https://doi.org/10.4081/ejh.2024.4033
Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway
Submitted: 1 April 2024
Accepted: 1 May 2024
Published: 22 May 2024
Accepted: 1 May 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Osteoarthritis (OA) is a common degenerative joint disease in the elderly, while oxidative stress-induced chondrocyte degeneration plays a key role in the pathologic progression of OA. One possible reason is that the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which acts as the intracellular defense factor against oxidative stress, is significantly inhibited in chondrocytes. Spinosin (SPI) is a potent Nrf2 agonist, but its effect on OA is still unknown. In this study, we found that SPI can alleviate tert-Butyl hydroperoxide (TBHP)-induced extracellular matrix degradation of chondrocytes. Additionally, SPI can effectively activate Nrf2, heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) in chondrocytes under the TBHP environment. When Nrf2 was silenced by siRNA, the cartilage protective effect of SPI was also weakened. Finally, SPI showed good alleviative effects on OA in mice. Thus, SPI can ameliorate oxidative stress-induced chondrocyte dysfunction and exhibit a chondroprotective effect through activating the Nrf2/HO-1 pathway, which may provide a novel and promising option for the treatment of OA.
Yang L, Sun L, Zhang H, Bian F, Zhao Y. Ice-inspired lubricated drug delivery particles from microfluidic electrospray for osteoarthritis treatment. ACS Nano 2021;15:20600-6.
DOI: https://doi.org/10.1021/acsnano.1c09325
Chen WH, Tsai WC, Wang HT, Wang CH, Tseng YT. Can early rehabilitation after osteoarthritis reduce knee and hip arthroplasty risk? A national representative cohort study. Medicine (Baltimore) 2019;98:e15723.
DOI: https://doi.org/10.1097/MD.0000000000015723
Selig DJ, Kress AT, Horton IM, Livezey JR, Sadik EJ, Deluca JP. Pharmacokinetics, safety and efficacy of intra-articular non-steroidal anti-inflammatory drug injections for the treatment of osteoarthritis: A narrative review. J Clin Pharm Ther 2022;47:1122-33.
DOI: https://doi.org/10.1111/jcpt.13669
Yu W, Tu Y, Long Z, Liu J, Kong D, Peng J, et al. Reactive oxygen species bridge the gap between chronic inflammation and tumor development. Oxid Med Cell Longev 2022;2022:2606928.
DOI: https://doi.org/10.1155/2022/2606928
Kvietys PR, Granger DN. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 2012;52:556-92.
DOI: https://doi.org/10.1016/j.freeradbiomed.2011.11.002
Phua CYH, Teoh ZL, Goh BH, Yap WH, Tang YQ. Triangulating the pharmacological properties of thymoquinone in regulating reactive oxygen species, inflammation, and cancer: Therapeutic applications and mechanistic pathways. Life Sci 2021;287:120120.
DOI: https://doi.org/10.1016/j.lfs.2021.120120
Tashkandi M, Ali F, Alsaqer S, Alhousami T, Cano A, Martin A, et al. Lysyl oxidase-like 2 protects against progressive and aging related knee joint osteoarthritis in mice. Int J Mol Sci 2019;20:4798.
DOI: https://doi.org/10.3390/ijms20194798
Collins AT, Hatcher CC, Kim SY, Ziemian SN, Spritzer CE, Guilak F, et al. Selective enzymatic digestion of proteoglycans and collagens alters cartilage T1rho and T2 relaxation times. Ann Biomed Eng 2019;47:190-201.
DOI: https://doi.org/10.1007/s10439-018-02143-7
Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 2016;73:3221-47.
DOI: https://doi.org/10.1007/s00018-016-2223-0
Kang TC. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitochondrial dynamics/mitophagy in neurological diseases. Antioxidants (Basel) 2020;9:617.
DOI: https://doi.org/10.3390/antiox9070617
Bukke VN, Moola A, Serviddio G, Vendemiale G, Bellanti F. Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease. World J Gastroenterol 2022;28:6909-21.
DOI: https://doi.org/10.3748/wjg.v28.i48.6909
Zeng X, Peng Y, Wang Y, Kang K. C1q/tumor necrosis factor-related protein-3 (CTRP3) activated by forkhead box O4 (FOXO4) down-regulation protects retinal pericytes against high glucose-induced oxidative damage through nuclear factor erythroid 2-related factor 2 (Nrf2)/Nuclear factor-kappaB (NF-κB) signaling. Bioengineered 2022;13:6080-91.
DOI: https://doi.org/10.1080/21655979.2022.2031413
Lee J, Roh JL. Targeting Nrf2 for ferroptosis-based therapy: Implications for overcoming ferroptosis evasion and therapy resistance in cancer. Biochim Biophys Acta Mol Basis Dis 2023;1869:166788.
DOI: https://doi.org/10.1016/j.bbadis.2023.166788
Dinicolantonio JJ, Mccarty M, Barroso-Aranda J. Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections. Open Heart 2021;8:e001568.
DOI: https://doi.org/10.1136/openhrt-2020-001568
Zhang X, Wang J, Gong G, Ma R, Xu F, Yan T, et al. Spinosin inhibits Aβ(1-42) production and aggregation via activating Nrf2/HO-1 pathway. Biomol Ther (Seoul) 2020;28:259-66.
DOI: https://doi.org/10.4062/biomolther.2019.123
Gu M, He P, Lyu C, Liu X, Xu Y, Cheng S, et al. Spinosin and 6'''‑Feruloylspinosin protect the heart against acute myocardial ischemia and reperfusion in rats. Mol Med Rep 2019;20:4253-61.
DOI: https://doi.org/10.3892/mmr.2019.10686
Li JW, Wang RL, Xu J, Sun KY, Jiang HM, Sun ZY, et al. Methylene blue prevents osteoarthritis progression and relieves pain in rats via upregulation of Nrf2/PRDX1. Acta Pharmacol Sin 2022;43:417-28.
DOI: https://doi.org/10.1038/s41401-021-00646-z
Jung IH, Lee HE, Park SJ, Ahn YJ, Kwon G, Woo H, et al. Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice. Pharmacol Biochem Behav 2014;120:88-94.
DOI: https://doi.org/10.1016/j.pbb.2014.02.015
Cai D, Yin S, Yang J, Jiang Q, Cao W. Histone deacetylase inhibition activates Nrf2 and protects against osteoarthritis. Arthritis Res Ther 2015;17:269.
DOI: https://doi.org/10.1186/s13075-015-0774-3
Sun H, Shang Y, Guo J, Maihemuti A, Shen S, Shi Y, et al. Artificial periosteum with oriented surface nanotopography and high tissue adherent property. ACS Appl Mater Interfaces 2023;15:45549-60.
DOI: https://doi.org/10.1021/acsami.3c07561
Liu S, Zhao M, Zhou Y, Li L, Wang C, Yuan Y, et al. A self-assembling peptide hydrogel-based drug co-delivery platform to improve tissue repair after ischemia-reperfusion injury. Acta Biomater 2020;103:102-14.
DOI: https://doi.org/10.1016/j.actbio.2019.12.011
Braconi D, Giustarini D, Marzocchi B, Peruzzi L, Margollicci M, Rossi R, et al. Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project. Osteoarthritis Cartilage 2018;26:1078-86.
DOI: https://doi.org/10.1016/j.joca.2018.05.017
Portal-Núñez S, Esbrit P, Alcaraz MJ, Largo R. Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochem Pharmacol 2016;108:1-10.
DOI: https://doi.org/10.1016/j.bcp.2015.12.012
Castejón ML, Rosillo M, Montoya T, González-Benjumea A, Fernández-Bolaños JG, Alarcón-De-La-Lastra C. Oleuropein down-regulated IL-1β-induced inflammation and oxidative stress in human synovial fibroblast cell line SW982. Food Funct 2017;8:1890-8.
DOI: https://doi.org/10.1039/C7FO00210F
Chen Y, Liu Y, Jiang K, Wen Z, Cao X, Wu S. Linear ubiquitination of LKB1 activates AMPK pathway to inhibit NLRP3 inflammasome response and reduce chondrocyte pyroptosis in osteoarthritis. J Orthop Translat 2023;39:1-11.
DOI: https://doi.org/10.1016/j.jot.2022.11.002
Napodano C, Carnazzo V, Basile V, Pocino K, Stefanile A, Gallucci S, et al. NLRP3 inflammasome involvement in heart, liver, and lung diseases-a lesson from cytokine storm syndrome. Int J Mol Sci 2023;24:16556.
DOI: https://doi.org/10.3390/ijms242316556
Zhou Z, Jiang W, Yan J, Liu H, Ren M, Li Y, et al. Trichostatin A enhances the titanium rods osseointegration in osteoporotic rats by the inhibition of oxidative stress through activating the AKT/Nrf2 pathway. Sci Rep 2023;13:22967.
DOI: https://doi.org/10.1038/s41598-023-50108-1
Magrin GL, Di Summa F, Strauss FJ, Panahipour L, Mildner M, Magalhães Benfatti CA, et al. Butyrate decreases ICAM-1 expression in human oral squamous cell carcinoma cells. Int J Mol Sci 2020;21:1679.
DOI: https://doi.org/10.3390/ijms21051679
Wang D, Ho CT, Bai N. Ziziphi Spinosae Semen: An updated review on pharmacological activity, quality control, and application. J Food Biochem 2022;46:e14153.
DOI: https://doi.org/10.1111/jfbc.14153
Liu Z, Zhao X, Liu B, Liu AJ, Li H, Mao X, et al. Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Aβ 1-42. Eur J Pharmacol 2014;738:206-13.
DOI: https://doi.org/10.1016/j.ejphar.2014.05.041
Wijesinghe SN, Badoume A, Nanus DE, Sharma-Oates A, Farah H, Certo M, et al. Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets. Clin Transl Med 2023;13:e1232.
DOI: https://doi.org/10.1002/ctm2.1232
Edd SN, Giori NJ, Andriacchi TP. The role of inflammation in the initiation of osteoarthritis after meniscal damage. J Biomech 2015;48:1420-26.
DOI: https://doi.org/10.1016/j.jbiomech.2015.02.035
Ethics Approval
This study was approved by the Ethics Committee and the Institutional Animal Care and Use Committee of Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical SchoolSupporting Agencies
Changzhou Sci&Tech Program, Changzhou UniversityHow to Cite
Lu, P., Li, S., Zhang, C., Jiang, X., Xiang, J., Xu, H., … Shi, Y. (2024). Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway. European Journal of Histochemistry, 68(2). https://doi.org/10.4081/ejh.2024.4033
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