Ramulus mori (Sangzhi) alkaloids regulates gut microbiota disorder and its metabolism profiles in obese mice induced by a high-fat diet

Abstract

The imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to Bacteroides changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites

“…The anti-inflammatory bacteria Parvibacter and anti-obesity bacteria Bifidobacterium increased significantly after SLBZS intervention. It was also found that Bifidobacterium was a beneficial probiotic for health ( Shu et al, 2023 ) as it reduces insulin resistance, blood lipids, and obesity in HFD-induced obese mice ( Safari and Gérard, 2019 ; Wang Y. et al, 2020 ; Liu D. et al, 2023 ) while balancing gut-derived 5-HT ( Pirozzi et al, 2023 ) and negatively correlating with TC and low-density lipoprotein cholesterol ( Zhang et al, 2021 ). A previous study reported that Parvibacter was a beneficial genus whose function could prevent obesity ( Li Y. et al, 2022 ) and inhibit inflammatory factors ( Pang et al, 2021 ).…”

Molecular Mechanism Pathways of Natural Compounds for the Treatment of Non-Alcoholic Fatty Liver Disease

“…Studies have shown that SZ-A can regulate the gut microbiota of obese mice and change the composition of metabolites. In addition, SZ-A enriched the number of goblet cells and reduced inflammatory colon injury and proinflammatory macrophage infiltration induced by a high-fat diet in obese mice, reducing the symptoms of NAFLD to some extent [99] (Table 2).…”

Integration of Transcriptomics and Lipidomics Profiling to Reveal the Therapeutic Mechanism Underlying Ramulus mori (Sangzhi) Alkaloids for the Treatment of Liver Lipid Metabolic Disturbance in High-Fat-Diet/Streptozotocin-Induced Diabetic Mice

“…A previous study found that SZ-As ameliorated the overall glucose metabolism and systemic inflammation in KKAy mice with signs of T2DM by improving insulin secretion and modulating the abundance of gut microbiota and gut metabolites [ 8 ]. Further study has supported the potential of SZ-As to alleviate HFD-induced obesity by regulating gut microbiota and lipid metabolism profiles [ 9 , 10 ]. It was also demonstrated that SZ-As protected mice from HFD-mediated hepatic steatosis, triglyceride accumulation and adipose tissue inflammation, while the anti-inflammatory role appeared to depend on the blockage of p38 MAPK, ERK and JNK signaling pathway activation in macrophages [ 11 , 12 ].…”