Oxymatrine attenuated isoproterenol-induced heart failure via the TLR4/NF-κB and MAPK pathways in vivo and in vitro

Oxymatrine (OMT) is a quinoline alkaloid isolated from the root of the Sophora flavescens that has a variety of biological activities. However, the effect and potential mechanism of OMT on isoproterenol (ISO)-induced heart failure (HF) are not clear. In this study, we found that OMT improved the survival of HL-1 cells induced by ISO. We also demonstrated that OMT significantly inhibited the levels of the inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). OMT decreased the levels of the TLR4 and reduced the phosphorylation levels of nuclear factor-xB (NF-xB) inhibitor (IxB), p65, c-Jun N-terminal kinases (JNK) and p38. The inhibitory effect of the TLR4 inhibitor TAK242 on HL-1 cells was evaluated. The results showed that the effect of OMT on the phosphorylation levels of IxBa and p65 was enhanced in HL-1 cells treated with TAK242. Using animal models, OMT significantly reduced ISO-induced cardiac injury, myocardial necrosis, interstitial edema, and fibrosis. In addition, OMT attenuated TNF-a and IL-6 and inhibited the expression of TLR4/NF-xB and MAPK pathway-related proteins. This finding suggests that OMT may alleviate HF by interfering with the TLR4/NF-xB and MAPK pathways.

Automated summary

Our study found that Oxymatrine improved the survival of isoproterenol-induced heart failure mice. It achieved this by inhibiting the expression of inflammatory cytokines TNF-a and IL-6, reducing TLR4 levels, and decreasing the phosphorylation levels of NF-xB, p65, JNK, and p38. Animal experiments showed that Oxymatrine alleviated isoproterenol-induced cardiac injury, necrosis, interstitial edema, and fibrosis, while inhibiting the expression of TLR4/NF-xB and MAPK pathway-related proteins.