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Anti-neuroinflammatory effects of sesquiterpenoids isolated from Nardostachys jatamansi
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2017-11-24 , DOI: 10.1016/j.bmcl.2017.11.041
Chi-Su Yoon , Kwan-Woo Kim , Sang-Chan Lee , Youn-Chul Kim , Hyuncheol Oh

Two new nardosinone-type sesquiterpenoids, namely kanshone J (1) and kanshone K (2) along with seven known terpenoids (39) 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 15 and 9 exhibited dose-dependent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 cells, with IC50 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 IC50 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 E2 (PGE2), 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.



中文翻译:

Nardostachys jatamansi分离的倍半萜的抗神经炎作用

Nardostachys jatamansi DC(Valerianaceae)的根茎和根中分离出两个新的nardosinone型倍半萜,即kanshone J(1)和kanshone K(2)以及七个已知的萜类化合物(39)。这些化合物的结构主要通过1D-,2D-NMR和MS数据分析确定。另外,化合物1的绝对构型是通过应用改进的Mosher法确定的。在初始试验,以评估其抗神经炎效果,化合物1 - 59在BV2细胞中表现出对脂多糖(LPS)诱导的一氧化氮(NO)产生剂量依赖性抑制作用,IC 50值为2.43至46.54μM。尤其是,去氧萘酚A(3)和萘酚B(4)显着抑制BV2细胞中LPS诱导的NO过量产生,其IC 50值分别为3.48±0.47和2.43±0.23μM。此外,化合物34通过抑制促炎性介质(包括前列腺素E 2(PGE 2),诱导型一氧化氮合酶(iNOS)和环氧合酶2(COX-2)蛋白以及促炎性细胞因子,例如白介素(IL)-1β,IL-6和肿瘤坏死因子-α(TNF)- LPS刺激的BV2和原代小胶质细胞中的α。

更新日期:2017-11-24
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