Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Commun Biol. 2021 May 10;4(1):549. doi: 10.1038/s42003-021-02084-3.
By a pilot trial on investigating immunomodulatory activity and target of ginsenosides, the major bioactive components of ginseng, here we report that structural analogues in herbal medicines hit a shared target to achieve cumulative bioactivity. A ginsenoside analogues combination with definite immunomodulatory activity in vivo was designed by integrating pharmacodynamics, serum pharmacochemistry and pharmacokinetics approaches. The cumulative bioactivity of the ginsenoside analogues was validated on LPS/ATP-induced RAW264.7 macrophages. The potentially shared target NLRP3 involved in this immunomodulatory activity was predicted by systems pharmacology. The steady binding affinity between each ginsenoside and NLRP3 was defined by molecular docking and bio-layer interferometry assay. The activation of NLRP3 inflammasomes in LPS/ATP-induced RAW264.7 was significantly suppressed by the combination, but not by any individual, and the overexpression of NLRP3 counteracted the immunomodulatory activity of the combination. All these results demonstrate that the ginsenoside analogues jointly hit NLRP3 to achieve cumulative immunomodulatory activity.
通过一项关于人参主要生物活性成分——人参皂苷的免疫调节活性和作用靶点的初步试验，我们报告了草药中的结构类似物针对共同靶点来实现累积生物活性。通过整合药效学、血清药化学和药代动力学方法，设计了一种具有明确体内免疫调节活性的人参皂苷类似物组合。通过 LPS/ATP 诱导的 RAW264.7 巨噬细胞验证了人参皂苷类似物的累积生物活性。通过系统药理学预测了该免疫调节活性涉及的潜在共同靶点 NLRP3。通过分子对接和生物层干涉测定法定义了每个人参皂苷与 NLRP3 之间的稳定结合亲和力。该组合显著抑制了 LPS/ATP 诱导的 RAW264.7 中 NLRP3 炎性小体的激活，但任何单个成分都没有抑制作用，并且 NLRP3 的过表达抵消了该组合的免疫调节活性。所有这些结果表明，人参皂苷类似物共同作用于 NLRP3 以实现累积的免疫调节活性。
