Safety And Efficacy Evaluation Of Chaigui Granules

Objective: Chaigui granule has the effect of soothing the liver and relieving the surface and reconciling Ying and Wei.Clinically,it is mainly used to treat all kinds of cold.At present,there is no systematic experimental study on Chaigui granule,so this topic starts with the safety and efficacy of Chaigui granule,in order to provide theoretical basis for its safe drug use and clinical medication guidance.Methods:(1)Acute toxicity testing: Through the pre-experiment,the maximum dose method was adopted to determine the health status,weight gain,food consumption,organ state and organ index,liver and kidney function index level,blood routine,organ histopathology of mice to explore the acute toxicity of Chaigui particles.(2)Network pharmacology study: The chemical composition and targets of Cha Gui granules were searched using TCM system pharmacology database(TCMSP)and target prediction database(Swiss Target Prediction),and human gene database(Gene Cards),drug target information database(Drugbank)and OMIM for "cold" and the "active ingredient-target-disease" network using Cytoscape software.The STRING database was used to establish a protein interaction(PPI)network,and then the gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were enriched by the Matescape database system.(3)Efficacy evaluation: The method of air conditioning and alternating cold heat surface cooling air was used to build a cold surface model.Genkang was a positive drug and different concentrations of Chaigui particles were treated.Record the basic information of the observed groups of animals,On Day 10,Blood collection was obtained from each group of mice,Anticoagulant blood is used for routine blood testing,Serum was used for ELISA to determine the content of tumor necrosis factor(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10);After the execution,Various organs were dissected,Calculate the organ index;The lungs of mice were used for HE staining and the detection of tumor necrosis factor(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10)in lung tissue.Results:(1)Results of the acute toxicity experiment: After 14 days of observation,the mice were not dead and were in good condition.Therefore,the maximum concentration of Chaigui particles was 1.07g/m L(with the limit of the injection through the 12 mice),the maximum volume was 40 m L/kg,and the maximum dose was 85600mg/kg,which was 171 times higher than the intended dose in clinical adults.Compared with the blank group,the body weight changes from the food intake and organ index were not different in routine blood tests,and the serum biochemical measurements showed that AST(transaminase)and DBIL(direct bilirubin)were significantly lower in the treated female group(P<0.05).None of the remaining groups of mice showed any significant difference compared with the blank group.There was no substantial damage to each organ,and HE staining results showed no significant histopathology of each organ.(2)Results of the network pharmacology study: After database screening,191 active ingredients,605 drug targets,3983 disease targets and 388 intersection targets of Chaigui particles were obtained.The drugs and targets were input into Cytoscape software,and finally the key TCM components were quercetin,kaempferol,β-sitosterol,stigmasterol and rutin.After PPI network analysis,we found 30 key targets of wind cold,including ALB,AKT1,IL6,IL1 B,VEGFA,CASP3,PTGS2,etc.Moreover,GO analysis revealed enrichment information on three aspects of biological process,cellular components and molecular function.The KEGG signaling pathways screened the Kaposi sarcoma-associated heerpesvirus infection signaling pathway,Hepatitis B signaling pathway,Human cytomegalovirus infection signaling pathway,and AGE-RAGE signaling pathway.(3)Efficacy evaluation results: During the 10-day molding period,the weight growth rate of mice was slowly or decreased,and the body temperature increased significantly(P<0.05),which improved after intervention,and the effect of the high dose group was more prominent(P<0.05);compared with the blank group,the number of red blood cells,platelets and hemoglobin did not change significantly,but the leukocyte level decreased(P<0.01),lymphocyte ratio increased(P<0.05),granulocytes and monocytes decreased(P<0.05),and the cell ratio returned to the normal group after intervention.Compared to the blank group,The other groups of liver,kidney and organ index showed no significant changes;In the model group,the organ index of lung and large intestine increased significantly(P<0.01,P<0.05),The organ index of the spleen and thymus all decreased significantly(P<0.0001,P<0.05);After the intervention in different dose groups of Chai GUI granules,Higher spleen index(P<0.05),Lung index was decreased(P<0.05),A decreased large intestine index,Thymus index change is not obvious;The results of the histopathological examination showed that,The pulmonary interstitial hyperplasia in the model group,Vascular wall thickening,Local bleeding,Neutrophil infiltration,The pathological changes improved after treatment with Chaigui granules,The lesion level was less severe.In the model group,the expression of IL-1β,IL-6 and TNF-α was increased(P<0.001,P<0.0001),IL-10 was decreased(P<0.05),and the levels of each inflammation factor were regressed to the normal group.Conclusion:Chaigui granules have no obvious acute toxic reaction,have a large safety range,and are safe and reliable at conventional doses.Chaigui granules have a certain therapeutic effect on cold,and its effect of fighting cold may be related to the proliferation,apoptosis and immune response of cells involved in the inflammatory response of the body.This study can provide an experimental basis for the safety and efficacy of Chaigui granules.