Transcriptome Analysis Revealed the Therapeutic Effect of Scutellarin on MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disease. Scutellarin (Scu) is one of the active components extracted from Erigeron breviscapus (Vaniot) Hand.-Mazz., which has been shown to fight multiple diseases. However, there is not enough evidence to support the effectiveness of Scu in treating MASLD. We aimed to investigate whether Scu could be a potential drug for MASLD. The rat model of MASLD was established after a high-fat and high-sugar (HFHS) diet for 16 weeks. After the model had been successfully built, 100 mg/kg/d Scu was given for 8 weeks. The biochemical indexes of serum were determined by an automatic biochemical analyzer. The process involved staining liver tissues by oil red "O" and hematoxylin and eosin (HE) staining, followed by the extraction of total RNA from the liver. Then, high-throughput sequencing was used to screen the changes in the transcriptome. Verification of the associated key genes was achieved through bioinformatics, Western blot, RT-PCR, and immunohistochemical analyses. The results demonstrated that Scu could decrease the ratio of liver weight to body weight, as well as the levels of ALT, AST, ALP, TG, and TC in SD rats induced by HFHS diets, thereby improving liver function and lipid accumulation in rats. Furthermore, Scu was capable of reversing pathological changes in SD rats. The transcriptomic analysis corroborated these findings and further identified Pdk4 as a crucial gene mediating the beneficial effects of Scu on MASLD in rats. This was also supported by RT-PCR, Western blot, and immunohistochemical analyses. This study is the first to identify Pdk4 as a key gene for Scu treatment of MASLD through transcriptomes and confirms that Scu is a potentially effective drug for MASLD.