Curculigoside inhibits osteoarthritis via the regulation of NLRP3 pathway

Submitted: 23 October 2023
Accepted: 27 November 2023
Published: 13 December 2023
Abstract Views: 444
PDF: 317
HTML: 4
Publisher's note
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 characterized by degenerative articular cartilage. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) plays an important role in inflammation. This study aims to investigate whether protective effects of curculigoside on OA are medicated by the regulation of NLRP3 pathway. Destabilization of the medial meniscus (DMM) was performed to build an OA mouse model. After surgery, OA mice were treated with curculigoside. Immunohistochemistry was conducted to evaluate OA cartilage. In addition, human chondrocytes were isolated and treated with curculigoside. The mRNA and protein expression of iNOS, MMP-9, NLRP3 was detected by PCR and Western blot analysis. Curculigoside inhibited mRNA and protein levels of iNOS and MMP-9 induced by DMM surgery in a dose-dependent manner. Furthermore, the expression of NLRP3, NF-κB and PKR was downregulated after curculigoside administration. Moreover, curculigoside reversed the effects of IL-1β on MMP-9, iNOS and type II collagen expression at mRNA and protein levels in human chondrocytes in a dose-dependent manner. In conclusion, curculigoside exhibits beneficial effect on cartilage via the inhibition of NLRP3 pathway.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Li YY, Feng YP, Liu L, Ke J, Long X. Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis via NF-κB signaling pathway. Eur J Histochem 2022;66:3357. DOI: https://doi.org/10.4081/ejh.2022.3357
Timmins KA, Leech RD, Batt ME, Edwards KL. Running and knee osteoarthritis: a systematic review and meta-analysis. Am J Sports Med 2017;45:1447-57. DOI: https://doi.org/10.1177/0363546516657531
Bian Q, Wang YJ, Liu SF, Li YP. Osteoarthritis: genetic factors, animal models, mechanisms, and therapies. Front Biosci (Elite Ed) 2012;4:74-100. DOI: https://doi.org/10.2741/e361
Lian WS, Ko JY, Wu RW, Sun YC, Chen YS, Wu SL, et al. MicroRNA-128a represses chondrocyte autophagy and exacerbates knee osteoarthritis by disrupting Atg12. Cell Death Dis 2018;9:919. DOI: https://doi.org/10.1038/s41419-018-0994-y
Ouyang K, Xu M, Liang Y, Xu X, Xu L, Wen C, et al. Ex vivo cartilage explant model for the evaluation of chondrocyte-targeted exosomes. Biocell 2022;46:1521-6. DOI: https://doi.org/10.32604/biocell.2022.018788
Nasi S, Ea HK, So A, Busso N. Revisiting the role of interleukin-1 pathway in osteoarthritis: interleukin-1α and -1β, and NLRP3 inflammasome are not involved in the pathological features of the murine menisectomy model of osteoarthritis. Front Pharmacol 2017;8:282. DOI: https://doi.org/10.3389/fphar.2017.00282
Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature 2012;488:670-4. DOI: https://doi.org/10.1038/nature11290
Mizushina Y, Shirasuna K, Usui F, Karasawa T, Kawashima A, Kimura H, et al. NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β. J Biol Chem 2015;290:5065-77. DOI: https://doi.org/10.1074/jbc.M114.603217
Tang P, Gu JM, Xie ZA, Gu Y, Jie ZW, Huang KM, et al. Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway. Free Radic Biol Med 2018;120:368-79. DOI: https://doi.org/10.1016/j.freeradbiomed.2018.04.008
Wang L, He YJ, Han T, Zhao L, Lv L, He YQ, et al. Metabolites of curculigoside in rats and their antiosteoporotic activities in osteoblastic MC3T3-E1 cells. Fitoterapia 2017;117:109-17. DOI: https://doi.org/10.1016/j.fitote.2017.01.009
Ding H, Gao G, Zhang L, Shen G, Sun W, Gu Z, Fan W. The protective effects of curculigoside A on adjuvant-induced arthritis by inhibiting NF-кB/NLRP3 activation in rats. Int Immunopharmacol 2016;30:43-9. DOI: https://doi.org/10.1016/j.intimp.2015.11.026
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001;25:402-8. DOI: https://doi.org/10.1006/meth.2001.1262
Lin J, Jia S, Zhang W, Nian M, Liu P, Yang L, et al. Recent advances in small molecule inhibitors for the treatment of osteoarthritis. J Clin Med 2023;12:1986. DOI: https://doi.org/10.3390/jcm12051986
Jung YK, Han MS, Park HR, Lee EJ, Jang JA, Kim GW, et al. Calcium-phosphate complex increased during subchondral bone remodeling affects early stage osteoarthritis. Sci Rep 2018;8:487. DOI: https://doi.org/10.1038/s41598-017-18946-y
Tan S, Xu J, Lai A, Cui R, Bai R, Li S, et al. Curculigoside exerts significant anti-arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF‑κB signaling pathway. Mol Med Rep 2019;19:2057-64. DOI: https://doi.org/10.3892/mmr.2019.9854
Wang P, Li G, Gao L, Zhao C. Human β-defensin 2 enhances IL-1β production and pyroptosis through P2X7-mediated NLRP3 expression in macrophages. Biocell 2022;46:1197-207. DOI: https://doi.org/10.32604/biocell.2022.016607
Liu M1, Li Y, Yang ST. Curculigoside improves osteogenesis of human amniotic fluid-derived stem cells. Stem Cells Dev 2014;23:146-54. DOI: https://doi.org/10.1089/scd.2013.0261
Wu L, Chai R, Lin Z, Wu R, Yao D, Jiang T, et al. Evolution-driven crosstalk between glioblastoma and the tumor microenvironment. Cancer Biol Med 2023;20:319-24. DOI: https://doi.org/10.20892/j.issn.2095-3941.2022.0771
Zhang T, Wang J, Wang D, Xu K, Wu L, Wang X, et al. The time-series behavior of systemic inflammation-immune status in predicting survival of locally advanced non-small cell lung cancer treated with chemoradiotherapy. J Natl Cancer Inst 2022;2:33-40. DOI: https://doi.org/10.1016/j.jncc.2021.11.003
Bertuglia A, Pagliara E, Grego E, Ricci A, Brkljaca-Bottegaro N. Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career. BMC Vet Res 2016;12:246. DOI: https://doi.org/10.1186/s12917-016-0873-7
Li Z, Liu B, Zhao D, Wang B, Liu Y, Zhang Y, et al. Protective effects of nebivolol against interleukin-1β (IL-1β)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13). Cell Stress Chaperones 2017;22:767-74. DOI: https://doi.org/10.1007/s12192-017-0805-x
Tu C, Huang X, Xiao Y, Song M, Ma Y, Yan J, et al. Schisandrin A inhibits the IL-1β-induced inflammation and cartilage degradation via suppression of MAPK and NF-κB signal pathways in rat chondrocytes. Front Pharmacol 2017;10:41. DOI: https://doi.org/10.3389/fphar.2019.00041
Montaseri A, Busch F, Mobasheri A, Buhrmann C, Aldinger C, Rad JS, et al. IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: involvement of Src/PI-3K/AKT pathway. PLoS One 2011;6:e28663. DOI: https://doi.org/10.1371/journal.pone.0028663
Dai X, Tohyama M, Murakami M, Sayama K. Epidermal keratinocytes sense dsRNA via the NLRP3 inflammasome, mediating interleukin (IL)-1β and IL-18 release. Exp Dermatol 2017;26:904-11. DOI: https://doi.org/10.1111/exd.13334

Ethics Approval

this study was approved by the Ethics Committee of Shanxi Bethune Hospital, All animal study protocols were approved by the Animal Care and Use Committee of Shanxi Bethune Hospital

How to Cite

Wang, X., Liu, Y., Zhou, Y., Zhou, Y., & Li, Y. (2023). Curculigoside inhibits osteoarthritis <em>via</em> the regulation of NLRP3 pathway. European Journal of Histochemistry, 67(4). https://doi.org/10.4081/ejh.2023.3896