Gentiopicrin

Lean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on. It is plausible to speculate that GPS may hold potential as a therapeutic strategy for lean NASH. However, no related studies have been conducted thus far.

The present work aimed to investigate the benefit of GPS on NASH in a lean mouse model.

NASH in a lean mouse model was successfully established via a published method. GPS of 50 and 100 mg/kg were orally administered to verify the effect. Untargeted metabolomics, 16S rDNA sequencing and bile acid (BA) profiling, as well as qPCR and Western blotting analysis were employed to investigate the mechanism underlying the alleviating effect.

GPS significantly reduced the increase in serum biochemicals and liver index, and attenuated the accumulation of fat in the livers of lean mice with NASH. Forty-two potential biomarkers were identified by metabolomics analysis, leading to abnormal metabolic pathways of primary bile acid biosynthesis and fatty acid biosynthesis, which were subsequently rebalanced by GPS. A decreased Firmicutes/Bacteroidetes (F/B) ratio and disturbed BA related GM profiles were revealed in lean mice with NASH but were partially recovered by GPS. Furthermore, serum profiling of 23 BAs confirmed that serum BA levels were elevated in the lean model but downregulated by GPS treatment. Pearson correlation analysis validated associations between BA profiles, serum biochemical indices and related GM. qPCR and Western blotting analysis further elucidated the regulation of genes associated with liver lipid synthesis and bile acid metabolism.

GPS may ameliorate steatosis in lean mice with NASH, regulating the metabolomic profile, BA metabolism, fatty acid biosynthesis, and BA-related GM. All these factors may contribute to its beneficial effect.

Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD’s therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.

Developing effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.