Hepatoprotection of Jianpi Qingre Lishi prescription (健脾清热利湿法) on non-alcoholic steatohepatitis via miRNA-27/peroxisome proliferator-activated receptor gamma axis

OBJECTIVE: To elucidate the molecular targets and physiological mechanisms underlying the therapeutic efficacy of Jianpi Qingre Lishi prescription (健脾清热利湿法, JQLP) in the treatment of non-alcoholic steatohepatitis (NASH). METHODS: This study used 120 Sprague-Dawley rats to establish six groups at random (n = 20): blank control (BC), model, low-dose JQLP (L-JQLP), medium-dose JQLP (M-JQLP), high-dose JQLP (H-JQLP), and positive control (PC) groups. Rats in the BC group received a diet with methionine- and choline-sufficient (MCS), while those in the remaining groups were fed with methionine- and choline-deficient (MCD) diet. Blood samples were collected for biochemical analyses and inflammatory factors determination; while liver tissues were harvested to identify the histological alterations through hematoxylin-eosin staining and oil red O staining. In addition, the levels of miRNA-27 (miR-27) and peroxisome proliferator-activated receptor γ (PPARγ) were determined utilizing quantitative real-time polymerase chain reaction and Western blotting. RESULTS: Compared to the BC group, the model group showed no significant changes in fasting blood glucose (FBG), which was substantially reduced after both M-JQLP and H-JQLP treatments. MCD diet induced a series of pathological alterations, such as extensive vacuole-like steatosis, disorganized hepatic plates, and significant inflammatory cell infiltration in liver tissues, which were dose-dependently weakened by JQLP intervention. Rats fed with MCD diet demonstrated increase in total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase activities, but decrease in high-density lipoprotein cholesterol. JQLP treatment effectively normalized these parameters in a dose-dependent manner. Furthermore, rats with MCD diet were detected with largely secreted tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); while JQLP intervention decreased TNF-α and IL-6 secretion, but enhanced IL-4 content. Additionally, miR-27 upregulation and PPARγ downregulation were induced in liver tissues of rats with MCD diet, which were counteracted by JQLP treatment. CONCLUSIONS: JQLP can ameliorate NASH progression, potentially through the regulation of miR-27/ PPARγ axis. JQLP may be a promising therapeutic candidate worthy of further clinical investigation for NASH treatment.