The State Key Laboratory of Functions and Applications of Medicinal Plants, School of Basic Medical Sciences, Guizhou Medical University, University Town, Guian New District, 550025, Guizhou, China.
The Department of Pharmacology of Materia Medica (The high efficacy application of natural medicinal resources engineering center of Guizhou Province and The high educational key laboratory of Guizhou province for natural medicianl Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, 550025, Guizhou, China.
Sci Rep. 2020 Apr 14;10(1):6427. doi: 10.1038/s41598-020-63498-3.
Diabetic cardiomyopathy (DCM) is the principal cause of death in people with diabetes. However, there is currently no effective strategy to prevent the development of DCM. Although cyclovirobuxine D (CVB-D) has been widely used to treat multiple cardiovascular diseases, the possible beneficial effects of CVB-D on DCM remained unknown. The present aim was to explore the potential effects and underlying mechanisms of CVB-D on DCM. We explored the effects of CVB-D in DCM by using high fat high sucrose diet and streptozotocin-induced rat DCM model. Cardiac function and survival in rats with DCM were improved via the amelioration of oxidative damage after CVB-D treatment. Our data also demonstrated that pre-treatment with CVB-D exerted a remarkable cytoprotective effect against high glucose -or HO -induced neonatal rat cardiomyocyte damage via the suppression of reactive oxygen species accumulation and restoration of mitochondrial membrane potential; this effect was associated with promotion of Nrf2 nuclear translocation and its downstream antioxidative stress signals (NQO-1, Prdx1). Overall, the present data has provided the first evidence that CVB-D has potential therapeutic in DCM, mainly by activation of the Nrf2 signalling pathway to suppress oxidative stress. Our findings also have positive implications on the novel promising clinical applications of CVB-D.
糖尿病心肌病（DCM）是糖尿病患者死亡的主要原因。然而，目前尚无有效的策略来预防 DCM 的发生。虽然环维黄杨星 D（CVB-D）已被广泛用于治疗多种心血管疾病，但 CVB-D 对 DCM 的可能有益作用尚不清楚。本研究旨在探讨 CVB-D 对 DCM 的潜在作用及机制。我们通过高脂肪高蔗糖饮食和链脲佐菌素诱导的大鼠 DCM 模型探讨了 CVB-D 对 DCM 的影响。CVB-D 治疗可改善氧化损伤，从而改善 DCM 大鼠的心脏功能和存活率。我们的数据还表明，CVB-D 预处理通过抑制活性氧积累和恢复线粒体膜电位，对高葡萄糖或 HO 诱导的新生大鼠心肌细胞损伤具有显著的细胞保护作用；这种作用与促进 Nrf2 核易位及其下游抗氧化应激信号（NQO-1、Prdx1）有关。总的来说，本研究首次提供了 CVB-D 对 DCM 具有潜在治疗作用的证据，主要通过激活 Nrf2 信号通路来抑制氧化应激。我们的研究结果也对 CVB-D 的新的有前途的临床应用具有积极意义。
