Objective:To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer.Methods:PubMed database,Embase database and Cochrane Library database,CNKI,Wanfang database,VIP database...Objective:To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer.Methods:PubMed database,Embase database and Cochrane Library database,CNKI,Wanfang database,VIP database and Sinomed database were used to search for the randomized controlled trials of cinobufagin injection combined with Western medicine in the treatment of primary liver cancer.The retrieval time was from the establishment to December 15,2020.Two independent researchers conducted systematic screening,literature inclusion and quality assessment of the articles according to the inclusion criteria,respectively.Meta-analysis of the data was performed using RevMan 5.4 software.Results:A total of 30 studies with a total of 2355 patients were included.Compared with conventional western medicine treatment,the clinical effective rate of Hububutin injection combined with western medicine was significantly higher[RR=1.16,95%CI=(1.11,1.22),P<0.00001].It could effectively reduce the tumor size[RR=1.33,95%CI=(1.17,1.51),P<0.00001],prolong the survival time of patients[RR=1.41,95%CI=(1.31,1.52),P<0.00001],improve the quality of life[RR=1.37,95%CI=(1.19,1.57),P<0.00001],improve the liver function of patients[RR=-14.52,95%CI=(-16.15,-12.88),P<0.00001],and reduce the occurrence of adverse reactions[RR=0.94,95%CI=(0.85,1.42),P=0.25]such as bone marrow suppression[RR=0.44,95%CI=(0.31,0.62),P<0.00001].Conclusion:Cinobufagin injection combined with western medicine therapy can effectively improve the clinical symptoms of primary liver cancer,and the safety is good.However,the methodological quality of the included literature is low,which affects the objectivity of the outcome,and it still needs to be verified by multi-sample,multi-center,randomized double-blind controlled trial.展开更多
Objective:To explore the effects of cinobufagin (CBF),an active component of toad venom (Bufo bufo gargarizans CANTOR),on the proliferation and apoptosis of PC3 human prostate cancer cells in vitro and preliminarily i...Objective:To explore the effects of cinobufagin (CBF),an active component of toad venom (Bufo bufo gargarizans CANTOR),on the proliferation and apoptosis of PC3 human prostate cancer cells in vitro and preliminarily investigate the mechanism of CBF in suppressing tumor cell growth in vivo.Methods:The effect of CBF on PC3 cells proliferation was detected using MTT assay.The morphological changes of PC3 cells were observed under an optical microscope.Colony formation assays were used to observe the CBF effect on colony formation by PC3 cells.PC3 cell apoptosis after treatment with CBF for 48 hours was monitored using flow cytometry.Furthermore,the effect of CBF on the expression of myeloid cell leukemia-1 (MCL-1) and related apoptotic proteins was examined using western blotting.A xenograft model was established in BALB/c nude mice to evaluate the effect of CBF on prostate cancer in vivo.Results:The MT-T assay results illustrated that PC3 cell proliferation was inhibited in vitro by CBF in a concentration-and time-dependent manner.Compared with the control group findings,CBF significantly inhibited the formation of PC3 cells (P =.005).Flow cytometry revealed that after treatment with 50 nM CBF for 48 hours,the apoptotic rate of PC3 cells was 41.97 (5.16)%,indicating that CBF could significantly induce its apoptosis (P =.003).In addition,optical and fluorescence microscopy uncovered remarkable inhibition of cell proliferation accompanied by morphologic changes.The western blotting result indicated that CBF obviously downregulated the expression of the anti-apoptotic protein MCL-1.Most importantly,ClBF reduced the carcinogenicity of PC3 xenografts in nude mice.Conclusion:CBF can inhibit the growth of PC3 cells both in vitro and in vivo and induce apoptosis of tumor cells.The corresponding mechanism may be correlated with the activation of caspase family proteins via MCL-1.展开更多
Objective:To evaluate the efficacy and safety of Cinobufagin capsules combined with chemotherapy in the treatment of gastric cancer by Meta-analysis.Methods:Randomized controlled trials(RCTs)of Cinobufagin capsules co...Objective:To evaluate the efficacy and safety of Cinobufagin capsules combined with chemotherapy in the treatment of gastric cancer by Meta-analysis.Methods:Randomized controlled trials(RCTs)of Cinobufagin capsules combined with chemotherapy for gastric cancer included in Chinese database(VIP,CNKI,WanFang,CBM)and English database(PubMed,Cochrane Library,EMBase)were retrieved from the inception to June 2020.Data extraction and methodological quality evaluation were carried out for the included literature.The methodological quality assessment was based on Cochrane bias risk assessment tool.RevMan 5.3 and GRADEpro 3.6 were used for meta-analysis and evidence quality assessment,respectively.Results:12 trials with 830 patients were included in the review.Meta-analysis results showed that:the addition of Cinobufagin capsules for gastric cancer enhanced the objective remission rate(ORR)(RR=1.65,95%CI[1.41,1.93],P<0.00001);improved quality of Life Score(KPS score)(RR=1.77,95%CI[1.43,2.19],P<0.00001);reduced the incidence of nausea and vomiting(RR=0.46,95%CI[0.29,0.74],P=0.001),leukocyte toxicity(RR=0.40,95%CI[0.25,0.64],P<0.0001),and platelet toxicity(RR=0.45,95%CI[0.22,0.93],P=0.03);increased the level of CD4+(MD=6.99,95%CI[4.32,9.66],P<0.00001)was better than chemotherapy alone,with statistically significant differences.The quality of evidence is low by GRADE evaluation.Conclusion:In chemotherapy for gastric cancer,combined with Cinobufagin capsule has better efficacy and safety.展开更多
Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injecti...Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injection respectively for middleand advanced primary hepatic carcinoma. Methods: A total of 104 cases of patients with middle and advanced primary hepaticcarcinoma who were treated in the oncology department from August 2018 to January 2020 were included as the study objects, andwere randomly divided into two groups according to different treatment regimens, 52 cases in each group. Both groups were treatedwith TACE once;the cinobufagin injection group was given intravenous infusion with 500 mL of 5% glucose injection and 10 mLof cinobufagin injection once a day. The elemene injection group was given intravenous infusion with elemene injection of 0.4 geach time and once a day. Both groups were treated for two courses, 15 days of continuous treatment with a rest of 15 days beingone course. The clinical effect, the changes in the indexes of liver function including alanine amino transferase(ALT), aspartatetransaminase(AST) and total bilirubin(TBil), the scores of alpha-fetoprotein(AFP) and Karnofsky (KPS) and tumor volumes aswell as the difference in the incidences of adverse reactions between the two groups were observed and compared. Results: Thetotal clinical effective rate was 88.46% in the elemene injection group and 71.15% in the cinobufagin injection group, and thedifference was significant(P<0.05). After treatment, the levels of ALT, AST and TBil in serum in the two groups were significantlydecreased when compared with those before treatment, differences being significant(P<0.05). There was no significant differencebeing found in the comparison of the levels of ALT, AST and TBil in serum between the two groups (P>0.05). After treatment, thedecrease of AFP, tumor volume and the increase of KPS scores in the elemene injection group were significantly more than thosein the cinobufagin injection group, differences being significant (P<0.01). During treatment, there was no significant differencebeing found in the comparison of the total incidences of adverse reactions between the two groups(P>0.05). The adverse reactionsin the cinobufagin injection group were mainly nausea and vomiting, with higher incidence than that in the elemene injection group,the difference being significant (P<0.05). The adverse reactions in the elemene injection group were mainly pain at the injectionsite, with higher incidence than that in the cinobufagin injection group, the difference being significant (P<0.05). Conclusion: Thetherapy of elemene injection combined with TACE for middle and advanced primary hepatic carcinoma has better clinical effect thanthat of cinobufagin injection, but the occ.展开更多
Objective:The aim of this study is to observe the clinical effect of hand exercise combined with jinhuang ointment on the prevention of phlebitis due to cinobufagin.Methods:A total of 90 cancer patients who have been ...Objective:The aim of this study is to observe the clinical effect of hand exercise combined with jinhuang ointment on the prevention of phlebitis due to cinobufagin.Methods:A total of 90 cancer patients who have been receiving intravenous(Ⅳ)infusion of cinobufagin from May 2018 to June 2019 in the oncology department of our hospital were selected.They were then divided into three groups in a random manner,which include 30 cases in the control group,30 cases in the jinhuang ointment group,and 30 cases in the group of hand exercise combined with jinhuang ointment.The control group had a routine care before cinobufagin was infused from the first day of hospitalization.During the routine care mentioned previously,the jinhuang ointment group was given locally jinhuang ointment inunction,qd,and kept for 6 hours.Hand exercises were then done on the combined group excluding jinhuang ointment application,qd,at 10min.After treatment for 1 week,the phlebitis and pain incidences on the venipuncture site were then compared between the three groups.Results:After the 1-week treatment,the incidences of grade Ⅰ/Ⅱ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 53.5%,23.3%,and 10%,respectively.The results have shown a significant decrease in the jinhuang ointment group and the combined group as in comparison with the control group(P=0.0169,P=0.0003).Even with the incidence of the combined group being lower than that of the jinhuang ointment group,no statistically significant difference(P=0.1659)was found.The incidences of grade Ⅲ/Ⅳ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 23.3%,3.3%,and 3.3%,respectively.Both the jinhuang ointment group and the combined group had significantly lower results than that of the control group(P=0.0003,P=0.0227).There was no difference in the results of the combined group and the jinhuang ointment group.The incidences of pain in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 56.7%,36.7%,and 20%,respectively.There was no significant difference in the results of the jinhuang ointment group and the control group(P=0.1205);the combined group has shown a significant decrease in the incidence compared with the control group(P=0.0035);the incidence of pain in the combined group was lower than that of the jinhuang ointment group,but without a statistical difference(P=0.1520).Conclusion:Hand exercise together with jinhuang ointment inunction can significantly reduce the incidence of phlebitis produced by cinobufagin.展开更多
In vitro models of human colon carcinoma cell line(Caco-2 cell monolayer) and human intestinal bacteria were used to investigate the intestinal transport and biotransformation of resibufogenin and cinobufagin in Chan ...In vitro models of human colon carcinoma cell line(Caco-2 cell monolayer) and human intestinal bacteria were used to investigate the intestinal transport and biotransformation of resibufogenin and cinobufagin in Chan Su by HPLC/APCI-MSn. The experimental results of Caco-2 cell monolayer demonstrate that the apparent permeability coefficients(Papp) of resibufogenin and cinobufagin are higher than 10-6 cm/s, which indicates that both resibufogenin and cinobufagin have a good absorption in the small intestine. And the biotransformation result of human intestinal bacteria shows that resibufogenin has been transformed to 3-epiresibufogenin and cinobufagin has been transformed to 3-epicinobufagin, deacetylcinobufagin and 3-epideacetycinobufagin, respectively.展开更多
The title compound cinobufagin 3-hemisuberate methyl ester(1) was isolated from the venom of Bufo bufo gargarizans CANTOR. The crystal structure of 1, C35H48O9, was determined by single-crystal X-ray diffraction analy...The title compound cinobufagin 3-hemisuberate methyl ester(1) was isolated from the venom of Bufo bufo gargarizans CANTOR. The crystal structure of 1, C35H48O9, was determined by single-crystal X-ray diffraction analysis. It belongs to orthorhombic, space group P212121 with a = 8.9338(3), b = 16.2970(4), c = 22.4019(6) , V = 3261.59(16) 3, Mr = 612.73, Z = 4, Dc = 1.248 g/cm3, μ = 0.725 mm-1, F(000) = 1320, S = 1.040, the final R = 0.0374 and wR = 0.0412 for 4458 unique reflections, of which 4088 were observed(I > 2σ(I)). In the solid state, short intermolecular C-H...O interactions involving a methine and the ester carbonyl group in cinobufagin moiety and a methyl in the suberate moiety linked adjacent molecules into a three-dimensional network. Detailed analysis of the 1H-NMR data showed that X-ray structure of 1 would be expected to closely resemble the solution conformation in chloroform. Compound 1 was inactive for the inhibition of PC3 and HepG2 cancer cells, but the parent compound cinobufagin showed potent inhibition with IC50 values of 0.145 and 5.48 μM, respectively, indicating that esterification at C(3) decreased the cytotoxic effect of 1.展开更多
基金Shaanxi University of Traditional Chinese Medicine Innovation Team Project(2019-YL14,2019-YL11)。
文摘Objective:To evaluate the clinical efficacy and safety of cinobufagin injection in the treatment of liver cancer.Methods:PubMed database,Embase database and Cochrane Library database,CNKI,Wanfang database,VIP database and Sinomed database were used to search for the randomized controlled trials of cinobufagin injection combined with Western medicine in the treatment of primary liver cancer.The retrieval time was from the establishment to December 15,2020.Two independent researchers conducted systematic screening,literature inclusion and quality assessment of the articles according to the inclusion criteria,respectively.Meta-analysis of the data was performed using RevMan 5.4 software.Results:A total of 30 studies with a total of 2355 patients were included.Compared with conventional western medicine treatment,the clinical effective rate of Hububutin injection combined with western medicine was significantly higher[RR=1.16,95%CI=(1.11,1.22),P<0.00001].It could effectively reduce the tumor size[RR=1.33,95%CI=(1.17,1.51),P<0.00001],prolong the survival time of patients[RR=1.41,95%CI=(1.31,1.52),P<0.00001],improve the quality of life[RR=1.37,95%CI=(1.19,1.57),P<0.00001],improve the liver function of patients[RR=-14.52,95%CI=(-16.15,-12.88),P<0.00001],and reduce the occurrence of adverse reactions[RR=0.94,95%CI=(0.85,1.42),P=0.25]such as bone marrow suppression[RR=0.44,95%CI=(0.31,0.62),P<0.00001].Conclusion:Cinobufagin injection combined with western medicine therapy can effectively improve the clinical symptoms of primary liver cancer,and the safety is good.However,the methodological quality of the included literature is low,which affects the objectivity of the outcome,and it still needs to be verified by multi-sample,multi-center,randomized double-blind controlled trial.
基金This study was supported by the National Natural Science Foundation of China(81260540).
文摘Objective:To explore the effects of cinobufagin (CBF),an active component of toad venom (Bufo bufo gargarizans CANTOR),on the proliferation and apoptosis of PC3 human prostate cancer cells in vitro and preliminarily investigate the mechanism of CBF in suppressing tumor cell growth in vivo.Methods:The effect of CBF on PC3 cells proliferation was detected using MTT assay.The morphological changes of PC3 cells were observed under an optical microscope.Colony formation assays were used to observe the CBF effect on colony formation by PC3 cells.PC3 cell apoptosis after treatment with CBF for 48 hours was monitored using flow cytometry.Furthermore,the effect of CBF on the expression of myeloid cell leukemia-1 (MCL-1) and related apoptotic proteins was examined using western blotting.A xenograft model was established in BALB/c nude mice to evaluate the effect of CBF on prostate cancer in vivo.Results:The MT-T assay results illustrated that PC3 cell proliferation was inhibited in vitro by CBF in a concentration-and time-dependent manner.Compared with the control group findings,CBF significantly inhibited the formation of PC3 cells (P =.005).Flow cytometry revealed that after treatment with 50 nM CBF for 48 hours,the apoptotic rate of PC3 cells was 41.97 (5.16)%,indicating that CBF could significantly induce its apoptosis (P =.003).In addition,optical and fluorescence microscopy uncovered remarkable inhibition of cell proliferation accompanied by morphologic changes.The western blotting result indicated that CBF obviously downregulated the expression of the anti-apoptotic protein MCL-1.Most importantly,ClBF reduced the carcinogenicity of PC3 xenografts in nude mice.Conclusion:CBF can inhibit the growth of PC3 cells both in vitro and in vivo and induce apoptosis of tumor cells.The corresponding mechanism may be correlated with the activation of caspase family proteins via MCL-1.
文摘Objective:To evaluate the efficacy and safety of Cinobufagin capsules combined with chemotherapy in the treatment of gastric cancer by Meta-analysis.Methods:Randomized controlled trials(RCTs)of Cinobufagin capsules combined with chemotherapy for gastric cancer included in Chinese database(VIP,CNKI,WanFang,CBM)and English database(PubMed,Cochrane Library,EMBase)were retrieved from the inception to June 2020.Data extraction and methodological quality evaluation were carried out for the included literature.The methodological quality assessment was based on Cochrane bias risk assessment tool.RevMan 5.3 and GRADEpro 3.6 were used for meta-analysis and evidence quality assessment,respectively.Results:12 trials with 830 patients were included in the review.Meta-analysis results showed that:the addition of Cinobufagin capsules for gastric cancer enhanced the objective remission rate(ORR)(RR=1.65,95%CI[1.41,1.93],P<0.00001);improved quality of Life Score(KPS score)(RR=1.77,95%CI[1.43,2.19],P<0.00001);reduced the incidence of nausea and vomiting(RR=0.46,95%CI[0.29,0.74],P=0.001),leukocyte toxicity(RR=0.40,95%CI[0.25,0.64],P<0.0001),and platelet toxicity(RR=0.45,95%CI[0.22,0.93],P=0.03);increased the level of CD4+(MD=6.99,95%CI[4.32,9.66],P<0.00001)was better than chemotherapy alone,with statistically significant differences.The quality of evidence is low by GRADE evaluation.Conclusion:In chemotherapy for gastric cancer,combined with Cinobufagin capsule has better efficacy and safety.
文摘Objective: To observe and compare the differences in the clinical effect and the incidences of adverse reactions oftranscatheter arterial chemoembolization(TACE) combined with elemene injection and cinobufagin injection respectively for middleand advanced primary hepatic carcinoma. Methods: A total of 104 cases of patients with middle and advanced primary hepaticcarcinoma who were treated in the oncology department from August 2018 to January 2020 were included as the study objects, andwere randomly divided into two groups according to different treatment regimens, 52 cases in each group. Both groups were treatedwith TACE once;the cinobufagin injection group was given intravenous infusion with 500 mL of 5% glucose injection and 10 mLof cinobufagin injection once a day. The elemene injection group was given intravenous infusion with elemene injection of 0.4 geach time and once a day. Both groups were treated for two courses, 15 days of continuous treatment with a rest of 15 days beingone course. The clinical effect, the changes in the indexes of liver function including alanine amino transferase(ALT), aspartatetransaminase(AST) and total bilirubin(TBil), the scores of alpha-fetoprotein(AFP) and Karnofsky (KPS) and tumor volumes aswell as the difference in the incidences of adverse reactions between the two groups were observed and compared. Results: Thetotal clinical effective rate was 88.46% in the elemene injection group and 71.15% in the cinobufagin injection group, and thedifference was significant(P<0.05). After treatment, the levels of ALT, AST and TBil in serum in the two groups were significantlydecreased when compared with those before treatment, differences being significant(P<0.05). There was no significant differencebeing found in the comparison of the levels of ALT, AST and TBil in serum between the two groups (P>0.05). After treatment, thedecrease of AFP, tumor volume and the increase of KPS scores in the elemene injection group were significantly more than thosein the cinobufagin injection group, differences being significant (P<0.01). During treatment, there was no significant differencebeing found in the comparison of the total incidences of adverse reactions between the two groups(P>0.05). The adverse reactionsin the cinobufagin injection group were mainly nausea and vomiting, with higher incidence than that in the elemene injection group,the difference being significant (P<0.05). The adverse reactions in the elemene injection group were mainly pain at the injectionsite, with higher incidence than that in the cinobufagin injection group, the difference being significant (P<0.05). Conclusion: Thetherapy of elemene injection combined with TACE for middle and advanced primary hepatic carcinoma has better clinical effect thanthat of cinobufagin injection, but the occ.
文摘Objective:The aim of this study is to observe the clinical effect of hand exercise combined with jinhuang ointment on the prevention of phlebitis due to cinobufagin.Methods:A total of 90 cancer patients who have been receiving intravenous(Ⅳ)infusion of cinobufagin from May 2018 to June 2019 in the oncology department of our hospital were selected.They were then divided into three groups in a random manner,which include 30 cases in the control group,30 cases in the jinhuang ointment group,and 30 cases in the group of hand exercise combined with jinhuang ointment.The control group had a routine care before cinobufagin was infused from the first day of hospitalization.During the routine care mentioned previously,the jinhuang ointment group was given locally jinhuang ointment inunction,qd,and kept for 6 hours.Hand exercises were then done on the combined group excluding jinhuang ointment application,qd,at 10min.After treatment for 1 week,the phlebitis and pain incidences on the venipuncture site were then compared between the three groups.Results:After the 1-week treatment,the incidences of grade Ⅰ/Ⅱ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 53.5%,23.3%,and 10%,respectively.The results have shown a significant decrease in the jinhuang ointment group and the combined group as in comparison with the control group(P=0.0169,P=0.0003).Even with the incidence of the combined group being lower than that of the jinhuang ointment group,no statistically significant difference(P=0.1659)was found.The incidences of grade Ⅲ/Ⅳ phlebitis in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 23.3%,3.3%,and 3.3%,respectively.Both the jinhuang ointment group and the combined group had significantly lower results than that of the control group(P=0.0003,P=0.0227).There was no difference in the results of the combined group and the jinhuang ointment group.The incidences of pain in the control group,the jinhuang ointment group,and the group of hand exercise combined with jinhuang ointment were 56.7%,36.7%,and 20%,respectively.There was no significant difference in the results of the jinhuang ointment group and the control group(P=0.1205);the combined group has shown a significant decrease in the incidence compared with the control group(P=0.0035);the incidence of pain in the combined group was lower than that of the jinhuang ointment group,but without a statistical difference(P=0.1520).Conclusion:Hand exercise together with jinhuang ointment inunction can significantly reduce the incidence of phlebitis produced by cinobufagin.
基金Supported by the National Natural Science Foundation of China(Nos.30772721 and 30873360)
文摘In vitro models of human colon carcinoma cell line(Caco-2 cell monolayer) and human intestinal bacteria were used to investigate the intestinal transport and biotransformation of resibufogenin and cinobufagin in Chan Su by HPLC/APCI-MSn. The experimental results of Caco-2 cell monolayer demonstrate that the apparent permeability coefficients(Papp) of resibufogenin and cinobufagin are higher than 10-6 cm/s, which indicates that both resibufogenin and cinobufagin have a good absorption in the small intestine. And the biotransformation result of human intestinal bacteria shows that resibufogenin has been transformed to 3-epiresibufogenin and cinobufagin has been transformed to 3-epicinobufagin, deacetylcinobufagin and 3-epideacetycinobufagin, respectively.
基金supported by the National Natural Science Foundation of China(81102518)
文摘The title compound cinobufagin 3-hemisuberate methyl ester(1) was isolated from the venom of Bufo bufo gargarizans CANTOR. The crystal structure of 1, C35H48O9, was determined by single-crystal X-ray diffraction analysis. It belongs to orthorhombic, space group P212121 with a = 8.9338(3), b = 16.2970(4), c = 22.4019(6) , V = 3261.59(16) 3, Mr = 612.73, Z = 4, Dc = 1.248 g/cm3, μ = 0.725 mm-1, F(000) = 1320, S = 1.040, the final R = 0.0374 and wR = 0.0412 for 4458 unique reflections, of which 4088 were observed(I > 2σ(I)). In the solid state, short intermolecular C-H...O interactions involving a methine and the ester carbonyl group in cinobufagin moiety and a methyl in the suberate moiety linked adjacent molecules into a three-dimensional network. Detailed analysis of the 1H-NMR data showed that X-ray structure of 1 would be expected to closely resemble the solution conformation in chloroform. Compound 1 was inactive for the inhibition of PC3 and HepG2 cancer cells, but the parent compound cinobufagin showed potent inhibition with IC50 values of 0.145 and 5.48 μM, respectively, indicating that esterification at C(3) decreased the cytotoxic effect of 1.
基金Supported by the National Natural Science Foundation of China（No.81573315）, the Guangdong Natural Science Fund, China（No.2015A030313313） and the Guangzhou Industry-University Collaborative Innovation Major Projects, China（No. 201508030016）.
