Natural Phytochemicals As SIRT Activators-Focus on Potential Biochemical Mechanisms

Overview

Journal Nutrients

Date 2023 Aug 26

PMID 37630770

Authors

Michal Wicinski

Jakub Erdmann

Agnieszka Nowacka

Oskar Kuzminski

Klaudia Michalak

Kacper Janowski

Jakub Ohla

Adrian Biernaciak

Monika Szambelan

Jan Zabrzynski

Affiliations

Soon will be listed here.

Abstract

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.

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References

Tomaselli D, Steegborn C, Mai A, Rotili D . Sirt4: A Multifaceted Enzyme at the Crossroads of Mitochondrial Metabolism and Cancer. Front Oncol. 2020; 10:474. PMC: 7177044. DOI: 10.3389/fonc.2020.00474. View

Zhang M, Tang J, Li Y, Xie Y, Shan H, Chen M . Curcumin attenuates skeletal muscle mitochondrial impairment in COPD rats: PGC-1α/SIRT3 pathway involved. Chem Biol Interact. 2017; 277:168-175. DOI: 10.1016/j.cbi.2017.09.018. View

Heshmati J, Golab F, Morvaridzadeh M, Potter E, Akbari-Fakhrabadi M, Farsi F . The effects of curcumin supplementation on oxidative stress, Sirtuin-1 and peroxisome proliferator activated receptor γ coactivator 1α gene expression in polycystic ovarian syndrome (PCOS) patients: A randomized placebo-controlled clinical trial. Diabetes Metab Syndr. 2020; 14(2):77-82. DOI: 10.1016/j.dsx.2020.01.002. View

Sun Q, Jia N, Wang W, Jin H, Xu J, Hu H . Activation of SIRT1 by curcumin blocks the neurotoxicity of amyloid-β25-35 in rat cortical neurons. Biochem Biophys Res Commun. 2014; 448(1):89-94. DOI: 10.1016/j.bbrc.2014.04.066. View

DiNicolantonio J, McCarty M, OKeefe J . Nutraceutical activation of Sirt1: a review. Open Heart. 2022; 9(2). PMC: 9756291. DOI: 10.1136/openhrt-2022-002171. View

BinMowyna M, ALFaris N . Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1. Pharm Biol. 2021; 59(1):146-156. PMC: 8871688. DOI: 10.1080/13880209.2021.1877734. View

McCubrey J, Lertpiriyapong K, Steelman L, Abrams S, Yang L, Murata R . Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY). 2017; 9(6):1477-1536. PMC: 5509453. DOI: 10.18632/aging.101250. View

Zhou S, Sun L, Qian S, Ma Y, Ma R, Dong Y . Iron overload adversely effects bone marrow haematogenesis via SIRT-SOD2-mROS in a process ameliorated by curcumin. Cell Mol Biol Lett. 2021; 26(1):2. PMC: 7805071. DOI: 10.1186/s11658-020-00244-7. View

Melk A . Senescence of renal cells: molecular basis and clinical implications. Nephrol Dial Transplant. 2003; 18(12):2474-8. DOI: 10.1093/ndt/gfg322. View

10.

Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S . SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ. 2017; 25(2):229-240. PMC: 5762839. DOI: 10.1038/cdd.2017.144. View

11.

Zheng W, Feng Z, You S, Zhang H, Tao Z, Wang Q . Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol. 2017; 45:135-147. DOI: 10.1016/j.intimp.2017.02.009. View

12.

Tan M, Peng C, Anderson K, Chhoy P, Xie Z, Dai L . Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014; 19(4):605-17. PMC: 4108075. DOI: 10.1016/j.cmet.2014.03.014. View

13.

Lee J, Choi M, Ro S, Yang W, Cho A, Ju H . Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1. Eur J Cancer Prev. 2015; 25(1):54-64. PMC: 4885538. DOI: 10.1097/CEJ.0000000000000141. View

14.

Fouquerel E, Goellner E, Yu Z, Gagne J, Barbi de Moura M, Feinstein T . ARTD1/PARP1 negatively regulates glycolysis by inhibiting hexokinase 1 independent of NAD+ depletion. Cell Rep. 2014; 8(6):1819-1831. PMC: 4177344. DOI: 10.1016/j.celrep.2014.08.036. View

15.

Zou P, Liu X, Li G, Wang Y . Resveratrol pretreatment attenuates traumatic brain injury in rats by suppressing NLRP3 inflammasome activation via SIRT1. Mol Med Rep. 2017; 17(2):3212-3217. DOI: 10.3892/mmr.2017.8241. View

16.

Sharma A, Sinha S, Keswani H, Shrivastava N . Kaempferol and Apigenin suppresses the stemness properties of TNBC cells by modulating Sirtuins. Mol Divers. 2022; 26(6):3225-3240. DOI: 10.1007/s11030-022-10384-x. View

17.

Tsuda T . Curcumin as a functional food-derived factor: degradation products, metabolites, bioactivity, and future perspectives. Food Funct. 2017; 9(2):705-714. DOI: 10.1039/c7fo01242j. View

18.

Lewinska A, Wnuk M, Grabowska W, Zabek T, Semik E, Sikora E . Curcumin induces oxidation-dependent cell cycle arrest mediated by SIRT7 inhibition of rDNA transcription in human aortic smooth muscle cells. Toxicol Lett. 2015; 233(3):227-38. DOI: 10.1016/j.toxlet.2015.01.019. View

19.

Murtaza G, Khan A, Rashid R, Muneer S, Hasan S, Chen J . FOXO Transcriptional Factors and Long-Term Living. Oxid Med Cell Longev. 2017; 2017:3494289. PMC: 5574317. DOI: 10.1155/2017/3494289. View

20.

Lee Y, Song N, Suh J, Kim D, Kim W, Ann J . Curcumin suppresses oncogenicity of human colon cancer cells by covalently modifying the cysteine 67 residue of SIRT1. Cancer Lett. 2018; 431:219-229. DOI: 10.1016/j.canlet.2018.05.036. View