China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100007, China.
China Academy of Chinese Medical Sciences, Institute of Chinese Materia Medica, Beijing 100007, China.
Phytomedicine. 2023 Jan;108:154527. doi: 10.1016/j.phymed.2022.154527. Epub 2022 Oct 27.
The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear.
An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification.
Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB).
According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well.
In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.
新型冠状病毒肺炎（COVID-19）在全球迅速传播。作为抗疫成员之一，清肺排毒汤（QFPDD）已在中国获批用于治疗 COVID-19。然而，其抗病毒机制在很大程度上仍不清楚。
采用整合策略探讨 QFPDD 在寒湿环境中的抗病毒机制，包括药代动力学（PK）、网络药理学、代谢组学和蛋白质验证。
首先，采用 UHPLC-QqQ-MS 分析原型吸收成分的药代动力学研究。其次，进行内源性成分的代谢组学分析。基于上述结果，构建综合网络以识别治疗成分、关键内源性差异代谢物和相关途径。最后，通过分子对接和 Western blot（WB）进行验证测试。
根据 31 种体内原型成分的药代动力学行为分析，黄酮类化合物的停留时间更长，暴露量更高。QFPDD 的功效和抗病毒机制通过多药理学、代谢组学、分子对接和 WB 得到了验证。对于代谢紊乱的发生，不能忽视氨基酸转运体的变化。随后，通过化合物-反应-酶-基因网络筛选出 8 种治疗化合物、6 个关键基因和相应的代谢途径。分子对接验证了活性成分与相关靶点结合良好。
本研究首次分析了 QFPDD 的体内综合药代动力学行为。结果表明，QFPDD 可以通过免疫调节、抗感染、抗炎和代谢紊乱来发挥相应的治疗作用。此外，我们的研究结果强调了氨基酸转运体在冠状病毒感染情况下的作用。
