Background and Purpose. DCM (diabetic cardiomyopathy), which may lead to significant complications including cardiovascular lesions, arrhythmia, and even heart failure, has a beginning element now known to be myocardial energy rebuilding. There are limited research on Celastrol’s ability to guard against this in the United States and elsewhere. Since it has not been known, whether Celastrol could reverse the early energy remodeling process, thus, it was hypothesized that triptolide Celastrol is suitable for the reversal of early myocardial energy remodeling in DCM. And our aim is to predict the targets and underlying mechanism of Celastrol in reversing the early energy remodeling for DCM. Methods. Data from TCMSP and GEO databases were utilized to identify targets for Celastrol on DCM. The relationship between the major targets and conventional glycolipid metabolism was obtained with Spearman correlation analysis. Experiments on animals were conducted utilizing healthy control (HC), low-dose Celastrol interventions (CL), and no intervention groups (NC), all of which had 8 SD rats in each group. To study alterations in signaling molecules, RT-PCR was performed. Results. There were 76 common targets and 5 major targets for Celastrol-DCM. Celastrol have been found to regulate AGE-RAGE, TNF, MAPK, TOLL-like receptors, insulin resistance, and other signaling pathways, and they are closely linked to adipocytokines, fatty acid metabolism, glycolipid biosynthesis, and glycosylphosphati-dylinositol biosynthesis on DCM. These five major targets have been found to regulate these pathways. Experiments on rats indicated that P38 MAPK was considerably elevated in the cardiac tissue from rats in the CL and NC groups compared to the HC group, and the difference was statistically significant (). Significant differences were seen between the CL and NC groups in P38 MAPK levels, with a statistical significance level of less than 0.05. Conclusion. Celastrol may play a role in reversing energy remodeling, anti-inflammation, and oxidative stress via modulating p38 protein expression in the MAPK pathway, which have been shown in the treatment of DCM.

中文翻译：

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通过网络药理学和实验验证研究雷公藤红素的抗 DCM 靶点和机制


背景和目的。 DCM（糖尿病心肌病）可能导致严重的并发症，包括心血管病变、心律失常，甚至心力衰竭，目前已知其起始要素是心肌能量重建。在美国和其他地方，关于雷公藤红素预防这种情况的能力的研究有限。由于雷公藤红醇是否能够逆转早期能量重塑过程尚不清楚，因此推测雷公藤内酯醇雷公藤红素适合逆转DCM早期心肌能量重塑。我们的目标是预测雷公藤红素逆转 DCM 早期能量重塑的目标和潜在机制。方法。利用 TCMSP 和 GEO 数据库的数据来确定 DCM 上雷公藤红素的靶标。通过Spearman相关分析得出主要靶点与常规糖脂代谢之间的关系。动物实验采用健康对照组（HC）、低剂量雷公藤红素干预组（CL）和无干预组（NC），每组8只SD大鼠。为了研究信号分子的变化，进行了 RT-PCR。结果。雷公藤红素-DCM 有 76 个共同靶标和 5 个主要靶标。研究发现雷公藤红素可调节 AGE-RAGE、TNF、MAPK、TOLL 样受体、胰岛素抵抗等信号通路，并且与 DCM 中的脂肪细胞因子、脂肪酸代谢、糖脂生物合成和糖基磷酸肌醇生物合成密切相关。已发现这五个主要目标可以调节这些途径。 大鼠实验表明，与HC组相比，CL组和NC组大鼠心脏组织中P38 MAPK显着升高，且差异有统计学意义（）。 CL组和NC组之间P38 MAPK水平存在显着性差异，统计学显着性水平小于0.05。结论。雷公藤红素可能通过调节 MAPK 通路中 p38 蛋白的表达，在逆转能量重塑、抗炎和氧化应激方面发挥作用，这已在 DCM 的治疗中得到证实。