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

Yang, Yupei ¹Liu, Yongbei ¹Yu, Huanghe ¹Xie, Qingling ¹Wang, Bin ¹Jiang, Sai ¹Su, Wei ¹Mao, Yu ¹Li, Bin ¹Peng, Caiyun ¹Jian, Yuqing ¹Wang, Wei¹

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作者信息

1. Hunan Univ Chinese Med
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Abstract

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 mu M. In the same line, nine compounds exhibited significant inhibition effects against TNF-alpha and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 mu M. 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-kappa B and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and antiinflammatory studies.

Key words

Kadsura coccinea/Schisandraceae/Sesquiterpenoid/Rheumatoid arthritis/Anti-Inflammatory/Tujia ethnomedicine/FIBROBLAST-LIKE SYNOVIOCYTES/HEARTWOOD/FRUITS

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出版年

2022

Phytochemistry

CCR

ISSN：0031-9422

被引量5

参考文献量40

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