OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of ...OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.展开更多
Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respi...Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003.CKI is known to inhibit inflammation,and its main chemical components,namely matrine and oxymatrine,can promote Th cells to recognize and eliminate viruses.In this study,network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients.The“ingredient-target”network was constructed using the Cytoscape software.The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets.Results:Sophocarpine,sophoridine,matrine,(+)-allomatrine,AIDS211310,and sophranol were the six active ingredients.After docking the active ingredients with severe acute respiratory syndrome coronavirus 23CL hydrolase and angiotensin-converting enzyme 2(ACE2),they displayed suitable affinity,which could block viral replication and its binding to ACE2.The key targets mainly involved inflammatory factors,such as interleukin-6(IL-6)and tumor necrosis factor(TNF).Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway.The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway.Conclusion:The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors.They regulate the IL-6-mediated signaling pathway,TNF signaling pathway,and steroid hormone biosynthesis,thereby initiating therapeutic responses against coronavirus disease 2019.展开更多
Compound Kushen Injection(CKI),as a clinical traditional Chinese medicine preparation,has prominent antitumor effect but with several side effects.A large number of studies have shown that CKI plays an antitumor role ...Compound Kushen Injection(CKI),as a clinical traditional Chinese medicine preparation,has prominent antitumor effect but with several side effects.A large number of studies have shown that CKI plays an antitumor role by regulating tumor cell proliferation,inducing tumor cell differentiation and apoptosis,inhibitrng tumor cell invasion and metastasis,reducing tumor angiogenesis,regulating the immunity,and so on.Clinically,CKI is widely used to treat various tumors,where it is often combined with surgery,chemotherapy,radiotherapy,targeted therapy,and other antitumor treatments.This article reviews the antitumor mechanism of CKI and the progress of its clinical application in order to provide a theoretical basis for further clinical application.展开更多
Bladder cancer is the most common malignancy of the urinary system.Compound Kushen Injection(CKI)is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past tw...Bladder cancer is the most common malignancy of the urinary system.Compound Kushen Injection(CKI)is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades.However,the pharmacological effect of CKI on bladder cancer is not still completely understood.In the current study,network pharmacology com-bined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer.The mech-anism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24.Net-work pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data indicated 5500 differen-tially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerted anti-blad-der cancer effects by regulating genes such as MMP-9,JUN,EGFR,and ERK1.Functional enrichment analysis indicated that CKI ex-erted therapeutic effects on bladder cancer by regulating certain biological processes,including cell proliferation,cell migration,and cell apoptosis.In addition,Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer,bladder cancer,and the PI3K-Akt signaling pathway.Consistently,cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells,and induced their apoptosis.Moreover,RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9,JUN,EGFR,and ERK1.CKI inhibited the prolif-eration and migration,and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets.CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer.Overall,our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer,and further support its clinical use.展开更多
文摘OBJECTIVE Compound Kushen injection(CKI)is a bis-herbal formulation extracted from Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma Heterosmilacis Japonicae).Clinically,it is used as the adjuvant treatment of cancer.However,with the increased application,the cases of immediate hypersensitivity reactions(IHRs)also gradually rise.In this study,we investigated the underlying mechanism(s)and active constituent(s)for CKI-induced IHRs in experimental models.METHODS T helper 2(Th2)immunity-amplified mice were prepared by aluminum adjuvant.Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice.For evaluating microvascular permeability,Evans blue extravasation assay was used.Platelet-activating factor(PAF),serum total IgE(tIgE)and mouse mast cell protease 1(MMCP1)were measured by ELISA.RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks,but could induce Evans blue extravasation(local)and cause obvious hypothermia(systemic)after a single injection.Further study showed that alkaloids in Kushen,especially matrine,were responsible for CKI-induced IHRs.Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically.In cell system,CKI was able to promote PAF production in a non-cell-selective manner.In cell lysate,the effect of CKI on PAF production became stronger and could be abolished by blocking de novo pathway.CONCLUSION In conclusion,our study identifies,for the first time,that CKI is a PAF inducer.It causes non-immunologic IHRs,rather than IgE-dependent IHRs,by promoting PAF production through de novo pathway.Alkaloids in Kushen,especially matrine,are the prime culprits for IHRs.Our findings may provide a potential approach for preventing and treating CKI-induced IHRs.
基金Natural Science Foundation of Hebei Province(H2018201179)Youth Fund of Education Department of Hebei Province(QN2019146)Scientific Research Fund of Health Department of Hebei Province(NO:20190948).
文摘Background:As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia,compound Kushen injection(CKI)played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003.CKI is known to inhibit inflammation,and its main chemical components,namely matrine and oxymatrine,can promote Th cells to recognize and eliminate viruses.In this study,network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients.The“ingredient-target”network was constructed using the Cytoscape software.The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets.Results:Sophocarpine,sophoridine,matrine,(+)-allomatrine,AIDS211310,and sophranol were the six active ingredients.After docking the active ingredients with severe acute respiratory syndrome coronavirus 23CL hydrolase and angiotensin-converting enzyme 2(ACE2),they displayed suitable affinity,which could block viral replication and its binding to ACE2.The key targets mainly involved inflammatory factors,such as interleukin-6(IL-6)and tumor necrosis factor(TNF).Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway.The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway.Conclusion:The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors.They regulate the IL-6-mediated signaling pathway,TNF signaling pathway,and steroid hormone biosynthesis,thereby initiating therapeutic responses against coronavirus disease 2019.
文摘Compound Kushen Injection(CKI),as a clinical traditional Chinese medicine preparation,has prominent antitumor effect but with several side effects.A large number of studies have shown that CKI plays an antitumor role by regulating tumor cell proliferation,inducing tumor cell differentiation and apoptosis,inhibitrng tumor cell invasion and metastasis,reducing tumor angiogenesis,regulating the immunity,and so on.Clinically,CKI is widely used to treat various tumors,where it is often combined with surgery,chemotherapy,radiotherapy,targeted therapy,and other antitumor treatments.This article reviews the antitumor mechanism of CKI and the progress of its clinical application in order to provide a theoretical basis for further clinical application.
基金the Training Pro-gram for Outstanding Clinical Medical Talents funded by the govern-ment(2020)the Outstanding Youth Scientific Research and Innova-tion Team(Science and Technology)Project of Hebei University(2020-8)+3 种基金the Medical Science Foundation of Hebei University(No.2020A15)the National Natural Science Foundation of Hebei Province(No.H2018201179)the Health and Family Planning Com-mission of Hebei Province(No.20190948)Hebei University Re-search Project of Science and Technology(No.QN2019146)。
文摘Bladder cancer is the most common malignancy of the urinary system.Compound Kushen Injection(CKI)is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades.However,the pharmacological effect of CKI on bladder cancer is not still completely understood.In the current study,network pharmacology com-bined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer.The mech-anism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24.Net-work pharmacology analysis identified 35 active compounds and 268 target genes of CKI.Bioinformatics data indicated 5500 differen-tially expressed genes associated with bladder cancer.Common genes of CKI and bladder cancer suggested that CKI exerted anti-blad-der cancer effects by regulating genes such as MMP-9,JUN,EGFR,and ERK1.Functional enrichment analysis indicated that CKI ex-erted therapeutic effects on bladder cancer by regulating certain biological processes,including cell proliferation,cell migration,and cell apoptosis.In addition,Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer,bladder cancer,and the PI3K-Akt signaling pathway.Consistently,cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells,and induced their apoptosis.Moreover,RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9,JUN,EGFR,and ERK1.CKI inhibited the prolif-eration and migration,and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets.CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer.Overall,our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer,and further support its clinical use.
