Aloperine Improves Renal Fibrosis via Regulation of Toll‑Like Receptor 4/Myeloid Differentiation Factor 88 Signaling Pathway

Abstract

Objectives: The primary goal of this study was to elucidate the effects and mechanisms of aloperine (Alo) in the renal fibrosis mice with unilateral ureteral obstruction (UUO).Materials and Methods: C57BL/6 mice were randomly separated into five groups: sham, model, Alo‑L, Alo‑M, and Alo‑H. Serum creatinine and blood urea nitrogen were measured by chemical methods. The histopathological changes and collagen deposition in the affected kidney were evaluated under optical microscope by performing hematoxylin and eosin and Masson staining. The expression of alpha smooth muscle actin, fibronectin, Toll‑like receptor (TLR)‑4, and myeloid differentiation factor 88 (MyD88) proteins was evaluated by immunohistochemistry, and the protein expression of interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α was evaluated via Western blot analysis.Results: The degree of fibrosis and histopathological damage was most clear in the kidney tissues obtained from model group. Furthermore, the expression of TLR4 and MyD88 was the maximum in the model group. However, Alo decreased the injury to the kidney, thereby improving their condition. It also decreased the levels of terminal inflammatory cytokines (i.e., TNF‑α and IL‑6).Conclusion: Alo may progress renal fibrosis by inhibiting TLR4/MyD88 pathway.

Keywords: Aloperine; immune and inflammatory responses; renal fibrosis; Toll‑like receptor 4/myeloid differentiation factor 88 pathway; unilateral ureteral ligation