Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Overview

Journal Metabolites

Publisher MDPI

Date 2024 Mar 27

PMID 38535306

Authors

Eleni Mavrogonatou

Dimitris Kletsas

Affiliations

Soon will be listed here.

Abstract

Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration. The mode of action of these senotherapeutics, as well as the challenges in their practical application, will also be explicitly discussed in an attempt to direct their more targeted and effective use in exclusive or combinatorial therapeutic schemes for the prevention and/or treatment of disc degenerative disorders.

Citing Articles

Investigating the Effects of Chelidonic Acid on Oxidative Stress-Induced Premature Cellular Senescence in Human Skin Fibroblast Cells.

Turkoglu B, Mansuroglu B Life (Basel). 2024; 14(9).

PMID: 39337855 PMC: 11433492. DOI: 10.3390/life14091070.

References

Jung Y, Kim J, Choi Y, Lee S, Kang K, Kim Y . Eupatilin with PPARα agonistic effects inhibits TNFα-induced MMP signaling in HaCaT cells. Biochem Biophys Res Commun. 2017; 493(1):220-226. DOI: 10.1016/j.bbrc.2017.09.043. View

Liao S, Meng H, Li J, Zhao J, Xu Y, Wang A . Potential and recent advances of microcarriers in repairing cartilage defects. J Orthop Translat. 2021; 27:101-109. PMC: 7810913. DOI: 10.1016/j.jot.2020.10.005. View

Hsiao H, Lin H, Wu J, Lin W . Kinsenoside prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis by regulating classical NF-κB pathways. Osteoporos Int. 2012; 24(5):1663-76. PMC: 3627854. DOI: 10.1007/s00198-012-2199-z. View

Li X, Phillips F, An H, Ellman M, Thonar E, Wu W . The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine (Phila Pa 1976). 2008; 33(24):2586-95. PMC: 2905225. DOI: 10.1097/BRS.0b013e3181883883. View

Ashinsky B, Bonnevie E, Mandalapu S, Pickup S, Wang C, Han L . Intervertebral Disc Degeneration Is Associated With Aberrant Endplate Remodeling and Reduced Small Molecule Transport. J Bone Miner Res. 2020; 35(8):1572-1581. PMC: 8207249. DOI: 10.1002/jbmr.4009. View

Chen Y, Tsai K, Chan D, Lan K, Chen C, Yang R . Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes. J Orthop Res. 2013; 32(4):573-80. DOI: 10.1002/jor.22577. 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

Wang W, Yang R, Zhang M, Li J, Peng J, Xu M . Glycitin Suppresses Cartilage Destruction of Osteoarthritis in Mice. Inflammation. 2020; 43(4):1312-1322. DOI: 10.1007/s10753-020-01210-3. View

Wang W, Jing X, Du T, Ren J, Liu X, Chen F . Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes. Free Radic Biol Med. 2022; 190:234-246. DOI: 10.1016/j.freeradbiomed.2022.08.018. View

10.

Shi Y, Hua Q, Li N, Zhao M, Cui Y . Protective Effects of Evodiamine against LPS-Induced Acute Kidney Injury through Regulation of ROS-NF-B-Mediated Inflammation. Evid Based Complement Alternat Med. 2019; 2019:2190847. PMC: 6421037. DOI: 10.1155/2019/2190847. View

11.

Chung S, Yao H, Caito S, Hwang J, Arunachalam G, Rahman I . Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys. 2010; 501(1):79-90. PMC: 2930135. DOI: 10.1016/j.abb.2010.05.003. View

12.

Ding F, Li X . Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor α (TNF-α) Signaling Pathway. Med Sci Monit. 2020; 26:e924587. PMC: 7523418. DOI: 10.12659/MSM.924587. View

13.

Rivas-Chacon L, Yanes-Diaz J, De Lucas B, Riestra-Ayora J, Madrid-Garcia R, Sanz-Fernandez R . Cocoa Polyphenol Extract Inhibits Cellular Senescence via Modulation of SIRT1 and SIRT3 in Auditory Cells. Nutrients. 2023; 15(3). PMC: 9921725. DOI: 10.3390/nu15030544. View

14.

Dai S, Wang H, Wang M, Zhang Y, Zhang Z, Lin Z . Comparative transcriptomics and network pharmacology analysis to identify the potential mechanism of celastrol against osteoarthritis. Clin Rheumatol. 2021; 40(10):4259-4268. DOI: 10.1007/s10067-021-05726-3. View

15.

Gao G, Chang F, Zhang T, Huang X, Yu C, Hu Z . Naringin Protects Against Interleukin 1β (IL-1β)-Induced Human Nucleus Pulposus Cells Degeneration via Downregulation Nuclear Factor kappa B (NF-κB) Pathway and p53 Expression. Med Sci Monit. 2020; 25:9963-9972. PMC: 6944037. DOI: 10.12659/MSM.918597. View

16.

Mbara K, Devnarain N, Owira P . Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection. Pharmaceut Med. 2022; 36(6):331-352. PMC: 9470070. DOI: 10.1007/s40290-022-00444-w. View

17.

Wang W, Li P, Xu J, Wu X, Guo Z, Fan L . Resveratrol attenuates high glucose-induced nucleus pulposus cell apoptosis and senescence through activating the ROS-mediated PI3K/Akt pathway. Biosci Rep. 2017; 38(2). PMC: 5897744. DOI: 10.1042/BSR20171454. View

18.

Singireesu S, Mondal S, Misra S, Yerramsetty S, K S . Dehydrocostus lactone induces prominent apoptosis in kidney distal tubular epithelial cells and interstitial fibroblasts along with cell cycle arrest in ovarian epithelial cells. Biomed Pharmacother. 2018; 99:956-969. DOI: 10.1016/j.biopha.2018.01.099. View

19.

Yamaura K, Nelson A, Nishimura H, Rutledge J, Ravuri S, Bahney C . The effects of fisetin on bone and cartilage: A systematic review. Pharmacol Res. 2022; 185:106504. DOI: 10.1016/j.phrs.2022.106504. View

20.

Hwang M, Son H, Kim J, Choi H . In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration. Sci Rep. 2020; 10(1):20596. PMC: 7691345. DOI: 10.1038/s41598-020-77785-6. View