A simple, reliable and accurate high performance liquid chromatography(HPLC) coupled with a UV detector at varied wavelength was developed for the quantitation of two types of anti-carcinogenic compounds, namely, Kush...A simple, reliable and accurate high performance liquid chromatography(HPLC) coupled with a UV detector at varied wavelength was developed for the quantitation of two types of anti-carcinogenic compounds, namely, Kushen alkaloids(KS-As) and Kushen flavonoids(KS-Fs), in Kushen. Their remarkable difference in physicochemical properties was circumvented by integrated optimization of column and mobile phase. The separation was achieved on an alkaline-resisting C18 column via gradient elution with acetonitrile(ACN) and 0.025%(volume ratio) diethylamine(DEA) in water as mobile phase. The flow rate was 0.7 mL/min, and the column temperature was maintained at 35 °C. UV detection wavelength was set at 225 nm to monitor KS-As, and then changed to 335 nm for KS-Fs at 26th min, which was kept for 30 min before returning to the original wavelength. All the calibration curves show good linearity(r20.999) within test ranges. The intra- and inter-day precision values of these components were less than 3.82%, and the average recovery rates obtained were in a range of 97.24%―102.64% for all the samples with RSD below 3.94%. This assay was successfully applied to determining the major active components in commercial herbal samples of Kushen. Moreover, the possible relationship between sample and the geographical region was visualized based on the contents of the 6 compounds in the light of principal component analysis(PCA). The results suggest that the proposed method facilitates the quality control of Kushen.展开更多
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
Objective: The present study aimed to analyze the association rules of Fufang Kushen injection in combination with other traditional Chinese medicine ( TCM) or modern medications in treating cervical cancer (CC) based...Objective: The present study aimed to analyze the association rules of Fufang Kushen injection in combination with other traditional Chinese medicine ( TCM) or modern medications in treating cervical cancer (CC) based on the electrical medical records extracted from real-world hospital information system. Methods: The clinicians’ prescriptions regarding to the combination of with TCM or modern medications were from hospital information system electronic medical data integration warehouse established by the Institute of Basic Medical Research of Chinese Medicine, China Academy of Chinese Medical Sciences, which integrated the hospital information system data of 22 hospitals. The association rules of the drug characteristics were analyzed through Apriori algorithm. Results: A total of 839 patients with CC were included. We found that is often combined with prescriptions which could clear heat, remove toxicity, supplement Qi. also combined with chemotherapeutic drugs, immunomodulatory drugs, 5-HT receptor blockers, and glucocorticoids. The combination presents a specific law. Conclusion: Fufang Kushen injection combined with hepatoprotective drugs, immunomodulators and glucocorticoids is often used to treat cervical cancer.展开更多
Objective: This study aims to systematically evaluate the efficacy and safety of compound kushen injection (CKI) in combination with chemotherapy in patients with gastric cancer (GC). Methods: A comprehensive electron...Objective: This study aims to systematically evaluate the efficacy and safety of compound kushen injection (CKI) in combination with chemotherapy in patients with gastric cancer (GC). Methods: A comprehensive electronic search was conducted by searching PubMed, EMBASE, Cochrane Library, Chinese Biological Medical disc, China National Knowledge Infrastructure and Wanfang databases (the last update January 20, 2018). All randomized controlled trials (RCTs) of CKI plus chemotherapy versus chemotherapy alone in GC patients were identified. The quality of each study was evaluated using the Jadad’s scale, and the meta-analysis was performed using Review Manager 5.3 and STATA 14 software. Results: A total of nine studies on 688 cases were included in this study. The results showed that CKI combined with chemotherapy had a better effect on improving patients’ overall response rate (ORR) and life quality. The consequences of Egger’s and Begg’s tests showed there was no significant publication bias. Conclusion: The current evidence showed that CKI may enhance the clinical efficacy of chemotherapy, improve the quality of life and increase the safety in patients with gastric cancer.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
OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We ran...OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.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
OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),...OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice,was investigated on 24 specific pathogen-free male Sprague-Dawley rats.Liver tissues were compared using RNA-Seq technology.The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction(q PCR and Western blot(WB).RESULTS:Serum triglycerides(TG),liver low-density lipoprotein cholesterol(LDL-C),body weight,body length,and Lee’s index were significantly increased in the untreated hyperlipidemia-induced group(model)compared with the control group,whereas liver highdensity lipoprotein cholesterol(HDL-C)was significantly decreased.Serum TG,liver LDL-C,bodyweight,and Lee’s index were decreased in the high-dose Kushen decoction group(HDKS)compared with the model group,whereas liver HDL-C was significantly increased.Similarly,liver TG tended to decline in the HDKS group.Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways,PPAR signalling pathway,and circadian rhythm(Q≤0.05),with the genes ARNTL,PER3,and CLOCK being differentially expressed.qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis.CONCLUSION:The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular,their related genes ARNTL,PER3,and CLOCK.展开更多
In this overview,the current knowledge of the constituents of flavonoids isolated from the roots of Sophora flavescens(kushen)is updated.Flavonoids consist of several classes,such as flavanones,flavonols,chalcones,iso...In this overview,the current knowledge of the constituents of flavonoids isolated from the roots of Sophora flavescens(kushen)is updated.Flavonoids consist of several classes,such as flavanones,flavonols,chalcones,isoflavones,biflavonoids,flavanols,and flavones.The most common compounds are kurarinone(KRN),sophoraflavanone G(SFG),2′-methoxykurarinone,kuraridine,isoxanthohumol,and formononetin.KRN and SFG are two major flavanones with more vital anticancer properties than other flavonoids.From the literature,the cytotoxic values of KRN and SFG are variable and depend on the type of cancer cells tested.The anticancer activities of these two flavonoids involve different molecular mechanisms.Clinical trials are needed before anticancer drugs from KRN and SFG can be developed.展开更多
基金Supported by the National S&T Major Project of China(Nos.2009ZX09502-012 and 2009ZX09304-002)the Natural Science Foundation of Zhejiang Province, China(No.R2080693)
文摘A simple, reliable and accurate high performance liquid chromatography(HPLC) coupled with a UV detector at varied wavelength was developed for the quantitation of two types of anti-carcinogenic compounds, namely, Kushen alkaloids(KS-As) and Kushen flavonoids(KS-Fs), in Kushen. Their remarkable difference in physicochemical properties was circumvented by integrated optimization of column and mobile phase. The separation was achieved on an alkaline-resisting C18 column via gradient elution with acetonitrile(ACN) and 0.025%(volume ratio) diethylamine(DEA) in water as mobile phase. The flow rate was 0.7 mL/min, and the column temperature was maintained at 35 °C. UV detection wavelength was set at 225 nm to monitor KS-As, and then changed to 335 nm for KS-Fs at 26th min, which was kept for 30 min before returning to the original wavelength. All the calibration curves show good linearity(r20.999) within test ranges. The intra- and inter-day precision values of these components were less than 3.82%, and the average recovery rates obtained were in a range of 97.24%―102.64% for all the samples with RSD below 3.94%. This assay was successfully applied to determining the major active components in commercial herbal samples of Kushen. Moreover, the possible relationship between sample and the geographical region was visualized based on the contents of the 6 compounds in the light of principal component analysis(PCA). The results suggest that the proposed method facilitates the quality control of Kushen.
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Objective: The present study aimed to analyze the association rules of Fufang Kushen injection in combination with other traditional Chinese medicine ( TCM) or modern medications in treating cervical cancer (CC) based on the electrical medical records extracted from real-world hospital information system. Methods: The clinicians’ prescriptions regarding to the combination of with TCM or modern medications were from hospital information system electronic medical data integration warehouse established by the Institute of Basic Medical Research of Chinese Medicine, China Academy of Chinese Medical Sciences, which integrated the hospital information system data of 22 hospitals. The association rules of the drug characteristics were analyzed through Apriori algorithm. Results: A total of 839 patients with CC were included. We found that is often combined with prescriptions which could clear heat, remove toxicity, supplement Qi. also combined with chemotherapeutic drugs, immunomodulatory drugs, 5-HT receptor blockers, and glucocorticoids. The combination presents a specific law. Conclusion: Fufang Kushen injection combined with hepatoprotective drugs, immunomodulators and glucocorticoids is often used to treat cervical cancer.
文摘Objective: This study aims to systematically evaluate the efficacy and safety of compound kushen injection (CKI) in combination with chemotherapy in patients with gastric cancer (GC). Methods: A comprehensive electronic search was conducted by searching PubMed, EMBASE, Cochrane Library, Chinese Biological Medical disc, China National Knowledge Infrastructure and Wanfang databases (the last update January 20, 2018). All randomized controlled trials (RCTs) of CKI plus chemotherapy versus chemotherapy alone in GC patients were identified. The quality of each study was evaluated using the Jadad’s scale, and the meta-analysis was performed using Review Manager 5.3 and STATA 14 software. Results: A total of nine studies on 688 cases were included in this study. The results showed that CKI combined with chemotherapy had a better effect on improving patients’ overall response rate (ORR) and life quality. The consequences of Egger’s and Begg’s tests showed there was no significant publication bias. Conclusion: The current evidence showed that CKI may enhance the clinical efficacy of chemotherapy, improve the quality of life and increase the safety in patients with gastric cancer.
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.
文摘OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.
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.
基金Supported by National Natural Science Foundation of China(No.81760787)China Postdoctoral Science Foundation(No.2017M622101)+6 种基金Scientific Foundation of the Education Department of Jiangxi Province(No.GJJ190643)Traditional Chinese Medicine Scientific Research Subject of Jiangxi Province(No.2019A111,2019B110)Health and Family Planning Commission of Jiangxi Province(No.20195651,No.20203766,No.20203773,No.202131047 and No.202131054)Collaborative Innovation of Modern Science and Technology and Industrial Development of Jiangxi National Traditional Medicine(Gan Jiao Gao Zi,[2013]No.109)Jiangxi middle-aged and young backbone Talents Project of traditional Chinese medicine(Gan TCM Ke Jiao Zi[2021]No.2)the Specialized Research Fund for the First-Class Discipline of Chinese Herb from Jiangxi Province(No.JXSYLXK-ZHYAO111)Key Discipline Project of Jiangxi University of Chinese Medicine(No.2013jzzdxk069)
文摘OBJECTIVE:To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fatdiet-induced hyperlipidemia in rats using RNA-seq technology.METHODS:The efficacy of a Kushen decoction(苦参汤),at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice,was investigated on 24 specific pathogen-free male Sprague-Dawley rats.Liver tissues were compared using RNA-Seq technology.The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction(q PCR and Western blot(WB).RESULTS:Serum triglycerides(TG),liver low-density lipoprotein cholesterol(LDL-C),body weight,body length,and Lee’s index were significantly increased in the untreated hyperlipidemia-induced group(model)compared with the control group,whereas liver highdensity lipoprotein cholesterol(HDL-C)was significantly decreased.Serum TG,liver LDL-C,bodyweight,and Lee’s index were decreased in the high-dose Kushen decoction group(HDKS)compared with the model group,whereas liver HDL-C was significantly increased.Similarly,liver TG tended to decline in the HDKS group.Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways,PPAR signalling pathway,and circadian rhythm(Q≤0.05),with the genes ARNTL,PER3,and CLOCK being differentially expressed.qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis.CONCLUSION:The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular,their related genes ARNTL,PER3,and CLOCK.
文摘In this overview,the current knowledge of the constituents of flavonoids isolated from the roots of Sophora flavescens(kushen)is updated.Flavonoids consist of several classes,such as flavanones,flavonols,chalcones,isoflavones,biflavonoids,flavanols,and flavones.The most common compounds are kurarinone(KRN),sophoraflavanone G(SFG),2′-methoxykurarinone,kuraridine,isoxanthohumol,and formononetin.KRN and SFG are two major flavanones with more vital anticancer properties than other flavonoids.From the literature,the cytotoxic values of KRN and SFG are variable and depend on the type of cancer cells tested.The anticancer activities of these two flavonoids involve different molecular mechanisms.Clinical trials are needed before anticancer drugs from KRN and SFG can be developed.