Dioscin ameliorates doxorubicin-induced heart failure via inhibiting autophagy and apoptosis by controlling the PDK1-mediated Akt/mTOR signaling pathway.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway.

[Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway].

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.