Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

Zhifu Cui; Xingtao Zhao; Felix Kwame Amevor; Xiaxia Du; Yan Wang; Diyan Li; Gang Shu; Yaofu Tian; Xiaoling Zhao

doi:10.3389/fimmu.2022.943321

Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism

Front Immunol. 2022 Jul 22:13:943321. doi: 10.3389/fimmu.2022.943321. eCollection 2022.

Authors

Zhifu Cui¹, Xingtao Zhao², Felix Kwame Amevor¹, Xiaxia Du¹, Yan Wang¹, Diyan Li¹, Gang Shu³, Yaofu Tian¹, Xiaoling Zhao¹

Affiliations

¹ Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.
² State Key Laboratory of Southwestern Chinese Medicine Resources, Ministry of Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
³ Department of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Abstract

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in the treatment of aging-related diseases. Sirtuin 1 (SIRT1), a member of NAD⁺-dependent deacetylase enzyme family, is extensively explored as a potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against aging-related diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) and reperfusion (MI/R), Atherosclerosis (AS), and Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, SIRT1 regulates cellular senescence and multiple aging-related cellular processes, including SIRT1/Keap1/Nrf2/HO-1 and SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB and SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP and SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mediated mitochondrial damage, SIRT1/FoxO mediated autophagy, and SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin mediated neuroprotective effects. In this review, we summarized the role of SIRT1 in the improvement of the attenuation effect of quercetin on aging-related diseases and the relationship between relevant signaling pathways regulated by SIRT1. Moreover, the functional regulation of quercetin in aging-related markers such as oxidative stress, inflammatory response, mitochondrial function, autophagy and apoptosis through SIRT1 was discussed. Finally, the prospects of an extracellular vesicles (EVs) as quercetin loading and delivery, and SIRT1-mediated EVs as signal carriers for treating aging-related diseases, as well as discussed the ferroptosis alleviation effects of quercetin to protect against aging-related disease via activating SIRT1. Generally, SIRT1 may serve as a promising therapeutic target in the treatment of aging-related diseases via inhibiting oxidative stress, reducing inflammatory responses, and restoring mitochondrial dysfunction.

Keywords: aging-related diseases; inflammatory response; mitochondrial dysfunction; oxidative stress; quercetin; sirtuin 1.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Cellular Senescence
Glycogen Synthase Kinase 3 beta / metabolism
Kelch-Like ECH-Associated Protein 1 / metabolism
NF-E2-Related Factor 2 / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Quercetin* / pharmacology
Quercetin* / therapeutic use
Sirtuin 1* / metabolism

Substances

Kelch-Like ECH-Associated Protein 1
NF-E2-Related Factor 2
Quercetin
Glycogen Synthase Kinase 3 beta
Sirtuin 1