Sesquiterpenes from Kadsura coccinea attenuate rheumatoid arthritis-related inflammation by inhibiting the NF-κB and JAK2/STAT3 signal pathways

• Published in: Phytochemistry (Oxford) 2022-02, Vol.194, p.113018-113018, Article 113018
• Main Authors: Yang, Yupei, Liu, Yongbei, Yu, Huanghe, Xie, Qingling, Wang, Bin, Jiang, Sai, Su, Wei, Mao, Yu, Li, Bin, Peng, Caiyun, Jian, Yuqing, Wang, Wei
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory; Arthritis, Rheumatoid - drug therapy; Inflammation; Janus Kinase 2; Kadsura - chemistry; Kadsura coccinea; Mice; NF-kappa B; Phytochemicals - pharmacology; RAW 264.7 Cells; Rheumatoid arthritis; Schisandraceae; Sesquiterpenes - pharmacology; Sesquiterpenoid; Signal Transduction - drug effects; STAT3 Transcription Factor; Tujia ethnomedicine
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2021.113018

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named “heilaohu”, having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC50 value of 9.37 μM. In the same line, nine compounds exhibited significant inhibition effects against TNF−α and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 μM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies. [Display omitted] •Two undescribed sesquiterpenes were isolated from roots of K. coccinea.•Nine compounds exhibited significant anti-inflammation effects.•Compound 19 was good cytotoxic against RA-FLS cells with an IC50 value of 9.37 μM.•The potential molecular mechanisms established by pharmacological network analysis.•Compound 19 suppressed inflammation by inhibiting the NF-κB and JAK2/STAT3 pathways.