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广藿香醇通过JAK2/STAT3信号通路保护心脏免受糖尿病相关心肌病的侵害。

Patchouli Alcohol Protects the Heart against Diabetes-Related Cardiomyopathy through the JAK2/STAT3 Signaling Pathway.

作者信息

Ji Lijun, Lou Shuaijie, Fang Yi, Wang Xu, Zhu Weiwei, Liang Guang, Lee Kwangyoul, Luo Wu, Zhuang Zaishou

机构信息

The Affiliated Cangnan Hospital and Chemical Biology Research Center, Wenzhou Medical University, Wenzhou 325000, China.

College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.

出版信息

Pharmaceuticals (Basel). 2024 May 14;17(5):631. doi: 10.3390/ph17050631.

Abstract

Diabetic cardiomyopathy (DCM) represents a common pathological state brought about by diabetes mellitus (DM). Patchouli alcohol (PatA) is known for its diverse advantageous effects, notably its anti-inflammatory properties and protective role against metabolic disorders. Despite this, the influence of PatA on DCM remains relatively unexplored. To explore the effect of PatA on diabetes-induced cardiac injury and dysfunction in mice, streptozotocin (STZ) was used to mimic type 1 diabetes in mice. Serological markers and echocardiography show that PatA treatment protects the heart against cardiomyopathy by controlling myocardial fibrosis but not by reducing hyperglycemia in diabetic mice. Discovery Studio 2017 software was used to perform reverse target screening of PatA, and we found that JAK2 may be a potential target of PatA. RNA-seq analysis of heart tissues revealed that PatA activity in the myocardium was primarily associated with the inflammatory fibrosis through the Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of the transcription 3 (STAT3) pathway. In vitro, we also found that PatA alleviates high glucose (HG) + palmitic acid (PA)-induced fibrotic and inflammatory responses via inhibiting the JAK2/STAT3 signaling pathway in H9C2 cells. Our findings illustrate that PatA mitigates the effects of HG + PA- or STZ-induced cardiomyopathy by acting on the JAK2/STAT3 signaling pathway. These insights indicate that PatA could potentially serve as a therapeutic agent for DCM treatment.

摘要

糖尿病性心肌病(DCM)是由糖尿病(DM)引发的一种常见病理状态。广藿香醇(PatA)因其多种有益作用而闻名,尤其是其抗炎特性以及对代谢紊乱的保护作用。尽管如此,PatA对DCM的影响仍相对未被探索。为了探究PatA对糖尿病诱导的小鼠心脏损伤和功能障碍的影响,使用链脲佐菌素(STZ)在小鼠中模拟1型糖尿病。血清学标志物和超声心动图显示,PatA治疗通过控制心肌纤维化保护心脏免受心肌病影响,但不是通过降低糖尿病小鼠的高血糖来实现。使用Discovery Studio 2017软件对PatA进行反向靶点筛选,我们发现JAK2可能是PatA的潜在靶点。对心脏组织的RNA测序分析表明,PatA在心肌中的活性主要通过Janus酪氨酸激酶2(JAK2)/信号转导和转录激活因子3(STAT3)途径与炎症纤维化相关。在体外,我们还发现PatA通过抑制H9C2细胞中的JAK2/STAT3信号通路减轻高糖(HG)+棕榈酸(PA)诱导的纤维化和炎症反应。我们的研究结果表明,PatA通过作用于JAK2/STAT3信号通路减轻HG + PA或STZ诱导的心肌病的影响。这些见解表明,PatA可能潜在地用作DCM治疗的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d94f/11124524/3596a1761d41/pharmaceuticals-17-00631-g001.jpg

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