Aucubin Alleviates Intervertebral Disc Degeneration by Repressing NF-κB-NLRP3 Inflammasome Activation in Endplate Chondrocytes

References

• Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391(10137):2356–2367. doi:10.1016/S0140-6736(18)30480-X
   PubMed Web of Science ®Google Scholar
• Chou R. Low Back Pain. Ann Intern Med. 2021;174(8):ITC113–ITC128. doi:10.7326/AITC202108170
   PubMed Web of Science ®Google Scholar
• Vergroesen PP, Kingma I, Emanuel KS, et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis Cartilage. 2015;23(7):1057–1070. doi:10.1016/j.joca.2015.03.028
   PubMed Web of Science ®Google Scholar
• Wang F, Cai F, Shi R, Wang XH, Wu XT. Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration. Osteoarthritis Cartilage. 2016;24(3):398–408. doi:10.1016/j.joca.2015.09.019
   PubMed Web of Science ®Google Scholar
• Qian J, Ge J, Yan Q, Wu C, Yang H, Zou J. Selection of the optimal puncture needle for induction of a rat intervertebral disc degeneration model. Pain Physician. 2019;22(4):353–360.
   PubMed Web of Science ®Google Scholar
• Li G, Zhang W, Liang H, Yang C. Epigenetic regulation in intervertebral disc degeneration. Trends Mol Med. 2022;28(10):803–805. doi:10.1016/j.molmed.2022.07.007
   PubMed Web of Science ®Google Scholar
• Vlaeyen JWS, Maher CG, Wiech K, et al. Low back pain. Nat Rev Dis Primers. 2018;4(1):52. doi:10.1038/s41572-018-0052-1
   PubMed Web of Science ®Google Scholar
• Francisco V, Pino J, Gonzalez-Gay MA, et al. A new immunometabolic perspective of intervertebral disc degeneration. Nat Rev Rheumatol. 2022;18(1):47–60. doi:10.1038/s41584-021-00713-z
   PubMed Web of Science ®Google Scholar
• Roberts S, Evans H, Trivedi J, Menage J. Histology and pathology of the human intervertebral disc. J Bone Joint Surg Am. 2006;88(Suppl 2):10–14. doi:10.2106/JBJS.F.00019
   PubMed Web of Science ®Google Scholar
• Risbud MV, Shapiro IM. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat Rev Rheumatol. 2014;10(1):44–56. doi:10.1038/nrrheum.2013.160
   PubMed Web of Science ®Google Scholar
• Sun K, Jiang J, Wang Y, et al. The role of nerve fibers and their neurotransmitters in regulating intervertebral disc degeneration. Ageing Res Rev. 2022;81:101733. doi:10.1016/j.arr.2022.101733
   PubMed Web of Science ®Google Scholar
• Shao Y, Sun L, Yang G, et al. Icariin protects vertebral endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 pathway. Front Pharmacol. 2022;13:937502. doi:10.3389/fphar.2022.937502
   PubMed Web of Science ®Google Scholar
• Fontana G, See E, Pandit A. Current trends in biologics delivery to restore intervertebral disc anabolism. Adv Drug Deliv Rev. 2015;84:146–158. doi:10.1016/j.addr.2014.08.008
   PubMed Web of Science ®Google Scholar
• Gong Y, Qiu J, Jiang T, et al. Maltol ameliorates intervertebral disc degeneration through inhibiting PI3K/AKT/NF-kappaB pathway and regulating NLRP3 inflammasome-mediated pyroptosis. Inflammopharmacology. 2023;31(1):369–384. doi:10.1007/s10787-022-01098-5
   PubMedGoogle Scholar
• Zehra U, Tryfonidou M, Iatridis JC, Illien-Junger S, Mwale F, Samartzis D. Mechanisms and clinical implications of intervertebral disc calcification. Nat Rev Rheumatol. 2022;18(6):352–362. doi:10.1038/s41584-022-00783-7
   PubMed Web of Science ®Google Scholar
• Lu A, Magupalli VG, Ruan J, et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell. 2014;156(6):1193–1206. doi:10.1016/j.cell.2014.02.008
   PubMed Web of Science ®Google Scholar
• Wang L, Hauenstein AV. The NLRP3 inflammasome: mechanism of action, role in disease and therapies. Mol Aspects Med. 2020;76:100889. doi:10.1016/j.mam.2020.100889
   PubMed Web of Science ®Google Scholar
• Chen F, Jiang G, Liu H, et al. Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1beta/NF-kappaB-NLRP3 inflammasome positive feedback loop. Bone Res. 2020;8(1):10. doi:10.1038/s41413-020-0087-2
   PubMed Web of Science ®Google Scholar
• Chao-Yang G, Peng C, Hai-Hong Z. Roles of NLRP3 inflammasome in intervertebral disc degeneration. Osteoarthritis Cartilage. 2021;29(6):793–801. doi:10.1016/j.joca.2021.02.204
   PubMed Web of Science ®Google Scholar
• Gao F, Li H, Feng Y, Tian W, Cao R, Fu K. Aucubin ameliorates the LPS-induced inflammatory response in bovine endometrial epithelial cells by inhibiting NF-kappaB and activating the Keap1/Nrf2 signalling pathway. Reprod Domest Anim. 2021;56(7):972–982. doi:10.1111/rda.13939
   PubMed Web of Science ®Google Scholar
• Park KS, Chang IM. Anti-inflammatory activity of aucubin by inhibition of tumor necrosis factor-alpha production in RAW 264.7 cells. Planta Med. 2004;70(8):778–779. doi:10.1055/s-2004-827211
   PubMed Web of Science ®Google Scholar
• Park KS. Aucubin, a naturally occurring iridoid glycoside inhibits TNF-alpha-induced inflammatory responses through suppression of NF-kappaB activation in 3T3-L1 adipocytes. Cytokine. 2013;62(3):407–412. doi:10.1016/j.cyto.2013.04.005
   PubMed Web of Science ®Google Scholar
• Zhang Y, Tang LD, Wang JY, et al. Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis. Chin J Nat Med. 2022;20(6):458–472. doi:10.1016/S1875-5364(22)60182-1
   PubMed Web of Science ®Google Scholar
• Wang SN, Xie GP, Qin CH, et al. Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix degradation via inhibition of NF-kappaB signaling pathway in rat articular chondrocytes. Int Immunopharmacol. 2015;24(2):408–415. doi:10.1016/j.intimp.2014.12.029
   PubMed Web of Science ®Google Scholar
• Yang S, Li L, Zhu L, et al. Aucubin inhibits IL-1beta- or TNF-alpha-induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR-140-5p/CREB1 axis. J Cell Physiol. 2019;234(8):13639–13648. doi:10.1002/jcp.28044
   PubMed Web of Science ®Google Scholar
• Oichi T, Taniguchi Y, Soma K, et al. A mouse intervertebral disc degeneration model by surgically induced instability. Spine. 2018;43(10):E557–E564. doi:10.1097/BRS.0000000000002427
   PubMed Web of Science ®Google Scholar
• Mao J, Wang D, Wang D, et al. SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis. Exp Mol Med. 2023;55(1):253–268. doi:10.1038/s12276-023-00928-y
   PubMed Web of Science ®Google Scholar
• Fu F, Bao R, Yao S, et al. Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth. Sci Rep. 2021;11(1):772. doi:10.1038/s41598-020-80756-6
   PubMed Web of Science ®Google Scholar
• Bian Q, Jain A, Xu X, et al. Excessive activation of TGFbeta by spinal instability causes vertebral endplate sclerosis. Sci Rep. 2016;6(1):27093. doi:10.1038/srep27093
   PubMedGoogle Scholar
• Xue J, Hu B, Xing W, et al. Low expression of miR-142-3p promotes intervertebral disk degeneration. J Orthop Surg Res. 2021;16(1):55. doi:10.1186/s13018-020-02194-4
   PubMed Web of Science ®Google Scholar
• Zhao K, An R, Xiang Q, et al. Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration. Cell Prolif. 2021;54(1):e12941. doi:10.1111/cpr.12941
   PubMed Web of Science ®Google Scholar
• Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol. 2021;18(9):2114–2127. doi:10.1038/s41423-021-00740-6
   PubMed Web of Science ®Google Scholar
• Raftery MN, Sarma K, Murphy AW, De la Harpe D, Normand C, McGuire BE. Chronic pain in the Republic of Ireland--community prevalence, psychosocial profile and predictors of pain-related disability: results from the Prevalence, Impact and Cost of Chronic Pain (PRIME) study, part 1. Pain. 2011;152(5):1096–1103. doi:10.1016/j.pain.2011.01.019
   PubMed Web of Science ®Google Scholar
• Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–1222.
   PubMed Web of Science ®Google Scholar
• Belitskaya-Levy I, Clark JD, Shih MC, Bair MJ. Treatment preferences for chronic low back pain: views of veterans and their providers. J Pain Res. 2021;14:161–171. doi:10.2147/JPR.S290400
   PubMed Web of Science ®Google Scholar
• Mohd Isa IL, Mokhtar SA, Abbah SA, Fauzi MB, Devitt A, Pandit A. Intervertebral disc degeneration: biomaterials and tissue engineering strategies toward precision medicine. Adv Healthc Mater. 2022;11(13):e2102530. doi:10.1002/adhm.202102530
   PubMed Web of Science ®Google Scholar
• Guo Q, Zhu D, Wang Y, et al. Targeting STING attenuates ROS induced intervertebral disc degeneration. Osteoarthritis Cartilage. 2021;29(8):1213–1224. doi:10.1016/j.joca.2021.04.017
   PubMed Web of Science ®Google Scholar
• Bian Q, Ma L, Jain A, et al. Mechanosignaling activation of TGFbeta maintains intervertebral disc homeostasis. Bone Res. 2017;5(1):17008. doi:10.1038/boneres.2017.8
   PubMedGoogle Scholar
• Luo L, Jian X, Sun H, et al. Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. Stem Cells. 2021;39(4):467–481. doi:10.1002/stem.3322
   PubMed Web of Science ®Google Scholar
• Zhang Y, He F, Chen Z, et al. Melatonin modulates IL-1beta-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation. Aging. 2019;11(22):10499–10512. doi:10.18632/aging.102472
   PubMedGoogle Scholar
• Yang G, Liu X, Jing X, et al. Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway. Int Immunopharmacol. 2023;119:110159. doi:10.1016/j.intimp.2023.110159
   PubMed Web of Science ®Google Scholar
• Zuo R, Wang Y, Li J, et al. Rapamycin induced autophagy inhibits inflammation-mediated endplate degeneration by enhancing Nrf2/Keap1 signaling of cartilage endplate stem cells. Stem Cells. 2019;37(6):828–840. doi:10.1002/stem.2999
   PubMed Web of Science ®Google Scholar
• Huang B, Liu J, Wei X, et al. Damage to the human lumbar cartilage endplate and its clinical implications. J Anat. 2021;238(2):338–348. doi:10.1111/joa.13321
   PubMed Web of Science ®Google Scholar
• Rade M, Maatta JH, Freidin MB, Airaksinen O, Karppinen J, Williams FMK. Vertebral endplate defect as initiating factor in intervertebral disc degeneration: strong association between endplate defect and disc degeneration in the general population. Spine. 2018;43(6):412–419. doi:10.1097/BRS.0000000000002352
   PubMed Web of Science ®Google Scholar
• Xiao ZF, Su GY, Hou Y, et al. Mechanics and biology interact in intervertebral disc degeneration: a novel composite mouse model. Calcif Tissue Int. 2020;106(4):401–414. doi:10.1007/s00223-019-00644-8
   PubMed Web of Science ®Google Scholar
• Wang X, Lu Y, Wang W, et al. Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo. Regen Biomater. 2020;7(6):583–595. doi:10.1093/rb/rbaa028
   PubMed Web of Science ®Google Scholar
• Wang L, Gu Y, Zhao H, et al. Dioscin Attenuates Interleukin 1beta (IL-1beta)-induced catabolism and apoptosis via modulating the toll-like receptor 4 (TLR4)/Nuclear Factor kappa B (NF-kappaB) signaling in human nucleus pulposus cells. Med Sci Monit. 2020;26:e923386. doi:10.12659/MSM.923386
   PubMed Web of Science ®Google Scholar
• Li Y, Cao L, Li J, et al. Influence of microgravity-induced intervertebral disc degeneration of rats on expression levels of p53/p16 and proinflammatory factors. Exp Ther Med. 2019;17(2):1367–1373. doi:10.3892/etm.2018.7085
   PubMed Web of Science ®Google Scholar
• Krupkova O, Sekiguchi M, Klasen J, et al. Epigallocatechin 3-gallate suppresses interleukin-1beta-induced inflammatory responses in intervertebral disc cells in vitro and reduces radiculopathic pain in rats. Eur Cell Mater. 2014;28:372–386. doi:10.22203/eCM.v028a26
   PubMed Web of Science ®Google Scholar
• Huang H, Chang YH, Xu J, et al. Aucubin as a natural potential anti-acute hepatitis candidate: inhibitory potency and hepatoprotective mechanism. Phytomedicine. 2022;102:154170. doi:10.1016/j.phymed.2022.154170
   PubMed Web of Science ®Google Scholar
• Jeong HJ, Koo HN, Na HJ, et al. Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappaB activation RBL-2H3 mast cells. Cytokine. 2002;18(5):252–259. doi:10.1006/cyto.2002.0894
   PubMed Web of Science ®Google Scholar
• Xu XE, Liu L, Wang YC, et al. Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis. Brain Behav Immun. 2019;80:859–870. doi:10.1016/j.bbi.2019.05.038
   PubMed Web of Science ®Google Scholar
• Abulafia DP, de Rivero Vaccari JP, Lozano JD, Lotocki G, Keane RW, Dietrich WD. Inhibition of the inflammasome complex reduces the inflammatory response after thromboembolic stroke in mice. J Cereb Blood Flow Metab. 2009;29(3):534–544. doi:10.1038/jcbfm.2008.143
   PubMed Web of Science ®Google Scholar
• Chen D, Jiang X, Zou H. hASCs-derived exosomal miR-155-5p targeting TGFbetaR2 promotes autophagy and reduces pyroptosis to alleviate intervertebral disc degeneration. J Orthop Translat. 2023;39:163–176. doi:10.1016/j.jot.2023.02.004
   PubMed Web of Science ®Google Scholar
• Deng Z, Zhang Y, Zhu Y, et al. BRD9 inhibition attenuates matrix degradation and pyroptosis in nucleus pulposus by modulating the NOX1/ROS/NF-kappaB axis. Inflammation. 2023;46(3):1002–1021. doi:10.1007/s10753-023-01786-6
   PubMed Web of Science ®Google Scholar
• Tang P, Zhu R, Ji WP, et al. The NLRP3/Caspase-1/Interleukin-1beta axis is active in human lumbar cartilaginous endplate degeneration. Clin Orthop Relat Res. 2016;474(8):1818–1826. doi:10.1007/s11999-016-4866-4
   PubMed Web of Science ®Google Scholar
• Xiao S, Zhong N, Yang Q, et al. Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model. Int Immunopharmacol. 2022;111:109163. doi:10.1016/j.intimp.2022.109163
   PubMed Web of Science ®Google Scholar
• Wu QQ, Xiao Y, Duan MX, et al. Aucubin protects against pressure overload-induced cardiac remodelling via the beta(3) -adrenoceptor-neuronal NOS cascades. Br J Pharmacol. 2018;175(9):1548–1566. doi:10.1111/bph.14164
   PubMed Web of Science ®Google Scholar
• Wang H, Zhou XM, Wu LY, et al. Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury. J Neuroinflammation. 2020;17(1):188. doi:10.1186/s12974-020-01863-9
   PubMed Web of Science ®Google Scholar