Nuciferine Protects Against High-Fat Diet-Induced Hepatic Steatosis via Modulation of Gut Microbiota and Bile Acid Metabolism in Rats

Abstract

Our previous study showed that nuciferine (NF) attenuated non-alcoholic fatty liver disease (NAFLD), which is attributed to a high-fat diet (HFD) through reinforcing intestinal barrier functions, regulating lipid metabolism, and improving inflammation. To clarify whether other mechanisms contribute to the anti-NAFLD efficacy of NF, the present study investigated the influence of NF on bile acid (BA) metabolism and gut microbiota in HFD-fed rats. The data demonstrated that NF changed the composition of colonic BA, particularly elevating conjugated BA and non-12OH BA levels. As shown by downregulated protein levels of FXR, FGF15, FGFR4, and ASBT and upregulated protein levels of CYP7A1 and CYP27A1, NF inhibited ileal FXR signaling, promoted BA synthesis, suppressed BA reabsorption, and facilitated fecal BA excretion. NF might affect hepatic FXR signaling, BA conjugation, and enterohepatic circulation by the changed mRNA levels of Fxr, Shp, Baat, Bacs, Bsep, Ntcp, Ibabp, and Ostα/β. Meanwhile, NF regulated the gut microbiota, characterized by decreased BSH-producing genus, 7α-dehydroxylation genus, and increased taurine metabolism-related genus. Spearman rank correlation analysis implied that Colidextribacter, Adlercreutzia, Family_XIII_AD3011_group, Lachnospiraceae_UCG-010, Eisenbergiella, and UCG-005 were robustly associated with particular BA monomers. In conclusion, our experiment results suggested that NF could exert a mitigating effect on NAFLD via regulating BA metabolism and modulating the gut microbiota.

Zhuyu Pill Alleviates Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism through the Gut–Liver Axis

“…55 Nuciferine changes the composition of colonic BA, increases the level of conjugated Bas, inhibits ileal FXR signal transduction, upregulates the expression of CYP7A1, promotes BA synthesis, inhibits BA reabsorption, and promotes fecal BA excretion, thereby alleviating NAFLD. 56 The hepatic FXR-liver X receptor α (LXRα) pathway and the intestinal FXR-FGF15 pathway work together in the synthesis of BA. 57 Our previous research has shown that berberine and evodiamine, the main active ingredient of ZYP, effectively increase the expression of LXRα and CYP7A1.…”

“…Similarly, l -theanine intervention produced low FXR and FGF15 expression and high CYP7A1 expression, reduced TC, TG, and LDL-C content, increased HDL-C content, and improved lipid metabolism . Nuciferine changes the composition of colonic BA, increases the level of conjugated Bas, inhibits ileal FXR signal transduction, upregulates the expression of CYP7A1, promotes BA synthesis, inhibits BA reabsorption, and promotes fecal BA excretion, thereby alleviating NAFLD …”

Dietary polyphenols maintain homeostasis via regulating bile acid metabolism: a review of possible mechanisms

“…Nuciferine has been found to alleviate alcoholic fatty liver in Sprague-Dawley rats fed with a high-fat diet, reduce the level of Lactobacillus , reduce BSH production, reduce 7α-dehydroxylation genus, and increase taurine metabolism-related genus. 76 In addition, Penthorum chinense Pursh. extract (PCPE) was also found to improve the NAFLD of C57BL/6J mice by reducing the relative abundance of BSH-producing bacteria, especially Lactobacillus .…”

The potential role of alfalfa polysaccharides and their sulphated derivatives in the alleviation of obesity

“…Studies have found that natural medicines from plants are effective in reducing inflammation and restoring intestinal flora. [8][9][10] However, these natural drugs have the corresponding disadvantages of weak activity and low yield, which hamper their application. 11,12 By breaking down the molecular structure of natural drugs, some products with the same structure can be obtained by artificial synthesis.…”