Synergistic Effects Of Monarch Drugs In Taikong Yangxin Fang(Ginseng C.A. Mey And Astragalus Membranaceus(Fisch.)Bunge) On Activating Mice Splenic Lymphocytes Detected By Microcalorimetry And The Underlying Mechanisms Predicted By In Silico Network Analys

Objective and Significance Spatial immunosuppression has been a major problem plaguing aerospace medicine.Traditional Chinese medicine has attracted much attention in manned spaceflight with its unique advantages.This project intends to use astronauts’ essential medicine ginseng and astragalus which are monarch drug in Taikong Yangxin Fang as research objects,and combines multidisciplinary means to study its immune activation and its synergistic mechanism.In order to preliminarily clarify the scientific connotation of the synergy between ginseng and astragalus,and provides a reference for the research of aerospace drugs in ChinaMethod The research drugs were Ginseng,Astragalus,Ginseng and astragalus compatibility extracts respectively;the mouse spleen lymphocytes were used as the research model.Pt curve,maximum heat production(Pmax),heat production peak time(tmax),total heat production(Q),cell proliferation rate,synergy effect index,etc.were used as evaluation indicators to investigate the activation of spleen lymphocytes by test drugs.Through the LC-Q-TOF-MS detection technology,system pharmacology technology and molecular docking technology,the biological mechanism of the test drug to activate spleen lymphocytes and the connotation of its synergy is revealed,which is based on the evaluation indicators of system network topology parameters,molecular-protein binding energy,and binding constant.Results1.Study on the activation of spleen lymphocytes by Ginseng and Astragalus and their compatibility by microcalorimetry and CCK-8.By plotting the P-t curve of spleen lymphocytes and analyzing Pmax,Q and tmax,we found that compared with the control group,the Ginseng group,the Astragalus group and the compatibility group significantly promoted the heat production of mouse spleen lymphocytes.Regression analysis showed that the Astragalus group and the compatibility group showed a good dose-effect relationship.Compared with the control group,the drug group significantly increased the proliferation rate of spleen lymphocytes(P < 0.05),showing a better promotion of cell proliferation.By synergistic effect analysis,it is found that compatibility of Ginseng and Astragalus in the low dose can cause heat production and splenic lymphocyte activation than Ginseng and Astragalus alone(CI = 0.780;CI = 0.811).2.Exploring the biological mechanism of Ginseng and Astragalus activation of spleen lymphocytes based on systemic pharmacology and molecular docking.Through the LC-Q-TOF-MS detection technology,the components of the test drug were qualitatively analyze,and combined with the active ingredient database,which can obtain 23 Ginseng active ingredients and 15 Astragalus active ingredients,to construct a biological mechanism network.The median and point centrality(Dgree)of the topological parameters of Ginseng was calculated to be 1,the Betweenness centrality was 0,and the Closeness centrality was 0.23752495.The median and point centrality(Dgree)of the topological parameters of Astragalus was calculated to be 1,the Betweenness centrality was 0.000001645,and the Closeness centrality was0.24401164.Finally,we screened 27 targets(ginseng)and 29 targets(astragalus)as the main pharmacodynamic targets.Molecular docking studies showed that the Gibbs free energy of the main active ingredients of Ginseng and Astragalus combined with the main pharmacodynamic protein was lower(FE < 0),showing better binding.3.Synergistic mechanism of activated spleen lymphocytes activated by Ginseng and Astragalus based on pathway enrichment analysis Through KEGG pathway enrichment analysis,it was found that Ginseng participates in lymphocyte activation through 21 pathways,and Astragalus participates in lymphocyte activation through 24 pathways.According to the screening conditions of P-value < 0.01,the correlation of Ginseng and Astragalus was ranked,and the top ten traits with the highest correlation with the two drugs were screened.We found that there are 6 pathways shared by Ginseng and Astragalus,which may be the intrinsic biological basis for the compatibility of Ginseng and Astragalus.Conclusion This study preliminarily confirmed the activation of spleen lymphocytes in mice by compatibility of Ginseng and Astragalus.At the same time,it revealed the mechanism of its action and the scientific connotation of compatibility from various angles.Further,it provides a certain theoretical basis for the combination of Ginseng and Astragalus in clinical practice.Moreover,it provides a reference for the research of aerospace drugs in China.