Monoterpene indole alkaloids from the seeds of Strychnos nux-vomica L. with anti-rheumatoid arthritis activity.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by abnormal proliferation of fibroblast-like synoviocytes and excessive secretion of pro-inflammatory cytokines. Strychnos nux-vomica L. (S. nux-vomica) is a traditional medicinal herb used for treating arthritic disorders, while the material basis for its anti-RA activity remains poorly understood. In the present study, twenty-three monoterpene indole alkaloids (MIAs), including eight undescribed compounds (1-8) and fifteen known analogues (9-23), were isolated from the seeds of S. nux-vomica. All isolates were screened for their anti-proliferative activities on TNF-α-induced human RA fibroblast-like synoviocyte MH7A cells. Fourteen MIAs showed inhibitory effects with IC50 values ranging from 9.2 to 48.3 μM. Among them, protostrychnine A (8) exhibited the most potent effect with an IC50 of 9.2 μM. Further mechanistic studies revealed that compound 8 significantly suppressed MH7A cell proliferation and inhibited the NF-κB signaling pathway. These findings enrich the structural diversity of MIAs from S. nux-vomica, and provide a promising lead compound for the development of anti-RA agents.