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YQWY Decoction Improves Myocardial Remodeling via Activating the IL-10/Stat3 Signaling Pathway
He Li1,2, Zhi-Jun Gong1, Yun He1
1Department of Cardiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China.
Insights
YQWY decoction protects against heart failure (HF) by reducing inflammation, fibrosis, and apoptosis. It activates the interleukin-10 (IL-10)/Stat3 pathway, improving cardiac function and remodeling in rats with HF.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Traditional Chinese Medicine
Background:
- Heart failure (HF) is a global health concern, with cardiac remodeling playing a critical role in its development.
- Understanding the molecular mechanisms underlying HF is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the cardioprotective effects of YQWY decoction in a rat model of HF.
- To elucidate the role of the interleukin-10 (IL-10)/Stat3 signaling pathway in mediating these effects.
Main Methods:
- A rat model of HF was established using minimally invasive transverse aortic constriction (MTAC).
- Echocardiography, Masson staining, Picrosirius red staining, and TUNEL staining were used to assess cardiac function, fibrosis, and apoptosis.
- ELISA, western blot, and immunohistochemistry were employed to analyze the expression of key proteins and cytokines, including IL-10, TNF-α, Stat3, and inflammatory markers.
Main Results:
- YQWY decoction significantly improved left ventricular function and reduced myocardial fibrosis and apoptosis in HF rats.
- The treatment decreased levels of pro-inflammatory cytokine TNF-α and attenuated inflammatory cell infiltration.
- YQWY decoction upregulated IL-10 expression, suppressed NF-κB activation, and enhanced Stat3 phosphorylation in heart tissues.
Conclusions:
- YQWY decoction demonstrates significant cardioprotective effects against MTAC-induced heart failure in rats.
- These benefits are mediated by the activation of the IL-10/Stat3 signaling pathway, leading to reduced inflammation, fibrosis, apoptosis, and improved cardiac function.
- YQWY decoction holds therapeutic potential for treating heart failure.
Abstract:
Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin-10 (IL-10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL-10, tumor necrosis factor-α (TNF-α), Stat3 (P-Stat3), P65 (P-P65), CD68, collagen I, TGF-β, CTGF, Bax, Bcl-2, cleaved caspase-3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high-dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, P < 0.01;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, P < 0.01). Furthermore, YQWY decoction markedly inhibited MTAC-induced myocardial fibrosis as evidenced by downregulated collagen I, TGF-β, and CTGF in myocardium and alleviated apoptosis (downregulated caspase-3 and PARP and increased Bcl-2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF-α in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC-induced NF-κB activation and phosphorylated Stat3 by upregulating IL-10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC-induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL-10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.
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