Monomeric and dimeric sesquiterpenoids from Artemisia princeps Pamp and their anti-inflammatory activity

Seven undescribed sesquiterpenoids, including three germacranolides (1-3), a germacranoic acid (14), a 5/8/3 tricyclic sesquiterpenoid (16), an elemane methyl ester (18), and a germacranolide dimer (22), along with 15 known analogues (4-13, 15, 17, and 19-21) were obtained from the aerial part of Artemisia princeps Pamp. Among them, compound 16 is a sesquiterpenoid featuring a 5/8/3 ring system, while compound 22 possesses an unusual carbon framework characterized by a dihydropyran ring that connects two germacranolides. The structural elucidation of these compounds was accomplished through comprehensive analyses of HRESIMS, NMR, single-crystal X-ray diffraction data, ECD and ¹³C NMR calculations. The anti-inflammatory activities of all isolates were evaluated for their inhibitory effects on NO release in LPS-induced BV-2 microglia cells. As a result, compounds 1-13, 16, 17, and 19-22 exhibited significant inhibitory activities, with IC₅₀ values of 1.00-22.39 μM. Moreover, the results of the PCR (qRT-PCR) analysis showed that compound 1 could dose-dependently reduce the mRNA expression levels of inducible nitric oxide synthase (iNOS) and interleukin-1 beta (IL-1β).