The interventional role and mechanism of total flavonoids in lychee seeds on rats with liver fibrosis.

This study explored the interventional role and potential mechanism of total flavonoids from lychee seeds (TFL) on rats with liver fibrosis, focusing on the LPS/TLR2/4 signaling pathway and intestinal mucosal barrier theories. Male Sprague-Dawley (SD) rats were randomly divided into six groups: Control, Model, Silymarin (43.19 mg·kg⁻¹), TFL low dose (TFL-L, 25 mg·kg⁻¹), TFL medium dose (TFL-M, 50 mg·kg⁻¹), and TFL high dose (TFL-H, 100 mg·kg⁻¹). All groups received oral administration once daily for six weeks. Histopathological evaluations of liver tissues were conducted using HE and Masson staining, while fibrosis scores were assessed. Colon tissues were examined by HE staining for signs of inflammation and cellular infiltration. Immunohistochemistry detected the expression of tight junction proteins ZO-1, occludin, claudin 1, and claudin 4 related to the intestinal barrier. Serum levels of HA, IV-C, LN, PC-III, ALT, AST, and LPS were determined via ELISA. RT-qPCR was used to measure gene expression levels of TNF-α, IL-6, IL-1β, Ccl2, Ccl4, TLR2, TLR4 in liver tissue, and ZO-1, occludin, claudin 1, and claudin 4 in colon tissue. Compared to the Control group, the Model group exhibited significantly higher fibrosis scores, increased serum LPS, ALT, AST, LN, HA, IV-C, and PC-III levels, as well as elevated relative expression levels of Ccl2, TLR2, TLR4, IL-6, IL-1β, and TNF-α genes. After treatment with TFL, pathological scores in all TFL groups were significantly reduced, along with decreased serum levels of LPS, ALT, AST, HA, IV-C, and PC-III compared to the Model group. The relative expression levels of Ccl2, TLR2, TLR4, IL-1β, IL-6, and TNF-α genes in the TFL-H group were also notably lower than those in the Model group. No significant differences were observed in the relative expression of Ccl4 across groups. In addition, the expression of various tight junction-related proteins in the colonic mucosa of the Model group was significantly reduced, whereas the TFL-H group showed significantly richer staining compared to the Model group. TFL demonstrates a good anti-fibrotic effect, with a clear dose-response relationship, where the highest dosage produced the best results. Its anti-fibrotic effect may be associated with restoring intestinal mucosal barrier function and inhibiting the LPS/TLR2/4 signaling pathway.