Key Laboratory of Modern Preparation of TCM, Ministry of Education and School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P. R. China.
Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL 60637, USA.
Am J Chin Med. 2019;47(6):1345-1363. doi: 10.1142/S0192415X19500691. Epub 2019 Sep 9.
exerts good neuroprotective activity at the cell and animal level, but the specific bioactive compounds and action mechanism are needed to be investigated, verified, and confirmed. In this work, affinity ultrafiltration (AUF), UPLC-QTOF-MS, and molecular docking were integrated into one strategy to screen, identify, and evaluate the bioactive compounds in ginseng at the molecular level. Three biological macromolecules (AChE, MAO-B, and NMDA receptor) were selected as the target protein for AUF-MS screening for the first time, and 16 potential neuroactive compounds were found with suitable binding degree. Then, the bioactivity of ginseng and its components were evaluated by AChE-inhibitory test and DPPH assay, and the data indicate that ginseng extract and the screened compounds have good neuroactivity. The interaction between the three targets and the screened compounds was further analyzed by molecular docking, and the results were consistent with a few discrepancies in comparison with the AUF results. Finally, according to the corresponding relation between component-target-pathway, the action mechanism of ginseng elucidated that ginseng exerts a therapeutic effect on AD through multiple relations of components, targets, and pathways, which is in good accordance with the TCM theory.
在细胞和动物水平上发挥良好的神经保护活性，但需要对其特定的生物活性化合物和作用机制进行研究、验证和确认。在这项工作中，亲和超滤（AUF）、UPLC-QTOF-MS 和分子对接被整合到一个策略中，从分子水平上筛选、鉴定和评估人参中的生物活性化合物。三种生物大分子（AChE、MAO-B 和 NMDA 受体）首次被选为 AUF-MS 筛选的靶蛋白，发现了 16 种具有合适结合度的潜在神经活性化合物。然后，通过 AChE 抑制试验和 DPPH 试验评估了人参及其成分的生物活性，结果表明人参提取物和筛选出的化合物具有良好的神经活性。通过分子对接进一步分析了三个靶标和筛选出的化合物之间的相互作用，结果与 AUF 结果有一些差异。最后，根据成分-靶标-通路的对应关系，阐明了人参对 AD 的作用机制，即人参通过成分、靶标和通路的多种关系发挥治疗作用，这与中医理论相符。
