PURPOSE: To examine the protective effects of Isoliquiritigenin (ISL) in angiotensin II (ANG II)-induced inflammation and fibrosis on Human Tenon's capsule Fibroblasts (HTFs) and Mouse Peritoneal Macrophages (MPMs). This study also investigated the potential mechanism of action of ISL. METHOD: Methyl-thiazolyl tetrazolium (MTT) assay was used to test ISL toxicity. An ELISA and an RT-qPCR assay detected the inflammatory cytokines (TNF-&#945;, IL-6, COX-2, and ICAM-1). A Western blot investigated the expression levels of inflammation-related signals [nuclear factor-&#954;B (NF-&#954;B), peroxisome proliferator-activated receptor Î³ (PPARÎ³)], and fibrogenesis, including fibronectin and alpha-smooth muscle actin (&#945;-SMA)]. Protein expressions of &#945;-SMA were measured by immunofluorescence. RESULTS: Pre-treatment with ISL (10 or 20â¯µM) dose-dependently decreased the mRNA levels of TNF-&#945;, IL-6, ICAM-1, and COX-2 induced by ANG II (1â¯µg/ml) in both MPMs and HTFs. ANG II remarkably increased the amount of P65 in the nuclei and decreased the amount of P65 in the cytoplasm. Additionally, ANG II reduced PPARÎ³ expression levels in a time-dependent manner. Furthermore, these effects which were induced by ISL were remarkably neutralized by ISL pre-treatment. Finally, ANG II markedly elevated the expression of fibronectin and &#945;-SMA. CONCLUSION: ISL could alleviate ANG II-induced fibrogenesis by inhibiting the NF-&#954;B/PPARÎ³ inflammatory pathway. In addition, ISL may be a potential agent for the treatment of conjunctival fibrosis. Most importantly, the NF-&#954;B/PPARÎ³ signaling pathway could be an effective therapeutic target for the prevention and treatment of conjunctival fibrosis after glaucoma surgery.
Isoliquiritigenin protects against angiotensin II-induced fibrogenesis by inhibiting NF-κB/PPARÎ³ inflammatory pathway in human Tenon's capsule fibroblasts