OBJECTIVE

2

To investigate the improvement effect and mechanism of different extracts from

Tylophora yunnanensis

on non-alcoholic steatohepatitis （NASH）.

METHODS

2

Normal human liver LO2 cells were induced to steatosis by free fatty acid， then were divided into normal group， model group， silybin group （100 μmol/mL），

T. yunnanensis

ethanol extracts （TYS） group （50 μg/mL），

T. yunnanensis

ethyl acetate extracts （TYSA） group （50 μg/mL）， and

T. yunnanensis

n-butanol extracts （TYSB） group （50 μg/mL）. After 24 hours of drug intervention， the deposition of lipid droplets was observed in LO2 cells in each group. The contents of total cholesterol （TC）， triacylglycerol （TG）， malondialdehyde （MDA） and glutathione （GSH）， the activities of aspartate transaminase （AST）， alanine transaminase （ALT） and superoxide dismutase （SOD）， the mRNA expressions of Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor E2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） were detected. NASH rat model was induced by a high-fat diet， and then divided into normal group， model group， silybin group （12.6 mg/kg）， TYS group （80 mg/kg）， TYSA group （80 mg/kg） and TYSB group （80 mg/kg）， with six rats in each group. The liver indexes of rats in each group were calculated after 6 weeks of drug intervention. The liver histopathological changes were observed， and the contents of TC， TG， HDL-C and LDL-C， AST and ALT activities in serum， the contents of MDA and GSH， SOD activities in liver tissue were detected.

RESULTS

2

Compared with model group， TYS， TYSA and TYSB could reduce lipid droplet deposition， intracellular TC， TG and MDA contents， AST and ALT activities， and increase SOD activity， GSH content， and Keap1， Nrf2， HO-1 mRNA expression levels in LO2 cells after steatosis to varying degrees， with some differences being statistically significant （

P

＜0.05）. They also significantly improved liver injury in NASH model rats， reduced their liver indexes， TC， TG， LDL-C and MDA contents， AST and ALT activities， and increased HDL-C （except for TYS and TYSB）， GSH contents and SOD activity， with TYSA having the most significant effect （

P

＜0.05）.

CONCLUSIONS

2

TYS， TYSA and TYSB have a certain improvement effect on NASH， among which TYSA has the most obvious effect. Its mechanism of action may be related to upregulating the Keap1/Nrf2/HO-1 signaling pathway and inhibiting oxidative stress