Morehouse School of Medicine, Department of Microbiology, Biochemistry and Immunology & Department of Pathology and Laboratory Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA.
Phytomedicine. 2013 Nov 15;20(14):1323-9. doi: 10.1016/j.phymed.2013.07.001. Epub 2013 Aug 6.
We have previously demonstrated that ADAPT-232, a fixed combination of adaptogenic substances derived from Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract stimulated the expression and release of neuropeptide Y (NPY) and molecular chaperone Hsp72 from isolated human neurolgia cells. Both of these mediators of stress response are known to play an important role in regulation of neuroendocrine system and immune response. We further demonstrated that ADAPT-232 induced release of Hsp70 is mediated by NPY, suggesting an existence of NPY-mediated pathway of activation of Hsp72 release into the blood circulation system. The objective of this study was to determine whether this pathway is common for adaptogens and whether NPY and/or Hsp72 can be considered as necessary specific biomarkers for adaptogenic activity. The release of NPY and Hsp72 from neuroglia cells in response to treatment with various plant extracts (n=23) including selected validated adaptogens, partly validated adaptogens, claimed but negligibly validated adaptogens and some other plant extracts affecting neuroendocrine and immune systems but never considered as adaptogens was measured using high throughput ELISA techniques. We demonstrated that adaptogens, e.g. R. rosea, S. chinensis and E. senticosus stimulate both NPY and Hsp70 release from neuroblastoma cells, while tonics and stimulants have no significant effect on NPY in this in vitro test. In the groups of partly validated adaptogens the effect of Panax ginseng and Withania somnifera was not statistically significant both on NPY and Hsp70 release, while the activating effect of Bryonia alba and Rhaponticum cartamoides was significant only on Hsp70. In contrast, all tested non-adaptogens, such as antiinflammatoty plant extracts Matricaria recutita, Pelargonium sidoides, Hedera helix and Vitis vinifera significantly inhibit Hsp70 release and have no influence on NPY release from neuroblastoma cells. These experiments were further validated using primary human neurons and confirmed that adaptogens activate the release of both NPY and Hsp70, while tested non adaptogens were inactive in NPY assay and inhibit the release of Hsp70. Taken together, our data demonstrates for the first time that neuropeptide Y and heat shock protein Hsp70 can be used as molecular biomarkers for adaptogenic activity.
我们之前的研究表明，ADAPT-232 是一种源自刺五加根提取物、五味子浆果提取物和红景天根提取物的适应性物质的固定组合，可刺激神经胶质细胞中神经肽 Y（NPY）和分子伴侣热休克蛋白 72（Hsp72）的表达和释放。这两种应激反应的介质都已知在神经内分泌系统和免疫反应的调节中发挥重要作用。我们进一步证明，ADAPT-232 诱导的 Hsp70 释放是通过 NPY 介导的，这表明存在 NPY 介导的途径，将 Hsp72 释放到血液循环系统中。本研究的目的是确定该途径是否对适应性物质普遍适用，以及 NPY 和/或 Hsp72 是否可以被视为适应性活性的必要特异性生物标志物。使用高通量 ELISA 技术测量了各种植物提取物（n=23）对神经胶质细胞中 NPY 和 Hsp72 的释放，包括选定的经证实的适应性物质、部分经证实的适应性物质、声称但可忽略不计的适应性物质以及一些影响神经内分泌和免疫系统但从未被认为是适应性物质的其他植物提取物。我们证明了适应性物质，如红景天、五味子和刺五加，刺激神经母细胞瘤细胞中 NPY 和 Hsp70 的释放，而补品和兴奋剂在这种体外试验中对 NPY 没有显著影响。在部分经证实的适应性物质组中，人参和南非钩麻的作用在 NPY 和 Hsp70 释放方面均无统计学意义，而白屈菜和拉潘托辛的激活作用仅在 Hsp70 上显著。相比之下，所有测试的非适应性物质，如抗炎植物提取物母菊、贯叶连翘、常春藤和葡萄，均显著抑制 Hsp70 的释放，对神经母细胞瘤细胞中 NPY 的释放没有影响。这些实验进一步使用原代人神经元进行了验证，并证实适应性物质激活了 NPY 和 Hsp70 的释放，而测试的非适应性物质在 NPY 测定中无活性，并抑制了 Hsp70 的释放。总之，我们的数据首次证明，神经肽 Y 和热休克蛋白 Hsp70 可用作适应性活性的分子生物标志物。
