Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS-cholesterol broth with ammonium ferric sulfate method. Male Sprague–Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7α-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR)-α protein was significantly increased while the expression of PPAR-γ and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up-regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up-regulating CYP7A1, LDL-R, FXR mRNA and PPAR-α protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-γ and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function.

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

“…Likewise, the gut microbiota composition could also contribute to the development of NAFLD independently of obesity [29]. It has been previously reported that feeding a high fat diet caused gut microbiota imbalance as a mechanism involved in obese-related NAFLD development, justifying the adequacy of the current study [38,39]. As expected, in our murine model of NAFLD metagenomic studies revealed differences at phylum, class and genus levels between HFD-fed mice and controls, leading to dysbiosis.…”

The PPAR–microbiota–metabolic organ trilogy to fine‐tune physiology

“…A few studies have indicated possible roles of the gut microbiota in influencing host energy metabolism through PPAR-a (204)(205)(206)(207)(208). It is now known that the gut microbiota responds to nutrient deprivation by augmenting the PPAR-a-dependent fatty acid oxidation and the hepatic production of ketone bodies via the PPAR-a-dependent ketogenesis pathway (205,209).…”

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…Adipose tissue releases cytokines to increase inflammation and fibrosis. Gut microbiota is also believed to play a role in the development of NASH via alterations in the BA pool level and composition (Jiang et al, 2015; Liu et al, 2016b; Mei et al, 2015; Wang et al, 2016). Recently, vitamin D deficiency has been proposed as another possible factor as mice fed a high fat diet (HFD) exhibited increased steatosis and hepatic ballooning when coupled with a vitamin D deficiency (Kong et al, 2014).…”