Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity
Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity
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DOI：
10.1016/j.vaccine.2009.07.011
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发表时间：
2009-10-09
期刊：
影响因子：
5.5
通讯作者：
Singh, Jaswant
中科院分区：
文献类型：
--
作者：
Khan, Sheema;Malik, Fayaz;Singh, Jaswant
Withania somnifera，在印度传统医学系统中通常称为Ashwagandha，已报道了几种药理活性。本研究首次证明了化学标准化的催眠树叶提取物（WSL）及其鉴定成分在激活免疫系统中的潜在作用。WSL增强ConA致敏的脾细胞中Th 1细胞因子IFN-γ的体外表达。当口服给予用弗氏佐剂中的OVA的乳液（OVA-FCA）免疫的BALB/c小鼠2周时，其引起T细胞的剂量依赖性增殖，并提高它们分泌IL-2和IFN-γ的能力，但适度下调Th 2细胞因子IL-4。流式细胞仪检测T细胞表面标志物CD 3（+）、CD 4（+）、CD 8（+）和B细胞表面标志物CD 19（+），结果显示，淋巴细胞增殖和分化明显增强。此外，WSL在免疫小鼠中的作用引起脾细胞中β-整联蛋白LFA（CD 11 a）和Mac-1（CD 11b）的上调。共刺激分子CD 80和CD 86是激活免疫系统的重要次级信号，当在从WSL处理的小鼠分离的脾源性巨噬细胞中观察时，其引起显著增强的表达。WSL的化学标准化表明，2，3-二氢-3-磺酰丙酮是WSL的主要成分，其通过刺激IFN-γ的表达和B细胞转换为分泌IgG 2a，同时增强共刺激分子和整联蛋白的表达，负责向Th 1免疫极化倾斜。这些研究证明了WSL及其主要成分WSL-2作为Th 1免疫佐剂用于慢性感染性疾病的可能有用性，其中患者遭受Th 1免疫力减弱。(C)2009爱思唯尔有限公司保留所有权利。
Withania somnifera, commonly called Ashwagandha in the Indian traditional system of medicine has been reported for several pharmacological activities. This study demonstrates, for the first time, the potential role of the chemically standardized leaf extract of W somnifera (WSL) and it's identified component in activating immune system. WSL enhanced Th1 cytokine IFN-gamma expression in Con A primed splenocytes in vitro. When given orally for 2 weeks to BALB/c mice immunized with emulsion of OVA in Freund's adjuvant (OVA-FCA), it caused dose-dependent proliferation of T cells and improved their ability to secrete IL-2 and IFN-gamma, but moderately down-regulated Th2 cytokine IL-4. Flow cytometric analysis of lymphocyte surface markers of T cells CD3(+), CD4(+) and CD8(+), and B cells CD19(+) indicated prominent enhancement in proliferation and differentiation of lymphocytes. Further, the effect of WSL in immunized mice elicited upregulation of beta-integrins LFA (CD11a) and Mac-1 (CD11b) in splenocytes. Co-stimulatory molecules CD80 and CD86 that are important secondary signals for the activation of immune system elicited remarkable enhanced expression when observed in spleen-derived macrophages isolated from WSL treated mice. Chemical standardization of WSL suggested that the withanolide 2,3 dihydro-3-sulphonile withanone is a major constituent of WSL responsible for skewing to Th1 immune polarization by stimulating the expression of IFN-gamma and B cell switch over to secrete IgG2a while simultaneously enhancing the expression of co-stimulatory molecules and integrins. These studies demonstrate the possible usefulness of WSL and its major constituent WSL-2 as Th1 immune adjuvants for chronic infectious ailments where patients suffer from weakened Th1 immunity. (C) 2009 Elsevier Ltd. All rights reserved.