Sesquiterpenoids and Polyacetylenes From <i>Notopterygium Incisum</i> With Anti–Rheumatoid Arthritis Activity

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.