Inotodiol ameliorates the progression of osteoarthritis: An in vitro and in vivo study

Abstract

Osteoarthritis is a common chronic degenerative disease, of which the essence is the degenerative changes of bone and joint cartilage, involving damage in multiple structures such as bone, synovium and joints. In the mechanism of arthritis inflammation is closely related, and therefore the exploration to inhibit inflammatory mediators is crucial for the clinical prevention and treatment of osteoarthritis. Inotodiol is a lanostane triterpenoid isolated from Inonotus obliquus, which had been extensively reported to be an anti-inflammatory agent, but its effect on arthritis remains unknown. In this study, we firstly demonstrated that inotodiol significantly reduced IL-1β-induced chondrocyte injury and inhibited the release of inflammatory factors. At the same time, experiments in vivo showed that inotodiol could effectively improve the symptoms of joint injury in mice and reduce the area of cartilage destruction, indicating that inotodiol may be a potential therapeutic drug for osteoarthritis.

Key words

osteoarthritis - inflammation - inotodiol - chondrocyte injury

^* contributed equally to this work.

Publication History

Received: 19 April 2023

Accepted: 11 September 2023

Article published online:
07 November 2023

• References

• 1 GLYN-JONES S, PALMER AJR, AGRICOLA R. Osteoarthritis. Lancet. 2015; 386: 376-387
• 2 Noble PhilipC, Conditt MichaelA, Cook KaronF. et al. The John Insall Award: Patient Expectations Affect Satisfaction with Total Knee Arthroplasty. Clin Orthop Relat Res 2006; 452: 35-43
• 3 Bannuru RR, Osani MC, Vaysbrot EE. et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019; 27: 1578-1589
• 4 Haywood L, McWilliams DF, Pearson CI. et al. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum 2014; 48: 2173-2177
• 5 Wood MatthewJ, Miller RachelE, Malfait AM. The Genesis of Pain in Osteoarthritis: Inflammation as a Mediator of Osteoarthritis Pain. 2022; 38: 221-238
• 6 Wojdasiewicz P, Poniatowski ŁA, Szukiewicz D. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis. Mediators Inflamm 2014; 2014: 561459
• 7 Woodell-Ma Jennifer, Matuska Andrea, Oyster Megan. et al. Autologous protein solution inhibits MMP-13 production by IL-1β and TNFα-stimulated human articular chondrocytes. J Orthop Res 2011; 29: 1320-1326
• 8 Chabane N, Zayed N, Afif H. et al. Histone deacetylase inhibitors suppress interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthritis Cartilage 2008; 16: 1267-1274
• 9 Ludwiczak RS, Wrzeciono U. Investigations of the chemical constituents of Inonotus obliquus.I. Inotodiol. Roczniki Chemii 1958; 32: 39-47
• 10 Ludwiczak RS, Wrzeciono U. Active substances of Inonotus obliquus. Acta Biologica Hungarica 1961; 31: 17-21
• 11 Kempska k, Ludwicak RS, Wrzeciono U. Investigation of chemical components of Inonotus obliquus..
• 12 V. Further investigations of the structure of inotodiol. Roczniki Chemii 1962; 36: 497-502
• 13 Huijing Fu, Yana Song, Xiujuan Sun. In vitro antioxidant activity of polysaccharides from Inonotus obliquus. Journal of Edible Fungi 2006; 13: 29-31
• 14 Mizuno T, Zhuang C, Abe K. Antiumor and hypoglycemic activities of polysaccharides from the scleritia and mycelia of Inonotus obliquus. Int J Med Mushrooms 1999; 1: 301-316
• 15 Burczyk J, Gawron A, Slotwinska M. et al. K Terminska. Antimitot activity of aqueous extracts of Inonotus Ob1iquus. Boll Chim Farm 1996; 135: 306-309
• 16 Yanqiu Chen, Lijie Zhou, Yu Li. Artificially cultured mycelia, sclerotia and wild fungi of Inonotus obliquus Comparative Experimental Study on Hypoglycemic Effect of Polysaccharides. Edible Fungi 2006; 3: 52-54
• 17 Nguyen TMN, Le HS, Le BV. et al. Anti-allergic effect of inotodiol, a lanostane triterpenoid from Chaga mushroom, via selective inhibition of mast cell function. Int Immunopharmacol 2020; 81: 106244
• 18 Shen J, Abu-Amer Y, O’Keefe RJ. et al. Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res 2017; 58: 49-63
• 19 Zhao FQ, Yan L, Cui XH. et al. Triterpenoids from Inonotus obliquus protect mice against oxidative damage induced by CCl4. Yao Xue Xue Bao 2012; 47: 680-684
• 20 PAMA Maza, Lee JH, Kim YS. et al. Inotodiol From Inonotus obliquus Chaga Mushroom Induces Atypical Maturation in Dendritic Cells. Front Immunol 2021; 12: 650841
• 21 Chen Ximiao, Li Zhengli, Hong Haofeng. et al. Xanthohumol suppresses inflammation in chondrocytes and ameliorates osteoarthritis in mice. Biomed Pharmacother 2021; 137: 111238
• 22 Zhang SD, Yu L, Wang P. et al. Inotodiol inhibits cells migration and invasion and induces apoptosis via p53-dependent pathway in HeLa cells. Phytomedicine. 2019; 60: 152957
• 23 Zhong XH, Wang LB, Sun DZ. Effects of inotodiol extracts from inonotus obliquus on proliferation cycle and apoptotic gene of human lung adenocarcinoma cell line A549. Chin J Integr Med 2011; 17: 218-223