Gardenia jasminoides Ellis polysaccharide ameliorates cholestatic liver injury by alleviating gut microbiota dysbiosis and inhibiting the TLR4/NF-κB signaling pathway.

Abstract

Gardenia jasminoides Ellis is a well-known herbal medicine. In this study, the effect of G. jasminoides Ellis polysaccharide (GPS) on liver injury in an alpha-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model and the associated molecular mechanisms were investigated. GPS administration dose-dependently ameliorated impaired hepatic function, including a 2-7-fold decrease in aminotransferase levels, ameliorating tissue damage, upregulating the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) and their downstream efflux transporters, and decreasing the levels of 12 bile acids (BAs), in cholestatic mice. Furthermore, GPS ameliorated gut microbiota dysbiosis, improved intestinal barrier function, and reduced serum and hepatic lipopolysaccharide levels 1.5-fold. GPS also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling, decreased the expression of inflammatory factor genes, and ameliorated hepatic inflammation. Notably, fecal microbiota transplantation from GPS-fed mice also increased the hepatic expression of FXR, PXR, and efflux transporters; decreased the levels of 12 BAs; restored intestinal barrier function; and decreased hepatic inflammation mediated by the TLR4/NF-κB pathway. In conclusion, GPS has a protective effect against cholestatic liver injury through modulation of gut microbiota and inhibition of the TLR4/NF-κB pathway. Regulating gut microbiota using herbal medicine polysaccharides may hold unique therapeutic promise for cholestatic liver diseases.

• Authors: Su Fang, Tianming Wang, Yuanyuan Li, Haoyu Xue, Juan Zou, Jingyi Cai, Rong Shi, Jiasheng Wu, Yueming Ma
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 205 Pg. 23-36 (Apr 30 2022) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 35176320 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier B.V.

Chemical References

• NF-kappa B
• Polysaccharides
• Tlr4 protein, mouse
• Toll-Like Receptor 4

Topics

• Animals
• Dysbiosis (drug therapy)
• Gardenia
• Gastrointestinal Microbiome
• Liver
• Mice
• Mice, Inbred C57BL
• NF-kappa B (genetics)
• Polysaccharides (pharmacology, therapeutic use)
• Signal Transduction
• Toll-Like Receptor 4 (genetics)