Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Biochemistry, Traian Vuia 6, 020956 Bucharest, Romania.
Carol Davila University of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacology, Traian Vuia 6, 020956 Bucharest, Romania.
Ageing Res Rev. 2023 Jul;88:101936. doi: 10.1016/j.arr.2023.101936. Epub 2023 Apr 26.
Sirtuins are a family of NAD-dependent deacylases with numerous physiological and pathological implications, which lately became an attractive therapeutic target. Sirtuin-activating compounds (STACs) could be useful in disease prevention and treatment. Despite its bioavailability issues, resveratrol exerts a myriad of beneficial effects, known as the "resveratrol paradox". Modulation of sirtuins' expression and activity may, in fact, underlie many of resveratrol revered actions; however, the cellular pathways affected by modulating the activity of each sirtuin isoform, in different physio-pathological conditions, are not fully known. The purpose of this review was to summarize recent reports concerning the effects of resveratrol on the activity of sirtuins in different experimental settings, focusing on in vitro and in vivo preclinical studies. Most reports concern SIRT1, however recent studies dive into the effects initiated via other isoforms. Numerous cellular signaling pathways were reported to be modulated by resveratrol in a sirtuin-dependent manner (increased phosphorylation of MAPKs, AKT, AMPK, RhoA, BDNF, decreased activation of NLRP3 inflammasome, NF-κB, STAT3, upregulation of SIRT1/SREBP1c pathway, reduced β-amyloid via SIRT1-NF-κB-BACE1 signaling and counteracting mitochondrial damage by deacetylating PGC-1α). Thus, resveratrol may be the ideal candidate in the search for STACs as a tool for preventing and treating inflammatory and neurodegenerative diseases.
去乙酰化酶 Sirtuins 是一类依赖 NAD 的去酰基酶，具有许多生理和病理意义，最近成为一个有吸引力的治疗靶点。Sirtuin 激活化合物 (STACs) 可用于疾病的预防和治疗。尽管存在生物利用度问题，但白藜芦醇发挥了许多有益的作用，这被称为“白藜芦醇悖论”。事实上，调节 Sirtuins 的表达和活性可能是白藜芦醇许多受推崇作用的基础；然而，在不同的生理病理条件下，调节每种 Sirtuin 同工型活性所影响的细胞途径尚不完全清楚。本综述的目的是总结最近关于白藜芦醇在不同实验条件下对 Sirtuins 活性影响的报道，重点关注体外和体内临床前研究。大多数报道涉及 SIRT1，然而最近的研究深入探讨了其他同工型引发的作用。许多细胞信号通路被报道以 Sirtuins 依赖的方式被白藜芦醇调节（MAPKs、AKT、AMPK、RhoA、BDNF 的磷酸化增加，NLRP3 炎性小体、NF-κB、STAT3 的激活减少，SIRT1/SREBP1c 通路的上调，通过 SIRT1-NF-κB-BACE1 信号减少β-淀粉样蛋白，通过去乙酰化 PGC-1α 对抗线粒体损伤）。因此，白藜芦醇可能是寻找 STACs 的理想候选物，作为预防和治疗炎症和神经退行性疾病的工具。
