Monoterpenes As Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2022 Jul 27

PMID 35883477

Authors

Catia Sousa

Alexandrina Ferreira Mendes

Affiliations

Soon will be listed here.

Abstract

Sirtuin 1 (SIRT) is a class III, NAD-dependent histone deacetylase that also modulates the activity of numerous non-histone proteins through deacylation. SIRT1 plays critical roles in regulating and integrating cellular energy metabolism, response to stress, and circadian rhythm by modulating epigenetic and transcriptional regulation, mitochondrial homeostasis, proteostasis, telomere maintenance, inflammation, and the response to hypoxia. SIRT1 expression and activity decrease with aging, and enhancing its activity extends life span in various organisms, including mammals, and improves many age-related diseases, including cancer, metabolic, cardiovascular, neurodegenerative, respiratory, musculoskeletal, and renal diseases, but the opposite, that is, aggravation of various diseases, such as some cancers and neurodegenerative diseases, has also been reported. Accordingly, many natural and synthetic SIRT1 activators and inhibitors have been developed. Known SIRT1 activators of natural origin are mainly polyphenols. Nonetheless, various classes of non-polyphenolic monoterpenoids have been identified as inducers of SIRT1 expression and/or activity. This narrative review discusses current information on the evidence that supports the role of those compounds as SIRT1 activators and their potential both as tools for research and as pharmaceuticals for therapeutic application in age-related diseases.

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References

Zhu F, Wang J, Zhang Y, Hu Y, Yue Z, Zeng L . Mechanisms underlying the antiapoptotic and anti-inflammatory effects of monotropein in hydrogen peroxide-treated osteoblasts. Mol Med Rep. 2016; 14(6):5377-5384. DOI: 10.3892/mmr.2016.5908. View

Delerive P, Monte D, Dubois G, Trottein F, Fruchart-Najib J, Mariani J . The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response. EMBO Rep. 2001; 2(1):42-8. PMC: 1083804. DOI: 10.1093/embo-reports/kve007. View

Nakagawa T, Guarente L . SnapShot: sirtuins, NAD, and aging. Cell Metab. 2014; 20(1):192-192.e1. DOI: 10.1016/j.cmet.2014.06.001. View

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

Dvir-Ginzberg M, Gagarina V, Lee E, Booth R, Gabay O, Hall D . Tumor necrosis factor α-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes. Arthritis Rheum. 2011; 63(8):2363-73. PMC: 3174010. DOI: 10.1002/art.30279. View

Ma Z, Kong C, Song P, Zhang X, Yuan Y, Tang Q . Geniposide Protects against Obesity-Related Cardiac Injury through AMPK- and Sirt1-Dependent Mechanisms. Oxid Med Cell Longev. 2018; 2018:6053727. PMC: 6247476. DOI: 10.1155/2018/6053727. View

Kong S, McBurney M, Fang D . Sirtuin 1 in immune regulation and autoimmunity. Immunol Cell Biol. 2011; 90(1):6-13. DOI: 10.1038/icb.2011.102. View

Kim K, Shim S, Ahn H, Jung S . Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage. Toxicol Appl Pharmacol. 2013; 269(2):109-20. DOI: 10.1016/j.taap.2013.03.017. View

Hong H, Maury E, Ramsey K, Perelis M, Marcheva B, Omura C . Requirement for NF-κB in maintenance of molecular and behavioral circadian rhythms in mice. Genes Dev. 2018; 32(21-22):1367-1379. PMC: 6217733. DOI: 10.1101/gad.319228.118. View

10.

Pina L, Serafini M, Oliveira M, Sampaio L, Guimaraes J, Guimaraes A . Carvone and its pharmacological activities: A systematic review. Phytochemistry. 2022; 196:113080. DOI: 10.1016/j.phytochem.2021.113080. View

11.

Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F . SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008; 134(2):317-28. DOI: 10.1016/j.cell.2008.06.050. View

12.

Wang Y, Lv D, Liu W, Li S, Chen J, Shen Y . Disruption of the Circadian Clock Alters Antioxidative Defense via the SIRT1-BMAL1 Pathway in 6-OHDA-Induced Models of Parkinson's Disease. Oxid Med Cell Longev. 2018; 2018:4854732. PMC: 5932489. DOI: 10.1155/2018/4854732. View

13.

Morselli E, Maiuri M, Markaki M, Megalou E, Pasparaki A, Palikaras K . Caloric restriction and resveratrol promote longevity through the Sirtuin-1-dependent induction of autophagy. Cell Death Dis. 2011; 1:e10. PMC: 3032517. DOI: 10.1038/cddis.2009.8. View

14.

Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D . The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008; 134(2):329-40. PMC: 3526943. DOI: 10.1016/j.cell.2008.07.002. View

15.

Gomes P, Leal H, Mendes A, Reis F, Cavadas C . Dichotomous Sirtuins: Implications for Drug Discovery in Neurodegenerative and Cardiometabolic Diseases. Trends Pharmacol Sci. 2019; 40(12):1021-1039. DOI: 10.1016/j.tips.2019.09.003. View

16.

Yang W, Kang X, Liu J, Li H, Ma Z, Jin X . Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1. Endocrinology. 2016; 157(8):3096-107. PMC: 4967114. DOI: 10.1210/en.2015-2042. View

17.

Yuan J, Cheng W, Zhang G, Ma Q, Li X, Zhang B . Protective effects of iridoid glycosides on acute colitis via inhibition of the inflammatory response mediated by the STAT3/NF-кB pathway. Int Immunopharmacol. 2020; 81:106240. DOI: 10.1016/j.intimp.2020.106240. View

18.

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View

19.

Nikseresht S, Khodagholi F, Ahmadiani A . Protective effects of ex-527 on cerebral ischemia-reperfusion injury through necroptosis signaling pathway attenuation. J Cell Physiol. 2018; 234(2):1816-1826. DOI: 10.1002/jcp.27055. View

20.

Sousa C, Leitao A, Miguel Neves B, Judas F, Cavaleiro C, Ferreira Mendes A . Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity. Sci Rep. 2020; 10(1):7199. PMC: 7190660. DOI: 10.1038/s41598-020-64032-1. View