9.1 Agonists of TGR5 and FXR
Progress has been made in the study of the efficacy of natural or
synthetic TGR5 and FXR agonists in the treatment of liver and intestinal
diseases. In an oxazolone-induced colitis model, the GPBAR1 agonist
BAR501 alleviated the symptoms of enteritis and inhibited inflammatory
markers68. GW4064 activates FXR and improves
LPS-induced ileocolitis by inhibiting mitochondrial dysfunction in
mice118. FXR activation also inhibits endoplasmic
reticulum stress and inflammation 119. In
tumor-bearing models, the FXR agonist synergistically inhibited the
growth of hepatocellular carcinoma with the anti-PD-1 antibody120. Obeticholic acid (OCA) is a clinically approved
selective FXR agonist and Nanoemulsion-loaded OCA (OCA-NE) results in
increased secretion of CXCL16, IFN-γ. The number of NKT cells in the
tumor increases, resulting in a better liver tumor inhibition effect.
The development of BA receptors, such as TGR5 and FXR agonists, and the
targeted delivery of these drugs have greatly facilitated precision
cancer therapy121. OCA is used to treat non-alcoholic
steatohepatitis (NASH) by inhibiting activation of the NLRP3
inflammasome122. OCA accelerates the maturation of
mouse intestinal epithelial cells in a constitutive androstane receptor
(CAR)-dependent manner123. Further research on OCA is
necessary to expand its application
range. Salvia-Nelumbinis
naturalis (SNN), a traditional Chinese medicine, is effective in the
treatment of NASH. It activates the FXR-FGF15 signaling pathway in the
colon by increasing BA-associated microbiome124.
Research on the regulatory mechanism of traditional Chinese medicine on
hepato-intestinal disease has important implications for better
application of traditional Chinese medicine and the development of new
targeted drugs.