Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Xiao-Long Hu; Ya-Jun Niu; Mi Chen; Jia-Hao Feng; Wei Shen; Zhen-Zhou Jiang; Xiao-Qi Zhang; Wen-Cai Ye; Fei Xiong; Hao Wang

doi:10.1055/a-0895-5838

Planta Medica, Table of Contents

Planta Med 2019; 85(08): 678-688
DOI: 10.1055/a-0895-5838

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Preventive Effects of Total Flavonoid C-Glycosides from Abrus mollis on Nonalcoholic Fatty Liver Disease through Activating the PPARα Signaling Pathway

Xiao-Long Hu^*

¹State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Ya-Jun Niu^*

¹State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Mi Chen

²Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Jia-Hao Feng

¹State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Wei Shen

¹State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Zhen-Zhou Jiang

²Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

,

Xiao-Qi Zhang

⁴Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Peopleʼs Republic of China

,

Wen-Cai Ye

⁴Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Peopleʼs Republic of China

,

Fei Xiong

³State Key Laboratory of Bioelectronics, Jiangsu Laboratory for Biomaterials and Devices, Southeast University, Nanjing, Peopleʼs Republic of China

,

Hao Wang

¹State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Peopleʼs Republic of China

› Author Affiliations

Abstract

Abrus pulchellus subsp. mollis (Hance) Verdc. (Leguminosae) is a well-known edible plant usually added to soups and beverages. In this study, vicenin-2 (1), isoschaftoside (2), schaftoside (3), and their enrichment fraction, total flavonoid C-glycosides, derived from the extracts of A. mollis, were firstly found to prevent nonalcoholic fatty liver disease both in vitro and in vivo. In the in vitro study, total flavonoid C-glycosides decreased the lipid accumulation in oleic acid-treated HepG2 cells. The mechanisms of total flavonoid C-glycosides are involved in the regulation of peroxisome proliferator-activated receptor α and its downstream, and the reduction of proinflammatory cytokines. In high-fat diet-induced fatty liver rats, total flavonoid C-glycosides decreased the levels of glutamic-oxalacetic transaminease and glutamic-pyruvic transaminase, and decreased the lipid accumulation both in the liver and blood without affecting food intake. In addition, total flavonoid C-glycosides also increased the activities of the antioxidant enzyme system in vivo. In conclusion, total flavonoid C-glycosides are active components of A. mollis on nonalcoholic fatty liver disease, and can be used in functional food and supplements for nonalcoholic fatty liver disease prevention and treatment.

Key words

Nonalcoholic fatty liver disease - Abrus pulchellus subsp. mollis - total flavonoid C-glycosides - high-fat diet - PPARα

Full Text

References

References
1 Allen AM, Therneau TM, Larson JJ, Coward A, Somers VK, Kamath PS. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year-community study. Hepatology 2018; 67: 1726-1736
2 Stankovic MN, Mladenovic DR, Duricic I, Sobajic SS, Timic J, Jorgacevic B, Aleksic V, Vucevic DB, Jesic-Vukicevic R, Radosavljevic TS. Time-dependent changes and association between liver free fatty acids, serum lipid profile and histological features in mice model of nonalcoholic fatty liver disease. Arch Med Res 2014; 45: 116-124
3 Cobbina E, Akhlaghi F. Non-alcoholic fatty liver disease (NAFLD) – pathogenesis, classification, and effect on drug metabolizing enzymes and transporters. Drug Metab Rev 2017; 49: 197-211
4 Henao-Mejia J, Elinav E, Jin CC, Hao LM, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482: 179-185
5 Serviddio G, Sastre J, Bellanti F, Vina J, Vendemiale G, Altomare E. Mitochondrial involvement in non-alcoholic steatohepatitis. Mol Aspects Med 2008; 29: 22-35
6 Zheng H, Li Z, Mu R. The research progress of the pharmacological effects of traditional Chinese medicine Abrus cantoniensis Hance. Chinaʼs Foreign Trade 2011; 12: 380
7 Miyao H, Sakai Y, Takeshita T, Ito Y, Kinjo J, Nohara T. Triterpene saponins from Abrus cantoniensis (Leguminosae). II. Characterization of six new saponins having a branched-chain sugar. Chem Pharm Bull 1996; 44: 1228-1231
8 Yan WY, Han QJ, Guo PP, Wang CY, Zhang ZJ. Simultaneous detection of flavonoids, phenolic acids and alkaloids in Abri herba and Abri mollis herba using liquid chromatography tandem mass spectrometry. Phytochem Analysis 2016; 27: 50-56
9 Xiao BD. Ling Nan Cai Yao Lu (Collection of Drugs in South of the Five Ridges of China). 1st edition. Guangzhou: Guangzhou Sinence Press; 2009: 80
10 Committee of National Pharmacopoeia. Pharmacopoeia of P.R. China. Beijing: Chemical Industry Press; 2000: 151-152
11 Xie MJ, Li AR, Liu RX, Huang KW, Wu F, Li CQ. Effects of Abrus mollis Hance on non-alcoholic fatty liver by different extraction methods. Pharm Today 2017; 27: 444-447
12 Du HB, Wang H, Yu J, Liang CY, Ye WC, Li P. Enrichment and purification of total flavonoid C-glycosides from Abrus mollis extracts with macroporous resins. Ind Eng Chem Res 2012; 51: 7349-7354
13 Chen M, Wang T, Jiang ZZ, Shan C, Wang H, Wu MJ, Zhang S, Zhang Y, Zhang LY. Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts. Chin J Nat Med 2014; 12: 590-598
14 Beaton MD. Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Can J Gastroenterol 2012; 26: 353-357
15 Food and Drug Administration. Guidance for Industry. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Silver Spring: Food and Drug Administration; 2005
16 Araya J, Rodrigo R, Videla LA, Thielemann L, Orellana M, Pettinelli P, Poniachik J. Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin Sci (Lond) 2004; 106: 635-643
17 Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha J, Park OJ. Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 2005; 338: 694-699
18 Rakhshandehroo M, Knoch B, Muller M, Kersten S. Peroxisome proliferator-activated receptor alpha target genes. PPAR Res 2010; 2010: 612089
19 Tailleux A, Wouters K, Staels B. Roles of PPARs in NAFLD: potential therapeutic targets. Biochim Biophys Acta 2012; 1821: 809-818
20 Rocchi S, Auwerx J. Peroxisome proliferator-activated receptor gamma, the ultimate liaison between fat and transcription. Br J Nutr 2000; 84: S223-S227
21 Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radical Bio Med 2012; 52: 59-69
22 Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231
23 Byrne CD, Olufadi R, Bruce KD, Cagampang FR, Ahmed MH. Metabolic disturbances in non-alcoholic fatty liver disease. Clin Sci (Lond) 2009; 116: 539-564
24 Higuchi N, Kato M, Tanaka M, Miyazaki M, Takao S, Kohjima M, Kotoh K, Enjoji M, Nakamuta M, Takayanagi R. Effects of insulin resistance and hepatic lipid accumulation on hepatic mRNA expression levels of apoB, MTP and L-FABP in non-alcoholic fatty liver disease. Exp Ther Med 2011; 2: 1077-1081
25 Patel RS, Scopelliti EM, Savelloni J. Therapeutic management of familial hypercholesterolemia: current and emerging drug therapies. Pharmacotherapy 2015; 35: 1189-1203
26 Zhou X, Han D, Xu R, Wu H, Qu C, Wang F, Wang X, Zhao Y. Glycine protects against high sucrose and high fat-induced non-alcoholic steatohepatitis in rats. Oncotarget 2016; 7: 80223-80237
27 Wang DD, Lao LL, Pang XH, Qiao Q, Pang LJ, Feng ZW, Bai FC, Sun XM, Lin X, Wei JB. Asiatic acid from Potentilla chinensis alleviates non-alcoholic fatty liver by regulating endoplasmic reticulum stress and lipid metabolism. Int Immunopharmacol 2018; 65: 256-267
28 Feng XJ, Yu W, Li XD, Zhou FF, Zhang WL, Shen Q, Li JX, Zhang C, Shen PP. Apigenin, a modulator of PPAR gamma, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation. Biochem Pharmacol 2017; 136: 136-149
29 Izdebska M, Piatkowska-Chmiel I, Korolczuk A, Herbet M, Gawronska-Grzywacz M, Gieroba R, Sysa M, Czajkowska-Bania K, Cygal M, Korga A, Dudka J. The beneficial effects of resveratrol on steatosis and mitochondrial oxidative stress in HepG2 cells. Can J Physiol Pharm 2017; 95: 1442-1453
30 Liu ZW, Que ZL, Ye ZW, Zhang XQ, Wang H, Ye WC, Zhao SX. Chemical constituents from the aerial parts of Abrus mollis . Chin J Nat Med 2008; 6: 415
31 Wang Y, Jiang ZZ, Chen M, Wu MJ, Guo HL, Sun LX, Wang H, Zhang S, Wang T, Zhang LY. Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice. Chin J Nat Med 2014; 12: 461-468
32 Wei JB, Huang QF, Huang RB, Chen YX, Lv SJ, Wei L, Liang CH, Liang S, Zhuo L, Lin X. Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and kupffer cell activation. Biol Pharm Bull 2013; 36: 1980-1989