Abstract
Rheumatoid arthritis (RA) is a chronic inflammation that can lead to loss of range of joint abnormalities in severe cases. Diosgenin has anti-inflammatory effects. This paper discussed the effect and mechanism of diosgenin on excessive proliferation and inflammatory response of synovial cells in RA. CCK-8 detected the cell viability, TUNEL assay detected the apoptosis of cells and western blot detected the expression of apoptosis-related proteins. Wound healing was used to detect cell migration and western blot detected the expression of migration-related proteins. ELISA kits were used to detect the levels of inflammatory cytokines in cells. Diosgenin can inhibit the proliferation and migration of RA synovial cells. At the same time, diosgenin could reduce the inflammatory response of RA synovial cells, during which the expression of PDE3B was significantly decreased. By overexpressing PDE3B, we found that diosgenin inhibited the proliferation, migration, and inflammatory response of RA synovial cells by downregulating PDE3B. Diosgenin can inhibit excessive proliferation and inflammatory response of synovial fibroblasts by targeting PDE3B.
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The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
References
Hamblin, M.J., and M.R. Horton. 2011. Rheumatoid arthritis-associated interstitial lung disease: Diagnostic dilemma. Pulm Med 2011: 872120.
Falconer, J., A.N. Murphy, S.P. Young, A.R. Clark, S. Tiziani, M. Guma, and C.D. Buckley. 2018. Review: Synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis & Rhematology 70 (7): 984–999.
Kaneshiro, K., Y. Sakai, K. Suzuki, K. Uchida, K. Tateishi, Y. Terashima, Y. Kawasaki, N. Shibanuma, K. Yoshida, and A. Hashiramoto. 2019. Interleukin-6 and tumour necrosis factor-alpha cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells. Scandinavian Journal of Rheumatology 48 (5): 353–361.
Sethi, G., et al. 2018. Pro-apoptotic and anti-cancer properties of diosgenin: A comprehensive and critical review. Nutrients: 10(5).
Wu, F.C., and J.G. Jiang. 2019. Effects of diosgenin and its derivatives on atherosclerosis. Food & Function 10 (11): 7022–7036.
Dong, M., Z. Meng, K. Kuerban, F. Qi, J. Liu, Y. Wei, Q. Wang, S. Jiang, M. Feng, and L. Ye. 2018. Diosgenin promotes antitumor immunity and PD-1 antibody efficacy against melanoma by regulating intestinal microbiota. Cell Death & Disease 9 (10): 1039.
Chen, Y., et al. 2015. Advances in the pharmacological activities and mechanisms of diosgenin. Chinese Journal of Natural Medicines 13 (8): 578–587.
Cai, H., L. Gong, J. Liu, Q. Zhou, and Z. Zheng. 2019. Diosgenin inhibits tumor angiogenesis through regulating GRP78-mediated HIF-1alpha and VEGF/VEGFR signaling pathways. Pharmazie 74 (11): 680–684.
McKoy, M.L., P.G. Thomas, H. Asemota, F. Omoruyi, and O. Simon. 2014. Effects of Jamaican bitter yam (Dioscorea polygonoides) and diosgenin on blood and fecal cholesterol in rats. Journal of Medicinal Food 17 (11): 1183–1188.
Liagre, B., P. Vergne-Salle, C. Corbiere, J.L. Charissoux, and J.L. Beneytout. 2004. Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression. Arthritis Research & Therapy 6 (4): R373–R383.
Cao, Y.J., Y. Xu, B. Liu, X. Zheng, J. Wu, Y. Zhang, X.S. Li, Y. Qi, Y.M. Sun, W.B. Wen, L. Hou, and C.P. Wan. 2019. Dioscin, a steroidal saponin isolated from Dioscorea nipponica, attenuates collagen-induced arthritis by inhibiting Th17 cell response. The American Journal of Chinese Medicine 47 (2): 423–437.
Pavlaki, N., and V.O. Nikolaev. 2018. Imaging of PDE2- and PDE3-mediated cGMP-to-cAMP cross-talk in cardiomyocytes. J Cardiovasc Dev Dis: 5(1).
Ahmad, F., Y.W. Chung, Y. Tang, S.C. Hockman, S. Liu, Y. Khan, K. Huo, E. Billings, M.J. Amar, A.T. Remaley, and V.C. Manganiello. 2016. Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue. Scientific Reports 6: 28056.
Beute, J., K. Ganesh, H. Nastiti, R. Hoogenboom, V. Bos, J. Folkerts, M.W.J. Schreurs, S. Hockman, R.W. Hendriks, and A. KleinJan. 2020. PDE3 inhibition reduces epithelial mast cell numbers in allergic airway inflammation and attenuates degranulation of basophils and mast cells. Frontiers in Pharmacology 11: 470.
Wu, S., M. Zhao, Y. Sun, M. Xie, K. le, M. Xu, and C. Huang. 2020. The potential of diosgenin in treating psoriasis: Studies from HaCaT keratinocytes and imiquimod-induced murine model. Life Sciences 241: 117115.
Du, S., et al. 2019. Dioscin alleviates crystalline silica-induced pulmonary inflammation and fibrosis through promoting alveolar macrophage autophagy. Theranostics 9 (7): 1878–1892.
Chen, Y., et al. 2016. Diosgenin regulates adipokine expression in perivascular adipose tissue and ameliorates endothelial dysfunction via regulation of AMPK. The Journal of Steroid Biochemistry and Molecular Biology 155 (Pt A): 155–165.
Guo, Y., E. Xing, X. Liang, H. Song, and W. Dong. 2016. Effects of total saponins from Rhizoma Dioscoreae Nipponicae on expression of vascular endothelial growth factor and angiopoietin-2 and Tie-2 receptors in the synovium of rats with rheumatoid arthritis. Journal of the Chinese Medical Association 79 (5): 264–271.
Liagre, B., D.Y. Leger, P. Vergne-Salle, and J.L. Beneytout. 2007. MAP kinase subtypes and Akt regulate diosgenin-induced apoptosis of rheumatoid synovial cells in association with COX-2 expression and prostanoid production. International Journal of Molecular Medicine 19 (1): 113–122.
Wu, J., Q. Li, L. Jin, Y. Qu, B.B. Liang, X.T. Zhu, H.Y. du, L.G. Jie, and Q.H. Yu. 2019. Kirenol inhibits the function and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis in vitro and in vivo. Frontiers in Immunology 10: 1304.
Mowers, J., M. Uhm, S.M. Reilly, J. Simon, D. Leto, S.H. Chiang, L. Chang, and A.R. Saltiel. 2013. Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKepsilon and TBK1. Elife 2: e01119.
Guo, C.H., W.L. Chen, C.H. Liao, K. Huang, P.Y. Chen, and C.P. Yang. 2018. Effects of Chinese medicinal formula BNG-1 on phosphodiesterase 3B expression, hepatic steatosis, and insulin resistance in high fat dieT-INDUCED NAFLD mice. International Journal of Medical Sciences 15 (11): 1194–1202.
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The Grants-in-Aid for Scientific Research (JC2019136) from the Ministry of Nantong Science and Technology.
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Wang, R., Sun, Y., Jin, X. et al. Diosgenin Inhibits Excessive Proliferation and Inflammatory Response of Synovial Fibroblasts in Rheumatoid Arthritis by Targeting PDE3B. Inflammation 44, 946–955 (2021). https://doi.org/10.1007/s10753-020-01389-5
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DOI: https://doi.org/10.1007/s10753-020-01389-5