Isolation of Novel Sesquiterpeniods and Anti-neuroinflammatory Metabolites from Nardostachys jatamansi

Abstract

<i>Nardostachys jatamansi</i> contains various types of sesquiterpenoids that may play an important role in the potency of plant's anti-inflammatory effects, depending on their structure. In this study, five new sesquiterpenoids, namely kanshone L (<b>1</b>), kanshone M (<b>2</b>), 7-methoxydesoxo-narchinol (<b>3</b>), kanshone N (<b>4</b>), and nardosdaucanol (<b>5</b>), were isolated along with four known terpenoids (kanshone D (<b>6</b>), nardosinanone G (<b>7</b>), narchinol A (<b>8</b>), and nardoaristolone B (<b>9</b>)) from the rhizomes and roots of <i>Nardostachys jatamansi</i>. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds <b>3</b>, <b>4</b>, and <b>8</b> were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds <b>3</b>, <b>4</b>, and <b>8</b> exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E₂ (PGE₂), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-12 and tumor necrosis factor-α (TNF-α), in LPS-stimulated BV2 microglial cells. Moreover, these compounds were shown to inhibit the activation of the NF-κB signaling pathway in LPS-stimulated BV2 microglial cells by suppressing the phosphorylation of IκB-α and blocking NF-κB translocation. In conclusion, five new and four known sesquiterpenoids were isolated from <i>Nardostachys jatamansi</i>, and compounds <b>3</b>, <b>4</b>, and <b>8</b> exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.