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Kushen （Radix Sophorae Flavescentis） has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection （CKI） is a mixture of natural compounds extracted from Kushen and Baituling （Rhizoma Smilacis Glabrae）. The main principles of CKI are matrine （MT） and oxymatrine （OMT） that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study.

Background Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. Methods Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. Results The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes ( NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN ) associated with the development of PC, and survival analysis found 5 genes ( TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28 ) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1 , JAK1 , EGFR , MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. Conclusions Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI.

Background The increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML. Methods Flow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI. Results We found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model. Conclusions Antioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.

Background Liver fibrosis and fibrosis‐related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor‐β (TGF‐β) is a critical mediator of chronic liver fibrosis, targeting TGF‐β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF‐β/Smad7 signaling. Methods A meta‐analysis was performed to evaluate CKI intervention on viral hepatitis‐induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl4) injection or methionine‐choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF‐β/Smad signaling and typical fibrosis‐related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT‐PCR, Western blotting, RNA‐seq, immunofluorescence, and immunohistochemistry. Results Based on meta‐analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF‐βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI. Conclusions Our results unveil the approach of CKI in rebalancing TGF‐β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis. 1. CKI ‐suppresses liver fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. 2. CKI inhibits HSCs activation by stabilizing the interaction of Smad7/TGFβR1 to rebalance Smad2/Smad3 signaling, acting as an alternative approach to target TGF‐β signaling. 3. High expression of Smad7 and low expression of TGFβR1 in HCC tumors and surrounding normal liver tissues can be tumor suppressive.

( ) preparations are widely used to control malignant pleural effusion (MPE) through intrapleural perfusion. This analysis aims to verify the therapeutic values of perfusion with preparations for controlling MPE, reveal the optimal treatment plan, suitable population, and usage, and to demonstrate their clinical effectiveness and safety. We performed and reported this systematic review/meta-analysis (PROSPERO: CRD42023430139) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning perfusion with preparation for MPE were collected from Chinese and English databases. We clustered all eligible studies into multiple homogeneous treatment units, assessed their methodological quality using a RoB 2, pooled the data from each unit, and summarized the quality of the evidence. We included 83 RCTs reporting three types of preparation: compound injection (CKI), injection, and matrine injection. All trials were clustered into perfusion with CKI alone or with the addition of sclerosants, , or matrine-plus platinum for controlling MPE. Compared with cisplatin alone, perfusion with CKI alone displayed a similar complete response, pleurodesis failure, and pleural progression (odds ratios =1.10, 95% CI 0.76 to 1.60; 0.80, 0.56 to 1.14; 0.63, 0.33 to 1.21). Of 14 homogeneous treatment plans, perfusion with CKI and cisplatin significantly improved the complete response (2.71, 2.30 to 3.19) and showed low pleurodesis failure (0.26, 0.22 to 0.32), pleural progression (0.22, 0.14 to 0.36), myelosuppression (0.34, 0.24 to 0.47), neutropenia (0.35, 0.26 to 0.46), gastrointestinal reaction (0.36, 0.29 to 0.44), hepatorenal toxicity (0.42, 0.28 to 0.63 and 0.32, 0.24 to 0.44), and fever (0.50, 0.30 to 0.82). These results were moderate quality (⊕⊕⊕Ο) supported by firm or conclusive information. Additionally, perfusion with or matrine and cisplatin also improved the complete response (3.04, 1.76 to 5.26 and 1.87, 1.26 to 2.78) and displayed low pleurodesis failure (0.23, 0.14 to 0.41 and 0.27, 0.17 to 0.44). The results were moderate to low quality (⊕⊕⊕Ο to ⊕⊕ΟΟ). Current moderate evidence demonstrates that CKI may be an effective palliative intervention for MPE which, combined with cisplatin, may be an optimal treatment plan. or matrine may be other potential choices. https://www.crd.york.ac.uk/PROSPERO/view/CRD42023430139.

Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. CKI significantly enhanced the anticancer activity of chemotherapy with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8 T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8 T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells . The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Chemotherapy and radiotherapy remain cornerstone treatments; however, they often lead to significant immune suppression and an increased risk of infection. Enhancing immune function in CRC patients is critical for improving clinical outcomes and prognosis. To evaluate the effects of Compound Kushen Injection (CKI) on immune function and its role in mitigating chemotherapy-induced adverse effects in patients with CRC. We retrieved randomized controlled trials (RCTs) evaluating the effects of CKI on immune function in patients with CRC from eight Chinese and English databases, up until 31 December 2024. The Cochrane Handbook was used to assess the quality of the included studies. For the meta-analysis, we utilized Review Manager 5.4.1 software. Sensitivity analysis and publication bias assessment were conducted using Stata 17.0 software. A total of 2,663 patients (1,550 males and 1,113 females) from 30 RCTs were included. Compared to conventional chemotherapy (CC), the combination of CKI with CC significantly enhanced immune function, increasing CD3 levels (MD = 6.15, 95% CI: 4.78 to 7.53, < 0.00001), CD4 levels (MD = 8.05, 95% CI: 6.99 to 9.11, < 0.00001), CD4+/CD8+ levels (MD = 0.36, 95% CI: 0.28 to 0.44, < 0.00001), NK cell levels (MD = 3.60, 95% CI: 2.85 to 4.34, < 0.00001), while reducing CD8 levels (MD = -4.19, 95% CI: -5.11 to -3.27, < 0.00001). CKI also improved the objective response rate (ORR, RR = 1.50, 95% CI: 1.38 to 1.62, < 0.00001) and disease control rate (DCR, RR = 1.15, 95% CI: 1.10 to 1.19, < 0.00001), decreased CEA levels (MD = -1.79, 95% CI: -2.81 to -0.76, = 0.0007) and CA199 levels (MD = -0.73, 95% CI: -1.35 to -0.12, = 0.02), and reduced chemotherapy-induced adverse reactions, including nausea, vomiting, hepatic dysfunction, myelosuppression, neurotoxicity, leukopenia, thrombocytopenia, and mouth ulcers. Current evidence suggests that the combination of CKI with CC may have beneficial effects on immune function, ORR, DCR, and chemotherapy-induced adverse reactions in CRC patients. However, given the variability in study quality and the absence of disease stage stratification, these findings should be interpreted with caution. Furthermore, the lack of long-term follow-up data limits the understanding of CKI's impact on survival and quality of life. High-quality, large-scale RCTs with extended follow-up are needed to further assess the long-term efficacy, safety, and clinical applicability of CKI in CRC management. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=632516, identifier CRD42025632516.

Primary liver cancer (PLC) is the third leading cause of cancer mortality worldwide. The heterogeneity of PLC and the complex immunosuppressive microenvironment make it difficult for single treatment regimens to meet patient needs. Therefore, it is crucial to find effective combination treatment strategies that enhance immune function in PLC therapy. To systematically evaluate the effect of compound kushen injection (CKI) on enhancing immune function in PLC patients and its role in treatment efficacy and related adverse reactions. Relevant Chinese and English electronic databases were searched to include randomized controlled trials (RCTs) assessing the impact of CKI on immune function in PLC patients published before June 2025. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Statistical analyses, Sensitivity analysis and publication bias assessment were conducted using Stata 18.0 software. A total of 2,359 patients from 25 RCTs were included (1,185 in the experimental group and 1,174 in the control group). Compared to conventional treatment alone, the combination of CKI and conventional treatment significantly enhanced immune function, as evidenced by increased CD3 levels, CD4 levels, CD4 /CD8 ratio, and natural killer (NK) cell levels, while CD8 levels showed no statistical significance. Additionally, CKI improved the objective response rate (ORR) and disease control rate (DCR), reduced AFP levels, increased KPS scores and the one-year overall survival period, reduced treatment-related adverse reactions, including nausea and vomiting, hepatic dysfunction, myelosuppression, fever, and pain. Existing evidence suggests that the combined use of CKI and conventional treatment may positively impact immune function, therapeutic effect and treatment-related adverse reactions in patients with PLC. However, the reliability of these conclusions is limited by the absence of disease staging stratification analysis and long-term follow-up data, which are essential for confirming the long-term efficacy and safety of the combined treatment. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251112494, identifier CRD420251112494.

Backgrounds: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. Methods: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger’s test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. Results: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = −5.25, 95% CI: −5.94 to −4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. Conclusion: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Protein arginine methyltransferase 5 (PRMT5) is overexpressed in lung carcinoma, which promotes tumor cell proliferation, survival, migration and invasion. Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling, which are mainly used to stop in cancer pain and bleeding. Here we found that cell viability and colony formation were inhibited after the incubation of AMI-1. Meanwhile, AMI-1 suppressed cell migration, enhanced apoptosis, induced cell cycle arrest, inhibited PRMT5 expression and histone H3R8 and H4R3 symmetric di-methylation (H3R8me2s and H4R3me2s) accumulation, down-regulated the expression of eukaryotic translation initiation factor 4E (eIF4E) in lung carcinoma cells. Moreover, AMI-1 suppressed tumor growth, decreased H3R8me2s and H4R3me2s accumulation, down-regulated eIF4E expression and increased p53 expression in lung carcinoma xenografts of BALB/c nude mice. Of note, combined and CKI markedly enhanced the anticancer efficacy CKI in lung carcinoma. The above findings demonstrated that AMI-1 has established antineoplastic activity and this role may be associated with affecting the function of eIF4E via inhibiting PRMT5 activity or protein levels in lung carcinoma. This study highlights evidence of novel selective anticancer activity of AMI-1 in combination with CKI in lung carcinoma.