Targeted isolation of lignans and triterpenoids from kadsura coccinea by molecular networking and anti-RA-FLS activity

In this study, six compounds (four triterpenoids named heilaohutriterpenes A-D and two lignans name heilaohusuins F and G) together with 21 known compounds were isolated from roots of Kadsura coccinea (Lem.) A. C. Smith guided by molecular networking. Their structures were determined using a combination of HR-ESI-MS, 1D, 2D-NMR anatysis, NMR calculation, and electronic circular dichroism (ECD) calculations. Moreover, the ability of the isolated compounds to inhibit the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells was evaluated in vitro. Heilaohutriterpene B (2), heilaohutriterpene D (4), coccinone B (7), and kadsuralignan H (24) demonstrated significant inhibitory activities against RA-FLS cells, with IC₅₀ values of 9.57 ± 0.84, 16.22 ± 1.71, 3.08 ± 1.59, and 19.09 ± 2.42 μM, respectively. Meanwhile, western blotting analysis revealed that compound 2 down-regulated the level of P-NF-κB p65 and up-regulated that of Bax and IκBα. These results collectively suggest that compound 2 promoted the apoptosis of RA-FLS cells by inhibiting the NF-κB pathway. Taken together, this study contributed to the structural diversity of compounds derived from K. coccinea and lays a basis for further anti-RA-related studies.