Wedelolactone mitigates mitochondrial dysfunction to enhance food-related biochemical interventions in disc degeneration
Main Article Content
Keywords
disc degeneration (IVDD), Wedelolactone, ROS, ECM, AMPK/SIRT1/PGC1α axis
Abstract
Intervertebral disc degeneration (IVDD), a prevalent age-related musculoskeletal disorder, poses a significant global health burden. While understanding that its pathogenesis and identifying its effective therapeutic compounds remain essential, increasing attention has been directed toward bioactive compounds derived from food sources for their potential role in health management. Wedelolactone, a phytochemical with diverse biological activities, has emerged as a promising candidate. This study examines its effects in an IVDD cell model, where nucleus pulposus (NP) cells isolated from Sprague Dawley rat intervertebral discs were exposed to 200 μM H2O2 for 24 hours to induce oxidative stress. Wedelolactone significantly reduced H2O2-induced reactive oxygen species (ROS) production and alleviated mitochondrial dysfunction in NP cells. It also inhibited cellular senescence and apoptosis while regulating the expression of genes involved in extracellular matrix synthesis and degradation. Mechanistic investigations revealed that Wedelolactone exerted its protective effects through the AMPK/SIRT1/PGC1α (adenosine monophosphate-activated protein kinase/silent information regulator 1/peroxisome proliferator-activated receptor coactivator-1 alpha) axis, highlighting its role in mitochondrial homeostasis. These findings suggest that Wedelolactone, a potential food-derived compound, could be a promising candidate for functional food development aimed at mitigating IVDD and associated mitochondrial dysfunction.
References
Bortolini, D. G., Barros, L., Maciel, G. M., Brugnari, T., Modkovski, T. A., Fachi, M. M., Pontarolo, R., Pinela, J., Ferreira, I. & Haminiuk, C. W. I. 2022. Bioactive profile of edible nasturtium and rose flowers during simulated gastrointestinal digestion. Food Chem, 381, 132267. 10.1016/j.foodchem.2022.132267
Dai, Z., Xia, C., Zhao, T., Wang, H., Tian, H., Xu, O., Zhu, X., Zhang, J. & Chen, P. 2023. Platelet-derived extracellular vesicles ameliorate intervertebral disc degeneration by alleviating mitochondrial dysfunction. Mater Today Bio, 18, 100512. 10.1016/j.mtbio.2022.100512
Guangzhen Zhao, J. J. 2023. HOMER1A restores sevoflurane-induced cognitive dysfunction by regulating microglia’s activation through activating the AMPK/TXNIP axis. Signa Vitae, 19, 202–212. 10.22514/sv.2023.065
Kang, L., Liu, S., Li, J., Tian, Y., Xue, Y. & Liu, X. 2020. The mitochondria-targeted anti-oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance. Cell Prolif, 53, e12779. 10.1111/cpr.12779
Kang, L., Zhang, H., Jia, C., Zhang, R. & Shen, C. 2023. Epigenetic modifications of inflammation in intervertebral disc degeneration. Ageing Res Rev, 87, 101902. 10.1016/j.arr.2023.101902
Kučírkov, T., Stiborek, M., DúCka, M., Navr Tilov, J., Bogdanović Pristov, J., Popović-Bijelić, A., Vojvodić, S., Preisler, J., Kanick, V., Šmarda, J., Spasojević, I. & Beneš, P. 2018. Anti-cancer effects of wedelolactone: interactions with copper and subcellular localization. Metallomics, 10, 1524–1531. 10.1039/c8mt00191j
Luan, Y., Luan, Y., Jiao, Y., Liu, H., Huang, Z., Feng, Q., Pei, J., Yang, Y. & Ren, K. 2023. Broadening Horizons: Exploring mtDAMPs as a Mechanism and Potential Intervention Target in Cardiovascular Diseases. Aging Dis, 15, 2395–2416. 10.14336/AD.2023.1130
Malik, N., Ferreira, B. I., Hollstein, P. E., Curtis, S. D., Trefts, E., Weiser Novak, S., Yu, J., Gilson, R., Hellberg, K., Fang, L., Sheridan, A., Hah, N., Shadel, G. S., Manor, U. & Shaw, R. J. 2023. Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1. Science, 380, eabj5559. 10.1126/science.abj5559
Mohd Isa, I. L., Teoh, S. L., Mohd Nor, N. H. & Mokhtar, S. A. 2022. Discogenic Low Back Pain: Anatomy, Pathophysiology and Treatments of Intervertebral Disc Degeneration. Int J Mol Sci, 24. 10.3390/ijms24010208
Nottingham, L. K., Yan, C. H., Yang, X., Si, H., Coupar, J., Bian, Y., Cheng, T. F., Allen, C., Arun, P., Gius, D., Dang, L., Van Waes, C. & Chen, Z. 2014. Aberrant IKKalpha and IKKbeta cooperatively activate NF-kappaB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer. Oncogene, 33, 1135–47. 10.1038/onc.2013.49
Ren, K., Pei, J., Guo, Y., Jiao, Y., Xing, H., Xie, Y., Yang, Y., Feng, Q. & Yang, J. 2023. Regulated necrosis pathways: a potential target for ischemic stroke. Burns Trauma, 11, tkad016. 10.1093/burnst/tkad016
Ren, K. D., Liu, W. N., Tian, J., Zhang, Y. Y., Peng, J. J., Zhang, D., Li, N. S., Yang, J., Peng, J. & Luo, X. J. 2019. Mitochondrial E3 ubiquitin ligase 1 promotes brain injury by disturbing mitochondrial dynamics in a rat model of ischemic stroke. Eur J Pharmacol, 861, 172617. 10.1016/j.ejphar.2019.172617
Rubalcava-Gracia, D., Garcia-Villegas, R. & Larsson, N. G. 2023. No role for nuclear transcription regulators in mammalian mitochondria? Mol Cell, 83, 832–842. 10.1016/j.molcel.2022.09.010
Trefts, E. & Shaw, R. J. 2021. AMPK: restoring metabolic homeostasis over space and time. Mol Cell, 81, 3677–3690. 10.1016/j.molcel.2021.08.015
Yang, J. Y., Tao, L. J., Liu, B., You, X. Y., Zhang, C. F., Xie, H. F. & Li, R. S. 2019. Wedelolactone Attenuates Pulmonary Fibrosis Partly Through Activating AMPK and Regulating Raf-MAPKs Signaling Pathway. Front Pharmacol, 10, 151. 10.3389/fphar.2019.00151
Yang, X., Karis, D. S.A. & Vleggeert-Lankamp, C. L. A. 2020. Association between Modic changes, disc degeneration, and neck pain in the cervical spine: a systematic review of literature. Spine J, 20, 754–764. 10.1016/j.spinee.2019.11.002
Zhang, T., Wang, Y., Li, R., Xin, J., Zheng, Z., Zhang, X., Xiao, C. & Zhang, S. 2023. ROS-responsive magnesium-containing microspheres for antioxidative treatment of intervertebral disc degeneration. Acta Biomater, 158, 475–492. 10.1016/j.actbio.2023.01.020
Zhang, Z., Wu, J., Teng, C., Wang, J., Yu, J., Jin, C., Wang, L., Wu, L., Lin, Z., Yu, Z. & Lin, Z. 2022. Orientin downregulating oxidative stress-mediated endoplasmic reticulum stress and mitochondrial dysfunction through AMPK/SIRT1 pathway in rat nucleus pulposus cells in vitro and attenuated intervertebral disc degeneration in vivo. Apoptosis, 27, 1031–1048. 10.1007/s10495-022-01770-9
Zhao, G. & Jing, J. 2023. HOMER1A restores sevoflurane-induced cognitive dysfunction by regulating microglia’s activation through activating the AMPK/TXNIP axis. Signa Vitae, 19. 10.22514/sv.2023.065
Zhao, Y., Qiu, C., Wang, W., Peng, J., Cheng, X., Shangguan, Y., Xu, M., Li, J., Qu, R., Chen, X., Jia, S., Luo, D., Liu, L., Li, P., Guo, F., Vasilev, K., Liu, L., Hayball, J., Dong, S., Pan, X., Li, Y., Guo, L., Cheng, L. & Li, W. 2020. Cortistatin protects against intervertebral disc degeneration through targeting mitochondrial ROS-dependent NLRP3 inflammasome activation. Theranostics, 10, 7015–7033. 10.7150/thno.45359
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