Meta-analysis And Network Pharmacology Investigation Of Compound Musk Injection In The Treatment Of Ischemic Stroke

Objectives:To systematically evaluate the effectiveness of compound musk injection(CMI)in the treatment of ischemic stroke(IS),network pharmacology,molecular docking technology and in vitro experiments were used to explore its mechanism in order to provide reference for clinical application.Methods:1.When conducting a meta-analysis,databases such as Pub Med,Wanfang,and China National Knowledge Infrastructure(CNKI)were accessed to retrieve clinical trials on the efficacy of CMI in treating IS.The search time range is from the establishment of the above platform to December 20,2022.Collect the data results of the nerve function defect score,clinical total effective rate and life activity index data,and select the corresponding statistical model for meta-analysis according to the size of heterogeneity.Subgroup analysis was performed to identify and deal with heterogeneity for highly heterogeneous results.Sensitivity analysis was applied to determine whether the statistical results were stable.The GRADE score was used to evaluate the quality of evidence.2.In the study of network pharmacology,a comprehensive network of drugs and disease targets was constructed using various online databases.Potential therapeutic targets were screened out,a PPI network was constructed,and GO and KEGG enrichment analysis were performed.Molecular docking techniques were used to calculate and simulate the docking models,and the m RNA expression of key target genes was observed through cell experiments.Results:1.Eight literatures were included in the meta-analysis,with a cumulative sample size of890 cases,including 446 cases in the observation group and 444 cases in the control group.Analysis results show that: when IS patients treated,CMI combined conventional western medicine in improving the degree of nerve function defect score,improve the clinical total effective rate and life activity index in a simple routine western medicine curative effect IS better,the degree of nerve function defect score of SMD = 0.91,95% CI [1.38,0.43],Z =3.75,P < 0.01;clinical total effective rate of the RR = 1.14,95% CI = [1.07,1.22],Z = 4.12,P< 0.01;life activity ability index of the SMD = 1.55,95% CI [0.42,2.68],Z = 2.68,P < 0.01.Total clinical efficacy rates were deemed to be of low-quality evidence,while the other two indicators were deemed to be of very low-quality evidence.2.Network pharmacology studies identified 353 potential target points for CMI treatment of IS,the critical target points for treatment were SRC,TP53,PIK3R1,MAPK3,PIK3 CA,MAPK1 and so on.GO enrichment analysis revealed 2851 entries for biological processes,183 entries for cellular components,and 375 entries for molecular functions.KEGG pathway enrichment analysis yielded 224 pathways,including PI3K/Akt signal pathway,Rap1 signal pathway,MAPK signal pathway,and other pathways.These pathways are mainly related to processes such as apoptosis,metabolism,and inflammatory response.Molecular docking results showed that six major active ingredients could stably bind with six key target proteins.In cell experiments,compared to the blank group,the model group showed a significantly decreased cell survival rate(P<0.01)and tended to decrease the expression of PIK3 CA and MAPK3 m RNA and increase the expression of SRC m RNA(P>0.05).However,the CMI group had a higher cell survival rate than the model group,and tended to increase the PIK3 CA and MAPK3 m RNA expression and reduce the SRC m RNA expression(P> 0.05).Conclusions:1.CMI combined with conventional western medicine can significantly improve the total clinical effective rate of patients with IS,reduce the degree of neurological function deficit scores,and improve the patients’ ability to carry out daily activities.However,the overall quality of the literature is low,and the level of evidence is low quality evidence on the whole.2.CMI for IS may act on multiple targets and pathways through multiple components,among which the key targets such as SRC,PIK3 CA and MAPK3 etc,and its efficacy may be closely related to multiple pharmacological mechanisms such as inhibiting apoptosis,antiinflammation and neuroprotection.