Isolation, structure modification, and anti-rheumatoid arthritis activity of isopimarane-type diterpenoids from Orthosiphon aristatus

• Published in: Journal of enzyme inhibition and medicinal chemistry 2024-12, Vol.39 (1), p.2296355-2296355
• Main Authors: Luo, Yong-Xin, Gong, Xu, Su, Zhi-Cheng, Mo, Jin-Feng, Li, Dong-Li, Wu, Ri-Hui, Jin, Jing-Wei, Lang, Ming, Wang, Jin-Ping, Xu, Xue-Tao, Gan, Li-She
• Format: Article
• Language: English
• Subjects: Isopimarane diterpenoid; MH7A; Orthosiphon aristatus; anti-rheumatoid arthritis; structure modification
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2023.2296355

is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids ( - ), including a new one with a rarely occurring α,β-unsaturated diketone C-ring, were isolated from . Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives ( ). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1β, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.