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从中分离得到强效免疫抑制和抗炎双吲哚生物碱。

Potent immunosuppressive and anti-inflammatory bisindole alkaloids from .

机构信息

Faculty of Agriculture and Food, Kunming University of Science and Technology, Kunming, China.

Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine, Yunnan University of Chinese Medicine, Kunming, China.

出版信息

Nat Prod Res. 2022 Mar;36(6):1536-1542. doi: 10.1080/14786419.2021.1883604. Epub 2021 Feb 11.

Abstract

Phytochemical investigation of led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19-hydroxyvenalstonidine (), together with three known BIAs (-). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA is an almost symmetrical structure, linked by C3-C14' bond, while BIAs - are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs - were evaluated . BIAs , and showed good toxicity against MOLT-4 cell lines with IC values in the range of 1.5-17.5 M. BIA exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC value of 7.1 μM. BIA significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs and were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 μM concentration. BIA showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 μM.

摘要

植物化学研究表明,从 led 中分离得到了一个新的阿皮斯帕玛-阿皮斯帕玛双吲哚生物碱(BIA),双-19-羟基文拉司丁(),以及三个已知的 BIA(-)。通过对其 HRESIMS、NMR 数据的广泛分析,并与已报道的数据进行比较,确定了这些化合物的结构。BIA 是一个几乎对称的结构,通过 C3-C14' 键连接,而 BIA(-)是首次从该植物中报道的。对 BIA(-)的细胞毒性、免疫抑制和抗炎活性进行了评价。BIA(-)对 MOLT-4 细胞系具有良好的毒性,IC 值范围为 1.5-17.5μM。BIA 对 MCF-7 细胞系表现出最强的抑制作用,IC 值为 7.1μM。BIA 以浓度依赖的方式显著抑制 ConA 刺激的小鼠脾细胞增殖,抑制作用与阳性对照(DXM)相当。BIA(-)能够在 30μM 浓度下降低 LPS 诱导的 RAW 264.7 细胞中 NO 的产生。BIA 对一氧化氮释放的抑制作用与 DXM 相似。此外,BIA 与 LPS 诱导组相比,显著降低了 IL-6 和 TNF-α 的水平。有趣的是,BIA 在 20μM 浓度下对 TNF-α 产生的抑制作用与地塞米松相似。

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