{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:31:52Z","timestamp":1792089112156,"version":"4.4.0"},"reference-count":298,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Metabolites"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/metabo14030146","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T06:14:22Z","timestamp":1709100862000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-6426","authenticated-orcid":false,"given":"Eleni","family":"Mavrogonatou","sequence":"first","affiliation":[{"name":"Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9828-3963","authenticated-orcid":false,"given":"Dimitris","family":"Kletsas","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research \u201cDemokritos\u201d, 15341 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.tibs.2020.03.008","article-title":"Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases","volume":"45","author":"Song","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/febs.16350","article-title":"Targeting cellular senescence with senotherapeutics: Senolytics and senomorphics","volume":"290","author":"Zhang","year":"2023","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mannarino, M., Wu-Martinez, O., Sheng, K., Li, L., Navarro-Ramirez, R., Jarzem, P., Ouellet, J.A., Cherif, H., and Haglund, L. (2023). Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs. Biomolecules, 13.","DOI":"10.3390\/biom13081257"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"The Lancet Rheumatology (2023). The global epidemic of low back pain. Lancet Rheumatol., 5, e305.","DOI":"10.1016\/S2665-9913(23)00133-9"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1172920","DOI":"10.3389\/fphar.2023.1172920","article-title":"Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration","volume":"14","author":"Xu","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/ar629","article-title":"Degeneration of the intervertebral disc","volume":"5","author":"Urban","year":"2003","journal-title":"Arthritis Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1007\/s00586-007-0475-y","article-title":"A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat","volume":"16","author":"Lee","year":"2007","journal-title":"Eur. Spine J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1042\/bst0300858","article-title":"The role of the physicochemical environment in determining disc cell behaviour","volume":"30","author":"Urban","year":"2002","journal-title":"Biochem. Soc. Trans."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.mad.2018.05.007","article-title":"Major traits of the senescent phenotype of nucleus pulposus intervertebral disc cells persist under the specific microenvironmental conditions of the tissue","volume":"177","author":"Kouroumalis","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.dnarep.2009.05.005","article-title":"High osmolality activates the G1 and G2 cell cycle checkpoints and affects the DNA integrity of nucleus pulposus intervertebral disc cells triggering an enhanced DNA repair response","volume":"8","author":"Mavrogonatou","year":"2009","journal-title":"DNA Repair"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.22203\/eCM.v030a07","article-title":"Oxidative stress inhibits the proliferation, induces premature senescence and promotes a catabolic phenotype in human nucleus pulposus intervertebral disc cells","volume":"30","author":"Dimozi","year":"2015","journal-title":"Eur. Cells Mater."},{"key":"ref_13","first-page":"9963677","article-title":"Natural Products of Pharmacology and Mechanisms in Nucleus Pulposus Cells and Intervertebral Disc Degeneration","volume":"2021","author":"Chen","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1076","DOI":"10.1002\/jsp2.1076","article-title":"Pathomechanism of intervertebral disc degeneration","volume":"3","author":"Oichi","year":"2020","journal-title":"JOR Spine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Perera, R.S., Dissanayake, P.H., Senarath, U., Wijayaratne, L.S., Karunanayake, A.L., and Dissanayake, V.H.W. (2017). Associations between disc space narrowing, anterior osteophytes and disability in chronic mechanical low back pain: A cross sectional study. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1562-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110358","DOI":"10.1016\/j.ejrad.2022.110358","article-title":"Evaluation of intervertebral disc degeneration using T2 signal ratio on magnetic resonance imaging","volume":"152","author":"Kamei","year":"2022","journal-title":"Eur. J. Radiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5398","DOI":"10.1038\/s41598-022-09348-w","article-title":"Comparison of MRI T1, T2, and T2* mapping with histology for assessment of intervertebral disc degeneration in an ovine model","volume":"12","author":"Bouhsina","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","article-title":"Hallmarks of aging: An expanding universe","volume":"186","author":"Blasco","year":"2023","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kumari, R., and Jat, P. (2021). Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645593"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.matbio.2017.10.004","article-title":"Extracellular matrix alterations in senescent cells and their significance in tissue homeostasis","volume":"75\u201376","author":"Mavrogonatou","year":"2019","journal-title":"Matrix Biol. J. Int. Soc. Matrix Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"C633","DOI":"10.1152\/ajpcell.00178.2023","article-title":"Senescence-associated alterations in the extracellular matrix: Deciphering their role in the regulation of cellular function","volume":"325","author":"Mavrogonatou","year":"2023","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_23","first-page":"9503562","article-title":"Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tominaga, K. (2015). The emerging role of senescent cells in tissue homeostasis and pathophysiology. Pathobiol. Aging Age Relat. Dis., 5.","DOI":"10.3402\/pba.v5.27743"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S312","DOI":"10.1007\/s00586-006-0126-8","article-title":"Senescence in human intervertebral discs","volume":"15","author":"Roberts","year":"2006","journal-title":"Eur. Spine J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111564","DOI":"10.1016\/j.mad.2021.111564","article-title":"Evaluation of senescent cells in intervertebral discs by lipofuscin staining","volume":"199","author":"Veroutis","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.spinee.2009.05.016","article-title":"Senescent cells in the intervertebral disc: Numbers and mechanisms","volume":"9","author":"Kletsas","year":"2009","journal-title":"Spine J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.spinee.2012.02.027","article-title":"Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration","volume":"13","author":"Vo","year":"2013","journal-title":"Spine J."},{"key":"ref_29","first-page":"21","article-title":"Cell-based therapies for the regeneration of the intervertebral disc: Promises and challenges","volume":"72","author":"Mavrogonatou","year":"2021","journal-title":"Acta Orthop. Traumatol. Hell."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1097\/BRS.0b013e318235457b","article-title":"Comparative effectiveness evidence from the spine patient outcomes research trial: Surgical versus nonoperative care for spinal stenosis, degenerative spondylolisthesis, and intervertebral disc herniation","volume":"36","author":"Tosteson","year":"2011","journal-title":"Spine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12927","DOI":"10.1111\/acel.12927","article-title":"Systemic clearance of p16(INK4a)-positive senescent cells mitigates age-associated intervertebral disc degeneration","volume":"18","author":"Patil","year":"2019","journal-title":"Aging Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e52570","DOI":"10.7554\/eLife.52570","article-title":"p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle","volume":"9","author":"Che","year":"2020","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nature16932","article-title":"Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan","volume":"530","author":"Baker","year":"2016","journal-title":"Nature"},{"key":"ref_35","first-page":"780","article-title":"Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice","volume":"72","author":"Xu","year":"2017","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mad.2019.05.001","article-title":"Emerging senolytic agents derived from natural products","volume":"181","author":"Li","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrd.2017.116","article-title":"Senescent cells: An emerging target for diseases of ageing","volume":"16","author":"Childs","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1002\/med.21702","article-title":"Emerging use of senolytics and senomorphics against aging and chronic diseases","volume":"40","author":"Martel","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s40290-022-00444-w","article-title":"Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection","volume":"36","author":"Mbara","year":"2022","journal-title":"Pharm. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Elshafie, H.S., Camele, I., and Mohamed, A.A. (2023). A Comprehensive Review on the Biological, Agricultural and Pharmaceutical Properties of Secondary Metabolites Based-Plant Origin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043266"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.nutres.2014.07.010","article-title":"Carotenoids, inflammation, and oxidative stress\u2014Implications of cellular signaling pathways and relation to chronic disease prevention","volume":"34","author":"Kaulmann","year":"2014","journal-title":"Nutr. Res."},{"key":"ref_42","first-page":"222","article-title":"Flavonoids: Biosynthesis, biological functions, and biotechnological applications","volume":"3","author":"Rius","year":"2012","journal-title":"Front. Plant Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"176298","DOI":"10.1016\/j.ejphar.2023.176298","article-title":"Fisetin suppresses ferroptosis through Nrf2 and attenuates intervertebral disc degeneration in rats","volume":"964","author":"Li","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.phymed.2016.12.002","article-title":"Butein in health and disease: A comprehensive review","volume":"25","author":"Padmavathi","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xie, C., Shi, Y., Chen, Z., Zhou, X., Luo, P., Hong, C., Tian, N., Wu, Y., Zhou, Y., and Lin, Y. (2021). Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.787278"},{"key":"ref_46","first-page":"7959573","article-title":"The Sirt1\/P53 Axis in Diabetic Intervertebral Disc Degeneration Pathogenesis and Therapeutics","volume":"2019","author":"Zhang","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3892\/etm.2021.11106","article-title":"p-Coumaric acid suppresses reactive oxygen species-induced senescence in nucleus pulposus cells","volume":"23","author":"Sheng","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7810320","DOI":"10.1155\/2019\/7810320","article-title":"Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration","volume":"2019","author":"Kang","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.joca.2019.01.009","article-title":"Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction","volume":"27","author":"Kakiuchi","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cherif, H., Bisson, D.G., Jarzem, P., Weber, M., Ouellet, J.A., and Haglund, L. (2019). Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040433"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"641098","DOI":"10.3389\/fphar.2021.641098","article-title":"Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1\/NF-\u03baB and MAPK Signaling","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wu, C., Zhao, X., Tan, H., Li, C., Deng, Y., Chen, X., Wu, Y., Tian, N., and Zhang, X. (2023). 20-Deoxyingenol alleviates intervertebral disc degeneration by activating TFEB in nucleus pulposus cells. Biochem. Pharmacol., 218.","DOI":"10.1016\/j.bcp.2023.115865"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"940475","DOI":"10.3389\/fphar.2022.940475","article-title":"Eupatilin attenuates the senescence of nucleus pulposus cells and mitigates intervertebral disc degeneration via inhibition of the MAPK\/NF-\u03baB signaling pathway","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xie, T., Gu, X., Pan, R., Huang, W., and Dong, S. (2023). Evodiamine ameliorates intervertebral disc degeneration through the Nrf2 and MAPK pathways. Cytotechnology, 1\u201314.","DOI":"10.1007\/s10616-023-00605-y"},{"key":"ref_55","first-page":"1","article-title":"Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration","volume":"50","author":"Wang","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_56","first-page":"135","article-title":"Pharmacological network analysis of the functions and mechanism of kaempferol from Du Zhong in intervertebral disc degeneration (IDD)","volume":"39","author":"Wang","year":"2023","journal-title":"J. Orthop. Transl."},{"key":"ref_57","first-page":"8786052","article-title":"Systematic Elaboration of the Pharmacological Targets and Potential Mechanisms of ZhiKe GanCao Decoction for Preventing and Delaying Intervertebral Disc Degeneration","volume":"2022","author":"Sun","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7961","DOI":"10.18632\/aging.102302","article-title":"Kinsenoside ameliorates intervertebral disc degeneration through the activation of AKT-ERK1\/2-Nrf2 signaling pathway","volume":"11","author":"Wang","year":"2019","journal-title":"Aging"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3892\/etm.2022.11396","article-title":"Luteolin suppresses TNF-\u03b1-induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6\/NF-\u03baB pathway","volume":"24","author":"Xie","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"942435","DOI":"10.3389\/fphar.2022.942435","article-title":"Morroniside attenuates nucleus pulposus cell senescence to alleviate intervertebral disc degeneration via inhibiting ROS-Hippo-p53 pathway","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13018-022-03463-0","article-title":"Myricetin alleviated hydrogen peroxide-induced cellular senescence of nucleus pulposus cell through regulating SERPINE1","volume":"18","author":"Chen","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"98","DOI":"10.5603\/FHC.a2023.0007","article-title":"Myricetin alleviates H2O2-induced senescence and apoptosis in rat nucleus pulposus-derived mesenchymal stem cells","volume":"61","author":"Xie","year":"2023","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1111\/jcmm.13848","article-title":"Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats","volume":"22","author":"Wang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/03008207.2022.2063121","article-title":"Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K\/Akt pathway delaying intervertebral disc degeneration","volume":"63","author":"Chen","year":"2022","journal-title":"Connect. Tissue Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1038\/s41467-021-25453-2","article-title":"Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice","volume":"12","author":"Novais","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.joca.2020.11.006","article-title":"Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2\/NF-\u03baB axis","volume":"29","author":"Shao","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"842","DOI":"10.4252\/wjsc.v15.i8.842","article-title":"Quercetin ameliorates oxidative stress-induced senescence in rat nucleus pulposus-derived mesenchymal stem cells via the miR-34a-5p\/SIRT1 axis","volume":"15","author":"Zhao","year":"2023","journal-title":"World J. Stem Cells"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E757","DOI":"10.1097\/BRS.0000000000001954","article-title":"Role of Sirt1 Plays in Nucleus Pulposus Cells and Intervertebral Disc Degeneration","volume":"42","author":"Guo","year":"2017","journal-title":"Spine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e54693","DOI":"10.7554\/eLife.54693","article-title":"Senotherapeutic drugs for human intervertebral disc degeneration and low back pain","volume":"9","author":"Cherif","year":"2020","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13075-021-02504-z","article-title":"Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin","volume":"23","author":"Mannarino","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Li, L., Sheng, K., Mannarino, M., Jarzem, P., Cherif, H., and Haglund, L. (2022). o-Vanillin Modulates Cell Phenotype and Extracellular Vesicles of Human Mesenchymal Stem Cells and Intervertebral Disc Cells. Cells, 11.","DOI":"10.3390\/cells11223589"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3945\/an.116.012948","article-title":"Flavones: Food Sources, Bioavailability, Metabolism, and Bioactivity","volume":"8","author":"Hostetler","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s40495-017-0113-2","article-title":"Plant flavone apigenin: An emerging anticancer agent","volume":"3","author":"Shankar","year":"2017","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2174\/1872213X13666190816160240","article-title":"Probing into Therapeutic Anti-cancer Potential of Apigenin: Recent Trends and Future Directions","volume":"13","author":"Sharma","year":"2019","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Salehi, B., Venditti, A., Sharifi-Rad, M., Kr\u0119giel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E.B., and Novellino, E. (2019). The Therapeutic Potential of Apigenin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061305"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.bcp.2015.06.013","article-title":"Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts","volume":"96","author":"Lim","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11357-017-9970-1","article-title":"Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells","volume":"39","author":"Perrott","year":"2017","journal-title":"GeroScience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.canlet.2017.10.041","article-title":"Apigenin: A dietary flavonoid with diverse anticancer properties","volume":"413","author":"Gajski","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ctcp.2015.06.003","article-title":"Efficacy and safety of topical Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: A randomized controlled clinical trial","volume":"21","author":"Shoara","year":"2015","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e13338","DOI":"10.1111\/cpr.13338","article-title":"Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration","volume":"56","author":"Chen","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13448","DOI":"10.1111\/cpr.13448","article-title":"Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment","volume":"56","author":"Wang","year":"2023","journal-title":"Cell Prolif."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.joca.2018.10.011","article-title":"TFEB protects nucleus pulposus cells against apoptosis and senescence via restoring autophagic flux","volume":"27","author":"Zheng","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2020.08.011","article-title":"The therapeutic effect of TBK1 in intervertebral disc degeneration via coordinating selective autophagy and autophagic functions","volume":"30","author":"Hu","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e924587","DOI":"10.12659\/MSM.924587","article-title":"Apigenin Mitigates Intervertebral Disc Degeneration through the Amelioration of Tumor Necrosis Factor \u03b1 (TNF-\u03b1) Signaling Pathway","volume":"26","author":"Ding","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.phytol.2014.12.014","article-title":"Butein: From ancient traditional remedy to modern nutraceutical","volume":"11","author":"Semwal","year":"2015","journal-title":"Phytochem. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/978-3-319-41334-1_17","article-title":"Butein and Its Role in Chronic Diseases","volume":"928","author":"Song","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/j.phymed.2015.08.015","article-title":"Potential of butein, a tetrahydroxychalcone to obliterate cancer","volume":"22","author":"Padmavathi","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.intimp.2016.11.009","article-title":"Butein inhibits IL-1\u03b2-induced inflammatory response in human osteoarthritis chondrocytes and slows the progression of osteoarthritis in mice","volume":"42","author":"Zheng","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/jor.22289","article-title":"Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration","volume":"31","author":"Jiang","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155","DOI":"10.4184\/asj.2015.9.2.155","article-title":"Effect of high glucose on stress-induced senescence of nucleus pulposus cells of adult rats","volume":"9","author":"Kong","year":"2015","journal-title":"Asian Spine J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3765173","DOI":"10.1155\/2016\/3765173","article-title":"High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells","volume":"2016","author":"Cheng","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Illien-J\u00fcnger, S., Lu, Y., Qureshi, S.A., Hecht, A.C., Cai, W., Vlassara, H., Striker, G.E., and Iatridis, J.C. (2015). Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116625"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nature08197","article-title":"Recent progress in the biology and physiology of sirtuins","volume":"460","author":"Finkel","year":"2009","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"24","DOI":"10.5483\/BMBRep.2019.52.1.290","article-title":"Sirtuin signaling in cellular senescence and aging","volume":"52","author":"Lee","year":"2019","journal-title":"BMB Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"E515","DOI":"10.1097\/BRS.0000000000000817","article-title":"SIRT1 Plays a Protective Role in Intervertebral Disc Degeneration in a Puncture-induced Rodent Model","volume":"40","author":"Xia","year":"2015","journal-title":"Spine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3329\/bpj.v26i2.67808","article-title":"Exploring Pharmacological Potentials of p-Coumaric Acid: A Prospective Phytochemical for Drug Discovery","volume":"26","author":"Zaman","year":"2023","journal-title":"Bangladesh Pharm. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.2174\/1389557521666210114163024","article-title":"An Updated Review of Various Medicinal Applications of p-Co umaric Acid: From Antioxidative and Anti-Inflammatory Properties to Effects on Cell Cycle and Proliferation","volume":"21","author":"Abazari","year":"2021","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1080\/10408347.2018.1459173","article-title":"A Review of Analytical Methods for p-Coumaric Acid in Plant-Based Products, Beverages, and Biological Matrices","volume":"49","author":"Ferreira","year":"2019","journal-title":"Crit. Rev. Anal. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/ptr.3095","article-title":"p-coumaric acid not only inhibits human tyrosinase activity in vitro but also melanogenesis in cells exposed to UVB","volume":"24","author":"An","year":"2010","journal-title":"Phytother. Res. PTR"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1017\/S0007114507657882","article-title":"p-Coumaric acid, a common dietary phenol, inhibits platelet activity in vitro and in vivo","volume":"97","author":"Luceri","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3109\/0886022X.2013.835268","article-title":"p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats","volume":"36","author":"Navaneethan","year":"2014","journal-title":"Ren. Fail."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10753-012-9532-8","article-title":"Immunomodulatory and anti-inflammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inflammation in rats","volume":"36","author":"Pragasam","year":"2013","journal-title":"Inflammation"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10753-019-01142-7","article-title":"p-Coumaric Acid Attenuates IL-1\u03b2-Induced Inflammatory Responses and Cellular Senescence in Rat Chondrocytes","volume":"43","author":"Huang","year":"2020","journal-title":"Inflammation"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/biof.1377","article-title":"p-Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails cartilage and bone erosion in the rheumatoid arthritis rat model","volume":"43","author":"Neog","year":"2017","journal-title":"BioFactors"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00296-012-2394-4","article-title":"Ameliorative effect of p-coumaric acid, a common dietary phenol, on adjuvant-induced arthritis in rats","volume":"33","author":"Pragasam","year":"2013","journal-title":"Rheumatol. Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5198594","DOI":"10.1155\/2018\/5198594","article-title":"Anti-Inflammatory Effects of p-Coumaric Acid, a Natural Compound of Oldenlandia diffusa, on Arthritis Model Rats","volume":"2018","author":"Zhu","year":"2018","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3892\/ijmm.2023.5242","article-title":"Pro-differentiating compounds for human intervertebral disc cells are present in Violina pumpkin leaf extracts","volume":"51","author":"Lambertini","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sundar Dhilip Kumar, S., Houreld, N.N., and Abrahamse, H. (2018). Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases. Molecules, 23.","DOI":"10.3390\/molecules23040835"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1080\/10408398.2015.1077195","article-title":"Curcumin, an active component of turmeric (Curcuma longa), and its effects on health","volume":"57","author":"Kocaadam","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Bielak-Zmijewska, A., Grabowska, W., Ciolko, A., Bojko, A., Mosieniak, G., Bijoch, \u0141., and Sikora, E. (2019). The Role of Curcumin in the Modulation of Ageing. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051239"},{"key":"ref_111","first-page":"2483","article-title":"Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-kappaB in the cultured human intervertebral disc cells","volume":"122","author":"Yu","year":"2009","journal-title":"Chin. Med. J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1476-9255-9-29","article-title":"Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity","volume":"9","author":"Klawitter","year":"2012","journal-title":"J. Inflamm."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbagen.2005.09.008","article-title":"Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues","volume":"1760","author":"Wei","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, K., Li, J., Yu, D., Fan, Q., Tang, T., Yao, X., and Wang, X. (2017). Curcumin Inhibits Apoptosis of Chondrocytes through Activation ERK1\/2 Signaling Pathways Induced Autophagy. Nutrients, 9.","DOI":"10.3390\/nu9040414"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1984742","DOI":"10.1155\/2022\/1984742","article-title":"Oxidative Stress and Intervertebral Disc Degeneration: Pathophysiology, Signaling Pathway, and Therapy","volume":"2022","author":"Li","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/advances\/nmx011","article-title":"The Problem of Curcumin and Its Bioavailability: Could Its Gastrointestinal Influence Contribute to Its Overall Health-Enhancing Effects?","volume":"9","author":"Lopresti","year":"2018","journal-title":"Adv. Nutr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s42452-023-05467-9","article-title":"GelMA hydrogel scaffold containing curcumin-loaded solid lipid nanoparticles promotes the regeneration of degenerative discs","volume":"5","author":"Wang","year":"2023","journal-title":"SN Appl. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"118213","DOI":"10.1016\/j.lfs.2020.118213","article-title":"Curcumin prevents tension-induced endplate cartilage degeneration by enhancing autophagy","volume":"258","author":"Xiao","year":"2020","journal-title":"Life Sci."},{"key":"ref_119","first-page":"1305","article-title":"The effect of curcumin on NF-\u03baB expression in rat with lumbar intervertebral disc degeneration","volume":"19","author":"Ma","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"6864","DOI":"10.3892\/mmr.2017.7464","article-title":"Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX-2, TGF-\u03b21\/2, MMP-9 and BDNF in a rat model","volume":"16","author":"Hu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.3390\/ijms160510888","article-title":"Potential anti-cancer activities and mechanisms of costunolide and dehydrocostuslactone","volume":"16","author":"Lin","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_122","first-page":"1270","article-title":"Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-\u03baB\/COX-2 signaling pathway by targeting IKK\u03b2","volume":"7","author":"Wang","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_123","first-page":"7925","article-title":"Dehydrocostus lactone suppresses cell growth and induces apoptosis in recombinant human papilloma virus-18 HaCaT cells via the PI3K\/Akt signaling pathway","volume":"17","author":"Li","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.biopha.2018.01.099","article-title":"Dehydrocostus lactone induces prominent apoptosis in kidney distal tubular epithelial cells and interstitial fibroblasts along with cell cycle arrest in ovarian epithelial cells","volume":"99","author":"Singireesu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"5762","DOI":"10.1111\/jcmm.14492","article-title":"Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast-induced bone loss by modulating NF-\u03baB signalling pathway","volume":"23","author":"Hu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Nie, Y., Wang, Z., Chai, G., Xiong, Y., Li, B., Zhang, H., Xin, R., Qian, X., Tang, Z., and Wu, J. (2019). Dehydrocostus Lactone Suppresses LPS-induced Acute Lung Injury and Macrophage Activation through NF-\u03baB Signaling Pathway Mediated by p38 MAPK and Akt. Molecules, 24.","DOI":"10.3390\/molecules24081510"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"dsab022","DOI":"10.1093\/dnares\/dsab022","article-title":"High-quality genome assembly of an important biodiesel plant, Euphorbia lathyris L.","volume":"28","author":"Wang","year":"2021","journal-title":"DNA Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"105361","DOI":"10.1016\/j.phrs.2020.105361","article-title":"20-Deoxyingenol alleviates osteoarthritis by activating TFEB in chondrocytes","volume":"165","author":"Gu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10286020.2018.1492565","article-title":"Eupatilin: A natural pharmacologically active flavone compound with its wide range applications","volume":"22","author":"Nageen","year":"2020","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phymed.2017.08.027","article-title":"Eupatilin suppresses the allergic inflammatory response in vitro and in vivo","volume":"42","author":"Song","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Bai, D., Sun, T., Lu, F., Shen, Y., Zhang, Y., Zhang, B., Yu, G., Li, H., and Hao, J. (2022). Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-\u03baB and MAPK and Activating Nrf2 Signaling Pathways in Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031582"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.bbrc.2017.09.043","article-title":"Eupatilin with PPAR\u03b1 agonistic effects inhibits TNF\u03b1-induced MMP signaling in HaCaT cells","volume":"493","author":"Jung","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2147\/JIR.S393850","article-title":"Pretreatment with Eupatilin Attenuates Inflammation and Coagulation in Sepsis by Suppressing JAK2\/STAT3 Signaling Pathway","volume":"16","author":"Lu","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Jeong, J.H., Moon, S.J., Jhun, J.Y., Yang, E.J., Cho, M.L., and Min, J.K. (2015). Eupatilin Exerts Antinociceptive and Chondroprotective Properties in a Rat Model of Osteoarthritis by Downregulating Oxidative Damage and Catabolic Activity in Chondrocytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130882"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"153180","DOI":"10.1016\/j.phymed.2020.153180","article-title":"Evodiamine and rutaecarpine from Tetradium ruticarpum in the treatment of liver diseases","volume":"68","author":"Li","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"120667","DOI":"10.1016\/j.ijpharm.2021.120667","article-title":"Intranasal co-delivery of berberine and evodiamine by self-assembled thermosensitive in-situ hydrogels for improving depressive disorder","volume":"603","author":"Xu","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"104978","DOI":"10.1016\/j.phrs.2020.104978","article-title":"Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production","volume":"159","author":"Wang","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3389\/fphar.2019.00290","article-title":"Evodiamine Augments NLRP3 Inflammasome Activation and Anti-bacterial Responses Through Inducing \u03b1-Tubulin Acetylation","volume":"10","author":"Li","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1744806920902563","DOI":"10.1177\/1744806920902563","article-title":"Evodiamine reduced peripheral hypersensitivity on the mouse with nerve injury or inflammation","volume":"16","author":"Zhang","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2190847","DOI":"10.1155\/2019\/2190847","article-title":"Protective Effects of Evodiamine against LPS-Induced Acute Kidney Injury through Regulation of ROS-NF-\u03baB-Mediated Inflammation","volume":"2019","author":"Shi","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3892\/mmr.2022.12781","article-title":"Upregulation of SIRT1 by Evodiamine activates PI3K\/AKT pathway and blocks intervertebral disc degeneration","volume":"26","author":"Kuai","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1089\/ars.2012.4901","article-title":"Fisetin: A dietary antioxidant for health promotion","volume":"19","author":"Khan","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.bcp.2012.07.012","article-title":"Dietary flavonoid fisetin: A novel dual inhibitor of PI3K\/Akt and mTOR for prostate cancer management","volume":"84","author":"Adhami","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.semcancer.2016.04.003","article-title":"Exploring the molecular targets of dietary flavonoid fisetin in cancer","volume":"40\u201341","author":"Syed","year":"2016","journal-title":"Semin. Cancer Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"58","DOI":"10.2741\/s425","article-title":"How fisetin reduces the impact of age and disease on CNS function","volume":"7","author":"Maher","year":"2015","journal-title":"Front. Biosci. (Sch. Ed.)"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: The flavone, fisetin, and the BCL-X(L) inhibitors, A1331852 and A1155463","volume":"9","author":"Zhu","year":"2017","journal-title":"Aging"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.18632\/aging.101100","article-title":"Discovery of piperlongumine as a potential novel lead for the development of senolytic agents","volume":"8","author":"Wang","year":"2016","journal-title":"Aging"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.4155\/fmc-2018-0234","article-title":"The emerging field of senotherapeutic drugs","volume":"10","author":"Myrianthopoulos","year":"2018","journal-title":"Future Med. Chem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"106504","DOI":"10.1016\/j.phrs.2022.106504","article-title":"The effects of fisetin on bone and cartilage: A systematic review","volume":"185","author":"Yamaura","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.intimp.2017.02.009","article-title":"Fisetin inhibits IL-1\u03b2-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice","volume":"45","author":"Zheng","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_152","first-page":"5572754","article-title":"The Senolytic Drug Fisetin Attenuates Bone Degeneration in the Zmpste24\u2212\/\u2212 Progeria Mouse Model","volume":"2023","author":"Hambright","year":"2023","journal-title":"J. Osteoporos."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e865","DOI":"10.1002\/iid3.865","article-title":"Fisetin regulates the biological effects of rat nucleus pulposus mesenchymal stem cells under oxidative stress by sirtuin-1 pathway","volume":"11","author":"Zhou","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"153647","DOI":"10.1016\/j.phymed.2021.153647","article-title":"Honokiol: A review of its pharmacological potential and therapeutic insights","volume":"90","author":"Rauf","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-2094-10-15","article-title":"Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells","volume":"10","author":"Chuang","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"26554","DOI":"10.1038\/srep26554","article-title":"Honokiol suppresses TNF-\u03b1-induced neutrophil adhesion on cerebral endothelial cells by disrupting polyubiquitination and degradation of I\u03baB\u03b1","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"956355","DOI":"10.3389\/fphar.2022.956355","article-title":"Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals","volume":"13","author":"Kang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_158","first-page":"186","article-title":"Honokiol antagonizes doxorubicin-induced cardiomyocyte senescence by inhibiting TXNIP-mediated NLRP3 inflammasome activation","volume":"45","author":"Huang","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/ijd.13569","article-title":"Honokiol protects skin cells against inflammation, collagenolysis, apoptosis, and senescence caused by cigarette smoke damage","volume":"56","author":"Costa","year":"2017","journal-title":"Int. J. Dermatol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/jor.22577","article-title":"Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes","volume":"32","author":"Chen","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.freeradbiomed.2018.04.008","article-title":"Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway","volume":"120","author":"Tang","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2174\/138955711795305335","article-title":"A review on the dietary flavonoid kaempferol","volume":"11","year":"2011","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_163","first-page":"2759","article-title":"Recent progress regarding kaempferol for the treatment of various diseases","volume":"18","author":"Ren","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41413-020-00125-x","article-title":"Painful intervertebral disc degeneration and inflammation: From laboratory evidence to clinical interventions","volume":"9","author":"Lyu","year":"2021","journal-title":"Bone Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.fct.2013.08.034","article-title":"Kaempferol induces chondrogenesis in ATDC5 cells through activation of ERK\/BMP-2 signaling pathway","volume":"62","author":"Nepal","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"114866","DOI":"10.1016\/j.indcrop.2022.114866","article-title":"Efficient short extraction and purification procedures of kinsenoside from Anoectochilus roxburghii with deep eutectic solvent by column chromatographic extraction","volume":"182","author":"Yuan","year":"2022","journal-title":"Ind. Crops Prod."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1097\/SHK.0b013e3181f0e7a3","article-title":"Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-stimulated inflammatory reactions in macrophages and endotoxin shock in mice","volume":"35","author":"Hsiao","year":"2011","journal-title":"Shock"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Hsiao, H.B., Hsieh, C.C., Wu, J.B., Lin, H., and Lin, W.C. (2016). Kinsenoside inhibits the inflammatory mediator release in a type-II collagen induced arthritis mouse model by regulating the T cells responses. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1054-8"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3389\/fphar.2018.00240","article-title":"Kinsenoside Ameliorates Oxidative Stress-Induced RPE Cell Apoptosis and Inhibits Angiogenesis via Erk\/p38\/NF-\u03baB\/VEGF Signaling","volume":"9","author":"Luo","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/hep.28825","article-title":"Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells\/CD8(+) T cells communication in mice","volume":"64","author":"Xiang","year":"2016","journal-title":"Hepatology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s00198-012-2199-z","article-title":"Kinsenoside prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis by regulating classical NF-\u03baB pathways","volume":"24","author":"Hsiao","year":"2013","journal-title":"Osteoporos. Int."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jep.2007.05.022","article-title":"Antihyperglycemic activity of kinsenoside, a high yielding constituent from Anoectochilus roxburghii in streptozotocin diabetic rats","volume":"114","author":"Zhang","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.fitote.2013.03.006","article-title":"The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition","volume":"86","author":"Liu","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e2350","DOI":"10.1038\/cddis.2016.255","article-title":"Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-\u03baB signaling in macrophages and protecting endothelial cells","volume":"7","author":"Han","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2174\/156800908786241050","article-title":"Luteolin, a flavonoid with potential for cancer prevention and therapy","volume":"8","author":"Lin","year":"2008","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Muruganathan, N., Dhanapal, A.R., Baskar, V., Muthuramalingam, P., Selvaraj, D., Aara, H., Shiek Abdullah, M.Z., and Sivanesan, I. (2022). Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review. Metabolites, 12.","DOI":"10.3390\/metabo12111145"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Akter, R., Afrose, A., Rahman, M.R., Chowdhury, R., Nirzhor, S.S.R., Khan, R.I., and Kabir, M.T. (2021). A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer\u2019s Disease, Aging, Cancer, Inflammation, and Diabetes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084180"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.biopha.2018.09.161","article-title":"Luteolin inhibits IL-1\u03b2-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model","volume":"109","author":"Fei","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.yexcr.2017.02.023","article-title":"Sirtuin 6 prevents matrix degradation through inhibition of the NF-\u03baB pathway in intervertebral disc degeneration","volume":"352","author":"Kang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jep.2017.11.010","article-title":"Ethnopharmacology, phytochemistry, and pharmacology of Cornus officinalis Sieb. et Zucc","volume":"213","author":"Huang","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"106240","DOI":"10.1016\/j.intimp.2020.106240","article-title":"Protective effects of iridoid glycosides on acute colitis via inhibition of the inflammatory response mediated by the STAT3\/NF-\u0138B pathway","volume":"81","author":"Yuan","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Pi, W.X., Feng, X.P., Ye, L.H., and Cai, B.C. (2017). Combination of Morroniside and Diosgenin Prevents High Glucose-Induced Cardiomyocytes Apoptosis. Molecules, 22.","DOI":"10.3390\/molecules22010163"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1080\/15384101.2021.1889186","article-title":"Morroniside protects OLN-93 cells against H(2)O(2)-induced injury through the PI3K\/Akt pathway-mediated antioxidative stress and antiapoptotic activities","volume":"20","author":"Li","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Xiao, J., Han, Q., Yu, Z., Liu, M., Sun, J., Wu, M., Yin, H., Fu, J., Guo, Y., and Wang, L. (2023). Morroniside Inhibits Inflammatory Bone Loss through the TRAF6-Mediated NF-\u03baB\/MAPK Signalling Pathway. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101438"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1007\/s10753-017-0699-x","article-title":"Cardioprotective Effects of Morroniside in Rats Following Acute Myocardial Infarction","volume":"41","author":"Yu","year":"2018","journal-title":"Inflammation"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1056460","DOI":"10.3389\/fphar.2022.1056460","article-title":"Morroniside ameliorates inflammatory skeletal muscle atrophy via inhibiting canonical and non-canonical NF-\u03baB and regulating protein synthesis\/degradation","volume":"13","author":"Yi","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_187","first-page":"1934578X19856526","article-title":"Pharmacokinetics and Pharmacodynamics of Morroniside: A Review","volume":"14","author":"Li","year":"2019","journal-title":"Nat. Prod. Commun."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.2147\/DDDT.S338439","article-title":"Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Liuwei Dihuang Decoction Against Intervertebral Disc Degeneration","volume":"15","author":"Zhang","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Zheng-Wei, S., Yuan, T., Chao-Shuai, F., Lei, Z., Zong-Rang, S., Tuan-Jiang, L., and Ding-Jun, H. (2023). Roles of Hippo-YAP\/TAZ signalling in intervertebral disc degeneration. Biomed. Pharmacother., 159.","DOI":"10.1016\/j.biopha.2022.114099"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.18632\/oncotarget.23299","article-title":"Dysregulation of YAP by the Hippo pathway is involved in intervertebral disc degeneration, cell contact inhibition, and cell senescence","volume":"9","author":"Zhang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1055\/a-1224-3625","article-title":"Current Pharmacological Trends on Myricetin","volume":"70","author":"Gupta","year":"2020","journal-title":"Drug Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"5854","DOI":"10.1002\/fsn3.2513","article-title":"Myricetin: A comprehensive review on its biological potentials","volume":"9","author":"Imran","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Song, X., Tan, L., Wang, M., Ren, C., Guo, C., Yang, B., Ren, Y., Cao, Z., Li, Y., and Pei, J. (2021). Myricetin: A review of the most recent research. Biomed. Pharmacother., 134.","DOI":"10.1016\/j.biopha.2020.111017"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"139708","DOI":"10.1016\/j.cplett.2022.139708","article-title":"The antioxidant capacity of myricetin. A molecular electrostatic potential analysis based on DFT calculations","volume":"801","author":"Kenouche","year":"2022","journal-title":"Chem. Phys. Lett."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.bcp.2010.01.004","article-title":"Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf","volume":"79","author":"Jung","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"105742","DOI":"10.1016\/j.intimp.2019.105742","article-title":"Activation of Nrf2\/HO-1 signal with Myricetin for attenuating ECM degradation in human chondrocytes and ameliorating the murine osteoarthritis","volume":"75","author":"Pan","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Karami, A., Fakhri, S., Kooshki, L., and Khan, H. (2022). Polydatin: Pharmacological Mechanisms, Therapeutic Targets, Biological Activities, and Health Benefits. Molecules, 27.","DOI":"10.3390\/molecules27196474"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.jep.2013.05.007","article-title":"Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb.et Zucc.: A review","volume":"148","author":"Peng","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"14473","DOI":"10.18632\/aging.205269","article-title":"Traditional herbs: Mechanisms to combat cellular senescence","volume":"15","author":"Wang","year":"2023","journal-title":"Aging"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.redox.2018.07.002","article-title":"Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1\/Nrf2 pathway","volume":"18","author":"Zhao","year":"2018","journal-title":"Redox Biol."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Sun, Z., Wang, X., and Xu, Z. (2021). SIRT1 provides new pharmacological targets for polydatin through its role as a metabolic sensor. Biomed. Pharmacother., 139.","DOI":"10.1016\/j.biopha.2021.111549"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0009-9120(02)00397-1","article-title":"Absorption of three wine-related polyphenols in three different matrices by healthy subjects","volume":"36","author":"Goldberg","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.phymed.2015.03.014","article-title":"Comparative studies of polydatin and resveratrol on mutual transformation and antioxidative effect in vivo","volume":"22","author":"Wang","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"944","DOI":"10.7150\/ijms.24111","article-title":"Polydatin, Natural Precursor of Resveratrol, Promotes Osteogenic Differentiation of Mesenchymal Stem Cells","volume":"15","author":"Posa","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.mce.2014.08.014","article-title":"Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating Sirt1 to resist AGEs-induced upregulation of fibronetin and transforming growth factor-\u03b21 in rat glomerular messangial cells","volume":"399","author":"Huang","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1039\/C7FO01555K","article-title":"Polydatin inhibits the IL-1\u03b2-induced inflammatory response in human osteoarthritic chondrocytes by activating the Nrf2 signaling pathway and ameliorates murine osteoarthritis","volume":"9","author":"Tang","year":"2018","journal-title":"Food Funct."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"101865","DOI":"10.1016\/j.tice.2022.101865","article-title":"Polydatin inhibits IL-1\u03b2-mediated chondrocyte inflammation and ameliorates cartilage degradation: Involvement of the NF-\u03baB and Wnt\/\u03b2-catenin pathways","volume":"78","author":"Hu","year":"2022","journal-title":"Tissue Cell"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"117244","DOI":"10.1016\/j.lfs.2019.117244","article-title":"Parkin and Nrf2 prevent oxidative stress-induced apoptosis in intervertebral endplate chondrocytes via inducing mitophagy and anti-oxidant defenses","volume":"243","author":"Kang","year":"2020","journal-title":"Life Sci."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/biof.79","article-title":"Healthy properties of proanthocyanidins","volume":"36","author":"Milagro","year":"2010","journal-title":"BioFactors"},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Rauf, A., Imran, M., Abu-Izneid, T., Iahtisham Ul, H., Patel, S., Pan, X., Naz, S., Sanches Silva, A., Saeed, F., and Rasul Suleria, H.A. (2019). Proanthocyanidins: A comprehensive review. Biomed. Pharmacother., 116.","DOI":"10.1016\/j.biopha.2019.108999"},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Tie, F., Wang, J., Liang, Y., Zhu, S., Wang, Z., Li, G., and Wang, H. (2020). Proanthocyanidins Ameliorated Deficits of Lipid Metabolism in Type 2 Diabetes Mellitus Via Inhibiting Adipogenesis and Improving Mitochondrial Function. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062029"},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-P\u00e9rez, C., Garc\u00eda-Villanova, B., Guerra-Hern\u00e1ndez, E., and Verardo, V. (2019). Grape Seeds Proanthocyanidins: An Overview of In Vivo Bioactivity in Animal Models. Nutrients, 11.","DOI":"10.3390\/nu11102435"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jfda.2019.02.002","article-title":"Proanthocyanidins from the stem bark of Rhus tripartita ameliorate methylgloxal-induced endothelial cell apoptosis","volume":"27","author":"Alqahtani","year":"2019","journal-title":"J. Food Drug Anal."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1089\/109662003772519831","article-title":"Polyphenolics in grape seeds-biochemistry and functionality","volume":"6","author":"Shi","year":"2003","journal-title":"J. Med. Food"},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Rivas-Chac\u00f3n, L.D.M., Yanes-D\u00edaz, J., de Lucas, B., Riestra-Ayora, J.I., Madrid-Garc\u00eda, R., Sanz-Fern\u00e1ndez, R., and S\u00e1nchez-Rodr\u00edguez, C. (2023). Cocoa Polyphenol Extract Inhibits Cellular Senescence via Modulation of SIRT1 and SIRT3 in Auditory Cells. Nutrients, 15.","DOI":"10.3390\/nu15030544"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2147\/JIR.S306456","article-title":"Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT\/SIRT1\/NLRP3 Pathway","volume":"14","author":"Wan","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"33527","DOI":"10.1038\/srep33527","article-title":"Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1\u03b2 activities before and after oral consumption","volume":"6","author":"Merceron","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3858\/emm.2011.43.10.062","article-title":"Grape seed proanthocyanidin extract ameliorates monosodium iodoacetate-induced osteoarthritis","volume":"43","author":"Woo","year":"2011","journal-title":"Exp. Mol. Med."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.ejmech.2018.06.053","article-title":"Therapeutic potential of quercetin as a cardiovascular agent","volume":"155","author":"Patel","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: From transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/S0090-4295(99)00358-1","article-title":"Quercetin in men with category III chronic prostatitis: A preliminary prospective, double-blind, placebo-controlled trial","volume":"54","author":"Shoskes","year":"1999","journal-title":"Urology"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1017\/S0007114509359127","article-title":"Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: A double-blinded, placebo-controlled cross-over study","volume":"102","author":"Egert","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Wang, D., He, X., Wang, D., Peng, P., Xu, X., Gao, B., Zheng, C., Wang, H., Jia, H., and Shang, Q. (2020). Quercetin Suppresses Apoptosis and Attenuates Intervertebral Disc Degeneration via the SIRT1-Autophagy Pathway. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.613006"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.arr.2012.03.008","article-title":"Autophagy, polyphenols and healthy ageing","volume":"12","author":"Pallauf","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.redox.2016.06.006","article-title":"Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction","volume":"9","author":"Li","year":"2016","journal-title":"Redox Biol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"18192","DOI":"10.1002\/jcp.28452","article-title":"Quercetin attenuates oxidative stress-induced apoptosis via SIRT1\/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model","volume":"234","author":"Feng","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.freeradbiomed.2019.09.024","article-title":"Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages","volume":"145","author":"Hu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2986796","DOI":"10.1155\/2016\/2986796","article-title":"Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More","volume":"2016","author":"Costa","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid","volume":"10","author":"Arulmoli","year":"2016","journal-title":"Pharmacogn. Rev."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.abb.2010.05.003","article-title":"Regulation of SIRT1 in cellular functions: Role of polyphenols","volume":"501","author":"Chung","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1111\/jgs.14969","article-title":"The Clinical Potential of Senolytic Drugs","volume":"65","author":"Kirkland","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_234","first-page":"112","article-title":"Increased renal cellular senescence in murine high-fat diet: Effect of the senolytic drug quercetin","volume":"213","author":"Kim","year":"2019","journal-title":"Transl. Res. J. Lab. Clin. Med."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Zhang, S., Liang, W., Abulizi, Y., Xu, T., Cao, R., Xun, C., Zhang, J., and Sheng, W. (2021). Quercetin Alleviates Intervertebral Disc Degeneration by Modulating p38 MAPK-Mediated Autophagy. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/6631562"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Shan, Q., Li, N., Zhang, F., Yu, P., and Meng, Q. (2021). Resveratrol Suppresses Annulus Fibrosus Cell Apoptosis through Regulating Oxidative Stress Reaction in an Inflammatory Environment. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/9100444"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"16509","DOI":"10.1038\/s41598-021-96069-1","article-title":"Natural phytoalexin stilbene compound resveratrol and its derivatives as anti-tobacco mosaic virus and anti-phytopathogenic fungus agents","volume":"11","author":"Song","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1096\/fj.03-0168rev","article-title":"Resveratrol: From grapevines to mammalian biology","volume":"17","author":"Pervaiz","year":"2003","journal-title":"FASEB J."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1089\/152308601317203567","article-title":"Biological Effects of Resveratrol","volume":"3","author":"Bhat","year":"2001","journal-title":"Antioxid. Redox Signal."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1111\/os.13560","article-title":"Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review","volume":"14","author":"Liu","year":"2022","journal-title":"Orthop. Surg."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.fct.2013.03.038","article-title":"Resveratrol and related stilbenes: Their anti-aging and anti-angiogenic properties","volume":"61","author":"Kasiotis","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1196\/annals.1397.047","article-title":"Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling pathway","volume":"1095","author":"Hwang","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"27","DOI":"10.7150\/thno.48987","article-title":"Small molecule-based treatment approaches for intervertebral disc degeneration: Current options and future directions","volume":"11","author":"Kamali","year":"2021","journal-title":"Theranostics"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s40001-021-00555-1","article-title":"Resveratrol protects human nucleus pulposus cells from degeneration by blocking IL-6\/JAK\/STAT3 pathway","volume":"26","author":"Wu","year":"2021","journal-title":"Eur. J. Med. Res."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"E1373","DOI":"10.1097\/BRS.0b013e318221e655","article-title":"The red wine polyphenol resveratrol shows promising potential for the treatment of nucleus pulposus-mediated pain in vitro and in vivo","volume":"36","author":"Wuertz","year":"2011","journal-title":"Spine"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s11357-012-9474-y","article-title":"SIRT1 inhibits apoptosis of degenerative human disc nucleus pulposus cells through activation of Akt pathway","volume":"35","author":"Wang","year":"2013","journal-title":"Age"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1080\/08941939.2019.1705941","article-title":"Resveratrol Combined with 17\u03b2-Estradiol Prevents IL-1\u03b2 Induced Apoptosis in Human Nucleus Pulposus Via The PI3K\/AKT\/Mtor and PI3K\/AKT\/GSK-3\u03b2 Pathway","volume":"34","author":"Bai","year":"2021","journal-title":"J. Investig. Surg."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1177\/1535370216637940","article-title":"Resveratrol attenuated TNF-\u03b1-induced MMP-3 expression in human nucleus pulposus cells by activating autophagy via AMPK\/SIRT1 signaling pathway","volume":"241","author":"Wang","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.bbrc.2017.09.015","article-title":"Resveratrol protects against mitochondrial dysfunction through autophagy activation in human nucleus pulposus cells","volume":"493","author":"Zhang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1097\/BRS.0b013e3181883883","article-title":"The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc","volume":"33","author":"Li","year":"2008","journal-title":"Spine"},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3346\/jkms.2013.28.6.939","article-title":"Resveratrol has anabolic effects on disc degeneration in a rabbit model","volume":"28","author":"Kwon","year":"2013","journal-title":"J. Korean Med. Sci."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.3892\/etm.2016.3878","article-title":"Protective effects of resveratrol on autologous nucleus pulposus model of radiculopathy","volume":"12","author":"Lin","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Triller, P., Bachorz, J., Synowitz, M., Kettenmann, H., and Markovic, D. (2020). O-Vanillin Attenuates the TLR2 Mediated Tumor-Promoting Phenotype of Microglia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082959"},{"key":"ref_255","first-page":"4829","article-title":"Treatment with toll-like receptor 2 inhibitor ortho-vanillin alleviates lipopolysaccharide-induced acute kidney injury in mice","volume":"18","author":"Peng","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"17184","DOI":"10.1038\/s41598-017-17472-1","article-title":"Toll-like Receptor Activation Induces Degeneration of Human Intervertebral Discs","volume":"7","author":"Krock","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1007\/s10753-019-00965-8","article-title":"Baicalein Inhibits the IL-1\u03b2-Induced Inflammatory Response in Nucleus Pulposus Cells and Attenuates Disc Degeneration in vivo","volume":"42","author":"Jin","year":"2019","journal-title":"Inflammation"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13018-023-03759-9","article-title":"Baicalein alleviates TNF-\u03b1-induced apoptosis of human nucleus pulposus cells through PI3K\/AKT signaling pathway","volume":"18","author":"Liu","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"682","DOI":"10.7150\/ijbs.24081","article-title":"Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model","volume":"14","author":"Chen","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"963506","DOI":"10.3389\/fphar.2022.963506","article-title":"Celastrol ameliorates osteoarthritis via regulating TLR2\/NF-\u03baB signaling pathway","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fmed.2017.00069","article-title":"Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases","volume":"4","author":"Fonseca","year":"2017","journal-title":"Front. Med."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2013.01.057","article-title":"Celastrol, an inhibitor of heat shock protein 90\u03b2 potently suppresses the expression of matrix metalloproteinases, inducible nitric oxide synthase and cyclooxygenase-2 in primary human osteoarthritic chondrocytes","volume":"708","author":"Ding","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_263","doi-asserted-by":"crossref","unstructured":"Jin, T., Wu, D., Liu, X.M., Xu, J.T., Ma, B.J., Ji, Y., Jin, Y.Y., Wu, S.Y., Wu, T., and Ma, K. (2020). Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis. J. Nanobiotechnol., 18.","DOI":"10.1186\/s12951-020-00651-0"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.biopha.2017.04.093","article-title":"Celastrol reduces IL-1\u03b2 induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo","volume":"91","author":"Chen","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1007\/s10067-021-05726-3","article-title":"Comparative transcriptomics and network pharmacology analysis to identify the potential mechanism of celastrol against osteoarthritis","volume":"40","author":"Dai","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"119324","DOI":"10.1016\/j.lfs.2021.119324","article-title":"Chlorogenic Acid retards cartilaginous endplate degeneration and ameliorates intervertebral disc degeneration via suppressing NF-\u03baB signaling","volume":"274","author":"Ge","year":"2021","journal-title":"Life Sci."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"13693","DOI":"10.18632\/aging.205251","article-title":"The antioxidant Glycitin protects against intervertebral disc degeneration through antagonizing inflammation and oxidative stress in nucleus pulposus cells","volume":"15","author":"Zhao","year":"2023","journal-title":"Aging"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1007\/s10753-020-01210-3","article-title":"Glycitin Suppresses Cartilage Destruction of Osteoarthritis in Mice","volume":"43","author":"Wang","year":"2020","journal-title":"Inflammation"},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1007\/s11010-021-04197-z","article-title":"Higenamine mitigates interleukin-1\u03b2-induced human nucleus pulposus cell apoptosis by ROS-mediated PI3K\/Akt signaling","volume":"476","author":"Zhu","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Bai, X., Ding, W., Yang, S., and Guo, X. (2019). Higenamine inhibits IL-1\u03b2-induced inflammation in human nucleus pulposus cells. Biosci. Rep., 39.","DOI":"10.1042\/BSR20190857"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"108352","DOI":"10.1016\/j.intimp.2021.108352","article-title":"Mangiferin exert protective effects on joints of adjuvant-induced arthritis rats by regulating the MAPKs\/NF-\u03baB pathway of fibroblast-like synoviocytes","volume":"101","author":"Wang","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"6632786","DOI":"10.1155\/2021\/6632786","article-title":"Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-\u03baB Signaling Pathway","volume":"2021","author":"Yu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"6179444","DOI":"10.1155\/2022\/6179444","article-title":"Naringin Inhibits Apoptosis Induced by Cyclic Stretch in Rat Annular Cells and Partially Attenuates Disc Degeneration by Inhibiting the ROS\/NF-\u03baB Pathway","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"7655142","DOI":"10.1155\/2022\/7655142","article-title":"Naringin protects human nucleus pulposus cells against TNF-\u03b1-induced inflammation, oxidative stress, and loss of cellular homeostasis by enhancing autophagic flux via AMPK\/SIRT1 activation","volume":"2022","author":"Chen","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"9963","DOI":"10.12659\/MSM.918597","article-title":"Naringin Protects Against Interleukin 1\u03b2 (IL-1\u03b2)-Induced Human Nucleus Pulposus Cells Degeneration via Downregulation Nuclear Factor kappa B (NF-\u03baB) Pathway and p53 Expression","volume":"25","author":"Gao","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2147\/DDDT.S338355","article-title":"The Effect of Naringin on the Apoptosis of Degenerative Nucleus Pulposus Cells: A Study on the Function and Mechanism","volume":"16","author":"Yuan","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Meiners, F., Secci, R., Sueto, S., Fuellen, G., and Barrantes, I. (2022). Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data. bioRxiv.","DOI":"10.1101\/2022.05.26.492763"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"176136","DOI":"10.1016\/j.ejphar.2023.176136","article-title":"Piperlongumine mediates amelioration of osteoarthritis via inhibition of chondrocyte senescence and inflammation in a goat ex vivo model","volume":"961","author":"Kapoor","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1186\/s13018-023-04014-x","article-title":"The mechanism by which Naru 3 pill protects against intervertebral disc cartilage endplate degeneration based on network pharmacology and experimental verification","volume":"18","author":"Guo","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/03008207.2016.1182998","article-title":"Sesamin inhibits lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc","volume":"57","author":"Li","year":"2016","journal-title":"Connect. Tissue Res."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1080\/03008207.2019.1651847","article-title":"Intradiscal injection of sesamin protects from lesion-induced degeneration","volume":"61","author":"Li","year":"2020","journal-title":"Connect. Tissue Res."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.intimp.2018.10.024","article-title":"Wogonin mitigates intervertebral disc degeneration through the Nrf2\/ARE and MAPK signaling pathways","volume":"65","author":"Fang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"20001","DOI":"10.1038\/s41598-023-47375-3","article-title":"Injectable kaempferol-loaded fibrin glue regulates the metabolic balance and inhibits inflammation in intervertebral disc degeneration","volume":"13","author":"Gao","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_284","doi-asserted-by":"crossref","unstructured":"Chen, B., Zhu, R., Hu, H., Zhan, M., Wang, T., Huang, F., Wei, F., Chai, Y., Ling, Z., and Zou, X. (2022). Elimination of Senescent Cells by Senolytics Facilitates Bony Endplate Microvessel Formation and Mitigates Disc Degeneration in Aged Mice. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.853688"},{"key":"ref_285","first-page":"167","article-title":"Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc","volume":"28","author":"Zhu","year":"2023","journal-title":"Bioact. Mater."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1038\/s41596-021-00505-5","article-title":"Algorithmic assessment of cellular senescence in experimental and clinical specimens","volume":"16","author":"Kohli","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.freeradbiomed.2022.08.018","article-title":"Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes","volume":"190","author":"Wang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"eaay2380","DOI":"10.1126\/scitranslmed.aay2380","article-title":"Combined nucleus pulposus augmentation and annulus fibrosus repair prevents acute intervertebral disc degeneration after discectomy","volume":"12","author":"Sloan","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/01.brs.0000150833.93248.09","article-title":"2004 Young Investigator Award Winner: Vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration","volume":"30","author":"Benneker","year":"2005","journal-title":"Spine"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1002\/jbmr.4009","article-title":"Intervertebral Disc Degeneration Is Associated With Aberrant Endplate Remodeling and Reduced Small Molecule Transport","volume":"35","author":"Ashinsky","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"20596","DOI":"10.1038\/s41598-020-77785-6","article-title":"In vitro model of distinct catabolic and inflammatory response patterns of endothelial cells to intervertebral disc cell degeneration","volume":"10","author":"Hwang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_292","first-page":"23","article-title":"Changes of the end plate cartilage are associated with intervertebral disc degeneration: A quantitative magnetic resonance imaging study in rhesus monkeys and humans","volume":"24","author":"Ling","year":"2020","journal-title":"J. Orthop. Transl."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/art.40364","article-title":"Brief Report: A Phase IIb Trial of a Novel Extended-Release Microsphere Formulation of Triamcinolone Acetonide for Intraarticular Injection in Knee Osteoarthritis","volume":"70","author":"Conaghan","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Christophoridis, C., Kouroumalis, A., and Kletsas, D. (2022). Accumulation of zoledronic acid in rabbit intervertebral discs. J. Chromatogr. B, 1197.","DOI":"10.1016\/j.jchromb.2022.123229"},{"key":"ref_295","first-page":"516","article-title":"Quantitative determination of myricetin in rat plasma by ultra performance liquid chromatography tandem mass spectrometry and its absolute bioavailability","volume":"64","author":"Dang","year":"2014","journal-title":"Drug Res."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2116\/analsci.31.1297","article-title":"In vitro Penetration and in vivo Distribution of Honokiol into the Intervertebral Disc in Rat","volume":"31","author":"Chen","year":"2015","journal-title":"Anal. Sci."},{"key":"ref_297","first-page":"101","article-title":"Potential and recent advances of microcarriers in repairing cartilage defects","volume":"27","author":"Liao","year":"2021","journal-title":"J. Orthop. Transl."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/dme.14202","article-title":"Hypoglycaemia is reduced with use of inhaled Technosphere(\u00ae) Insulin relative to insulin aspart in type 1 diabetes mellitus","volume":"37","author":"Seaquist","year":"2020","journal-title":"Diabet. Med."}],"updated-by":[{"DOI":"10.3390\/metabo16070474","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000}}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/3\/146\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:16:06Z","timestamp":1783512966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/14\/3\/146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":298,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["metabo14030146"],"URL":"https:\/\/doi.org\/10.3390\/metabo14030146","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,28]]}}}