Sesquiterpenoids and Polyacetylenes From Notopterygium Incisum With Anti–Rheumatoid Arthritis Activity

ABSTRACT Introduction Notopterygium incisum is a traditional Chinese and Tibetan medicinal herb widely used for treating colds, rheumatism, and musculoskeletal disorders. Objectives The aims of the study were to isolate sesquiterpenoids and polyacetylenes from N. incisum rhizomes and to evaluate their potential anti–rheumatoid arthritis activity. Methods Compounds were isolated using chromatographic techniques. Structures were elucidated by 1D/2D NMR, UV, IR, and HRESIMS, and absolute configurations were assigned using TD‐DFT ECD calculations. Their anti‐RA activity was assessed by measuring pro‐inflammatory cytokine inhibition in TNF‐α–induced MH7A cells. Some compounds were evaluated by molecular docking and molecular dynamics simulations to further explore possible molecular targets related to RA. Results Twenty‐one compounds, including seven new ones and one newly identified natural product, were obtained. Several compounds showed significant inhibition of pro‐inflammatory cytokines in TNF‐α–induced MH7A cells. Molecular docking also revealed varying degrees of binding affinity to RA‐relevant proteins, and dynamics simulations confirmed the stability of most selected complexes. Conclusions A series of sesquiterpenoids and polyacetylenes was isolated. Several compounds exhibited notable anti‐inflammatory activity, suggesting that these structural types may underlie the anti‐RA effects of N. incisum .