Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death

Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-alpha, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs-(miRNA-6881-5P-(lnc-SPARCL1-1:2) RNA panel.

Automated summary

This study investigated the pharmacological activity and potential mechanism of rosavin treatment on non-alcoholic steatohepatitis (NASH) by targeting hepatic cell death-related mRNAs and their upstream noncoding RNA regulators in NASH rats. The results showed that rosavin modulated the expression of hepatic cell death-related RNA panel and improved liver functions, lipid profile, hepatic inflammation, fibrosis, and apoptosis in NASH rats. The study suggests that rosavin may have the potential to attenuate disease progression and inhibit hepatic cell death in NASH.