Zhang Tao, Xu Lei, Guo Xiaowei, Tao Honglin, Liu Yue, Liu Xianfeng, Zhang Yi, Meng Xianli
State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
J Pharm Anal. 2024 Feb;14(2):157-176. doi: 10.1016/j.jpha.2023.09.001. Epub 2023 Sep 27.
Heart failure (HF) is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic burden. In addition to cardiac myocyte oxidative stress and apoptosis, which are considered mechanisms for the development of HF, alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately HF. Silent information regulator 1 (Sirt1) and adenosine monophosphate-activated protein kinase (AMPK) are nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and phosphorylated kinases, respectively. They play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), protein 38 mitogen-activated protein kinase (p38 MAPK), peroxisome proliferator-activated receptors (PPARs), and mammalian target of rapamycin (mTOR). We summarized the synergistic effects of Sirt1 and AMPK in the heart, and listed the traditional Chinese medicine (TCM) that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway, to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases (CVDs).
心力衰竭(HF)是一种高发病率的综合征,严重影响患者的身心健康,并产生巨大的社会经济负担。除了被认为是HF发生机制的心肌细胞氧化应激和凋亡外,心脏能量代谢的改变和病理性自噬也会导致心脏异常并最终引发HF。沉默信息调节因子1(Sirt1)和腺苷单磷酸激活蛋白激酶(AMPK)分别是烟酰胺腺嘌呤二核苷酸(NAD)依赖性脱乙酰酶和磷酸化激酶。它们通过调节过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)、丝裂原活化蛋白激酶38(p38 MAPK)、过氧化物酶体增殖物激活受体(PPARs)和雷帕霉素靶蛋白(mTOR)等靶点,在调节心脏的一些病理过程中发挥相似作用。我们总结了Sirt1和AMPK在心脏中的协同作用,并列出了通过调节Sirt1/AMPK途径发挥心脏保护作用的中药,为开发用于治疗HF和其他心血管疾病(CVDs)的Sirt1/AMPK激活剂或抑制剂提供依据。