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Published in: BMC Complementary Medicine and Therapies 1/2022

Open Access 01-12-2022 | Obesity | Research

Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats

Authors: Man Wang, Xufang Geng, Kaipeng Li, Yawen Wang, Xiaofeng Duan, Congcong Hou, Lili Zhao, Huimin Zhou, Ding Zhao

Published in: BMC Complementary Medicine and Therapies | Issue 1/2022

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Abstract

Background

Berberine (BBR) has been found to have antiobesity effects, and obesity can lead to adipose tissue degeneration. As a special adipose tissue, perivascular adipose tissue (PVAT) is closely related to vascular function and affects vasoconstriction and relaxation. What happens to PVAT in the early stages of diet-induced obesity and how BBR affects vascular function is the focus of our experimental study.

Methods

Sprague–Dawley rats were fed a high-fat diet (fat 34% kcal) for 4 weeks to simulate early obesity. Obese rats were treated with BBR (200 mg/kg) or metformin (MET, 100 mg/kg) by gavage for 2 weeks. The mesenteric arterioles were studied by atomic force microscopy (AFM). The force vs. time curves were observed and analysed to indicate vascular function. Nitric oxide (NO) and noradrenaline (NA) release was quantified using an organ bath with fluorescence assays and ELISA, respectively. Network pharmacology was used to analyse the overlapping targets related to BBR and obesity-related diseases, and the expression of NOS in mesenteric PVAT was further analysed with immunohistochemistry and real-time PCR. The serum inflammatory factor levels were tested.

Results

BBR significantly reduced the levels of blood glucose, blood lipids and inflammatory factors in serum. It also effectively improved abnormal mesenteric vasoconstriction and relaxation in obese rats. There was no significant change in mesenteric vascular structure, but NO production and eNOS expression were significantly increased in mesenteric PVAT (P < 0.01), and NA was decreased (P < 0.05) in obese rats. All these changes in the mesenteric arterioles and PVAT of obese rats were reversed by treatment with BBR and MET.

Conclusions

In diet-induced obesity in rats, the function of vasoconstriction and relaxation in mesenteric arterioles is altered, NO is increased, and NA is decreased in mesenteric PVAT. All these changes were reversed by BBR, suggesting a novel effect of BBR in ameliorating mesenteric vascular dysfunction by regulating PVAT.
Literature
1.
go back to reference Stanek A, Brozyna-Tkaczyk K, Myslinski W. The role of obesity-induced Perivascular Adipose Tissue (PVAT) dysfunction in vascular homeostasis. Nutrients. 2021;13(11):3843.CrossRef Stanek A, Brozyna-Tkaczyk K, Myslinski W. The role of obesity-induced Perivascular Adipose Tissue (PVAT) dysfunction in vascular homeostasis. Nutrients. 2021;13(11):3843.CrossRef
2.
go back to reference Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, Kaptoge S, Whitlock G, Qiao Q, Lewington S, et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS ONE. 2013;8(7): e65174.CrossRef Singh GM, Danaei G, Farzadfar F, Stevens GA, Woodward M, Wormser D, Kaptoge S, Whitlock G, Qiao Q, Lewington S, et al. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS ONE. 2013;8(7): e65174.CrossRef
3.
go back to reference Szasz T, Bomfim GF, Webb RC. The influence of perivascular adipose tissue on vascular homeostasis. Vasc Health Risk Manag. 2013;9:105–16.CrossRef Szasz T, Bomfim GF, Webb RC. The influence of perivascular adipose tissue on vascular homeostasis. Vasc Health Risk Manag. 2013;9:105–16.CrossRef
4.
go back to reference Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A. 1991;13(2):277–96.PubMed Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A. 1991;13(2):277–96.PubMed
5.
go back to reference Coffey JC, O’Leary DP. The mesentery: structure, function, and role in disease. Lancet Gastroenterol Hepatol. 2016;1(3):238–47.CrossRef Coffey JC, O’Leary DP. The mesentery: structure, function, and role in disease. Lancet Gastroenterol Hepatol. 2016;1(3):238–47.CrossRef
6.
go back to reference Geng X. The effects of early diabetes on small blood vessels and the surroundings and the improvement of berberine in rats Hebei Medical University. 2020. Geng X. The effects of early diabetes on small blood vessels and the surroundings and the improvement of berberine in rats Hebei Medical University. 2020.
7.
go back to reference Gil-Ortega M, Stucchi P, Guzman-Ruiz R, Cano V, Arribas S, Gonzalez MC, Ruiz-Gayo M, Fernandez-Alfonso MS, Somoza B. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. Endocrinology. 2010;151(7):3299–306.CrossRef Gil-Ortega M, Stucchi P, Guzman-Ruiz R, Cano V, Arribas S, Gonzalez MC, Ruiz-Gayo M, Fernandez-Alfonso MS, Somoza B. Adaptative nitric oxide overproduction in perivascular adipose tissue during early diet-induced obesity. Endocrinology. 2010;151(7):3299–306.CrossRef
8.
go back to reference Xia X, Wang H, Niu X, Wang H, Liu Z, Liu Y, Qi Z, Wang S, Liu S, Liu S. Assessment of the anti-diarrhea function of compound Chinese herbal medicine Cangpo Oral Liquid. Afr J Tradit Complement Altern Med. 2014;11(1):140–7.PubMed Xia X, Wang H, Niu X, Wang H, Liu Z, Liu Y, Qi Z, Wang S, Liu S, Liu S. Assessment of the anti-diarrhea function of compound Chinese herbal medicine Cangpo Oral Liquid. Afr J Tradit Complement Altern Med. 2014;11(1):140–7.PubMed
9.
go back to reference Chang Y. Effectiveness of berberine in bacillary dysentery. Zhonghua Nei Ke Za Zhi. 1959;7:741–3.PubMed Chang Y. Effectiveness of berberine in bacillary dysentery. Zhonghua Nei Ke Za Zhi. 1959;7:741–3.PubMed
10.
go back to reference Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015;243(2):449–61.CrossRef Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015;243(2):449–61.CrossRef
11.
go back to reference Zhang Z, Zhang H, Li B, Meng X, Wang J, Zhang Y, Yao S, Ma Q, Jin L, Yang J, et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun. 2014;5:5493.CrossRef Zhang Z, Zhang H, Li B, Meng X, Wang J, Zhang Y, Yao S, Ma Q, Jin L, Yang J, et al. Berberine activates thermogenesis in white and brown adipose tissue. Nat Commun. 2014;5:5493.CrossRef
12.
go back to reference Ma X, Chen Z, Wang L, Wang G, Wang Z, Dong X, Wen B, Zhang Z. The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its Inhibition by Berberine. Front Pharmacol. 2018;9:782.CrossRef Ma X, Chen Z, Wang L, Wang G, Wang Z, Dong X, Wen B, Zhang Z. The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its Inhibition by Berberine. Front Pharmacol. 2018;9:782.CrossRef
13.
go back to reference Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H, Lau CW, Vanhoutte PM, Xu A. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res. 2009;82(3):484–92.CrossRef Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H, Lau CW, Vanhoutte PM, Xu A. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc Res. 2009;82(3):484–92.CrossRef
14.
go back to reference Hou CC, Liang HY, Pan YH, Wang M, Zhao LL, Bian Y, Cao DY, Zhao D. Vanadium compounds induced damage of human umbilical vein endothelial cells and the protective effect of berberine. Biometals. 2019;32(5):785–94.CrossRef Hou CC, Liang HY, Pan YH, Wang M, Zhao LL, Bian Y, Cao DY, Zhao D. Vanadium compounds induced damage of human umbilical vein endothelial cells and the protective effect of berberine. Biometals. 2019;32(5):785–94.CrossRef
15.
go back to reference Zhao L, Liu S, Wang M, Zhi M, Geng X, Hou C, Wang W, Zhao D. Berberine restored nitrergic and adrenergic function in mesenteric and iliac arteries from streptozotocin-induced diabetic rats. J Ethnopharmacol. 2019;244:112140.CrossRef Zhao L, Liu S, Wang M, Zhi M, Geng X, Hou C, Wang W, Zhao D. Berberine restored nitrergic and adrenergic function in mesenteric and iliac arteries from streptozotocin-induced diabetic rats. J Ethnopharmacol. 2019;244:112140.CrossRef
16.
go back to reference Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget. 2018;9(11):10135–46.CrossRef Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget. 2018;9(11):10135–46.CrossRef
17.
go back to reference Sambe T, Mason RP, Dawoud H, Bhatt DL, Malinski T. Metformin treatment decreases nitroxidative stress, restores nitric oxide bioavailability and endothelial function beyond glucose control. Biomed Pharmacother. 2018;98:149–56.CrossRef Sambe T, Mason RP, Dawoud H, Bhatt DL, Malinski T. Metformin treatment decreases nitroxidative stress, restores nitric oxide bioavailability and endothelial function beyond glucose control. Biomed Pharmacother. 2018;98:149–56.CrossRef
18.
go back to reference Wang L, Ye X, Hua Y, Song Y. Berberine alleviates adipose tissue fibrosis by inducing AMP-activated kinase signaling in high-fat diet-induced obese mice. Biomed Pharmacother. 2018;105:121–9.CrossRef Wang L, Ye X, Hua Y, Song Y. Berberine alleviates adipose tissue fibrosis by inducing AMP-activated kinase signaling in high-fat diet-induced obese mice. Biomed Pharmacother. 2018;105:121–9.CrossRef
19.
go back to reference Sung YY, Kim SH, Yoo BW, Kim HK. The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice. BMC Complement Altern Med. 2015;15:370.CrossRef Sung YY, Kim SH, Yoo BW, Kim HK. The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice. BMC Complement Altern Med. 2015;15:370.CrossRef
20.
go back to reference Cameron NE, Cotter MA, Low PA. Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol. 1991;261(1 Pt 1):E1-8.PubMed Cameron NE, Cotter MA, Low PA. Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol. 1991;261(1 Pt 1):E1-8.PubMed
21.
go back to reference Mu YM, Ji LN, Ning G, Li GW, Shan ZY, Li Y. Chinese experts consensus statement on Metformin in the clinical practice. Chin J Diabetes. 2016;24:871–84. Mu YM, Ji LN, Ning G, Li GW, Shan ZY, Li Y. Chinese experts consensus statement on Metformin in the clinical practice. Chin J Diabetes. 2016;24:871–84.
22.
go back to reference Liu Y, Feng J, Shi L, Niu R, Sun Q, Liu H, Li J, Guo J, Zhu J, Han D. In situ mechanical analysis of cardiomyocytes at nano scales. Nanoscale. 2012;4(1):99–102.CrossRef Liu Y, Feng J, Shi L, Niu R, Sun Q, Liu H, Li J, Guo J, Zhu J, Han D. In situ mechanical analysis of cardiomyocytes at nano scales. Nanoscale. 2012;4(1):99–102.CrossRef
23.
go back to reference Kihara M, Low PA. Impaired vasoreactivity to nitric oxide in experimental diabetic neuropathy. Exp Neurol. 1995;132(2):180–5.CrossRef Kihara M, Low PA. Impaired vasoreactivity to nitric oxide in experimental diabetic neuropathy. Exp Neurol. 1995;132(2):180–5.CrossRef
24.
go back to reference Armenis I, Kalotychou V, Tzanetea R, Kollia P, Kontogeorgiou Z, Anastasopoulou D, Mantzourani M, Samarkos M, Pantos K, Konstantopoulos K, et al. Data on eNOS T786 and G894T polymorphisms and peripheral blood eNOS mRNA levels in Sickle Cell Disease. Data Brief. 2017;10:192–7.CrossRef Armenis I, Kalotychou V, Tzanetea R, Kollia P, Kontogeorgiou Z, Anastasopoulou D, Mantzourani M, Samarkos M, Pantos K, Konstantopoulos K, et al. Data on eNOS T786 and G894T polymorphisms and peripheral blood eNOS mRNA levels in Sickle Cell Disease. Data Brief. 2017;10:192–7.CrossRef
25.
go back to reference Li HYYC. Lu KY,: A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema. Clin Hemorheol Microcirc. 2016;63(4):411–21.CrossRef Li HYYC. Lu KY,: A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema. Clin Hemorheol Microcirc. 2016;63(4):411–21.CrossRef
26.
go back to reference Rosen ED, Spiegelman BMJC. What We Talk About When We Talk About Fat. Cell. 2014;156(1–2):20–44.CrossRef Rosen ED, Spiegelman BMJC. What We Talk About When We Talk About Fat. Cell. 2014;156(1–2):20–44.CrossRef
27.
go back to reference Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, Louche K, Bourlier V, Roussel B, Gui P, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7(4):1116–29.CrossRef Vila IK, Badin PM, Marques MA, Monbrun L, Lefort C, Mir L, Louche K, Bourlier V, Roussel B, Gui P, et al. Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis. Cell Rep. 2014;7(4):1116–29.CrossRef
28.
go back to reference Luo T, Nocon A, Fry J, Sherban A, Rui X, Jiang B, Xu XJ, Han J, Yan Y, Yang Q, et al. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity. Diabetes. 2016;65(8):2295–310.CrossRef Luo T, Nocon A, Fry J, Sherban A, Rui X, Jiang B, Xu XJ, Han J, Yan Y, Yang Q, et al. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity. Diabetes. 2016;65(8):2295–310.CrossRef
29.
go back to reference Zhao D, McCully BH, Brooks VL. Rosiglitazone improves insulin sensitivity and baroreflex gain in rats with diet-induced obesity. J Pharmacol Exp Ther. 2012;343(1):206–13.CrossRef Zhao D, McCully BH, Brooks VL. Rosiglitazone improves insulin sensitivity and baroreflex gain in rats with diet-induced obesity. J Pharmacol Exp Ther. 2012;343(1):206–13.CrossRef
30.
go back to reference Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator. Circ Res. 2016;119(2):375–96.CrossRef Vanhoutte PM, Zhao Y, Xu A, Leung SW. Thirty Years of Saying NO: Sources, Fate, Actions, and Misfortunes of the Endothelium-Derived Vasodilator Mediator. Circ Res. 2016;119(2):375–96.CrossRef
31.
go back to reference Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, Pemberton PW, Ammori B, Malik RA, Soran H, et al. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol. 2013;62(2):128–35.CrossRef Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, Pemberton PW, Ammori B, Malik RA, Soran H, et al. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. J Am Coll Cardiol. 2013;62(2):128–35.CrossRef
32.
go back to reference Elizalde M, Ryden M, van Harmelen V, Eneroth P, Gyllenhammar H, Holm C, Ramel S, Olund A, Arner P, Andersson K. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res. 2000;41(8):1244–51.CrossRef Elizalde M, Ryden M, van Harmelen V, Eneroth P, Gyllenhammar H, Holm C, Ramel S, Olund A, Arner P, Andersson K. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res. 2000;41(8):1244–51.CrossRef
33.
go back to reference Tanaka T, Nakatani K, Morioka K, Urakawa H, Maruyama N, Kitagawa N, Katsuki A, Araki-Sasaki R, Hori Y, Gabazza EC, et al. Nitric oxide stimulates glucose transport through insulin-independent GLUT4 translocation in 3T3-L1 adipocytes. Eur J Endocrinol. 2003;149(1):61–7.CrossRef Tanaka T, Nakatani K, Morioka K, Urakawa H, Maruyama N, Kitagawa N, Katsuki A, Araki-Sasaki R, Hori Y, Gabazza EC, et al. Nitric oxide stimulates glucose transport through insulin-independent GLUT4 translocation in 3T3-L1 adipocytes. Eur J Endocrinol. 2003;149(1):61–7.CrossRef
34.
go back to reference Wang C, Li J, Lv X, Zhang M, Song Y, Chen L, Liu Y. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol. 2009;620(1–3):131–7.CrossRef Wang C, Li J, Lv X, Zhang M, Song Y, Chen L, Liu Y. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol. 2009;620(1–3):131–7.CrossRef
35.
go back to reference Bartness TJ, Bamshad M. Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. Am J Physiol. 1998;275(5):R1399-1411.PubMed Bartness TJ, Bamshad M. Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. Am J Physiol. 1998;275(5):R1399-1411.PubMed
36.
go back to reference Bowers RR, Festuccia WT, Song CK, Shi H, Migliorini RH, Bartness TJ. Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol. 2004;286(6):R1167-1175.CrossRef Bowers RR, Festuccia WT, Song CK, Shi H, Migliorini RH, Bartness TJ. Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol. 2004;286(6):R1167-1175.CrossRef
37.
go back to reference Ayala-Lopez N, Martini M, Jackson WF, Darios E, Burnett R, Seitz B, Fink GD, Watts SW. Perivascular adipose tissue contains functional catecholamines. Pharmacol Res Perspect. 2014;2(3):e00041.CrossRef Ayala-Lopez N, Martini M, Jackson WF, Darios E, Burnett R, Seitz B, Fink GD, Watts SW. Perivascular adipose tissue contains functional catecholamines. Pharmacol Res Perspect. 2014;2(3):e00041.CrossRef
38.
go back to reference Simpson DS, Pang J, Weir A, Kong IY, Fritsch M, Rashidi M, Cooney JP, Davidson KC, Speir M, Djajawi TM, et al. Interferon-gamma primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity. 2022;55(3):423-441 e429.CrossRef Simpson DS, Pang J, Weir A, Kong IY, Fritsch M, Rashidi M, Cooney JP, Davidson KC, Speir M, Djajawi TM, et al. Interferon-gamma primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity. 2022;55(3):423-441 e429.CrossRef
39.
go back to reference WANG Xy LC. LIU P, LI PF: Nitric oxide mediates brain injury induced by acute anoxia asphyxia in mice. Journal of Xinxiang Medical College. 2002;9:90–1. WANG Xy LC. LIU P, LI PF: Nitric oxide mediates brain injury induced by acute anoxia asphyxia in mice. Journal of Xinxiang Medical College. 2002;9:90–1.
40.
go back to reference Barp CG, Bonaventura D, Assreuy J. NO, ROS, RAS, and PVAT: more than a soup of letters. Front Physiol. 2021;12:640021.CrossRef Barp CG, Bonaventura D, Assreuy J. NO, ROS, RAS, and PVAT: more than a soup of letters. Front Physiol. 2021;12:640021.CrossRef
Metadata
Title
Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats
Authors
Man Wang
Xufang Geng
Kaipeng Li
Yawen Wang
Xiaofeng Duan
Congcong Hou
Lili Zhao
Huimin Zhou
Ding Zhao
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2022
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-022-03667-1

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