Abstract
Nardostachys spp. have been widely used in Asia as a folk medicine. In particular, the extracts of Nardostachys jatamansi, a species that grows in China, India, and Tibet, have been used to treat mental disorders, hyperlipidemia, hypertension, and convulsions. In this investigation, the potential of 20% aqueous ethanol extract of N. jatamansi (NJ20) as a botanical drug was explored by chemically investigating its constituents and its anti-neuroinflammatory effects on lipopolysaccharide- (LPS-) induced in vitro and in vivo models. Nine secondary metabolites were isolated and identified from NJ20, and quantitative analysis of these metabolites revealed desoxo-narchinol A as the major constituent. In LPS-challenged cells, pretreatment with NJ20 inhibited the LPS-induced excessive production of proinflammatory mediators, such as nitric oxide, prostaglandin E2, interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α. NJ20 also attenuated the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2. Additionally, pre-intraperitoneal injection of NJ20 downregulated the mRNA overexpression of IL-1β, IL-6, and iNOS in the prefrontal cortex, hypothalamus, and hippocampus of the LPS-stimulated C57BL/c mouse model. Chemical and biological investigations of NJ20 revealed that it is a potential inhibitor of LPS-induced neuroinflammatory responses in microglial cells and mouse models. The major active constituent of NJ20, desoxo-narchinol A, demonstrated anti-neuroinflammatory effects. Hence, our findings indicate that NJ20 may be a promising herbal mixture for developing a functional product and/or herbal drug for treating neuroinflammatory diseases.