Abstract
Background
The prevalence of nonalcoholic steatohepatitis (NASH) is increasing every year, and there are very few approved therapeutic agents globally, making the search for potentially targeted therapeutic agents important.
Aims
To investigate the anti-NASH effect of tetrahydrocurcumin (THC) and to further study the biological mechanism of tetrahydrocurcumin anti-NASH from the perspective of intestinal flora.
Methods
Seven-week-old male and female C57BL/6J mice were randomly divided into six groups: (1) Control group, (2) Model group, (3) Positive control group, (4) THC low-dose group, (5) THC medium-dose group, and (6) THC high-dose group, and the remaining groups except the control group were fed with high-fat chow for 16 weeks. Serum and liver tissues were collected to study the anti-NASH mechanism of THC using network pharmacology, molecular docking, high-throughput sequencing, and RT-qPCR.
Results
The intervention of THC improved the pathology of NASH, ameliorated liver injury, lowered lipid levels, and inhibited hepatic oxidative stress, inflammatory response and apoptosis compared with the high-fat feed-induced model group. In network pharmacology and animal experimental validation we found that THC reduced the expression of m RNA of PPARG, which may be the key to the improvement of NASH by THC. Intestinal flora analysis showed that THC altered the composition of the intestinal flora, which was characterized by a decrease in the proportion of Firmicutes/Bacteroidota.
Conclusion
The results of this study suggest that THC exerts anti-NASH effects by improving lipid levels, decreasing oxidative stress, attenuating inflammatory responses, and increasing the anti-apoptotic capacity of liver cells, and its efficacy is importantly associated with decreasing the expression of PPARG and improving the intestinal flora. THC is expected to be a potential therapeutic agent for NASH.