Cancer is considered a leading cause of death worldwide due to its high morbidity and mortality rate.Conventional treatments for cancer therapy,such as chemotherapy,and radiotherapy,have been hampered by their side ef...Cancer is considered a leading cause of death worldwide due to its high morbidity and mortality rate.Conventional treatments for cancer therapy,such as chemotherapy,and radiotherapy,have been hampered by their side effects.Natural product-derived plants have been used for decades to treat diseases.Compared to conventional therapy,natural product has the potential to be effective against cancer with fewer side effects.This current review discussed the potential of scopoletin,a coumarin present in many edible plants,which elicits anticancer properties through multiple mechanisms,including modulating cell cycle arrest,inducing apoptosis,and regulating multiple signaling pathways.Understanding these mechanisms highlights the potential of scopoletin as a candidate for chemoprevention and chemotherapy.展开更多
Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lin...Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.展开更多
Objective:To explore the effects of arteannuin B,arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice.Methods:Artemisinin and a combination of artemisinin,arteannuin B,arteannuic acid and scop...Objective:To explore the effects of arteannuin B,arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice.Methods:Artemisinin and a combination of artemisinin,arteannuin B,arteannuic acid and scopoletin were administered together to mice via oral administration.Blood samples were collected at different time intervals and pretreated by liquid-liquid extraction.The contents of four compounds in mouse plasma were determined by a validated HPLC-MS/MS method.Results:Compared to single artemisinin group,the C_(max) values from the combination group rose from 947 ng/mL to 1 254 ng/mL.AUC_((0-t))(2 371 h·ng/mL) was significantly higher than that from single artemisinin group(747 h·ng/mL).The peak time lag and the CL values reduced at a proportion of 66%.Conclusions:Arteannuin B,arteannuic acid and scopoletin can markedly affect the pharmacokinetics of artemisinin.展开更多
[Objectives] This study was conducted to investigate the effect of scopoletin on the growth of breast cancer cell lines.[Methods] Cell culture,light microscopy and MTT assay for measuring cell viability were used to c...[Objectives] This study was conducted to investigate the effect of scopoletin on the growth of breast cancer cell lines.[Methods] Cell culture,light microscopy and MTT assay for measuring cell viability were used to compare the inhibition of different concentrations of scopoletin to breast cancer cells,so as to provide an experimental basis for finding new therapeutic drugs for breast cancer cells.[Results] It was shown that a high concentration of scopoletin can inhibit the growth of breast cancer cells and promote apoptosis.[Conclusions] Scopoletin can be used as a potential drug for the treatment of breast cancer.展开更多
[Objectives]This study was conducted to investigate the effect of scopoletin on the proliferation of breast cancer cell lines.[Methods]Cell viability,gene expression and cell cycle were measured by cell culture,RT-PCR...[Objectives]This study was conducted to investigate the effect of scopoletin on the proliferation of breast cancer cell lines.[Methods]Cell viability,gene expression and cell cycle were measured by cell culture,RT-PCR and flow cytometry.The effects of different concentrations of scopoletin on proliferation and cell cycle of breast cancer cells were compared.[Results]After a certain period of time,the breast cancer cells showed different degrees of apoptosis,and the growth cycle was arrested in the G1 phase,which promoted the down-regulation of three genes in breast cancer metastasis.[Conclusions]The study proves that scopoletin inhibits the proliferation and metastasis of breast cancer cells in a concentration-and time-dependent manner.展开更多
Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the enc...Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics,but the biological function and molecular basis of these phenomena are not fully understood.The promiscuous monolignol/phytoalexin glycosyltransferase NbUGT72AY1 exhibits substrate inhibition(Ki)at 4 mM scopoletin,whereas the highly homologous monolignol StUGT72AY2 is inhibited at 190 mM.We therefore used hydrogen/deuterium exchange mass spectrometry and structure-based mutational analyses of both proteins and introduced NbUGT72AY1 residues into StUGT72AY2 and vice versa to study promiscuity and substrate inhibition of UGTs.A single F87I and chimeric mutant of NbUGT72AY1 showed significantly reducedscopoletin substrate inhibition,whereas its monolignolgly cosylation activity was almost unaffected.Reverse mutations in StUGT72AY2 resulted in increased scopoletin glycosylation,leading to enhanced promiscuity,which was accompanied by substrate inhibition.Studies of 3D structures identified open and closed UGT conformers,allowing visualization of the dynamics of conformational changes that occur during catalysis.Previously postulated substrate access tunnels likely serve as drainage channels.The results suggest a two-site model in which the second substrate molecule binds near the catalytic site and blocks product release.Mutational studies showed that minor changes in amino acid sequence can enhance the promiscuity of the enzyme and add new capabilities such as substrate inhibition without affecting existing functions.The proposed subfunctionalization mechanism of expanded promiscuity may play a role in enzyme evolution and highlights the importance of promiscuous enzymes in providing new functions.展开更多
Artemisia annua （Asteraceae） is well known for its antimalarial activities due to presence of the compound artemisinin. We isolated a methoxy coumarin from the stem part of A. annua and confirmed its identity as sco...Artemisia annua （Asteraceae） is well known for its antimalarial activities due to presence of the compound artemisinin. We isolated a methoxy coumarin from the stem part of A. annua and confirmed its identity as scopoletin through mass spectral data. The structure was established from 1H-nuclear magnetic resonance （NMR）, 13C-NMR. The compound scopoletin was evaluated for its feeding deterrence and growth inhibitory potential against a noxious lepidopteran insect, Spilartctia obliqua Walker. Scopoletin gave FD50（feeding deterrence of 50%） value of 96.7 μg/g diet when mixed into artificial diet. S. obliqua larvae （12-day-old） exposed to the highest concentration （250μg/g diet） of scopoletin showed 77.1% feeding-deterrence. In a growth inhibitory assay, scopoletin provided 116.9% growth inhibition at the highest dose of 250μg/g diet with a GI50 （growth inhibition of 50%） value of 20.9μg/g diet. Statistical analysis showed a concentrationdependent dose response relationship toward both feeding deterrent and growth inhibitory activities. Artemisinin is found mainly in the leaves of A. annua and not in the stems, which are typically discarded as waste. Therefore identification of scopoletin in stems of A. annua may be important as a source of this material for pest control.展开更多
Objective:The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L.fruit juices and their cytotoxicity.Materials and Methods:Noni fruit juices were prepared by different...Objective:The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L.fruit juices and their cytotoxicity.Materials and Methods:Noni fruit juices were prepared by different treatments:unripe(T1),ripe(T2),purchased(T3),and Noni juices fermented with Lactobacillus plantarum(T4).These extracts were tested for Nrf2 activation and nuclear factor kappa B(NF-κB)inhibition activities.These active extracts were further studied for their nuclear Nrf2 translocation and induction of HO-1 protein expression.Finally,the active extracts were purified using open column chromatography and RP-high pressure liquid chromatography(HPLC)techniques through bioassay-guided separation.Moreover,all Noni juice samples were tested for cytotoxicity using mammalian cell-based methylthiazoltetrazolium(MTT)assay.Results:Only purchased(T3)and ripe Noni fruit juices fermented with LP at 22℃(T4–22)showed strongest Nrf2 activation and NF-κB inhibitory activity.Further,these two extracts enhanced the nuclear accumulation of Nrf2 after 2 h and also promoted Nrf2 and HO-1 nuclear translocation.Induction of HO-1 gene expression of Hep G2/ARE cells treated with T3 confirmed that it is a potent inducer of the Nrf2 target gene HO-1.Bioassay-guided separation resulted in subfractions with high Nrf2 activity.The strongest Nrf2 active subfraction led to the identification of scopoletin as an Nrf2 activator.Moreover,none of the tested samples showed any cytotoxicity for the MTT assay.Conclusions:The presence of potential Nrf2 activators in the Noni fruit juices that were nontoxic in our MTT assay could mitigate the production of harmful reactive species in the biological systems,and thereby,could helpful in alleviating and prevention of chronic diseases.展开更多
Background:Chinese Danggui(Angelica sinensis)and Japanese Danggui(Angelica acutiloba)are evaluated as the same in using and critical of quality control in Vietnamese Pharmacopoeia.In Vietnam,Japanese Danggui were accl...Background:Chinese Danggui(Angelica sinensis)and Japanese Danggui(Angelica acutiloba)are evaluated as the same in using and critical of quality control in Vietnamese Pharmacopoeia.In Vietnam,Japanese Danggui were acclimatized and cultivated in several regions in recent years.Despite the huge climatic difference between Vietnam and Japan,Japanese Danggui grows very well in Vietnam.However,there are no studies to assess the overall quality of this medicinal herbs.Aims and Objectives:The aim of this study is to develop a method to identify and assay simultaneously 5 component compounds of these crude herbs:chlorogenic acid,ferulic acid,scopoletin,xanthotoxin and ligustilide by high-performance liquid chromatography with photodiode array detector(HPLC-PDA).Materials and Methods:The procedure was optimized by using column Phenomenex Gemini 5μm PR C18,15 x 4,6 mm with the detection wavelength set at 321 nm for detector PDA and mobile phase was composed of(A)ACN and(B)aqueous solution 1%of acid acetic using a gradient elution.Analytes were performed at 30°C with a flow rate of 1.0 mL/min.Results:The developped method were fully validated for linearity,accuracy,recovery and met the validation requirements,proved practical applicability for the quality control of these herbs and related products.Conclusion:The method was successfully applied to the quantification of five markers simultaneously from collected samples.展开更多
文摘Cancer is considered a leading cause of death worldwide due to its high morbidity and mortality rate.Conventional treatments for cancer therapy,such as chemotherapy,and radiotherapy,have been hampered by their side effects.Natural product-derived plants have been used for decades to treat diseases.Compared to conventional therapy,natural product has the potential to be effective against cancer with fewer side effects.This current review discussed the potential of scopoletin,a coumarin present in many edible plants,which elicits anticancer properties through multiple mechanisms,including modulating cell cycle arrest,inducing apoptosis,and regulating multiple signaling pathways.Understanding these mechanisms highlights the potential of scopoletin as a candidate for chemoprevention and chemotherapy.
文摘Artemisinin,a constituent of Artemisia annua L.,is a well-known antimalarial drug.Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo.Herbal extracts of A.annua inhibit the growth of cancer cell lines.Here,we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma.The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A.annua.One cat and one dog with fibrosarcoma survived 40 and 37 months,respectively,without tumor relapse.Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months,respectively.A.annua was well tolerated without noticeable side effects.These four cases indicate that A.annua may be a promising herbal drug for cancer therapy.
基金supported by the National Natural Science Foundation of China (No.81573682 and No.81102752)the Beijing Natural Science Foundation (No.2112010)
文摘Objective:To explore the effects of arteannuin B,arteannuic acid and scopoletin on the pharmacokinetics of artemisinin in mice.Methods:Artemisinin and a combination of artemisinin,arteannuin B,arteannuic acid and scopoletin were administered together to mice via oral administration.Blood samples were collected at different time intervals and pretreated by liquid-liquid extraction.The contents of four compounds in mouse plasma were determined by a validated HPLC-MS/MS method.Results:Compared to single artemisinin group,the C_(max) values from the combination group rose from 947 ng/mL to 1 254 ng/mL.AUC_((0-t))(2 371 h·ng/mL) was significantly higher than that from single artemisinin group(747 h·ng/mL).The peak time lag and the CL values reduced at a proportion of 66%.Conclusions:Arteannuin B,arteannuic acid and scopoletin can markedly affect the pharmacokinetics of artemisinin.
基金Supported by Education Department of Sichuan Province(14ZA0152)Health Department of Sichuan Province(130279)
文摘[Objectives] This study was conducted to investigate the effect of scopoletin on the growth of breast cancer cell lines.[Methods] Cell culture,light microscopy and MTT assay for measuring cell viability were used to compare the inhibition of different concentrations of scopoletin to breast cancer cells,so as to provide an experimental basis for finding new therapeutic drugs for breast cancer cells.[Results] It was shown that a high concentration of scopoletin can inhibit the growth of breast cancer cells and promote apoptosis.[Conclusions] Scopoletin can be used as a potential drug for the treatment of breast cancer.
基金Supported by Education Department of Sichuan Province(14ZA0152)Health Department of Sichuan Province(130279)
文摘[Objectives]This study was conducted to investigate the effect of scopoletin on the proliferation of breast cancer cell lines.[Methods]Cell viability,gene expression and cell cycle were measured by cell culture,RT-PCR and flow cytometry.The effects of different concentrations of scopoletin on proliferation and cell cycle of breast cancer cells were compared.[Results]After a certain period of time,the breast cancer cells showed different degrees of apoptosis,and the growth cycle was arrested in the G1 phase,which promoted the down-regulation of three genes in breast cancer metastasis.[Conclusions]The study proves that scopoletin inhibits the proliferation and metastasis of breast cancer cells in a concentration-and time-dependent manner.
文摘Uridine diphosphate-dependent glycosyltransferases(UGTs)mediate the glycosylation of plant metabolites,thereby altering their physicochemical properties and bioactivities.Plants possess numerous UGT genes,with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics,but the biological function and molecular basis of these phenomena are not fully understood.The promiscuous monolignol/phytoalexin glycosyltransferase NbUGT72AY1 exhibits substrate inhibition(Ki)at 4 mM scopoletin,whereas the highly homologous monolignol StUGT72AY2 is inhibited at 190 mM.We therefore used hydrogen/deuterium exchange mass spectrometry and structure-based mutational analyses of both proteins and introduced NbUGT72AY1 residues into StUGT72AY2 and vice versa to study promiscuity and substrate inhibition of UGTs.A single F87I and chimeric mutant of NbUGT72AY1 showed significantly reducedscopoletin substrate inhibition,whereas its monolignolgly cosylation activity was almost unaffected.Reverse mutations in StUGT72AY2 resulted in increased scopoletin glycosylation,leading to enhanced promiscuity,which was accompanied by substrate inhibition.Studies of 3D structures identified open and closed UGT conformers,allowing visualization of the dynamics of conformational changes that occur during catalysis.Previously postulated substrate access tunnels likely serve as drainage channels.The results suggest a two-site model in which the second substrate molecule binds near the catalytic site and blocks product release.Mutational studies showed that minor changes in amino acid sequence can enhance the promiscuity of the enzyme and add new capabilities such as substrate inhibition without affecting existing functions.The proposed subfunctionalization mechanism of expanded promiscuity may play a role in enzyme evolution and highlights the importance of promiscuous enzymes in providing new functions.
文摘Artemisia annua （Asteraceae） is well known for its antimalarial activities due to presence of the compound artemisinin. We isolated a methoxy coumarin from the stem part of A. annua and confirmed its identity as scopoletin through mass spectral data. The structure was established from 1H-nuclear magnetic resonance （NMR）, 13C-NMR. The compound scopoletin was evaluated for its feeding deterrence and growth inhibitory potential against a noxious lepidopteran insect, Spilartctia obliqua Walker. Scopoletin gave FD50（feeding deterrence of 50%） value of 96.7 μg/g diet when mixed into artificial diet. S. obliqua larvae （12-day-old） exposed to the highest concentration （250μg/g diet） of scopoletin showed 77.1% feeding-deterrence. In a growth inhibitory assay, scopoletin provided 116.9% growth inhibition at the highest dose of 250μg/g diet with a GI50 （growth inhibition of 50%） value of 20.9μg/g diet. Statistical analysis showed a concentrationdependent dose response relationship toward both feeding deterrent and growth inhibitory activities. Artemisinin is found mainly in the leaves of A. annua and not in the stems, which are typically discarded as waste. Therefore identification of scopoletin in stems of A. annua may be important as a source of this material for pest control.
文摘Objective:The objective of the study was to identify Nrf2 activators from differently treated Morinda citrifolia L.fruit juices and their cytotoxicity.Materials and Methods:Noni fruit juices were prepared by different treatments:unripe(T1),ripe(T2),purchased(T3),and Noni juices fermented with Lactobacillus plantarum(T4).These extracts were tested for Nrf2 activation and nuclear factor kappa B(NF-κB)inhibition activities.These active extracts were further studied for their nuclear Nrf2 translocation and induction of HO-1 protein expression.Finally,the active extracts were purified using open column chromatography and RP-high pressure liquid chromatography(HPLC)techniques through bioassay-guided separation.Moreover,all Noni juice samples were tested for cytotoxicity using mammalian cell-based methylthiazoltetrazolium(MTT)assay.Results:Only purchased(T3)and ripe Noni fruit juices fermented with LP at 22℃(T4–22)showed strongest Nrf2 activation and NF-κB inhibitory activity.Further,these two extracts enhanced the nuclear accumulation of Nrf2 after 2 h and also promoted Nrf2 and HO-1 nuclear translocation.Induction of HO-1 gene expression of Hep G2/ARE cells treated with T3 confirmed that it is a potent inducer of the Nrf2 target gene HO-1.Bioassay-guided separation resulted in subfractions with high Nrf2 activity.The strongest Nrf2 active subfraction led to the identification of scopoletin as an Nrf2 activator.Moreover,none of the tested samples showed any cytotoxicity for the MTT assay.Conclusions:The presence of potential Nrf2 activators in the Noni fruit juices that were nontoxic in our MTT assay could mitigate the production of harmful reactive species in the biological systems,and thereby,could helpful in alleviating and prevention of chronic diseases.
文摘Background:Chinese Danggui(Angelica sinensis)and Japanese Danggui(Angelica acutiloba)are evaluated as the same in using and critical of quality control in Vietnamese Pharmacopoeia.In Vietnam,Japanese Danggui were acclimatized and cultivated in several regions in recent years.Despite the huge climatic difference between Vietnam and Japan,Japanese Danggui grows very well in Vietnam.However,there are no studies to assess the overall quality of this medicinal herbs.Aims and Objectives:The aim of this study is to develop a method to identify and assay simultaneously 5 component compounds of these crude herbs:chlorogenic acid,ferulic acid,scopoletin,xanthotoxin and ligustilide by high-performance liquid chromatography with photodiode array detector(HPLC-PDA).Materials and Methods:The procedure was optimized by using column Phenomenex Gemini 5μm PR C18,15 x 4,6 mm with the detection wavelength set at 321 nm for detector PDA and mobile phase was composed of(A)ACN and(B)aqueous solution 1%of acid acetic using a gradient elution.Analytes were performed at 30°C with a flow rate of 1.0 mL/min.Results:The developped method were fully validated for linearity,accuracy,recovery and met the validation requirements,proved practical applicability for the quality control of these herbs and related products.Conclusion:The method was successfully applied to the quantification of five markers simultaneously from collected samples.
