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

被引：2

作者：

Luo, Yong-Xin ^{[1
,2
]}

Gong, Xu ^{[2
]}

Su, Zhi-Cheng ^{[2
]}

Mo, Jin-Feng ^{[2
]}

Li, Dong-Li ^{[2
]}

Wu, Ri-Hui ^{[2
]}

Jin, Jing-Wei ^{[2
]}

Lang, Ming ^{[2
]}

Wang, Jin-Ping ^{[3
]}

Xu, Xue-Tao ^{[2
]}

Gan, Li-She ^{[1
,2
]}

机构：

[1] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou, Peoples R China

[2] Wuyi Univ, Sch Biotechnol & Hlth Sci, Int Healthcare Innovat Inst Jiangmen, Jiangmen, Peoples R China

[3] Shenzhen Univ, Shenzhen Peoples Hosp 2, Dept Urol, Affiliated Hosp 1, Shenzhen, Peoples R China

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2024年 / 39卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Isopimarane diterpenoid; MH7A; Orthosiphon aristatus; anti-rheumatoid arthritis; structure modification; HIGHLY-OXYGENATED DITERPENES; STAMINEUS;

D O I：

10.1080/14756366.2023.2296355

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Orthosiphon aristatus 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 (1-8), including a new one with a rarely occurring alpha,beta-unsaturated diketone C-ring, were isolated from O. aristatus. 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 (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-alpha induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1 beta, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of I kappa B alpha and decrease the expression of NF-kappa B p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

引用

页数：8