Jianpi Qingre Lishi prescription (JQLP) dose-dependently ameliorates NASH pathology and inflammation in rats

Non-alcoholic steatohepatitis (NASH), now often termed Metabolic Dysfunction-Associated Steatohepatitis (MASH) or MASLD, represents a severe form of fatty liver disease that can progress to cirrhosis and liver failure. Despite its growing global prevalence, therapeutic options remain limited, with only a few drugs like resmetirom and semaglutide recently approved. A key pathway involved in NASH pathogenesis is the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor crucial for lipid metabolism and inflammation. Its regulation by microRNAs, such as miRNA-27, offers a potential therapeutic target for mitigating liver injury and steatosis.

This study utilized 120 Sprague-Dawley rats, randomly assigned to six groups (n=20 each): blank control (BC), model, low-dose JQLP (L-JQLP), medium-dose JQLP (M-JQLP), high-dose JQLP (H-JQLP), and positive control (PC). The model and treatment groups received a methionine- and choline-deficient (MCD) diet to induce NASH, while the BC group received a methionine- and choline-sufficient (MCS) diet. Blood samples were collected for biochemical analyses and inflammatory factor determination. Liver tissues were harvested for histological evaluation via hematoxylin-eosin staining and oil red O staining. Additionally, miRNA-27 and PPARγ levels were determined using quantitative real-time polymerase chain reaction and Western blotting.

Compared to the BC group, the model group showed no significant changes in fasting blood glucose (FBG), but both M-JQLP and H-JQLP treatments substantially reduced FBG. The MCD diet induced severe pathological alterations in liver tissues, including extensive vacuole-like steatosis, disorganized hepatic plates, and significant inflammatory cell infiltration, all of which were dose-dependently weakened by JQLP intervention. Rats on the MCD diet exhibited increased total cholesterol, triglyceride, low-density lipoprotein cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, alongside decreased high-density lipoprotein cholesterol. JQLP treatment effectively normalized these parameters in a dose-dependent manner. Furthermore, MCD-fed rats showed largely secreted tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6).