Wogonin possesses potent inhibitory activities against cancer cell growth in vitro and in vivo and has attractive safety profiles.A highly sensitive liquid chromatography coupled with tandem mass spectrometry method w...Wogonin possesses potent inhibitory activities against cancer cell growth in vitro and in vivo and has attractive safety profiles.A highly sensitive liquid chromatography coupled with tandem mass spectrometry method was developed for the identification of major metabolites in mice liver after intravenous administration of wogonin.Five metabolites were identified and biotransformation pathways were elucidated as well.Furthermore,a method was developed and validated for the simultaneous quantitatively determination of wogonin and wogonin-7-O-glucuronide in mice liver.After liquid-liquid extraction by ethyl acetate,the analytes were separated on a C_（18）column with a mobile phase of methanol-10 mM ammonium acetate water （80：20,v/v）.The detection was operated with negative selected reaction monitoring mode using electrospray ionization technique. The linear response range was 0.2-40μg/g for both wogonin and wogonin-7-O-glucuronide in mice liver.The developed quantification method was suitable for distribution study after intravenous infusion of wogonin injection in animals.展开更多
Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis(Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerou...Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis(Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anticancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt(also known as protein kinase B) and AMP-activated protein kinase(AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity. Furthermore, wogonin also decreases DNA adduct formation with a carcinogenic compound 2-Aminofluorene and inhibits growth of drug resistant malignant cells and their migration and metastasis, without any side effects. Recently, newly synthesized wogonin derivatives have been developed with impressive anti-tumor activity. This review is the succinct appraisal of the pertinent articles on the mechanisms of anti-tumor properties of wogonin. We also summarize the potential of wogonin and its derivatives used alone or as an adjunct therapy for cancer treatment. Furthermore, pharmacokinetics and side effects of wogonin and its analogues have also been discussed.展开更多
Objective：To investigate the synergistic inhibitory effects of wogonin （WOG） and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts.Methods：The IC50 values of WOG,cisplatin （CDDP） and ...Objective：To investigate the synergistic inhibitory effects of wogonin （WOG） and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts.Methods：The IC50 values of WOG,cisplatin （CDDP） and paclitaxel （PTX） in four gastric cancer cell lines were determined by MTS assay.Hoechst staining and the median effect method of Chou-Talalay were used to assess the apoptosis of cells and the interaction of two drugs,respectively.BGC-823-derived xenografts in nude mice were established to investigate the effects of WOG combined with chemotherapeutic drugs in vivo.Results：WOG,CDDP and PTX inhibited the growth of BGC-823,MGC-803,MKN-45 and HGC-27 gastric cancer cells in a dose-dependent manner.WOG combined with CDDP or PTX synergistically inhibited the growth of all gastric cancer cell lines in vitro.In BGC-823,MGC-803,HGC-27 and MKN-45 cell lines,synergisms between WOG and PTX were shown when the fraction affected （Fa） values were ＜0.45,＜0.90,＜0.85 and ＜0.60.While WOG and CDDP had a synergistic inhibitory.effect when the Fa values were ＞0,＞0,＞0.65 and ＞0.10.From the results of in vivo experiments using tumor xenografts,WOG and low-dose PTX showed better efficacy than either drug alone.The inhibitory percentages of tumor weight were 61.58％,20.29％,and 22.28％ for the combination,WOG-alone,and low-dose PTX-alone groups,respectively.Notably,WOG combined with CDDP displayed very high toxicity.Conclusions：A synergistic inhibitory effect on growth was observed when WOG was combined with low-dose PTX in gastric cancer cells and tumor xenografts.These findings provide evidence for the design of a clinical trial to test the combination of WOG with low-dose PTX in human gastric cancer.展开更多
The in vitro effects of baicalein,wogonin,baicalin and Na_2MoO_4 on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of dimethylnitrosamine(DMN) and diethylnitrosa...The in vitro effects of baicalein,wogonin,baicalin and Na_2MoO_4 on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of dimethylnitrosamine(DMN) and diethylnitrosamine(DEN) produced using the UV-photclysis spectrophotometric and pyrolysis gas chromatography test. Baicalein,wogonin and Na_2MoO_4 showed varing extents of inhibition of the formation of DMN and DEN. Baicalin promoted the formation of DMN and DEN under the condition of simulating gastric Juices. It is also found that E. coli showed a remarkable promoting effect on the formation of DMN and DEN,but this promoting effect could be blocked to some extent by baicalein,wogonin,baicalin and Na_2MoO_4. Besides, Na_2MoO_4 and wogonin have shown synergic effect on the blocking of N-nitrosation reaction.展开更多
Background： Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles （MNPs） to increase water solubility of the drug...Background： Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles （MNPs） to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 （Wog-MNPs-Fe3O4） as an antileukemia agent. Methods： After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium （MTT） assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer （FCM） assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction （RT-PCR）. Results： With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group （28.64–68.36%） were significantly lower than those of the wogonin group （35.53–97.28%） in a dose-dependent manner in 48 h （P 〈 0.001）. The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4group （34.28%） compared with that in 50 μmol/L wogonin group （23.46%; P〈 0.001）. Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4groups （all P〈 0.001）. The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group （all P〈 0.001）. Conclusions： This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.展开更多
Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle’s dogs.Met...Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle’s dogs.Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples.The lower limit of quantification was 0.105 μg/L.Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride.In a randomized,self-control,and cross-over study,six male Beagle’s dogs were treated with different administration methods in three test periods.Pharmacokinetic parameters were calculated with DAS software(Ver.2.0).Results The calibration curve was linear in the range of 0.105-107.36 μg/L for wogonin in dog plasma samples.The main pharmacokinetic parameters of ig administration(native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows:Cmax(2.5 ± 1.1),(7.9 ± 3.3),and(6838.7 ± 1322.1) μg/L,tmax(0.7 ± 0.3) and(0.3 ± 0.2) h for the both former,AUC0-t(7.1 ± 2.0),(21.0 ± 3.2),and(629.7 ± 111.8) μg.h/L.The absolute bioavailability of native and solution of wogonin were(0.59 ± 0.35)% and(3.65 ± 2.00)%,respectively.Conclusion The validated method is convenient,sensitive,and specific,and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.展开更多
Wogonin(WOG)has been demonstrated to have anti-cancer activity,but the mechanisms remain unclear.In this study,new targets of WOG were predicted for lung cancer,bladder cancer,and colon cancer by using bioinformatics ...Wogonin(WOG)has been demonstrated to have anti-cancer activity,but the mechanisms remain unclear.In this study,new targets of WOG were predicted for lung cancer,bladder cancer,and colon cancer by using bioinformatics methods.wOG might primarily suppress cancers via regulating arachidonic acid,Ras,MAPK,linoleic acid,PI3K Akt,and folate biosynthesis pathways.3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)assay showed that WOG inhibited the proliferation of A549 cells.Real-time quantitative reverse transcription PCR(RT-qPCR)results indicated that anti-lung cancer effect of WOG was achieved by regulating the expression of 18 target genes,including AKRIBI0,AKRIC3,BDNF,CAVI,CXCL2,CYP2B6,CYP4F3,DAO,EGF,ENO3,IL6,PLA2GlB,PLA2G2F,PLA2G4A,PTGES,SLCOIBI,SLCOIB3,and TFAP2A.The Kaplan-Meier survival curves further confirmed that DAO,PLA2G1B,SLCO1B3 and TFAP2A were essential targets via which WOG affected lung cancer survival.Moreover,BDNF,FGF2,and PTGS1 were predicted to be the targets via which WOG alleviated cancer proliferation and invasion in bladder cancer.As for colon cancer,WOG might induce autophagy and inhibit proliferation by down-regulating NTF4 and TH.The study will provide clue for using wOG as a promising antineoplastic agent in basic and translational research,and bring light to the application of herbs containing WOG as food supplements.展开更多
基金China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs(Grant No.2009zx09102-032).
文摘Wogonin possesses potent inhibitory activities against cancer cell growth in vitro and in vivo and has attractive safety profiles.A highly sensitive liquid chromatography coupled with tandem mass spectrometry method was developed for the identification of major metabolites in mice liver after intravenous administration of wogonin.Five metabolites were identified and biotransformation pathways were elucidated as well.Furthermore,a method was developed and validated for the simultaneous quantitatively determination of wogonin and wogonin-7-O-glucuronide in mice liver.After liquid-liquid extraction by ethyl acetate,the analytes were separated on a C_（18）column with a mobile phase of methanol-10 mM ammonium acetate water （80：20,v/v）.The detection was operated with negative selected reaction monitoring mode using electrospray ionization technique. The linear response range was 0.2-40μg/g for both wogonin and wogonin-7-O-glucuronide in mice liver.The developed quantification method was suitable for distribution study after intravenous infusion of wogonin injection in animals.
基金supported by the 2015 scientific promotion program funded by Jeju National University
文摘Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis(Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anticancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt(also known as protein kinase B) and AMP-activated protein kinase(AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity. Furthermore, wogonin also decreases DNA adduct formation with a carcinogenic compound 2-Aminofluorene and inhibits growth of drug resistant malignant cells and their migration and metastasis, without any side effects. Recently, newly synthesized wogonin derivatives have been developed with impressive anti-tumor activity. This review is the succinct appraisal of the pertinent articles on the mechanisms of anti-tumor properties of wogonin. We also summarize the potential of wogonin and its derivatives used alone or as an adjunct therapy for cancer treatment. Furthermore, pharmacokinetics and side effects of wogonin and its analogues have also been discussed.
文摘Objective：To investigate the synergistic inhibitory effects of wogonin （WOG） and chemotherapeutic drugs on growth of gastric cancer cells and tumor xenografts.Methods：The IC50 values of WOG,cisplatin （CDDP） and paclitaxel （PTX） in four gastric cancer cell lines were determined by MTS assay.Hoechst staining and the median effect method of Chou-Talalay were used to assess the apoptosis of cells and the interaction of two drugs,respectively.BGC-823-derived xenografts in nude mice were established to investigate the effects of WOG combined with chemotherapeutic drugs in vivo.Results：WOG,CDDP and PTX inhibited the growth of BGC-823,MGC-803,MKN-45 and HGC-27 gastric cancer cells in a dose-dependent manner.WOG combined with CDDP or PTX synergistically inhibited the growth of all gastric cancer cell lines in vitro.In BGC-823,MGC-803,HGC-27 and MKN-45 cell lines,synergisms between WOG and PTX were shown when the fraction affected （Fa） values were ＜0.45,＜0.90,＜0.85 and ＜0.60.While WOG and CDDP had a synergistic inhibitory.effect when the Fa values were ＞0,＞0,＞0.65 and ＞0.10.From the results of in vivo experiments using tumor xenografts,WOG and low-dose PTX showed better efficacy than either drug alone.The inhibitory percentages of tumor weight were 61.58％,20.29％,and 22.28％ for the combination,WOG-alone,and low-dose PTX-alone groups,respectively.Notably,WOG combined with CDDP displayed very high toxicity.Conclusions：A synergistic inhibitory effect on growth was observed when WOG was combined with low-dose PTX in gastric cancer cells and tumor xenografts.These findings provide evidence for the design of a clinical trial to test the combination of WOG with low-dose PTX in human gastric cancer.
文摘The in vitro effects of baicalein,wogonin,baicalin and Na_2MoO_4 on N-nitrosation reaction have been studied. The N-nitrosation reaction has been determined by the amount of dimethylnitrosamine(DMN) and diethylnitrosamine(DEN) produced using the UV-photclysis spectrophotometric and pyrolysis gas chromatography test. Baicalein,wogonin and Na_2MoO_4 showed varing extents of inhibition of the formation of DMN and DEN. Baicalin promoted the formation of DMN and DEN under the condition of simulating gastric Juices. It is also found that E. coli showed a remarkable promoting effect on the formation of DMN and DEN,but this promoting effect could be blocked to some extent by baicalein,wogonin,baicalin and Na_2MoO_4. Besides, Na_2MoO_4 and wogonin have shown synergic effect on the blocking of N-nitrosation reaction.
文摘Background： Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles （MNPs） to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 （Wog-MNPs-Fe3O4） as an antileukemia agent. Methods： After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium （MTT） assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer （FCM） assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction （RT-PCR）. Results： With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group （28.64–68.36%） were significantly lower than those of the wogonin group （35.53–97.28%） in a dose-dependent manner in 48 h （P 〈 0.001）. The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4group （34.28%） compared with that in 50 μmol/L wogonin group （23.46%; P〈 0.001）. Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4groups （all P〈 0.001）. The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group （all P〈 0.001）. Conclusions： This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.
基金the Colleges and Universities Natural Science Foundation of Anhui Province (KJ2009B216Z)
文摘Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle’s dogs.Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples.The lower limit of quantification was 0.105 μg/L.Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride.In a randomized,self-control,and cross-over study,six male Beagle’s dogs were treated with different administration methods in three test periods.Pharmacokinetic parameters were calculated with DAS software(Ver.2.0).Results The calibration curve was linear in the range of 0.105-107.36 μg/L for wogonin in dog plasma samples.The main pharmacokinetic parameters of ig administration(native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows:Cmax(2.5 ± 1.1),(7.9 ± 3.3),and(6838.7 ± 1322.1) μg/L,tmax(0.7 ± 0.3) and(0.3 ± 0.2) h for the both former,AUC0-t(7.1 ± 2.0),(21.0 ± 3.2),and(629.7 ± 111.8) μg.h/L.The absolute bioavailability of native and solution of wogonin were(0.59 ± 0.35)% and(3.65 ± 2.00)%,respectively.Conclusion The validated method is convenient,sensitive,and specific,and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.
基金supported by the Fundamental Research Funds for the Central Universities(3332022085,3332022083,3332022084)the National Natural Science Foundation of China(82204720)。
文摘Wogonin(WOG)has been demonstrated to have anti-cancer activity,but the mechanisms remain unclear.In this study,new targets of WOG were predicted for lung cancer,bladder cancer,and colon cancer by using bioinformatics methods.wOG might primarily suppress cancers via regulating arachidonic acid,Ras,MAPK,linoleic acid,PI3K Akt,and folate biosynthesis pathways.3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)assay showed that WOG inhibited the proliferation of A549 cells.Real-time quantitative reverse transcription PCR(RT-qPCR)results indicated that anti-lung cancer effect of WOG was achieved by regulating the expression of 18 target genes,including AKRIBI0,AKRIC3,BDNF,CAVI,CXCL2,CYP2B6,CYP4F3,DAO,EGF,ENO3,IL6,PLA2GlB,PLA2G2F,PLA2G4A,PTGES,SLCOIBI,SLCOIB3,and TFAP2A.The Kaplan-Meier survival curves further confirmed that DAO,PLA2G1B,SLCO1B3 and TFAP2A were essential targets via which WOG affected lung cancer survival.Moreover,BDNF,FGF2,and PTGS1 were predicted to be the targets via which WOG alleviated cancer proliferation and invasion in bladder cancer.As for colon cancer,WOG might induce autophagy and inhibit proliferation by down-regulating NTF4 and TH.The study will provide clue for using wOG as a promising antineoplastic agent in basic and translational research,and bring light to the application of herbs containing WOG as food supplements.
