Abstract
Nardostachys jatamansi 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 (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the rhizomes and roots of Nardostachys jatamansi. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds 3, 4, and 8 were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds 3, 4, and 8 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 Nardostachys jatamansi, and compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.
Highlights
The rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae), a plant indigenous to China, India, and Tibet, have traditionally been used in the treatment of mental disorders, hyperlipidemia, hypertension, and convulsions [1]
Four known metabolites classified as nardosinone-type (6-8) and aristolene-type sesquiterpenoids (9) were isolated
For compounds 3, 4, and 8, which were the compounds that inhibited the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-treated BV2 microglial cell, we further evaluated their effects on the expression of inflammatory cytokines’ mRNA in LPS-treated BV2 microglial cells using quantitative real-time reverse transcriptase polymerase chain reaction (PCR) (Figure 2)
Summary
The rhizomes and roots of Nardostachys jatamansi DC (Valerianaceae), a plant indigenous to China, India, and Tibet, have traditionally been used in the treatment of mental disorders, hyperlipidemia, hypertension, and convulsions [1]. Binding to LPSs activate microglia, leading to the production of inflammatory cytokines and a number of neurotoxic factors that cause neuronal cell death [9,10]. The NF-κB dimer binds to its DNA binding site, the κB site, leading to the transcription of a number of genes that includes those coding for adhesion molecules, chemokine-inducible enzymes, and pro-inflammatory mediators like interferon-gamma (IFN-γ), NO, TNF-α, and PGE2 [20]. These inflammatory mediators are known to cause inflammatory reactions and neurodegenerative diseases. Suppression of the NF-κB pathway is a widely used strategy for inhibiting neuroinflammation [21,22]
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