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AMP激酶:治疗新冠后遗症的一个有前景的药物靶点。

AMP kinase: A promising therapeutic drug target for post-COVID-19 complications.

作者信息

Ashraf Mohammad Saquib, Tuli Kanika, Moiz Shadman, Sharma Satish Kumar, Sharma Deepa, Adnan Mohd

机构信息

Department of Medical Laboratory Science College of Pharmacy, Nursing and Medical Science Riyadh ELM University, Riyadh, P.O. Box 12734, Saudi Arabia.

Guru Nanak Institute of Pharmacy, Dalewal, Hoshiarpur 144208, Punjab, India.

出版信息

Life Sci. 2024 Dec 15;359:123202. doi: 10.1016/j.lfs.2024.123202. Epub 2024 Nov 1.

DOI:10.1016/j.lfs.2024.123202
PMID:39489398
Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life.

摘要

由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的2019冠状病毒病(COVID-19)大流行已导致严重的呼吸问题和持续的并发症,尤其影响葡萄糖代谢。有或没有糖尿病病史的患者症状往往会加重,这凸显了创新治疗方法的必要性。腺苷酸活化蛋白激酶(AMPK)是细胞能量平衡的关键调节因子,在葡萄糖代谢、胰岛素敏感性和炎症反应中起关键作用。通过变构或激酶依赖性机制激活AMPK,会影响葡萄糖摄取、脂肪酸氧化和自噬等细胞过程。AMPK的组织特异性分布强调了其在维持全身代谢稳态中的作用。有趣的是,SARS-CoV-2感染会抑制AMPK,导致代谢失调和COVID-19后的并发症。辣椒素类、姜黄素、植物雌激素、西洛他唑和罗汉果甜苷等AMPK激活剂已显示出调节AMPK活性的潜力。来自各种来源的化合物可改善脂肪酸氧化和胰岛素敏感性,二甲双胍与病毒相比对AMPK激活具有相反的作用,提示了潜在的治疗选择。AMPK激活的多种作用扩展到其在对抗病毒感染中的作用,进一步凸显了其在COVID-19中的重要性。本综述探讨了AMPK激活机制、其在代谢紊乱中的作用以及天然化合物针对COVID-19后并发症靶向AMPK的潜在用途。此外,它旨在综述激活AMPK以预防COVID-19后糖尿病和心血管并发症的可能方法。它还探讨了天然化合物在靶向AMPK途径中的治疗作用。靶向AMPK激活成为减轻COVID-19长期影响的有希望的途径,为改善患者预后和提高生活质量带来了希望。

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