An advanced network pharmacology study to explore the novel molecular mechanism of Compound Kushen Injection for treating hepatocellular carcinoma by bioinformatics and experimental verification.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that exerts curative effects in the clinical treatment of hepatocellular carcinoma (HCC). This study aimed to explore the targets and potential pharmacological mechanisms of CKI in the treatment of HCC. METHODS: In this study, network pharmacology was used in combination with molecular biology experiments to predict and verify the molecular mechanism of CKI in the treatment of HCC. The constituents of CKI were identified by UHPLC-MS/MS and literature search. The targets corresponding to these compounds and the targets related to HCC were collected based on public databases. To screen out the potential hub targets of CKI in the treatment of HCC, a compound-HCC target network was constructed. The underlying pharmacological mechanism was explored through the subsequent enrichment analysis. Interactive Gene Expression Profiling Analysis and Kaplan-Meier plotter were used to examine the expression and prognostic value of hub genes. Furthermore, the effects of CKI on HCC were verified through molecular docking simulations and cell experiments in vitro. RESULTS: Network analysis revealed that BCHE, SRD5A2, EPHX2, ADH1C, ADH1A and CDK1 were the key targets of CKI in the treatment of HCC. Among them, only CDK1 was highly expressed in HCC tissues, while the other 5 targets were lowly expressed. Furthermore, the six hub genes were all closely related to the prognosis of HCC patients in survival analysis. Molecular docking revealed that there was an efficient binding potential between the constituents of CKI and BCHE. Experiments in vitro proved that CKI inhibited the proliferation of HepG2 cells and up-regulated SRD5A2 and ADH1A, while down-regulated CDK1 and EPHX2. CONCLUSIONS: This study revealed and verified the targets of CKI on HCC based on network pharmacology and experiments and provided a scientific reference for further mechanism research.

Investigation on the Efficiency of Tonic Chinese Herbal Injections for Treating Dilated Cardiomyopathy Based on Bayesian Network Meta-Analysis.

INTRODUCTION: This network meta-analysis investigated the efficacy of six tonic Chinese herbal injections (Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, Shenqi Fuzheng injection, and Yiqifumai injection) compared to Western medicine for the treatment of the deteriorating state associated with dilated cardiomyopathy. METHODS: PubMed, the Cochrane Library, Embase, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Scientific Journal Database were searched from their inception to October 15, 2020, to retrieve randomized controlled trials (RCTs). Study selection and data extraction conformed to a priori criteria. The risk of bias of the included RCTs was determined, and GRADE was used to evaluate outcomes. The network meta-analysis was calculated using WinBUGS 1.4.3 and Stata 13.0 software. The clinical effective rate, left ventricular ejection fraction, 6-minute walk test, left ventricular end-diastolic dimension, heart rate, and cardiac output were deemed outcomes. All outcomes were summarized as odds ratios or mean differences with their 95% credible intervals. The ranking probability of the interventions across various outcomes was also presented. RESULTS: Forty RCTs and 2970 patients were enrolled. Integration of the outcome results revealed that a combination of Shenfu injection and Western medicine ranked ahead of the other injections in most outcomes, especially in the clinical effective rate (OR = 0.21, 95% CI: 0.12-0.34), left ventricular ejection fraction (MD = 7.43, 95% CI: 2.41-12.38), and 6-minute walk test (MD = 50.39, 95% CI: 25.78-76.33). Shenmai injection plus Western medicine ranked ahead of the other injections in left ventricular end-diastolic dimension (69.5%) and cardiac output (60.9%). The cluster analysis suggested that Shenfu injection plus Western medicine was the most effective intervention for dilated cardiomyopathy. CONCLUSIONS: Shenfu injection plus Western medicine may be a preferable treatment in dilated cardiomyopathy. Clinicians should also consider the specific patient's various conditions when making diagnostic decisions. Due to an insufficient network meta-analysis, more high-quality RCTs need to be implemented to support our conclusions.

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via a Network Pharmacology Approach.

OBJECTIVE: To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment. METHODS: A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets. RESULTS: Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway. CONCLUSIONS: The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

Comparative Efficacy of Chinese Herbal Injections Combined with Paclitaxel Plus Cisplatin for Non-Small-Cell Lung Cancer: A Multidimensional Bayesian Network Meta-Analysis.

INTRODUCTION: Considering the limitations of pure paclitaxel plus cisplatin chemotherapy in the treatment of non-small-cell lung cancer and the extensive exploration of Chinese herbal injections, this study performed a multidimensional network meta-analysis to systematically evaluate the clinical efficacy and safety of 12 Chinese herbal injections in the treatment of non-small-cell lung cancer. METHODS: Randomized controlled trials were obtained from several databases according to the eligibility criteria, and the study quality was assessed by the Cochrane risk of bias tool. Data analysis was performed by Stata 13.1 software and WinBUGS 14.0 software. Multidimensional cluster analysis was performed with the "scatterplot3d" package in R 3.6.1 software (PROSPERO ID: CRD42020163503). RESULTS: A total of 58 eligible randomized controlled trials involving 4578 patients and 12 Chinese herbal injections were included. Combined with paclitaxel plus cisplatin chemotherapy, Xiaoaiping injection exhibited a better impact on the clinical effective rate than paclitaxel plus cisplatin alone. Shenqifuzheng injection was associated with a preferable response in performance status and reduced leukopenia and gastrointestinal reactions. Kangai injection was dominant in the comprehensive results of the cluster analysis. CONCLUSIONS: Chinese herbal injections combined with paclitaxel plus cisplatin chemotherapy have a certain adjuvant effect in treating non-small-cell lung cancer, but the results of this study need to be verified by more well-designed, large-sample, multicenter randomized controlled trials.

A bioinformatics investigation into the pharmacological mechanisms of javanica oil emulsion injection in non-small cell lung cancer based on network pharmacology methodologies.

BACKGROUND: Javanica oil emulsion injection (JOEI) is an effective therapeutic option for patients with non-small cell lung cancer (NSCLC), but its mechanisms have not been fully elucidated. METHODS: In this study, we utilized network pharmacology to systematically investigate the bioactive components and targets of JOEI, identify common targets in NSCLC, and understand and evaluate the underlying mechanism of JOEI in the treatment of NSCLC through expression level, correlation, enrichment, Cox, survival and molecular docking analyses. The results indicated that five compounds of JOEI interact with five pivotal targets (LDLR, FABP4, ABCB1, PTGS2, and SDC4) that might be strongly correlated with the JOEI-mediated treatment of NSCLC. RESULTS: The expression level analysis demonstrated that NSCLC tissues exhibit low expression of FABP4, ABCB1, LDLR and PTGS2 and high SDC4 expression. According to the correlation analysis, a decrease in FABP4 expression was strongly correlated with decreases in LDLR and ABCB1, and a decrease in LDLR was strongly correlated with decreased PTGS2 and increased in SDC4 expression. Cox and survival analyses showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group (p = 0.00388). In the survival analysis, the area under the curve (AUC) showed that the pivotal gene model exhibited the best predictive capacity over 4 years (AUC = 0.613). Moreover, the molecular docking analysis indicated that LDLR, FABP4, ABCB1, PTGS2 and SDC4 exhibit good binding activity with the corresponding compounds. CONCLUSION: In conclusion, this study predicted and verified that the mechanism of JOEI against NSCLC involves multiple targets and signaling pathways. Furthermore, this study provides candidate targets for the treatment of NSCLC, lays a good foundation for further experimental research and promotes the reasonable application of JOEI in clinical treatment.

Comparative Efficacy of Chinese Herbal Injections for Pulmonary Heart Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Given the severity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease. METHODS: A literature search was performed in PubMed, Cochrane Library, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and the Chinese Scientific Journal Database from their inception to July14, 2019. This network meta-analysis was conducted in accordance with a priori eligibility criteria and methodological quality recommendations. Data analysis was performed with WinBUGS 1.4.3 and Stata 13.0 software focusing on clinical effectiveness rate, arterial blood gas analysis, hemorheology and hemodynamic indexes and right ventricular dimensions. In addition to the odds ratio or mean difference in various outcomes, the ranking probability of interventions calculated by the surface under the cumulative ranking area curve was demonstrated. The surface under the cumulative ranking area was equal to the rank of the intervention and was aimed to assess the best intervention. RESULTS: Ultimately, 118 randomized controlled trials including 10,085 patients were included. Integrating the outcome results, all eligible Chinese herbal injections plus Western medicines were superior to Western medicines alone, especially Shenfu injection+ Western medicines, Shenmai injection+ Western medicines, and Shenqi Fuzheng injection+ Western medicines. Regarding safety, the drip rate was an essential element for clinicians to consider during treatment. CONCLUSIONS: In conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis.

Investigating the multi-target pharmacological mechanism of danhong injection acting on unstable angina by combined network pharmacology and molecular docking.

BACKGROUND: Danhong injection (DHI), which is one of the most well-known Traditional Chinese Medicine (TCM) injections, widely used to treat unstable angina (UA). However, its underlying pharmacological mechanisms need to be further clarified. METHODS: In the present study, network pharmacology was adopted. Firstly, the relative compounds were obtained by a wide-scaled literatures-mining and potential targets of these compounds by target fishing were collected. Then, we built the UA target database by DisGeNET, DigSee, TTD, OMIM. Based on data, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were performed and screen the hub targets by topology. Furthermore, evaluation of the binding potential of key targets and compounds through molecular docking. RESULTS: The results showed that 12 ingredients of DHI and 27 putative known therapeutic targets were picked out. By systematic analysis, identified 4 hub targets (TNF, TLR4, NFKB1 and SERPINE1) mainly involved in the complex treating effects associated with coagulation and hemostasis, cell membrane region, platelet alpha granule, NF-kappa B signaling pathway and TNF signaling pathway. CONCLUSION: The results of this study preliminarily explained the potential targets and signaling pathways of DHI in the treatment of UA, which may help to laid a good foundation for experimental research and further clinical application.

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology.

BACKGROUND: As an effective prescription for gastric cancer (GC), Compound Kushen Injection (CKI) has been widely used even though few molecular mechanism analyses have been carried out. METHODS: In this study, we identified 16 active ingredients and 60 GC target proteins. Then, we established a compound-predicted target network and a GC target protein-protein interaction (PPI) network by Cytoscape 3.5.1 and systematically analyzed the potential targets of CKI for the treatment of GC. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. RESULTS: The results showed that the potential targets, including CCND1, PIK3CA, AKT1, MAPK1, ERBB2, and MMP2, are the therapeutic targets of CKI for the treatment of GC. Functional enrichment analysis indicated that CKI has a therapeutic effect on GC by synergistically regulating some biological pathways, such as the cell cycle, pathways in cancer, the PI3K-AKT signaling pathway, the mTOR signaling pathway, and the FoxO signaling pathway. Moreover, molecular docking simulation indicated that the compounds had good binding activity to PIK3CA, AKT1, MAPK1, ERBB2, and MMP2 in vivo. CONCLUSION: This research partially highlighted the molecular mechanism of CKI for the treatment of GC, which has great potential in the identification of the effective compounds in CKI and biomarkers to treat GC.

A bioinformatics investigation into the pharmacological mechanisms of the effect of the Yinchenhao decoction on hepatitis C based on network pharmacology.

BACKGROUND: Globally, more than 170 million people are infected with hepatitis C virus, a major cause of cirrhosis and hepatocellular carcinoma. The Yinchenhao Decoction (YCHD) is a classic formula comprising three herbal medicines. This decoction have long been used in China for clinically treating acute and chronic infectious hepatitis and other liver and gallbladder damp heat-accumulation disorders. METHODS: In this study, we identified 32 active ingredients and 200 hepatitis C proteins and established a compound-predicted target network and a hepatitis C protein-protein interaction network by using Cytoscape 3.6.1. Then, we systematically analyzed the potential targets of the YCHD for the treatment of hepatitis C. Finally, molecular docking was applied to verify the key targets. In addition, we analyzed the mechanism of action of the predicted targets by the Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses. RESULTS: This study adopted a network pharmacology approach, mainly comprising target prediction, network construction, module detection, functional enrichment analysis, and molecular docking to systematically investigate the mechanisms of action of the YCHD in hepatitis C. The targets of the YCHD in the treatment of hepatitis C mainly involved PIK3CG, CASP3, BCL2, CASP8, and MMP1. The module and pathway enrichment analyses showed that the YCHD had the potential to influence varieties of biological pathways, including the TNF signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, and pathways in cancer, that play an important role in the pathogenesis of hepatitis C. CONCLUSION: The results of this study preliminarily verified the basic pharmacological effects and related mechanisms of the YCHD in the treatment of hepatitis C.

Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology.

BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified. METHODS: In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs. RESULTS: Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer. CONCLUSIONS: This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.

Comparative efficacy of Chinese herbal injections combined with azithromycin for mycoplasma pneumonia in children: A Bayesian network meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: An increasing macrolide resistance leads to complex clinical treatment schemes in mycoplasma pneumonia in children. Chinese herbal injection (CHI) is widely used to treat it and may provide a new treatment regimen. This study was conducted to systematically evaluate the efficacy of CHIs combined with azithromycin for treating mycoplasma pneumonia in children by Bayesian network meta-analysis. METHODS: Randomized controlled trials (RCTs) of CHIs combined with azithromycin for mycoplasma pneumonia in children were searched in electronic databases and related references from initiation to 30 October 2018. Two researchers conducted data extraction and risk of bias assessment. WinBUGS software and STATA software were adopted to analyse the data. RESULTS: A total of 167 RCTs were included with 5 CHIs involving 16 144 patients. All CHIs combined with azithromycin had superior effects than azithromycin only among overall outcomes. Yanhuning injection combined with azithromycin ranked highest in four different outcomes and second in two based on surface under the cumulative ranking probabilities (SUCRA). Meanwhile, the results of MD and 95% CIs of concerned outcomes indicated that only Yanhuning injection combined with azithromycin had better response than other CHIs combined with azithromycin. Moreover, cluster analysis results revealed Reduning injection combined with azithromycin was associated with a positive effect on the three group outcomes. Similarly, it was found to be the top three ranking in all outcomes based on SUCRA. WHAT IS NEW AND CONCLUSION: Yanhuning injection combined with azithromycin and Reduning injection combined with azithromycin were found to be preferable treatments based on the data of this study.

Comparative efficacy of Chinese herbal injections for angina pectoris: A Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: The severity of angina pectoris has been recognized. It is believed that Chinese herbal injections have an outstanding clinical effect on this condition. This network meta-analysis was devised to investigate the comparative efficacy of eight Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, Shenqi Fuzheng injection, Yiqifumai injection) in the treatment of angina pectoris. METHODS: A literature search was performed in PubMed, Embase, and the Cochrane Library, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database from their inception to June 25, 2018. A pre-designed eligibility criterion was utilized in this network meta-analysis, and a methodological quality analysis was conducted. Data analysis was performed by WinGUGS 1.4.3, Stata 13.0 and TSA software, and the odds ratio or mean difference with the 95% credible interval was reported for symptomatic improvement, electrocardiography improvement, fibrinogen, triglyceride and cholesterol. The ranking probability of interventions in various outcomes was also utilized. RESULTS: A total of 73 randomized controlled trials with 6639 patients were identified. Integrating network meta-analysis results, Shenqi Fuzheng injection plus western medicine therapy and Shenmai injection plus western medicine therapy were shown to be more efficacious than other therapies. In addition, Huangqi injection plus western medicine therapy and Shenmai injection plus western medicine therapy performed well in improving the haemorheology index and serum lipid parameters. CONCLUSIONS: Eligible Chinese herbal injections plus western medicine therapy might have a better impact on angina pectoris patients than western medicine therapy alone. While this study had limitations, the findings should be interpreted with caution. In addition, more high-quality randomized controlled trials with a large sample must be conducted to support this study.

Shenqi Fuzheng Injection in the Treatment of Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This meta-analysis synthesized the available evidence on the effectiveness and safety of Shenqi Fuzheng injection (SQFZI) combined with chemotherapy for breast cancer. METHOD: A comprehensive systematic literature search was conducted to identify the randomized controlled trials (RCTs) on breast cancer treated by SQFZI in several electronic database up to October 29, 2017. The included RCTs were assessed using the Cochrane Collaboration tool; data were extracted and analyzed via RevMan 5.3 and Stata 13.0 software. RESULTS: A total of 31 eligible RCTs comprising 2543 participants were selected in this present meta-analysis. The results demonstrated that compared with receiving conventional chemotherapy alone, SQFZI treatment combined with chemotherapy was more efficient in improving clinical total effective rate (relative risk [RR] = 1.31, 95% CI 1.19-1.44, P < .00001) and performance status (RR = 2.23, 95% CI 1.88-2.65, P < .00001). Additionally, SQFZI combined with chemotherapy was capable of enhancing immune function and alleviating adverse drug reactions for patients with breast cancer. CONCLUSIONS: The current evidence suggested that using SQFZI as an adjunct treatment to chemotherapy may be preferable for patients with breast cancer compared to chemotherapy alone. Because of the limitations of the quantities and qualities of included RCTs, more well-designed RCTs are needed to further support our conclusion.

Network Pharmacology-Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer.

BACKGROUND: Hedyotis diffusa Willd. (HDW) is one of the renowned herbs often used in the treatment of gastric cancer (GC). However, its curative mechanism has not been fully elucidated. OBJECTIVE: To systematically investigate the mechanisms of HDW in GC. METHODS: A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study. RESULTS: A total of 353 targets of the 32 bioactive compounds in HDW were obtained. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2, P27Kip1, cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway. CONCLUSIONS: This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis.

The Optimal Chinese Herbal Injections for Use With Radiotherapy to Treat Esophageal Cancer: A Systematic Review and Bayesian Network Meta-Analysis.

Ethnopharmacological relevance: Esophageal cancer is one of the most common human cancers, and its incidence is highly endemic in China. The combination of Chinese herbal injections (CHIs) and radiotherapy should be informed by the best available evidence. Aim of the study: To update and expand on previous work in order to compare and rank the efficacy and safety of CHIs in combination with radiotherapy to treat esophageal cancer. Materials and Methods: We searched several electronic databases to identify randomized controlled trials (RCTs) regarding CHIs to treat esophageal cancer from their inception to March 15, 2017. In a network meta-analysis (NMA), the bias of the included trials was assessed by two individuals independently in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Outcomes such as the clinical effectiveness rate, performance status, adverse reactions (ADRs), and survival rate were evaluated. We performed a random-effects NMA to obtain estimates of efficacy and safety outcomes, and we present these estimates as odds ratios (ORs) and corresponding 95% confidence intervals (CIs) calculated via Stata 13.1 and WinBUGS 1.4 software. Furthermore, the surface under cumulative the ranking curve (SUCRA) was used to rank the efficacy and safety of different CHIs in relation to each outcome. Results: Of 685 identified trials, 55 were eligible for inclusion in the study. These 55 trials included 12 CHIs and 4,114 participants. The cluster analysis results suggested that Compound kushen injection therapy is the optimal CHI treatment for patients with esophageal cancer in terms of improving the clinical effectiveness rate and performance status. Huachansu and Kangai injection are superior in improving 1-year and 2-year survival rates. Lentinan injection may be considered a favorable choice for reliving ADRs, and Compound kushen injection may provide treatment benefits by reducing both gastrointestinal reaction and radiation esophagitis. Conclusions: The current clinical evidence indicated that Compound kushen injection combined with radiotherapy is the most preferable and beneficial option for patients with esophageal cancer in terms of efficacy and safety. However, the results of our study should be interpreted with caution given the limitations of the sample size and the methodological quality of the included trials.