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.