Hydroxysafflor yellow A mitigates myocardial fibrosis induced by isoproterenol and angiotensin II

Aims: To investigate the potential inhibitory effect of Hydroxysafflor yellow A (HSYA) on myocardial fibrosis induced by isoproterenol (ISO) and angiotensin II (Ang II) and the possible underlying mechanism. Methods: Mice were injected subcutaneously with ISO and given HSYA by gavage in vivo. Masson's trichrome staining, immunohis-tochemical staining and immunofluorescence assays were conducted to evaluate the expression and localization of collagen and inflammatory cytokines, respectively. In vitro, cardiac fibroblasts (CFs) were treated with various doses of HSYA and induced with Ang II. Cell proliferation and migration were assessed using wound healing assay. Cell counting kit-8 was used to measure the cell viability. Collagen I, collagen III, phosphorylation of Smad2/3, Smad2/3, TGF beta 1, interleukin (IL)-1 beta, IL-18, NLRP3 inflammasome-associated proteins were detected by Western blotting. Levels of reactive oxygen species (ROS) were evaluated using 2',7'-dichlorofluorescein diacetate assay. Results: HSYA significantly inhibited ISO-induced myocardial fibrosis, NLRP3 inflammasome activation as well as IL-18 and IL-1 beta expressions in mice. HSYA significantly reduced the proliferation and migration of CFs, and suppressed the accumulation of collagen I and collagen III. TGF beta 1 and P-Smad2/3 induced by Ang II was repressed by HSYA. HSYA downregulated IL-1 beta and IL-18, blocked NLRP3 activation, and reduced ROS in CFs. Conclusion: HSYA may inhibit myocardial fibrosis by blocking NLRP3 pathway in CFs.

Automated summary

This study investigated the potential inhibitory effect of Hydroxysafflor yellow A (HSYA) on myocardial fibrosis induced by isoproterenol (ISO) and angiotensin II (Ang II). The results showed that HSYA significantly inhibited myocardial fibrosis, NLRP3 inflammasome activation, and inflammatory cytokine expressions. In vitro, HSYA reduced the proliferation and migration of cardiac fibroblasts (CFs) and suppressed the accumulation of collagen. The study suggests that HSYA may inhibit myocardial fibrosis by blocking the NLRP3 pathway in CFs.