As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination ...As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination of the major alkaloids in U.rhynchophylla.In this research,a rapid quantitative analysis involving multi-components analysis by a single marker strategy coupled with core-shell column HPLC was adopted to analyse four alkaloids(corynoxeine,isocorynoxeine,isorhynchophylline,rhynchophylline)in U.rhynchophylla.Isorhynchophylline was selected as the internal reference substance,the content of which was determined by the traditional external standard method.Relative correction factors(RCF)between isorhynchophylline and the other three alkaloids were calculated respectively.The results showed that the QAMS method had good robustness under different HPLC instruments.Nineteen batches of U.rhynchophylla were tested.No significant difference was observed between the results by QAMS and EMS(Correlation coefficient>0.99,p>0.05).The QAMS method could be employed as a rapid,effective technique for the quality control of U.rhynchophylla.展开更多
Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological a...Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.展开更多
Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhyncho...Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhynchophylla were intensively reported.In current work,three new indole alkaloids(1–3),identified as geissoschizic acid(1),geissoschizic acid N4-oxide(2),and 3b-sitsirikine N4-oxide(3),as well as 26 known analogues were isolated from U.rhynchophylla.However,in the neural stem cells(NSCs)proliferation assay for all isolated compounds,geissoschizic acid(1),geissoschizic acid N4-oxide(2),isocorynoxeine(6),isorhynchophylline(7),(4S)-akuammigine N-oxide(8),and(4S)-rhynchophylline N-oxide(10)showed unexpected inhibitory activities at 10 μM.Unlike previous neuro-protective reports,as a warning or caution,our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U.rhynchophylla,while the structure–activity relationships of the isolated compounds were discussed also.展开更多
From the hook of Uncaria sinensis, a new alkaloid, isorhynchophyllic acid was isolated and its structure was elucidated by spectral data and chemical reaction.
Uncaria tomentosa presents tomentum that resembles cat’s claws, hence its common name, is a plant that produces various secondary metabolites that are traditionally used in alternative medicine. The natural distribut...Uncaria tomentosa presents tomentum that resembles cat’s claws, hence its common name, is a plant that produces various secondary metabolites that are traditionally used in alternative medicine. The natural distribution of this species has been affected by indiscriminate harvesting from its habitat. In the present research, cryopreservation (liquid nitrogen, LN, -196°C) was evaluated as an option for ex situ conservation of this species. The following techniques were evaluated: vitrification and encapsulation-dehydration of apices, vitrification of cell suspensions, and seed desiccation and vitrification. Preculture conditions and exposure times to LS and PVS2 were evaluated. Apex survival was the highest (82%) with preculture in 0.25 M sucrose followed by incubation for 20 and 30 min in LS and PVS2, respectively, prior to cooling in LN. The encapsulation-dehydration technique was evaluated by using sucrose preculture and different capsule moisture contents. Survival of apices cooled in LN was not significantly different between treatments and varied from 31.8% to 52.9% for capsule moisture contents between 22.7% and 20.3%. For cell suspensions precultured in 0.5 M sucrose, cell multiplication and formation of calli with very good appearance were observed in 61.1% of the cultures following vitrification. For cryopreservation of seeds, germination was 89.5% using the desiccation technique and 67.6% to78.1% using vitrification.展开更多
Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with agin...Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.展开更多
Uncaria rhynchophylla(Gouteng)is a famous traditional Chinese medicine used for psychiatric and hypotensive purposes in China.In this study,the ethyl acetate(EtOAc)part of U.rhynchophylla was revealed with protein tyr...Uncaria rhynchophylla(Gouteng)is a famous traditional Chinese medicine used for psychiatric and hypotensive purposes in China.In this study,the ethyl acetate(EtOAc)part of U.rhynchophylla was revealed with protein tyrosine phosphatase 1B(PTP1B)inhibitory activity.Subsequent investigation on the EtOAc part yielded one new triterpenoid,3β-formyloxy-6β,19α-dihydroxyurs-12-en-28-oic acid(1)and four known ones,3β,6β,19α-trihydroxyurs-12-en-28-oic acid(2),2-oxopomolic acid(3),3β,19α-dihydroxy-6-oxo-olean-12-en-28-oic acid(4)and sumaresinolic acid(5).The structure of compound 1 was determined by extensive HRESIMS,IR,1D and 2D NMR spectroscopic analyses.Two ursane-type triterpenoids(2 and 3)showed selective inhibition on PTP1B with IC50 values of 48.2 and 178.7μM.The enzyme kinetic study suggested that compounds 2 and 3 were mixtype inhibitors on PTP1B with Ki values of 15.6 and 132.5μM.This investigation manifests the antidiabetic potency of U.rhynchophylla with triterpenoids as the active constituents.展开更多
Ramulus et Uncus Uncariae is one of the 31 regional characteristic Chinese medicinal materials identified by Guangxi Zhuang Autonomous Region in 2021,with antihypertensive,antiarrhythmic,anti-cerebral ischemia,sedativ...Ramulus et Uncus Uncariae is one of the 31 regional characteristic Chinese medicinal materials identified by Guangxi Zhuang Autonomous Region in 2021,with antihypertensive,antiarrhythmic,anti-cerebral ischemia,sedative,antithrombotic,anti-tumor and other pharmacological effects,and is neurotoxic and hepatotoxic.In this article,the chemical constituents,pharmacological effects,toxic effects,toxic manifestations in whole animals and mechanism of toxicity of Ramulus et Uncus Uncariae are reviewed.展开更多
Uncarialines A-E(1-5),five undescribed monoterpene indole alkaloids,together with five known analogues were obtained from the stems of Uncaria rhynchophylla.Alkaloids 1-3 were unique 3,4-seco-tricyclic alkaloids with ...Uncarialines A-E(1-5),five undescribed monoterpene indole alkaloids,together with five known analogues were obtained from the stems of Uncaria rhynchophylla.Alkaloids 1-3 were unique 3,4-seco-tricyclic alkaloids with a 6/5/10 ring system,while 4 and 5 possessed a rare rearranged scaffold originated from corynantheine-type alkaloids with C-2/C-7 oxidation.Their structures were characterized by a comprehensive analysis of MS,NMR,and ECD.Their effects on blood clotting times of human plasma were evaluated and alkaloid 5 had a slight prolongation effect on both thrombin time and activated partial thromboplastin time(p<0.001).展开更多
The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH_2Cl_2 fraction by chromatography. The...The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH_2Cl_2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone(1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone(2), together with a known compound isorhynchophyllic acid(3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, Hep G2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, Hep G2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, Hep G2 and A2780 cells with IC_(50) values being 5.8, 12.8 and 11.8 μmol·L^(–1), respectively.展开更多
Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 a...Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey’s derivatization,along with comparison of their specific rotation and Cotton effect(CE)data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism(ECD)spectra.A plausible biosynthetic pathway of 1 and 2,associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus,is discussed.展开更多
OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to ...OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to evaluate the influence of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on the activities of CYP450 isoforms(CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6),which were determined by changes in the pharmacokinetic parameters of six probe drugs,theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide and dextromethorphan.Study groups included,Control group(CG),Tianma(Rhizoma Gastrodiae)group(TM),Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group(GT)and Tianma Gouteng(Gastrodia Uncaria)group(TMGT).RESULTS:No significant differences between Tianma(Rhizoma Gastrodiae)and control groups were found.Compared with the control group,in the Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group both the AUC and t1/2 of dapsone and tolbutamide were reduced,whereas the CL(clearance rate)of dapsone and tolbutamide were increased.Compared with the control group,in the Tianma Gouteng group,the AUC and t1/2 of dapsone and tolbutamide were reduced,the CL of dapsone and tolbutamide were increased,and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.CONCLUSION:Tianma(Rhizoma Gastrodiae)has no significant effect on the six CYP450 subtypes.The activities of CYP3A4 and CYP2C9 were increased by Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).The activities of CYP3A4 and CYP2C9 were increased,whereas the activity of CYP32E1 was reduced by combined Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).展开更多
文摘As a traditional herbal medicine,the major alkaloids in Uncaria rhynchophylla have been proven to have blood pressure-lowering and sedative effects.It is essential to develop an effective method for the determination of the major alkaloids in U.rhynchophylla.In this research,a rapid quantitative analysis involving multi-components analysis by a single marker strategy coupled with core-shell column HPLC was adopted to analyse four alkaloids(corynoxeine,isocorynoxeine,isorhynchophylline,rhynchophylline)in U.rhynchophylla.Isorhynchophylline was selected as the internal reference substance,the content of which was determined by the traditional external standard method.Relative correction factors(RCF)between isorhynchophylline and the other three alkaloids were calculated respectively.The results showed that the QAMS method had good robustness under different HPLC instruments.Nineteen batches of U.rhynchophylla were tested.No significant difference was observed between the results by QAMS and EMS(Correlation coefficient>0.99,p>0.05).The QAMS method could be employed as a rapid,effective technique for the quality control of U.rhynchophylla.
基金supported by the National Natural Science Foundation of China(81573322)the Yunnan Wanren Project(YNWR-QNBJ-2018-061)+1 种基金the Youth Innovation Promotion Association,CAS(2013252)the Program of Yunling Scholarship,the Yunnan Science Fund for Excellent Young Scholars(2019FI017)。
文摘Uncariae Ramulus Cum Uncis(Gou-Teng),the dried hook-bearing stems of several Uncaria plants(Rubiaceae),is a wellknown herbal medicine in China.The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between diferent species.In order to discern their chemical and biological diference,an ultra-fast liquid chromatography equipped with ion trap time-of-fight mass spectrometry(UFLC-IT/TOF-MS)combining with melatonin(MT1 and MT2)and 5-hydroxytryptamine(5-HT1A and 5-HT2C)receptors agonistic assay in vitro was conducted on seven Uncaria species.As a result,57 compounds including 35 indole alkaloids,ten favonoids,fve triterpenoids,fve chlorogenic analogues,and two other compounds were characterized based on their MS/MS patterns and UV absorptions.Specifcally,cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens,whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants.Three Uncaria species,U.rhynchophylla,U.macrophylla,and U.yunnanensis showed obviously agnostic activity on four neurotransmitter receptors(MT1,MT2,5-HT1A,and 5-HT_(2C)).This frst-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientifc viewpoints for the clinical application of Gou-Teng.
基金The authors are grateful to the National Natural Science Foundation of China(81225024,31500292,31770388)for financial support.
文摘Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness,cerebrovascular diseases,and nervous disorders in China.Previously,the neuro-protective activities of the alkaloids from U.rhynchophylla were intensively reported.In current work,three new indole alkaloids(1–3),identified as geissoschizic acid(1),geissoschizic acid N4-oxide(2),and 3b-sitsirikine N4-oxide(3),as well as 26 known analogues were isolated from U.rhynchophylla.However,in the neural stem cells(NSCs)proliferation assay for all isolated compounds,geissoschizic acid(1),geissoschizic acid N4-oxide(2),isocorynoxeine(6),isorhynchophylline(7),(4S)-akuammigine N-oxide(8),and(4S)-rhynchophylline N-oxide(10)showed unexpected inhibitory activities at 10 μM.Unlike previous neuro-protective reports,as a warning or caution,our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U.rhynchophylla,while the structure–activity relationships of the isolated compounds were discussed also.
基金Project supported by the National Natural Science Foundation of China.
文摘From the hook of Uncaria sinensis, a new alkaloid, isorhynchophyllic acid was isolated and its structure was elucidated by spectral data and chemical reaction.
文摘Uncaria tomentosa presents tomentum that resembles cat’s claws, hence its common name, is a plant that produces various secondary metabolites that are traditionally used in alternative medicine. The natural distribution of this species has been affected by indiscriminate harvesting from its habitat. In the present research, cryopreservation (liquid nitrogen, LN, -196°C) was evaluated as an option for ex situ conservation of this species. The following techniques were evaluated: vitrification and encapsulation-dehydration of apices, vitrification of cell suspensions, and seed desiccation and vitrification. Preculture conditions and exposure times to LS and PVS2 were evaluated. Apex survival was the highest (82%) with preculture in 0.25 M sucrose followed by incubation for 20 and 30 min in LS and PVS2, respectively, prior to cooling in LN. The encapsulation-dehydration technique was evaluated by using sucrose preculture and different capsule moisture contents. Survival of apices cooled in LN was not significantly different between treatments and varied from 31.8% to 52.9% for capsule moisture contents between 22.7% and 20.3%. For cell suspensions precultured in 0.5 M sucrose, cell multiplication and formation of calli with very good appearance were observed in 61.1% of the cultures following vitrification. For cryopreservation of seeds, germination was 89.5% using the desiccation technique and 67.6% to78.1% using vitrification.
基金supported by the Shanghai Sailing Program(No.21YF1455800)the National Key R&D Program of China(No.2019YFC1711000)+1 种基金the Qi-Huang Scholar of National Traditional Chinese Medicine Leading Talents Support Program(No.2018)the Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project(No.2020).
文摘Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.
基金the Yunnan Wanren Project(YNWR-QNBJ-2018-061)the Yunnan Science Fund for Excellent Young Scholars(2019FI017)+1 种基金the Reserve Talents of Young and Middle-aged Academic and Technical Leaders in Yunnan Province(2018HB067)the National Natural Science Foundation of China(81573322).
文摘Uncaria rhynchophylla(Gouteng)is a famous traditional Chinese medicine used for psychiatric and hypotensive purposes in China.In this study,the ethyl acetate(EtOAc)part of U.rhynchophylla was revealed with protein tyrosine phosphatase 1B(PTP1B)inhibitory activity.Subsequent investigation on the EtOAc part yielded one new triterpenoid,3β-formyloxy-6β,19α-dihydroxyurs-12-en-28-oic acid(1)and four known ones,3β,6β,19α-trihydroxyurs-12-en-28-oic acid(2),2-oxopomolic acid(3),3β,19α-dihydroxy-6-oxo-olean-12-en-28-oic acid(4)and sumaresinolic acid(5).The structure of compound 1 was determined by extensive HRESIMS,IR,1D and 2D NMR spectroscopic analyses.Two ursane-type triterpenoids(2 and 3)showed selective inhibition on PTP1B with IC50 values of 48.2 and 178.7μM.The enzyme kinetic study suggested that compounds 2 and 3 were mixtype inhibitors on PTP1B with Ki values of 15.6 and 132.5μM.This investigation manifests the antidiabetic potency of U.rhynchophylla with triterpenoids as the active constituents.
文摘Ramulus et Uncus Uncariae is one of the 31 regional characteristic Chinese medicinal materials identified by Guangxi Zhuang Autonomous Region in 2021,with antihypertensive,antiarrhythmic,anti-cerebral ischemia,sedative,antithrombotic,anti-tumor and other pharmacological effects,and is neurotoxic and hepatotoxic.In this article,the chemical constituents,pharmacological effects,toxic effects,toxic manifestations in whole animals and mechanism of toxicity of Ramulus et Uncus Uncariae are reviewed.
基金Yunnan Applied Basic Research Projects(No.202301AS070057)National Key R&D Program of China(No.2022YFF1100301)Yunnan Revitalization Talents Support Plan-Young Talent Project(to Y.Zhang).
文摘Uncarialines A-E(1-5),five undescribed monoterpene indole alkaloids,together with five known analogues were obtained from the stems of Uncaria rhynchophylla.Alkaloids 1-3 were unique 3,4-seco-tricyclic alkaloids with a 6/5/10 ring system,while 4 and 5 possessed a rare rearranged scaffold originated from corynantheine-type alkaloids with C-2/C-7 oxidation.Their structures were characterized by a comprehensive analysis of MS,NMR,and ECD.Their effects on blood clotting times of human plasma were evaluated and alkaloid 5 had a slight prolongation effect on both thrombin time and activated partial thromboplastin time(p<0.001).
基金financially supported by the National Natural Science Foundation of China(Nos.81373956 and 81274064)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The present study was designed to determine the chemical constituents of the stems and hooks of Uncaria rhynchophylla. The chemical constituents were isolated and purified from CH_2Cl_2 fraction by chromatography. Their structures were elucidated by spectroscopic analyses. Their cytotoxicity was tested using MTT method. Two new ortho benzoquinones, 3-diethylamino-5-methoxy-1, 2-benzoquinone(1) and 3-ethylamino-5-methoxy-1, 2-benzoquinone(2), together with a known compound isorhynchophyllic acid(3) were isolated from U. rhynchophylla. These compounds were evaluated for their cytotoxicity against cancer cells A549, Hep G2 and A2780. Compounds 1 and 2 were new ortho benzoquinones and showed weak antiproliferative activities on A549, Hep G2 and A2780 cells. Compound 3 significantly inhibited the proliferation of A549, Hep G2 and A2780 cells with IC_(50) values being 5.8, 12.8 and 11.8 μmol·L^(–1), respectively.
基金supported by the National Natural Sciences Foundation of China(Nos.81630094,21732008,and 81730093)CAMS Innovation Fund for Medical Science of China(Nos.2017-I2M-3-010 and 2016-I2M-1-010)the Drug Innovation Major Project(No.2018ZX09711001-001-001)
文摘Two new folate-derived analogues,named uncarophyllofolic acids A(1)and B(2),respectively,were isolated from the Uncaria rhynchophylla hook bearing stem(Gouteng in Chinese).The distinct stereochemical structures of 1 and 2 were determined by spectroscopic data analysis in combination with acidic hydrolysis and Marfey’s derivatization,along with comparison of their specific rotation and Cotton effect(CE)data with those of the biogenetically related known derivatives as well as theoretical calculations of electronic circular dichroism(ECD)spectra.A plausible biosynthetic pathway of 1 and 2,associating to folate metabolism and the previously reported orychophragines A-C from Orychophragmus violaceus,is discussed.
基金Supported by the Science and Technology Department of Sichuan Province[Project Name:Study on the Molecular Pharmacokinetic of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)in Liver Uptake and Elimination of Upper Hyperactivity of Liver-yang,No.2018FZ0096]and the Fundamental Research Funds for the Central Universities(Study on Pharmacodynamics and in Vivo Process of Chinese Herbal Compound in Treatment of ARDS Caused by Covid-19 Syndrome)。
文摘OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to evaluate the influence of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on the activities of CYP450 isoforms(CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6),which were determined by changes in the pharmacokinetic parameters of six probe drugs,theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide and dextromethorphan.Study groups included,Control group(CG),Tianma(Rhizoma Gastrodiae)group(TM),Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group(GT)and Tianma Gouteng(Gastrodia Uncaria)group(TMGT).RESULTS:No significant differences between Tianma(Rhizoma Gastrodiae)and control groups were found.Compared with the control group,in the Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group both the AUC and t1/2 of dapsone and tolbutamide were reduced,whereas the CL(clearance rate)of dapsone and tolbutamide were increased.Compared with the control group,in the Tianma Gouteng group,the AUC and t1/2 of dapsone and tolbutamide were reduced,the CL of dapsone and tolbutamide were increased,and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.CONCLUSION:Tianma(Rhizoma Gastrodiae)has no significant effect on the six CYP450 subtypes.The activities of CYP3A4 and CYP2C9 were increased by Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).The activities of CYP3A4 and CYP2C9 were increased,whereas the activity of CYP32E1 was reduced by combined Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).
