Effects of traditional Chinese medicine Chaihu-Shugan-San aqueous extract on high-fat diet-induced liver steatosis in rats via intestinal microbiota metabolite SCFAs and its receptor Gpr43/109a

다국어 초록 (Multilingual Abstract)

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in adults around China and the world. The study explores protective effect of traditional Chinese medicine Chaihu-Shugan-San decoction on high-fat diet-induced liver steatosis in rats via intestinal microbiota metabolite short-chain fatty acids (SCFAs) and its receptor Gpr43/109a. Fifteen male Sprague–Dawley rats were randomly divided into three groups of five rats each: the control group (standard diet), High-fat diet (HFD)-induced NAFLD group (83% standard diet + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and Chaihu-Shugan-San (CSS)-treated group (HFD + 9.6 g/kg body weight gastric administration of CSS decoction every day). Body composition, hepatic fat, intestinal mucosal permeability and SCFAs, Gpr43 and Gpr109a expression in colonic tissues were assessed. Compared with NAFLD group, CSS decoction significantly reduced body weight, liver weight, hepatic triglyceride and total cholesterol (P < 0.05), and increased colonic SCFAs and occludin expression.
The levels of Gpr43 and Gpr109a also changed significantly (P < 0.05). Protective effect of CSS decoction in HFD-induced NAFLD rats might improve intestinal mucosal permeability and intestinal microbiota metabolite SCFAs through Gpr43 and Gpr109a pathways in colonic tissues.

참고문헌 (Reference)

1 Liang Y, "Traditional Chinese Medicine and Intestinal Microbiota: A Complementary and Integrative Health Approach to Ameliorate Obesity-related Diseases" 2019

2 Zhang LD, "Systematic evaluation and meta analysis on nonalcoholic fatty liver disease treated with Chaihu Shugan San" 9 : 1004-1007, 2014

3 Donnelly KL, "Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease" 115 (115): 1343-1351, 2005

4 Willemsen LE, "Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1)and E(2)production by intestinal myofibroblasts" 52 : 1442-1447, 2003

5 Lu Y, "Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating g protein-coupled receptors and gut microbiota" 6 : 37589-, 2016

6 Wei Z, "Saikosaponin a inhibits LPSinduced inflammatory response by inducing liver X receptor alpha activation in primary mouse macrophages" 7 (7): 48995-49007, 2016

7 Lu CN, "Saikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of NF-kappaB signaling pathway" 14 (14): 121-126, 2012

8 Zhang L, "Paeoniflorin protects against nonalcoholic fatty liver disease induced by a high-fat diet in mice" 38 (38): 1005-1011, 2015

9 Cao W, "Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-alpha and IL-1beta release and augmentation of IL-10 production" 11 (11): 172-178, 2011

10 Ma Z, "Paeoniflorin alleviates non-alcoholic steatohepatitis in rats : Involvement with the ROCK/NF-kappaB pathway" 38 : 377-384, 2016

11 Byrne CD, "NAFLD: A multisystem disease" 62 (62): S47-S64, 2015

12 De VF, "Microbiotagenerated metabolites promote metabolic benefits via gut-brain neural circuits" 156 : 84-96, 2014

13 Macia L, "Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome" 6 : 6734-, 2015

14 Giorgio V, "Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity" 46 : 556-560, 2014

15 Giorgio V, "Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity" 46 (46): 556-560, 2014

16 Miele L, "Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease" 49 (49): 1877-1887, 2009

17 Hu ED, "High fiber dietary and sodium butyrate attenuate experimental autoimmune hepatitis through regulation of immune regulatory cells and intestinal barrier" 328 : 24-32, 2018

18 Mahmoud AM, "Hesperidin protects against cyclophosphamideinduced hepatotoxicity by upregulation of PPARgamma and abrogation of oxidative stress and inflammation" 92 (92): 717-724, 2014

19 Rotimi SO, "Hesperidin prevents lipopolysaccharide-induced endotoxicity in rats" 38 (38): 364-371, 2016

20 Younossi ZM, "Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes" 64 : 73-84, 2016

21 Naowaboot J, "Ferulic acid improves lipid and glucose homeostasis in high-fat diet-induced obese mice" 43 (43): 242-250, 2016

22 Gong XW, "Effects of soothing liver and invigorating spleen recipes on LPS-induced hepatocytes injury of rats and TLR4/p38MAPK signal pathway" 39 : 4027-4033, 2014

23 Cornall LM, "Dietinduced obesity up-regulates the abundance of GPR43 and GPR120 in a tissue specific manner" 28 : 949-958, 2011

24 Hudson BD, "Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor" 288 : 17296-17312, 2013

25 Hollander D, "Crohn’s disease–a permeability disorder of the tight junction?" 29 (29): 1621-1624, 1988

26 Pan C, "Clinical observation on the treatment of 82cases of non-alcoholic fatty liver disease" 20 (20): 2010-2011, 2009

27 Liang Y, "Chaihu-Shugan-San decoction modulates intestinal microbe dysbiosis and alleviates chronic metabolic inflammation in NAFLD Rats via the NLRP3 inflammasome pathway" 2018 : 9390786-, 2018

28 Schaefer K, "Analysis of short chain fatty acids from different intestinal samples by capillary gas chromatography" 40 : 550-556, 1995

29 Singh N, "Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis" 40 : 128-139, 2014

30 Singh N, "Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis" 40 (40): 128-139, 2014