Structurally diverse new eudesmane sesquiterpenoids with anti-inflammatory activity from the fruits of Alpinia oxyphylla

Abstract

The phytochemical investigation of the fruits of Alpinia oxyphylla led to the isolation and identification of 40 structurally diverse sesquiterpenoids, including 17 new eudesmane sesquiterpenoids (1–17) and 23 known analogues (18–40). Among the isolates, 14 and 17 were unusual rearranged eudesmane sesquiterpenoids, featuring rare 5/6-fused and 6/8-fused bicyclic carbon skeleton, respectively; 15 and 16 were the novel 6,7-seco-eudesmane sesquiterpenoids isolated from plant-origin for the first time, 1 and 3–6 were rare nor-eudesmane sesquiterpenoids. Their structures were elucidated by comprehensive spectroscopic data analysis (NMR, HRESIMS, IR, UV), single crystal X-ray diffraction, and quantum chemistry calculations (ECD and 13C NMR). Moreover, all isolates were evaluated by measuring their inhibitory effect on nitric oxide (NO) in LPS-stimulated BV-2 cells. As a result, compounds 11, 20, 24 and 40 showed moderate to strong inhibition on NO productions, with IC50 values ranging from 21.63 to 60.70 μM. Meanwhile, these compounds also partially decreased the secretion of TNF-α and IL-6 in LPS-stimulated BV-2 cells. Furthermore, 20 could down-regulate protein expressions (COX-2 and iNOS) and observably inhibit the mRNA expressions of TNF-α, IL-6, COX-2 and iNOS. In this study, the discovery of structurally diverse anti-inflammatory sesquiterpenoids from the fruits of A. oxyphylla could benefit the further development and utilization of this plant.