: 30719284 PMCID: PMC6344835 DOI: 10.1017/jns.2018.28] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 11/13/2018] [Accepted: 11/30/2018] [Indexed: 12/20/2022] Open
Abstract
Procyanidins have been reported to possess potential for the prevention of hyperglycaemia. However, there are very few data for procyanidins about the difference the degree of polymerisation (DP) has on anti-hyperglycaemic effects. Moreover, the underlying molecular mechanisms by which procyanidins suppress hyperglycaemia are not yet fully understood. In the present study, we prepared procyanidin fractions with different DP, namely low-DP (DP≤3) and high-DP (DP≥4) fractions, from a cacao liquor procyanidin-rich extract (CLPr). These fractions were administered orally to Institute of Cancer Research (ICR) mice and their anti-hyperglycaemic effects were examined. We found that CLPr and its fractions prevent postprandial hyperglycaemia accompanied by an increase in the plasma glucagon-like peptide-1 (GLP-1) level with or without glucose load. In the absence of glucose load, both fractions increased the plasma insulin level and activated its downstream signalling pathway in skeletal muscle, resulting in promotion of the translocation of GLUT4. Phosphorylation of AMP-activated protein kinase (AMPK) was also involved in the promotion of GLUT4 translocation. High- and low-DP fractions showed a similar activation of insulin and AMPK pathways. In conclusion, cacao liquor procyanidins prevent hyperglycaemia by promoting GLUT4 translocation in skeletal muscle, and both the GLP-1-activated insulin pathway and the AMPK pathway are involved in the underlying molecular mechanism.
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