Triptolide improves myocardial fibrosis in rats through inhibition of nuclear factor kappa B and NLR family pyrin domain containing 3 inflammasome pathway

Abstract

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM-1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

Fibroblast-derived interleukin-6 exacerbates adverse cardiac remodeling after myocardial infarction

“…Acute inflammation plays a crucial role in diverse cardiac injuries, including the participation in the regulation of cardiac remodeling after myocardial infarction [ 6 - 8 ]. In the present study, we found that there is high IL-6 expression in cardiac fibroblasts triggered by myocardial infarction.…”

Triptolide protects against podocyte injury in diabetic nephropathy by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome pathway

“…Likewise, TP induces GSDME-mediated pyroptosis of head and neck tumor cells by inhibiting mitochondrial hexokinase-ΙΙ [ 74 ]. Moreover, TP could prevent IgAN progression [ 75 ] and improve myocardial fibrosis by down-regulating NLRP3 inflammasomes [ 76 ]. Overall, this study strengthens the idea that TP may inhibit the inflammatory response and reduce the pyroptosis of renal podocytes in DN through the NLRP3 inflammasome pathway.…”

Exploration of the Mechanism of Tripterygium Wilfordii in the Treatment of Myocardial Fibrosis Based on Network Pharmacology and Molecular Docking

“…[ 11 ] have reported that not only does β-sitosterol reduce the level of inflammatory mediators in mice such as tumor necrosis factor (TNF-α), and interleukin 6 (IL-6), etc ., but it remarkably improved the antioxidative activities such as glutathione (GSH) and catalase (CAT), etc . Myocardial fibrosis rat models were treated with triptolide, NF-kB pathways were inhibited, and NLRP3 inflammasomes were activated to improve myocardial fibrosis in rats [ 12 ]. In vivo / vitro experiments in mice with myocardial infarction have indicated that Nobiletin reduced myocardial fibrosis and apoptosis by activating PPARγ and PGC1α [ 13 ].…”