ABSTRACT
ObjectiveTo investigate the pharmacological effect and metabolic mechanism of Linderae Radix on the intrauterine adhesion （IUA） rat model. MethodAn IUA rat model was induced by mechanical injury and infection. Molecular biology and pharmacology techniques were employed to evaluate the inhibitory effect of Linderae Radix extract （LAE） on fibrosis in IUA. Serum metabolomics analysis based on gas chromatography-mass spectrometry （GC-MS） was conducted to explore the metabolic regulation mechanism of LAE. ResultAnimal experiments showed that LAE significantly improved the morphology and structural damage of uterine tissue cells in the IUA rat model， promoted endometrial proliferation， vascular regeneration， and morphological recovery， inhibited the mRNA expression of transforming growth factor-β1 （TGF-β1）， Smad2， and Smad3， and increased the expression of Smad7 mRNA to suppress fibrosis. Additionally， LAE significantly suppressed the levels of estrogen （E2）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and tumor necrosis factor-α （TNF-α） expression （P<0.01）， thereby improving the uterine microenvironment. Metabolomics analysis revealed significant metabolic abnormalities in the serum of IUA rats compared with the results in the normal group， and nine differential metabolites were identified. LAE effectively ameliorated these metabolic abnormalities， primarily by influencing six differential metabolites， including five shared metabolites among the nine identified markers： L-aspartic acid， L-pyroglutamic acid， L-serine， glucose， and L-norvaline. Pathway enrichment analysis indicated that the aminoacyl-tRNA biosynthesis pathway was the main affecting mechanism. ConclusionIn combination with the pharmacological research results， LAE effectively improved uterine damage and inhibited fibrosis in the IUA rat model. Its mechanism may involve the inhibition of the aminoacyl-tRNA biosynthesis pathway and the improvement of the microenvironment.