Anti-neuroinflammatory effects of sesquiterpenoids isolated from Nardostachys jatamansi

Abstract Two new nardosinone-type sesquiterpenoids, namely kanshone J ( 1 ) and kanshone K ( 2 ) along with seven known terpenoids ( 3 – 9 ) were isolated from the rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae). The structures of these compounds were determined mainly by analysis of 1D-, 2D-NMR and MS data. In addition, the absolute configuration of compound 1 was assigned by application of the modified Mosher’s method. In an initial assay to evaluate their anti-neuroinflammatory effects, compounds 1 – 5 and 9 exhibited dose-dependent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 cells, with IC 50 values ranging from 2.43 to 46.54 μM. Particularly, desoxo-narchinol A ( 3 ) and narchinol B ( 4 ) significantly inhibited LPS-induced NO overproduction in BV2 cells with IC 50 values of 3.48 ± 0.47 and 2.43 ± 0.23 μM, respectively. Furthermore, compounds 3 and 4 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E 2 (PGE 2 ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF)-α, in LPS-stimulated BV2 and primary microglial cells.