The effect of salvianolic acid B on gut microbiota and short chain fatty acid metabolism in mice with liver injury
Liver injury refers to liver cell damage and abnormal liver function caused by various factors. Common pathogenic factors in clinical practice include drug stimulation, viral infection, alcohol or chemical toxins. Research has shown that severe or persistent liver damage can ultimately lead to cirrhosis and hepatocellular carcinoma.
Danshen is slightly cold in nature, bitter in taste, and enters the heart and liver meridians. It is a commonly used blood activating and stasis removing medicine in clinical practice, and has been widely used by medical practitioners throughout history in the treatment of liver diseases. Salvianolic acid B (Sal B) is one of the main active ingredients in the water-soluble extract of Danshen. Research has shown that Sal B can alleviate liver injury by inhibiting oxidative stress, TGF – β signaling pathway, and other mechanisms. Studies have shown that oral Sal B has low bioavailability, suggesting that regulating gut microbiota may be an important target for its biological activity.
The existence of the gut liver cycle connects the gut with the liver, and the gut and liver are not only physiologically interconnected, but also closely related in terms of physiological function. The disorder of the gut liver axis, including the imbalance of gut microbiota composition and proportion, as well as changes in microbial metabolites such as short chain fatty acids (SCFAs) and bile acids, is closely related to liver injury caused by various reasons. In recent years, literature has reported a large number of natural products targeting gut microbiota and regulating SCFAs levels to alleviate liver injury. This study reveals that SalB exerts anti liver injury effects by regulating gut microbiota and SCFAs disorders, providing new scientific evidence for the mechanism of SalB’s anti liver injury research.

Liver injury is a common pathological basis for various liver diseases, and understanding the potential mechanisms of anti acute and chronic liver injury drugs may contribute to the clinical treatment of liver injury. In recent years, changes in gut microbiota have been considered to play an important role in inducing and promoting liver function damage. Imbalance of gut microbiota, damage to the intestinal wall barrier, and intestinal endotoxemia caused by increased intestinal permeability can disrupt the balance between the gut and liver, thereby affecting various liver diseases through the gut liver axis.

Sal B is one of the main active ingredients of Danshen, a traditional Chinese medicine commonly used in clinical practice to treat liver injury. At present, research has reported that Sal B can have a significant inhibitory effect on liver injury induced by CCl4, high-fat diet, thioacetamide, etc. The related mechanism research is mostly focused on inhibiting the activation and proliferation of hepatic stellate cells, liver inflammation, oxidative stress, etc. This study further clarified the intervention effect of Sal B on carbon tetrachloride induced liver injury through in vivo experiments, and found that its activity is related to the regulation of intestinal microbiota and SCFAs by Sal B. The 16S rRNA sequencing results of this study showed that the gut microbiota distribution of Sal B was between the Con group and the Mod group. During liver injury, the ratio of Firmicutes to Bacteroidetes usually changes, with the former decreasing and the latter increasing. The Mod group in this study experienced this dysbiosis, and after Sal B intervention, this dysbiosis was significantly restored. At the genus level, Sal B intervention significantly increased the relative abundance of Lactobacillus and decreased the relative abundance of Fecal and Bifidobacterium. Among them, the genus Lactobacillus has been reported to have the ability to protect the liver, which can alleviate inflammation and fibrosis of damaged liver. These results all prove that SalB can alleviate liver damage by regulating intestinal microbiota.
SCFAs are the main energy source for colon cells, reducing local inflammation and promoting the production of antimicrobial peptides, which helps maintain the intestinal barrier and reduce intestinal permeability. Supplementation with SCFAs can delay the progression of liver injury by reducing portal vein transmission of pathogenic molecular patterns, including bacterial endotoxins. After quantitative analysis of SCFAs in the gut of mice, this study found that the levels of acetic acid, hexanoic acid, isobutyric acid, isovaleric acid, propionic acid, and valeric acid were significantly reduced in the Mod group, while Sal B intervention restored the levels of isobutyric acid, isovaleric acid, propionic acid, and valeric acid. This may be related to the increased abundance of Firmicutes in the gut microbiota of the Sal B group that we previously identified. There are research reports that Firmicutes account for about 60% of intestinal bacteria and are closely related to the production of SCFAs. The decrease in acetic acid levels in both the Mod group and Sal B group is speculated to be related to the relative abundance reduction of acetic acid secreting bacterial communities such as the Parabacterioides genus. In addition to alleviating liver damage by improving the intestinal barrier, recent literature has also shown that SCFAs can improve liver diseases such as NASH by inhibiting macrophage pro-inflammatory activation in liver tissue, reducing inflammatory responses. Our previous research did not observe the effect of Sal B on the intestinal barrier of mice with liver injury. Therefore, we speculate that the improvement of liver injury by SCFAs may be related to their direct effect on cells in liver tissue after entering the liver through the portal vein.
In summary, Sal B can inhibit CCl4 induced liver injury in mice by restoring the balance of gut microbiota. Meanwhile, Sal B can partially restore the content of intestinal SCFAs in mice with liver injury, but further research is needed on how these restored SCFAs participate in Sal B’s anti liver injury process.