(+)/(-)-Yanhusuosines A(1) and B(2), two pairs of trace benzylisoquinoline-protoberberine atropoenantiomeric homodimers featuring an unprecedented 6/7/6/6/6/6 hexacyclic skeleton, were isolated from the tubers of Cory...(+)/(-)-Yanhusuosines A(1) and B(2), two pairs of trace benzylisoquinoline-protoberberine atropoenantiomeric homodimers featuring an unprecedented 6/7/6/6/6/6 hexacyclic skeleton, were isolated from the tubers of Corydalis yanhusuo. The structures of(+)/(-)-1 and(+)/(-)-2 were elucidated using spectroscopic and quantum-chemical calculation approaches.(+)/(-)-Yanhusuosines A(1) and B(2)represent a new class of alkaloid dimers biogenetically constructed by a molecule of benzylisoquinoline with a unit of protoberberine via an intermolecular [4 + 3] cycloaddition. Their plausible biosynthetic pathways are discussed, and compound 2 exerted moderate inhibitory activity of NO formation in LPS induced RAW264.7 macrophages.展开更多
A new protoberberine alkaloid, named 5,6-dihydro- 10-hydroxy-2,3,9-trimethoxy- 13-methyldibenzo[α,g]quinoliziniurn （1） was isolated from the 60% ethanol extract of the tubers of Corydalis yanhusuo W. T. Wang, toget...A new protoberberine alkaloid, named 5,6-dihydro- 10-hydroxy-2,3,9-trimethoxy- 13-methyldibenzo[α,g]quinoliziniurn （1） was isolated from the 60% ethanol extract of the tubers of Corydalis yanhusuo W. T. Wang, together with a new natural product, 13methylpalmatrubine （2）. Their structures were established by spectroscopic methods. 2009 Xin Sheng Yao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.展开更多
Phytochemical investigation of the vinegar-prepared Corydalis yanhusuo led to the isolation of one aristolactam derivative,1,2,8,9-tetramethoxy-5-methyldibenzo[cd,f]indol-4-(5H)-one(1),and seven aporphine alkaloids,in...Phytochemical investigation of the vinegar-prepared Corydalis yanhusuo led to the isolation of one aristolactam derivative,1,2,8,9-tetramethoxy-5-methyldibenzo[cd,f]indol-4-(5H)-one(1),and seven aporphine alkaloids,including 2,9,10-trimethoxydibenz[de,g]quinolin-7-one(2),1-hydroxy-2,9,10-trimethoxy-7H-dibenzo(de,g)quinoline-7-one(3),oxoglaucine(4),N-methyloxoglaucine trifluoroacetate trifluoroacetate(5),corunine acetate(6),pontevedrine(7),and oxoglaucidaline trifluoroacetate(8).The structures of the isolated compounds were elucidated by extensive spectroscopic data analysis and comparison with the previous reports.Among them,compounds 1 and 2 were obtained as natural products for the first time,and their NMR data were unambiguously assigned.In addition,compound 1 exhibited moderate cytotoxic activity against HepG2 cells with an IC50 value of 16.0±6.4μM.展开更多
Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been a...Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.展开更多
The molecular mechanism underlying Corydalis Yanhusuo’s therapeutic potential in prostate cancer(PCa)treatment was elucidated using network pharmacology and molecular docking.Nineteen active ingredients,399 drug targ...The molecular mechanism underlying Corydalis Yanhusuo’s therapeutic potential in prostate cancer(PCa)treatment was elucidated using network pharmacology and molecular docking.Nineteen active ingredients,399 drug targets,1790 disease targets and 143 intersection targets were identified.Ten core targets were screened from the protein-protein interaction network.Enrichment analysis revealed 133 GO terms and 114 KEGG pathways.Corydalis Yanhusuo may potentially treat prostate cancer through pathways such as the Rap1 signaling pathway,phospholipase D signaling pathway,Ras signaling pathway,VEGF signaling pathway and JAK-STAT signaling pathway.Significant differences in expression were observed for EGFR,PDGFRA,PIK3CA,PIK3CD,PIK3CG and PIK3R1.Molecular docking and dynamics simulation analysis showed low binding energy between active components and the six core genes of Corydalis Yanhusuo,indicating a favorable docking effect.This study shows that Corydalis Yanhusuo exhibits promise in prostate cancer treatment through a synergistic“multi-component-multi-target-multi-pathway”effect.展开更多
As a traditional Chinese herbal medicine component,Corydalis yanhusuo is gradually attracting the attention of the skin care industry.In this study,Corydalis yanhusuo root extract dispersion(CTR50)was used as the rese...As a traditional Chinese herbal medicine component,Corydalis yanhusuo is gradually attracting the attention of the skin care industry.In this study,Corydalis yanhusuo root extract dispersion(CTR50)was used as the research object.The related activities of Corydalis yanhusuo root extract dispersion were studied by cytotoxicity test,in vitro and in vivo antioxidant test and cell scratch healing test.The results showed that the dispersion of Corydalis yanhusuo root extract had no cytotoxicity to HaCaT cells.When the concentration of Corydalis yanhusuo root extract dispersion was 5%,the scavenging rate of DPPH free radical was 35.05%,and the scavenging ability of hydroxyl radical was weak;CTR50 can significantly increase the activity of SOD in HaCaT cells,increase the content of antioxidant factor GSH in HaCaT cells induced by UVB,and improve the oxidative stability of skin;it significantly promoted the healing ability of HaCaT cells at the scratch site.It can be seen that the dispersion of Corydalis yanhusuo root extract has the potential to be used as a functional raw material for natural skin care products,which provides a theoretical basis for its development and application in the field of cosmetics.展开更多
This study aims to clarify the codon usage bias and influencing factors of protein-coding genes in the chloroplast genome of the medicinal plant Corydalis yanhusuo.The chloroplast genome sequence of C.yanhusuo was obt...This study aims to clarify the codon usage bias and influencing factors of protein-coding genes in the chloroplast genome of the medicinal plant Corydalis yanhusuo.The chloroplast genome sequence of C.yanhusuo was obtained by resequencing,approximately 50 protein-coding genes were screened,and the nucleotide composition and codon usage patterns were calculated and analyzed using CodonW 1.4.2 and EMBOSS software.The results showed that the total guanine and cytosine(GC)content of codons in the chloroplast genome of C.yanhusuo was 40.06%,and the GC contents at the third,second,and first codon positions(GC_(3),GC_(2),and GC_(1))were 32.12%,40.21%,and 47.84%,respectively,indicating that codons in the chloroplast genome of C.yanhusuo preferentially used adenine(A)or uracil(U).The effective number of codons(ENC)ranged from 42.87 to 61.00,with an average value of 50.54,indicating weak codon usage bias.A significant positive correlation existed between the GC content at the third codon position(GC_(3))and ENC,showing that codon bias was mainly affected by the third base.Neutral plot,ENC-plot,and PR2-plot analyses showed that the codon bias of the chloroplast genome of C.yanhusuo was mainly influenced by natural selection.Sixteen optimal codons—UUA,AUU,GUU,GUA,UCU,AGU,CCU,ACU,GCU,CAA,AAA,GAU,UGU,CGU,CGA,and GGU—were finally determined based on the relative synonymous codon usage analysis of high-frequency and highly expressed codons,all of which preferentially ended with A/U.Overall,this study reveals the codon usage bias of the chloroplast genome of C.yanhusuo and its influencing factors,and provides a theoretical basis for chloroplast genetic engineering and phylogenetic research.展开更多
A polysaccharide named YhPS- 1 was isolated from the root of Cordalis yanhusuo Wang and purified by means of gel-permeation chromatography and ionexchange chromatography. Its physicochemical properties, including mono...A polysaccharide named YhPS- 1 was isolated from the root of Cordalis yanhusuo Wang and purified by means of gel-permeation chromatography and ionexchange chromatography. Its physicochemical properties, including monosaccharide composition, carbohydrate content, molecular weight and elemental composition, were determined. The structure of YhPS-1 was elucidated by chemical methods along with ^1H and ^13C NMR spectroscopy ways, such as including two-dimensional HMQC and HMBC experiments. These results show that YhPS-1 possesses a backbone consisting of terminal α-Glcp-（1→, a-Glcp-（1→6）, a-Glcp-（1→4） and a-Glcp-（1→4,6）. The bioactive assay showed that it could inhibit the growth of Sarcoma 180 and Lewis pulmonary carcinoma implanted in mice.展开更多
A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids,(+)/(-)-yanhusamides A-C(1-3),...A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids,(+)/(-)-yanhusamides A-C(1-3),featuring an unprecedented 3,8-diazatricylco[5.2.2.0^(2,6)]undecane-8,10-diene bridged system.Their structures were exhaustively characterized by X-ray diffraction,comprehensive spectroscopic data analysis,and computational methods.Guided by the hypothetical biosynthetic pathway for 1-3,a gram-scale biomimetic synthesis of(±)-1 was achieved in 3 steps using photoenolization/Diels-Alder(PEDA)[4+2]cycloaddition.Compounds 1-3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages.The in vivo assay showed that oral administration of 30 mg/kg of(±)-1 attenuated the severity of rat adjuvant-induced arthritis(AIA).Additionally,(±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.展开更多
Objective: This study was designed to develop a method for detecting differences in the chemical composition of Corydalis yanhusuo W. T. Wang using high-performance liquid chromatography with a diode array detector te...Objective: This study was designed to develop a method for detecting differences in the chemical composition of Corydalis yanhusuo W. T. Wang using high-performance liquid chromatography with a diode array detector technology. Materials and Methods: We established a novel quantitative evaluation method for identifying multiple components in natural extracts using a single-marker method quantitative analysis of multi-components by single marker(QAMS). This method was then validated using eight alkaloid phytochemical markers designed to evaluate C. yanhusuo quality. Results: Our evaluations revealed good linearity(R^(2) ≥ 0.9991) within the range of tested concentrations for all eight alkaloids, with recovery ranging from 95.5% to 101.5%. The evaluations also returned stability results that fell within the acceptable range. Cluster analysis and Heatmap analyses were applied to classify and evaluate alkaloids across 21 different production areas. These results revealed a significant difference in the component profiles between samples from different origins. Conclusions: Thus, these data suggest that in the absence of a material reference, QAMS may help facilitate the stable production of C. yanhusuo. In addition, our data suggest that this method may have value as a promising alternative to common quality evaluations for controlling C. yanhusuo composition.展开更多
目的基于“病-药-量”分析中医古籍含延胡索复方用药规律,为临床运用及研发提供依据。方法从《中华医典》收集含延胡索复方,通过频次统计、关联规则及聚类分析解析配伍规律与剂量特征。基中药系统药理学数据库与分析平台(Traditional Ch...目的基于“病-药-量”分析中医古籍含延胡索复方用药规律,为临床运用及研发提供依据。方法从《中华医典》收集含延胡索复方,通过频次统计、关联规则及聚类分析解析配伍规律与剂量特征。基中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选延胡索活性成分及靶点,联合CTD、Drugbank等数据库获取疾病靶标,利用Cytoscape构建药效网络,经STRING建立蛋白质互作(protein-protein interaction,PPI)网络,通过Metascape进行基因本体论(gene ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。通过AutoDock Vina进行分子对接验证结合特性,SwissADME评估类药性,Pro-Tox 3.0预测毒性等级,GROMACS完成分子动力学模拟验证稳定性。结果共收集716首复方,主治133种病症。高频病症用药分析显示,治疗“月经不调”时,剂型多为丸剂,延胡索用量多为41.31 g,核心药物配伍为当归、川芎、肉桂;治疗“疝气”时,剂型多为丸剂,延胡索用量多为37.3 g,核心药物配伍为木香、八角茴香;治疗“闭经”时,剂型多为散剂,延胡索用量多为41.31 g,核心药物配伍为丁香、当归。网络药理学鉴定延胡索活性成分与月经不调有197个交集靶点,PPI拓扑分析识别出10个关键靶点。GO分析显示靶点富集于蛋白质结合功能,KEGG分析提示参与肿瘤坏死因子(tumor necrosis factor,TNF)通路等生物过程。分子对接与动力学模拟证实活性成分槲皮素、隐品碱、小檗碱、荷包牡丹碱与核心靶点CASP3、BCL2、TNF、IL-6具有高亲和力,且类药性良好、毒性较低。结论含延胡索复方主要用于月经不调类病症,高频配伍药物为当归、川芎、肉桂等温通活血类中药。网络药理学及计算机模拟证实,槲皮素、隐品碱、小檗碱等核心成分通过BCL2、TNF、CASP3、IL-6等靶点改善月经不调。展开更多
基金supported by the National Natural Science Foundation of China (No. 82073978)the Fundamental Research Funds for the Central Universities (No. 2022-JYB-JBZR-015)Beijing Natural Science Foundation (No. JQ18026)。
文摘(+)/(-)-Yanhusuosines A(1) and B(2), two pairs of trace benzylisoquinoline-protoberberine atropoenantiomeric homodimers featuring an unprecedented 6/7/6/6/6/6 hexacyclic skeleton, were isolated from the tubers of Corydalis yanhusuo. The structures of(+)/(-)-1 and(+)/(-)-2 were elucidated using spectroscopic and quantum-chemical calculation approaches.(+)/(-)-Yanhusuosines A(1) and B(2)represent a new class of alkaloid dimers biogenetically constructed by a molecule of benzylisoquinoline with a unit of protoberberine via an intermolecular [4 + 3] cycloaddition. Their plausible biosynthetic pathways are discussed, and compound 2 exerted moderate inhibitory activity of NO formation in LPS induced RAW264.7 macrophages.
文摘A new protoberberine alkaloid, named 5,6-dihydro- 10-hydroxy-2,3,9-trimethoxy- 13-methyldibenzo[α,g]quinoliziniurn （1） was isolated from the 60% ethanol extract of the tubers of Corydalis yanhusuo W. T. Wang, together with a new natural product, 13methylpalmatrubine （2）. Their structures were established by spectroscopic methods. 2009 Xin Sheng Yao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All fights reserved.
基金This work was financially supported by Beijing Natural Science Foundation(Grant No.JQ18026)the National Key R&D Program of China(Grant No.2017YFC1700400)+1 种基金the National Natural Science Foundation of China(Grant No.82073978)the Fundamental Research Funds for the Central Universities(Grant No.2021-BUCMXJKY007).
文摘Phytochemical investigation of the vinegar-prepared Corydalis yanhusuo led to the isolation of one aristolactam derivative,1,2,8,9-tetramethoxy-5-methyldibenzo[cd,f]indol-4-(5H)-one(1),and seven aporphine alkaloids,including 2,9,10-trimethoxydibenz[de,g]quinolin-7-one(2),1-hydroxy-2,9,10-trimethoxy-7H-dibenzo(de,g)quinoline-7-one(3),oxoglaucine(4),N-methyloxoglaucine trifluoroacetate trifluoroacetate(5),corunine acetate(6),pontevedrine(7),and oxoglaucidaline trifluoroacetate(8).The structures of the isolated compounds were elucidated by extensive spectroscopic data analysis and comparison with the previous reports.Among them,compounds 1 and 2 were obtained as natural products for the first time,and their NMR data were unambiguously assigned.In addition,compound 1 exhibited moderate cytotoxic activity against HepG2 cells with an IC50 value of 16.0±6.4μM.
基金The work was supported by the National Natural Science Foundation of China(No.81373942)the Key Science and Technology Research Projects of Tibet Autonomous Region of China(No.XZ201801-GA-16).
文摘Background:Yanhusuo powder,also known as Xuanhusuo powder,is a long-standing Chinese herbal formula mainly used in the treatment of osteoarthritis.Although the clinical effectiveness of Yanhusuo powder has long been acknowledged,its mechanism of action and bioactive components remain unknown.Methods:A novel analytical method combining the use of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and ultra-performance liquid chromatography-triple quadrupole mass spectrometry was applied to profile the formula and absorbed prototype components in plasma after oral administration of Yanhusuo powder.Then,the absorbed constituents were subjected to network pharmacology to predict targets and pathways.AutoDock software was then used for molecular docking studies to screen for potential pharmacodynamic substances.Results:A total of 34 in vitro formula components and 20 in vivo prototype compounds from the various relevant species were successfully separated and identified for the first time.Compound-target-pathway analysis revealed that 20 absorbed constituents,42 target genes and 42 pathways are probably related to the efficacy of Yanhusuo powder against osteoarthritis.The efficacy of Yanhusuo powder mainly involves AKT1,fibronectin 1 and matrix metalloproteinase 9 targets and apoptosis,as well as PI3K-AKT and mitogen-activated protein kinases signaling pathways.According to the results of the molecular docking studies,it can be preliminarily judged that protopine,dehydrocorybulbine and angelicin may be the pharmacologically active substances of Yanhusuo powder.Conclusion:The results provide a scientific basis for understanding the bioactive compounds and the pharmacological mechanism of Yanhusuo powder.
基金supported by local special projects in major health of Hubei Provincial Science and Technology Department(2022BCE054)key scientific research projects of Hubei Polytechnic University(23xjz08A)Hubei Polytechnic University·Huangshi Daye Lake high-tech Zone University Science Park Joint Open Fund Project(23xjz04AK).
文摘The molecular mechanism underlying Corydalis Yanhusuo’s therapeutic potential in prostate cancer(PCa)treatment was elucidated using network pharmacology and molecular docking.Nineteen active ingredients,399 drug targets,1790 disease targets and 143 intersection targets were identified.Ten core targets were screened from the protein-protein interaction network.Enrichment analysis revealed 133 GO terms and 114 KEGG pathways.Corydalis Yanhusuo may potentially treat prostate cancer through pathways such as the Rap1 signaling pathway,phospholipase D signaling pathway,Ras signaling pathway,VEGF signaling pathway and JAK-STAT signaling pathway.Significant differences in expression were observed for EGFR,PDGFRA,PIK3CA,PIK3CD,PIK3CG and PIK3R1.Molecular docking and dynamics simulation analysis showed low binding energy between active components and the six core genes of Corydalis Yanhusuo,indicating a favorable docking effect.This study shows that Corydalis Yanhusuo exhibits promise in prostate cancer treatment through a synergistic“multi-component-multi-target-multi-pathway”effect.
文摘As a traditional Chinese herbal medicine component,Corydalis yanhusuo is gradually attracting the attention of the skin care industry.In this study,Corydalis yanhusuo root extract dispersion(CTR50)was used as the research object.The related activities of Corydalis yanhusuo root extract dispersion were studied by cytotoxicity test,in vitro and in vivo antioxidant test and cell scratch healing test.The results showed that the dispersion of Corydalis yanhusuo root extract had no cytotoxicity to HaCaT cells.When the concentration of Corydalis yanhusuo root extract dispersion was 5%,the scavenging rate of DPPH free radical was 35.05%,and the scavenging ability of hydroxyl radical was weak;CTR50 can significantly increase the activity of SOD in HaCaT cells,increase the content of antioxidant factor GSH in HaCaT cells induced by UVB,and improve the oxidative stability of skin;it significantly promoted the healing ability of HaCaT cells at the scratch site.It can be seen that the dispersion of Corydalis yanhusuo root extract has the potential to be used as a functional raw material for natural skin care products,which provides a theoretical basis for its development and application in the field of cosmetics.
基金funded by General Program of Natural Sciences Basic Research of Shaanxi Provincial Department of Science and Technology(2024JC-YBMS-761)the Youth Innovation Team Construction Scientific Research Program of Shaanxi Provincial Department of Education(21JP030)+1 种基金the Special Funds Project for Traditional Chinese Medicine of the Shaanxi Provincial Administration of TCM(No.2021-QYZL-02)the Project of the Shaanxi Provincial Natural Science Foundation(2023-JC-QN-0996).
文摘This study aims to clarify the codon usage bias and influencing factors of protein-coding genes in the chloroplast genome of the medicinal plant Corydalis yanhusuo.The chloroplast genome sequence of C.yanhusuo was obtained by resequencing,approximately 50 protein-coding genes were screened,and the nucleotide composition and codon usage patterns were calculated and analyzed using CodonW 1.4.2 and EMBOSS software.The results showed that the total guanine and cytosine(GC)content of codons in the chloroplast genome of C.yanhusuo was 40.06%,and the GC contents at the third,second,and first codon positions(GC_(3),GC_(2),and GC_(1))were 32.12%,40.21%,and 47.84%,respectively,indicating that codons in the chloroplast genome of C.yanhusuo preferentially used adenine(A)or uracil(U).The effective number of codons(ENC)ranged from 42.87 to 61.00,with an average value of 50.54,indicating weak codon usage bias.A significant positive correlation existed between the GC content at the third codon position(GC_(3))and ENC,showing that codon bias was mainly affected by the third base.Neutral plot,ENC-plot,and PR2-plot analyses showed that the codon bias of the chloroplast genome of C.yanhusuo was mainly influenced by natural selection.Sixteen optimal codons—UUA,AUU,GUU,GUA,UCU,AGU,CCU,ACU,GCU,CAA,AAA,GAU,UGU,CGU,CGA,and GGU—were finally determined based on the relative synonymous codon usage analysis of high-frequency and highly expressed codons,all of which preferentially ended with A/U.Overall,this study reveals the codon usage bias of the chloroplast genome of C.yanhusuo and its influencing factors,and provides a theoretical basis for chloroplast genetic engineering and phylogenetic research.
文摘A polysaccharide named YhPS- 1 was isolated from the root of Cordalis yanhusuo Wang and purified by means of gel-permeation chromatography and ionexchange chromatography. Its physicochemical properties, including monosaccharide composition, carbohydrate content, molecular weight and elemental composition, were determined. The structure of YhPS-1 was elucidated by chemical methods along with ^1H and ^13C NMR spectroscopy ways, such as including two-dimensional HMQC and HMBC experiments. These results show that YhPS-1 possesses a backbone consisting of terminal α-Glcp-（1→, a-Glcp-（1→6）, a-Glcp-（1→4） and a-Glcp-（1→4,6）. The bioactive assay showed that it could inhibit the growth of Sarcoma 180 and Lewis pulmonary carcinoma implanted in mice.
基金supported by the National Natural Science Foundation of China(No.82073978)Beijing Natural Science Foundation(No.JQ18026,China)the Fundamental Research Funds for the Central Universities(2022-JYB-JBZR-015,China)。
文摘A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids,(+)/(-)-yanhusamides A-C(1-3),featuring an unprecedented 3,8-diazatricylco[5.2.2.0^(2,6)]undecane-8,10-diene bridged system.Their structures were exhaustively characterized by X-ray diffraction,comprehensive spectroscopic data analysis,and computational methods.Guided by the hypothetical biosynthetic pathway for 1-3,a gram-scale biomimetic synthesis of(±)-1 was achieved in 3 steps using photoenolization/Diels-Alder(PEDA)[4+2]cycloaddition.Compounds 1-3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages.The in vivo assay showed that oral administration of 30 mg/kg of(±)-1 attenuated the severity of rat adjuvant-induced arthritis(AIA).Additionally,(±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.
基金supported by The Scientific Research Project under the National Natural Science Foundation of China(No.81872979 and 81603418)。
文摘Objective: This study was designed to develop a method for detecting differences in the chemical composition of Corydalis yanhusuo W. T. Wang using high-performance liquid chromatography with a diode array detector technology. Materials and Methods: We established a novel quantitative evaluation method for identifying multiple components in natural extracts using a single-marker method quantitative analysis of multi-components by single marker(QAMS). This method was then validated using eight alkaloid phytochemical markers designed to evaluate C. yanhusuo quality. Results: Our evaluations revealed good linearity(R^(2) ≥ 0.9991) within the range of tested concentrations for all eight alkaloids, with recovery ranging from 95.5% to 101.5%. The evaluations also returned stability results that fell within the acceptable range. Cluster analysis and Heatmap analyses were applied to classify and evaluate alkaloids across 21 different production areas. These results revealed a significant difference in the component profiles between samples from different origins. Conclusions: Thus, these data suggest that in the absence of a material reference, QAMS may help facilitate the stable production of C. yanhusuo. In addition, our data suggest that this method may have value as a promising alternative to common quality evaluations for controlling C. yanhusuo composition.
文摘目的基于“病-药-量”分析中医古籍含延胡索复方用药规律,为临床运用及研发提供依据。方法从《中华医典》收集含延胡索复方,通过频次统计、关联规则及聚类分析解析配伍规律与剂量特征。基中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选延胡索活性成分及靶点,联合CTD、Drugbank等数据库获取疾病靶标,利用Cytoscape构建药效网络,经STRING建立蛋白质互作(protein-protein interaction,PPI)网络,通过Metascape进行基因本体论(gene ontology,GO)功能注释和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。通过AutoDock Vina进行分子对接验证结合特性,SwissADME评估类药性,Pro-Tox 3.0预测毒性等级,GROMACS完成分子动力学模拟验证稳定性。结果共收集716首复方,主治133种病症。高频病症用药分析显示,治疗“月经不调”时,剂型多为丸剂,延胡索用量多为41.31 g,核心药物配伍为当归、川芎、肉桂;治疗“疝气”时,剂型多为丸剂,延胡索用量多为37.3 g,核心药物配伍为木香、八角茴香;治疗“闭经”时,剂型多为散剂,延胡索用量多为41.31 g,核心药物配伍为丁香、当归。网络药理学鉴定延胡索活性成分与月经不调有197个交集靶点,PPI拓扑分析识别出10个关键靶点。GO分析显示靶点富集于蛋白质结合功能,KEGG分析提示参与肿瘤坏死因子(tumor necrosis factor,TNF)通路等生物过程。分子对接与动力学模拟证实活性成分槲皮素、隐品碱、小檗碱、荷包牡丹碱与核心靶点CASP3、BCL2、TNF、IL-6具有高亲和力,且类药性良好、毒性较低。结论含延胡索复方主要用于月经不调类病症,高频配伍药物为当归、川芎、肉桂等温通活血类中药。网络药理学及计算机模拟证实,槲皮素、隐品碱、小檗碱等核心成分通过BCL2、TNF、CASP3、IL-6等靶点改善月经不调。
