Furanone-Type Constituents from Aerial Parts of Fissistigma wallichii and Their Anti-rheumatoid Arthritis Activity

Abstract Most plants of the Fissistigma genus are used in folk medicine for treating rheumatoid arthritis and related diseases such as osteoarthritis. However, the chemical constituents and pharmacological effects of Fissistigma wallichii (Hook. f. & Thomson) Merr. (Annonaceae) have not been studied yet. In this study, seventeen furanone-type metabolites (1−17) were isolated from F. wallichii. Among them, sixteen undescribed metabolites were characterized by HRESIMS, NMR data, ECD calculations, and 13C NMR calculations with DP4+ probability analyses. Right-handed (+) optical rotations were recorded when the absolute configuration of C-4 on the α,β-unsaturated γ-butyrolactone ring was R, and left-handed (−) optical rotations when it was S. Compounds 1−4, 6−8, 10, 12, and 16−17 exhibited proliferation inhibitory activity on SW982 cells induced by IL-1β, and compounds 1, 2, 6, 7, and 16 effectively downregulated the mRNA levels of inflammatory factors TNF-α, IL-1β and IL-6. Preliminary structure−activity relationships (SARs) of those isolates were also discussed. Furthermore, the anti-rheumatoid arthritis activity of compound 1 was evaluated in vivo using a collagen-induced arthritis (CIA) rat model. At 15 mg/kg, compound 1 significantly reduced paw swelling and the arthritis index and ameliorated histopathological changes in the ankle joints of CIA rats.