BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is a severe threat to human health.Polygonum multiflorum(PM)has been proven to remedy mitochondria and relieve MAFLD,but the main pharmacodynamic i...BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is a severe threat to human health.Polygonum multiflorum(PM)has been proven to remedy mitochondria and relieve MAFLD,but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear.AIM To research the active ingredients of PM adjusting mitochondria to relieve highfat diet(HFD)-induced MAFLD in rats.METHODS Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms.The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats(mitochondrial pharmacology).PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry(mitochondrial pharmacochemistry).The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model,respectively.RESULTS PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD.PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis.Eight chemicals were found in the liver mitochondria of PM-administrated rats.The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.CONCLUSION PM restored mitochondrial structure and function and alleviated MAFLD,which may be associated with the remedy of oxidative stress and energy production.The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD.Thus,PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction.Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.展开更多
BACKGROUND Various types of drug-induced liver injury are induced by Polygonum multiflorum(PM);however,it rarely causes neutropenia.Herein,we report the case of a 65-year-old woman with concurrent severe hepatotoxicit...BACKGROUND Various types of drug-induced liver injury are induced by Polygonum multiflorum(PM);however,it rarely causes neutropenia.Herein,we report the case of a 65-year-old woman with concurrent severe hepatotoxicity and agranulocytosis induced by PM.CASE SUMMARY A 65-year-old woman reported with severe hepatotoxicity and agranulocytosis 17 d after ingestion of PM.The results of the Roussel Uclaf Causality Assessment Method demonstrated a highly probable relationship between hepatotoxicity and PM,with a total score of 10.The Naranjo algorithm results indicated that agranulocytosis had a probable relationship with PM,with an overall score of 6.Granulocyte colony-stimulating factor(for once),a steroid,compound glycyrrhizin,and polyene phosphatidylcholine therapy were initiated.After 15 d of treatment,there was a gradual improvement in liver biochemistry,leukocytes,and neutrophils levels.CONCLUSION Concurrent hepatotoxicity and agranulocytosis are rare and critical adverse drug reactions of PM,which should be highly valued.展开更多
In 2021,there are approximately 537 million adults ageing 20-79 years affected by diabetes worldwide and the number is rising rapidly,hence it is important to manage and control diabetes mellitus and its associated co...In 2021,there are approximately 537 million adults ageing 20-79 years affected by diabetes worldwide and the number is rising rapidly,hence it is important to manage and control diabetes mellitus and its associated complications.Food is one of the key factors in preventing and combating diseases such as diabetes.Both as a food and an herbal medicine,Polygonum multiflorum(PM)has been used as an anti-aging tonic,for hair darkening in traditional Chinese medicine for several centuries.The recent research effort of PM has been focused on antioxidant,anti-ageing and anti-tumor properties.In the present study,we utilized the traditional processing of harvested raw PM,and identified several stilbene components and then evaluated the potential anti-diabetic effects of the processed PM extract(PME).PME(0.075%)was given to diabetic mice(KK CgAy/J)in drinking water and after 7 weeks,PME-treated mice had significantly lower glucose levels than mice in the diabetic control group(P<0.01).The mechanism was explored with ELISA and Western blotting and results suggested that the effect was through maintainingβ-cell function.展开更多
<strong>Background:</strong> <em>Polygonum multiflorum</em> (brand name Fo-ti) is a Chinese herb used as an antioxidant, antiaging agent, and liver and kidney health. It can cause acute hepatot...<strong>Background:</strong> <em>Polygonum multiflorum</em> (brand name Fo-ti) is a Chinese herb used as an antioxidant, antiaging agent, and liver and kidney health. It can cause acute hepatotoxicity and even death. There is no published data on the effectiveness of N-Acetyl cysteine (NAC) as a sole effective therapy. <strong>Case:</strong> A 23-year-old, healthy male, presented with jaundice and malaise of one-month duration. He had been taking a Chinese herb named Fo-Ti for 2 months. Physical examination revealed jaundice, with no stigmata of chronic liver disease. His laboratory results showed transaminitis with markedly elevated transaminases. Testings for infectious and autoimmune causes were unremarkable. The patient was admitted to the hospital. Fo-Ti was stopped and he was started on oral NAC as peroral protocol. He was discharged home on esomeprazole and oral NAC. He returned on the second day with worsening jaundice. He was readmitted and esomeprazole was discontinued. NAC was continued and his liver enzymes eventually improved. The supplement was tested by gas-chromatography mass spectrometry and measured the presence of emodin. <strong>Discussion:</strong> This case highlights the potential benefit of NAC as treatment of <em>Polygonum multiflorum</em> induced hepatotoxicity. The proposed mechanism of emodin induced liver injury is through disturbing glutathione metabolism in liver cells. This could explain the favorable response as NAC has the ability to replenish intracellular glutathione. <strong>Conclusion:</strong> <em>Polygonum multiflorum</em> use has been associated with severe and prolonged hepatotoxicity. Oral NAC should be considered in the treatment of these patients due to the favorable risk-benefit ratio.展开更多
BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,li...BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.展开更多
[Objectives]This study aimed to optimize the preparation process of Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags.[Methods]Taking the comprehensive weighed score of total flavonoid content,soup color,ar...[Objectives]This study aimed to optimize the preparation process of Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags.[Methods]Taking the comprehensive weighed score of total flavonoid content,soup color,aroma and taste as an indicator,the preparation process of tea bags was optimized using an orthogonal test.[Results]The results of the orthogonal test show that the optimal preparation process for the Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags are as follows:particle size of 14 meshes,solid to liquid ratio of 1∶40,brewing temperature of 70℃,and brewing time of 10 min.[Conclusions]The optimized preparation process is reasonable and feasible.It is suitable for the production of Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags.展开更多
OBJECTIVE This study investigated transcriptional regulation of the main chemical con.stituents of Polygonum multiflorum Thunb.including Stilbene Glucoside(THSG) and anthraquinone constituents(Emodin,Rhein,Aloeemodin,...OBJECTIVE This study investigated transcriptional regulation of the main chemical con.stituents of Polygonum multiflorum Thunb.including Stilbene Glucoside(THSG) and anthraquinone constituents(Emodin,Rhein,Aloeemodin,Chrysophanol and Physcion) and six potential liver injury constituents(gallic acid,quercetin,luteolin,kaempferol,resveratrol) on mediated by PXR CYP3A4.Early establishment of pregnane X receptor mediated CYP3A4 drug induced rapid screening technique was used to determine the effects of these constituents.METHODS First,effect of constituents on the cell activity was detected by MTS cell viability assay.IC50 was calculated.Second,the expression vector and reporter vector were co-transfected into Hep G2 cells,10 μmol·L^(-1) Rifampicin as a positive control,10 μmol·L^(-1) Ketoconazole as a negative control.After treated with different concentrations of(the an.thraquinone constituents concentrations were 2.5,5 and 10 μmol·L^(-1);the concentrations of Gallic Acid,Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol concentrations were 5,10 and 20 μmol·L^(-1)) for24 h,the cells were tested for dual luciferase activity.RESULTS The results show that the inhibitory ef.fect of THSG,Chrysophanol,Emodin,Rhein and Aloeemodin on CYP3A4 was inhibited by co-transfec.tion of pcDNA3.1 and pGL4.17-CYP3A4.The expression of pcDNA3.14-PXR and pGL4.17-CYP3A4 was induced by the four constituents.Besides,Emodin has a directly inducing effect.Four anthraqui.none constituentscan induce the effect of CYP3A4 by PXR,but Emodin can directly induce CYP3A4.THSG can inhibit CYP3A4,but in the presence of PXR plasmid can induce CYP3A4.For the six poten.tial liver injury constituents,results show that the plasmid pcDNA3.1 was cotransfected with pGL4.17-CYP3A4 regulation of Gallic Acid and Resveratrol on CYP3A4 inhibitory effects of Quercetin,Luteolin,Kaempferol have an induce effect;after pcDNA3.14-PXR and pGL4.17-CYP3A4 cotransfected,Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol have induced effect,three constituents' induc.tion effect had significant difference.CONCLUSION 12 kinds of Polygonum multiflorum Thunb.constit.uents have inhibitory or activating effects on CYP3A4,after the participation of PXR,9 components have induced effects on CYP3A4,and the induction effect of 6 components has significant difference.The results suggested that we should pay attention to potential drug interactions when combined with Polygonum multiflorum Thunb.,and improve safety and efficacy.展开更多
Objective:To isolate the phenolic compounds obtained from the dried roots ofPolygonum multiflorum and investigate their pharmacological activities.Methods:The chemical constituents were isolated and purified by combin...Objective:To isolate the phenolic compounds obtained from the dried roots ofPolygonum multiflorum and investigate their pharmacological activities.Methods:The chemical constituents were isolated and purified by combining them with a macroporous resin(DM-8),MCI gel,and Sephadex LH-20 and by performing ODS column chromatography.Their structures were elucidated by 1D and 2D NMR analyses,as well as mass spectrometry.The isolated compounds were evaluated to determine their hepatoprotective andα-glucosidase inhibitory activities in vitro.Results:Two phenolic compounds,namely,polygonimitin E(1)and polygonimitin F(2),were isolated from the dried roots of P.multiflorum.Compound 2(10μmol/L)only showed moderate hepatoprotective activity against N-acetyl-p-aminophenol(APAP)-induced HepG2 cell damage.Unfortunately,these two compounds exhibited noα-glucosidase inhibitory activity.Conclusion:Compounds 1 and 2 were new compounds.Compound 2 could be one of the potential hepatoprotective constituents of P.multiflorum.展开更多
目的通过网络药理学、分子对接和实验验证探究何首乌-虎杖治疗脑小血管病(cerebral small vessel disease,CSVD)的作用机制。方法运用TCMSP数据库筛选何首乌和虎杖的化学成分及相关靶点蛋白,在GeneCards和OMIM数据库获取痴呆、中风、健...目的通过网络药理学、分子对接和实验验证探究何首乌-虎杖治疗脑小血管病(cerebral small vessel disease,CSVD)的作用机制。方法运用TCMSP数据库筛选何首乌和虎杖的化学成分及相关靶点蛋白,在GeneCards和OMIM数据库获取痴呆、中风、健忘相关靶点,通过Cytoscape构建中药-活性成分-靶点网络图和蛋白相互作用图,再利用DAVID数据库对作用靶点进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集。利用Autodock将关键有效成分和重要靶点进行分子对接,评估其结合活性。最后采用β-淀粉样多肽1-42(amyloidβ_(1-42),Aβ_(1-42))诱导BV-2细胞构建阿尔茨海默病(Alzheimer's disease,AD)细胞模型,采用Western blot法研究何首乌-虎杖对AD细胞模型关键靶点表达的影响。结果筛选出24个化学成分,120个活性成分-疾病共有靶点。KEGG结果涉及磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase and protein kinase B,PI3K-Akt)、丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)、白介素-17(interleukin-17,IL-17)、缺氧诱导因子(hypoxia-inducible factor-1α,HIF-1)、肿瘤坏死因子(tumor necrosis factor,TNF)等多条炎症相关信号通路。筛选出槲皮素、大黄素、β-谷甾醇、大黄素甲醚、芹菜素5个关键化学成分,c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、TNF-α、细胞肿瘤抗原p53(cellular tumor antigen p53,P53)、白介素-6(interleukin-6,IL-6)和表皮生长因子受体(epidermal growth factor receptor,EGFR)5个关键靶点。分子对接结果显示,上述化合物与靶点的结合能均为负值。实验验证结果显示,何首乌-虎杖能显著抑制AD细胞模型5个关键靶点的表达。结论何首乌-虎杖可能通过调节核心靶点JNK、TNF-α、P53、IL-6抑制炎症反应、抑制细胞凋亡,从而发挥治疗CSVD作用。展开更多
基金the National Natural Science Foundation of China,No.82060707 and 82104381the Application and Basis Research Project of Yunnan China,No.202201AW070016,202001AZ070001-006,and 2019IB009the Young and Middle-aged Academic and Technological Leader of Yunnan,No.202005AC160059.
文摘BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is a severe threat to human health.Polygonum multiflorum(PM)has been proven to remedy mitochondria and relieve MAFLD,but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear.AIM To research the active ingredients of PM adjusting mitochondria to relieve highfat diet(HFD)-induced MAFLD in rats.METHODS Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms.The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats(mitochondrial pharmacology).PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry(mitochondrial pharmacochemistry).The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model,respectively.RESULTS PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD.PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis.Eight chemicals were found in the liver mitochondria of PM-administrated rats.The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.CONCLUSION PM restored mitochondrial structure and function and alleviated MAFLD,which may be associated with the remedy of oxidative stress and energy production.The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD.Thus,PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction.Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.
基金Supported by Applied Basic Research Project of Changzhou,No.CJ20190080。
文摘BACKGROUND Various types of drug-induced liver injury are induced by Polygonum multiflorum(PM);however,it rarely causes neutropenia.Herein,we report the case of a 65-year-old woman with concurrent severe hepatotoxicity and agranulocytosis induced by PM.CASE SUMMARY A 65-year-old woman reported with severe hepatotoxicity and agranulocytosis 17 d after ingestion of PM.The results of the Roussel Uclaf Causality Assessment Method demonstrated a highly probable relationship between hepatotoxicity and PM,with a total score of 10.The Naranjo algorithm results indicated that agranulocytosis had a probable relationship with PM,with an overall score of 6.Granulocyte colony-stimulating factor(for once),a steroid,compound glycyrrhizin,and polyene phosphatidylcholine therapy were initiated.After 15 d of treatment,there was a gradual improvement in liver biochemistry,leukocytes,and neutrophils levels.CONCLUSION Concurrent hepatotoxicity and agranulocytosis are rare and critical adverse drug reactions of PM,which should be highly valued.
基金supported by Hubei Science and Technology Plan key Project,Hubei Province,China(2019ABA100)。
文摘In 2021,there are approximately 537 million adults ageing 20-79 years affected by diabetes worldwide and the number is rising rapidly,hence it is important to manage and control diabetes mellitus and its associated complications.Food is one of the key factors in preventing and combating diseases such as diabetes.Both as a food and an herbal medicine,Polygonum multiflorum(PM)has been used as an anti-aging tonic,for hair darkening in traditional Chinese medicine for several centuries.The recent research effort of PM has been focused on antioxidant,anti-ageing and anti-tumor properties.In the present study,we utilized the traditional processing of harvested raw PM,and identified several stilbene components and then evaluated the potential anti-diabetic effects of the processed PM extract(PME).PME(0.075%)was given to diabetic mice(KK CgAy/J)in drinking water and after 7 weeks,PME-treated mice had significantly lower glucose levels than mice in the diabetic control group(P<0.01).The mechanism was explored with ELISA and Western blotting and results suggested that the effect was through maintainingβ-cell function.
文摘<strong>Background:</strong> <em>Polygonum multiflorum</em> (brand name Fo-ti) is a Chinese herb used as an antioxidant, antiaging agent, and liver and kidney health. It can cause acute hepatotoxicity and even death. There is no published data on the effectiveness of N-Acetyl cysteine (NAC) as a sole effective therapy. <strong>Case:</strong> A 23-year-old, healthy male, presented with jaundice and malaise of one-month duration. He had been taking a Chinese herb named Fo-Ti for 2 months. Physical examination revealed jaundice, with no stigmata of chronic liver disease. His laboratory results showed transaminitis with markedly elevated transaminases. Testings for infectious and autoimmune causes were unremarkable. The patient was admitted to the hospital. Fo-Ti was stopped and he was started on oral NAC as peroral protocol. He was discharged home on esomeprazole and oral NAC. He returned on the second day with worsening jaundice. He was readmitted and esomeprazole was discontinued. NAC was continued and his liver enzymes eventually improved. The supplement was tested by gas-chromatography mass spectrometry and measured the presence of emodin. <strong>Discussion:</strong> This case highlights the potential benefit of NAC as treatment of <em>Polygonum multiflorum</em> induced hepatotoxicity. The proposed mechanism of emodin induced liver injury is through disturbing glutathione metabolism in liver cells. This could explain the favorable response as NAC has the ability to replenish intracellular glutathione. <strong>Conclusion:</strong> <em>Polygonum multiflorum</em> use has been associated with severe and prolonged hepatotoxicity. Oral NAC should be considered in the treatment of these patients due to the favorable risk-benefit ratio.
基金the National Natural Science Foundation of China,No.81470849the China Mega-Project for Infectious Diseases,No.2017ZX10203202.
文摘BACKGROUND Polygonum multiflorum is one of the leading causes of herb-induced liver injury in China.HLA-B*35:01 is reported to be a potential biomarker of Polygonum multiflorum-induced liver injury(PM-DILI).However,little is known about the relationship between single-nucleotide polymorphisms(SNPs) and PM-DILI.AIM To identify SNPs that indicate susceptibility to PM-DILI METHODS We conducted a systematic study enrolling 382 participants from four independent hospitals,including 73 PM-DILI patients,118 patients with other drug-induced liver injury(other-DILI) and 191 healthy controls.Whole-exome sequencing was performed for 8 PM-DILI patients and 8 healthy controls who were randomly selected from the above subjects.Nineteen SNPs that showed high frequencies in the 8 PM-DILI patients were selected as candidate SNPs and then screened in 65 PM-DILI patients,118 other-DILI patients and 183 healthy controls using the MassARRAY system.HLA-B high-resolution genotyping was performed for the 73 PM-DILI and 118 other-DILI patients.The Han-MHC database was selected as a population control for HLA-B analysis.P <6.25 x 103 after Bolferroni correction was considered significant.RESULTS The frequencies of rslll686806 in the HLA-A gene,rs1055348 in the HLA-B gene,and rs202047044 in the HLA-DRB1 gene were significantly higher in the PM-DILI group than in the control group [27.2% vs 11.6%,P=1.72×105,odds ratio(OR)=3.96,95% confidence interval(Cl):2.21-7.14;42.5% vs 8.6%,P=1.72×10-19 OR=13.62,95% CI:7.16-25.9;22.9% vs 8.1%,P=4.64×106,OR=4.1,95% CI:2.25-7.47].Only rs1055348 showed a significantly higher frequency in the PM-DILI group than in the other-DILI group(42.5% vs 13.6%,P=1.84×10-10,OR=10.06,95% Cl:5.06-20.0),which suggested that it is a specific risk factor for PM-DILI.rs1055348 may become a tag for HLA-B*35:01 with 100% sensitivity and 97.7% specificity in the PM-DILI group and 100% sensitivity and 98.1% specificity in the other-DILI group.Furthermore,HLA-B*35:01 was confirmed to be associated with PM-DILI with a frequency of 41.1% in the PM-DILI group compared with 11.9%(P=4.30×10-11,OR=11.11,95% CI:5.57-22.19) in the other-DILI group and 2.7%(P=6.22×10-166,OR=62.62,95% Cl:35.91-109.20) in the Han-MHC database.CONCLUSION rslll686806,rs1055348,and rs202047044 are associated with PM-DILI,of which,rs1055348 is specific to PM-DILI.As a tag for HLA-B*35:01,rs1055348 may become an alternative predictive biomarker of PM-DILI.
基金Supported by Development and Research Center for China-ASEAN Traditional Medicine(05018017)Natural Science Foundation of Guangxi(2014GXNSFBA118195)
文摘[Objectives]This study aimed to optimize the preparation process of Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags.[Methods]Taking the comprehensive weighed score of total flavonoid content,soup color,aroma and taste as an indicator,the preparation process of tea bags was optimized using an orthogonal test.[Results]The results of the orthogonal test show that the optimal preparation process for the Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags are as follows:particle size of 14 meshes,solid to liquid ratio of 1∶40,brewing temperature of 70℃,and brewing time of 10 min.[Conclusions]The optimized preparation process is reasonable and feasible.It is suitable for the production of Radix Polygonum Multiflorum Preparata-Herba Taxilli tea bags.
基金supported by Beijing Natural Science Fund(7164291)Major National S&T Program(2015ZX09501004-003-003)Chinese Medicine Industry Projects(201507004)
文摘OBJECTIVE This study investigated transcriptional regulation of the main chemical con.stituents of Polygonum multiflorum Thunb.including Stilbene Glucoside(THSG) and anthraquinone constituents(Emodin,Rhein,Aloeemodin,Chrysophanol and Physcion) and six potential liver injury constituents(gallic acid,quercetin,luteolin,kaempferol,resveratrol) on mediated by PXR CYP3A4.Early establishment of pregnane X receptor mediated CYP3A4 drug induced rapid screening technique was used to determine the effects of these constituents.METHODS First,effect of constituents on the cell activity was detected by MTS cell viability assay.IC50 was calculated.Second,the expression vector and reporter vector were co-transfected into Hep G2 cells,10 μmol·L^(-1) Rifampicin as a positive control,10 μmol·L^(-1) Ketoconazole as a negative control.After treated with different concentrations of(the an.thraquinone constituents concentrations were 2.5,5 and 10 μmol·L^(-1);the concentrations of Gallic Acid,Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol concentrations were 5,10 and 20 μmol·L^(-1)) for24 h,the cells were tested for dual luciferase activity.RESULTS The results show that the inhibitory ef.fect of THSG,Chrysophanol,Emodin,Rhein and Aloeemodin on CYP3A4 was inhibited by co-transfec.tion of pcDNA3.1 and pGL4.17-CYP3A4.The expression of pcDNA3.14-PXR and pGL4.17-CYP3A4 was induced by the four constituents.Besides,Emodin has a directly inducing effect.Four anthraqui.none constituentscan induce the effect of CYP3A4 by PXR,but Emodin can directly induce CYP3A4.THSG can inhibit CYP3A4,but in the presence of PXR plasmid can induce CYP3A4.For the six poten.tial liver injury constituents,results show that the plasmid pcDNA3.1 was cotransfected with pGL4.17-CYP3A4 regulation of Gallic Acid and Resveratrol on CYP3A4 inhibitory effects of Quercetin,Luteolin,Kaempferol have an induce effect;after pcDNA3.14-PXR and pGL4.17-CYP3A4 cotransfected,Quercetin,Luteolin,Kaempferol,Apigenin,Resveratrol have induced effect,three constituents' induc.tion effect had significant difference.CONCLUSION 12 kinds of Polygonum multiflorum Thunb.constit.uents have inhibitory or activating effects on CYP3A4,after the participation of PXR,9 components have induced effects on CYP3A4,and the induction effect of 6 components has significant difference.The results suggested that we should pay attention to potential drug interactions when combined with Polygonum multiflorum Thunb.,and improve safety and efficacy.
基金The authors are grateful to the members of the analytical group of the State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College,Beijing,China for the spectroscopic data measurements and bioactivity tests.This project was financially supported by the National Natural Science Foundation of China(Nos.81703665,81773874,81973476 and 81903807)the National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2018ZX09735006).
文摘Objective:To isolate the phenolic compounds obtained from the dried roots ofPolygonum multiflorum and investigate their pharmacological activities.Methods:The chemical constituents were isolated and purified by combining them with a macroporous resin(DM-8),MCI gel,and Sephadex LH-20 and by performing ODS column chromatography.Their structures were elucidated by 1D and 2D NMR analyses,as well as mass spectrometry.The isolated compounds were evaluated to determine their hepatoprotective andα-glucosidase inhibitory activities in vitro.Results:Two phenolic compounds,namely,polygonimitin E(1)and polygonimitin F(2),were isolated from the dried roots of P.multiflorum.Compound 2(10μmol/L)only showed moderate hepatoprotective activity against N-acetyl-p-aminophenol(APAP)-induced HepG2 cell damage.Unfortunately,these two compounds exhibited noα-glucosidase inhibitory activity.Conclusion:Compounds 1 and 2 were new compounds.Compound 2 could be one of the potential hepatoprotective constituents of P.multiflorum.
基金Acknowledgements This work was supported by the National Key Technology R＆D Program （No. 2015ZX09501-004-001-008）, the National TCM Industry Science and Technology Program （No. 201507004-04）, the National Natural Science Foundation of China （Nos. 81373984, 81503350, and 81403126）, and the Beijing Natural Science Foundation （No. 7152142）. The authors wish to acknowledge Jiyan Chen for providing photographs of fraudulent Heshouwu, Yonghe Zhang for determining the pesticides, and Dongping Xu for his suggestion regarding the scale table of ECCIA.
文摘草药的药最近在美国作为导致药的肝损害(DILI ) 的第二个很普通的原因被认出了。然而，识别一些植物的 DILI 诱发性的可靠方法例如 Heshouwu (蓼 multiflorum 的弄干的根) ，留下缺乏。在这研究，有肝机能障碍和 Heshouwu DILI 的 147 个报导文学的案例的 12 307 个住院病人的一个总数被屏蔽。一个一般算法仅仅显示了那 22.5%(9/40 ) 并且(45/147 ) 分别地， 30.6% 所有住院和文学案例报告表明 Heshouwu 的 DILI 诱发性的高概率。由对比，(19/20 )95% 生药学，植物化学，和 metabolomic 有希望地调查的所有情况测试展出高度可能的诱发性，包括不正确地以前被归因的一个病人和从由 pharmacognostic 证据的 Heshouwu 诱发性被排除的一个案例。污染也是的毒素(重金属，杀虫剂，和 mycotoxins ) 从 Heshouwu DILI 诱发性排除了。为 Heshouwu DILI 诊断地址安全的这些屏蔽方法的客观性担心考虑包含芪的草药的药和饮食的补充。
文摘目的通过网络药理学、分子对接和实验验证探究何首乌-虎杖治疗脑小血管病(cerebral small vessel disease,CSVD)的作用机制。方法运用TCMSP数据库筛选何首乌和虎杖的化学成分及相关靶点蛋白,在GeneCards和OMIM数据库获取痴呆、中风、健忘相关靶点,通过Cytoscape构建中药-活性成分-靶点网络图和蛋白相互作用图,再利用DAVID数据库对作用靶点进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集。利用Autodock将关键有效成分和重要靶点进行分子对接,评估其结合活性。最后采用β-淀粉样多肽1-42(amyloidβ_(1-42),Aβ_(1-42))诱导BV-2细胞构建阿尔茨海默病(Alzheimer's disease,AD)细胞模型,采用Western blot法研究何首乌-虎杖对AD细胞模型关键靶点表达的影响。结果筛选出24个化学成分,120个活性成分-疾病共有靶点。KEGG结果涉及磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase and protein kinase B,PI3K-Akt)、丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)、白介素-17(interleukin-17,IL-17)、缺氧诱导因子(hypoxia-inducible factor-1α,HIF-1)、肿瘤坏死因子(tumor necrosis factor,TNF)等多条炎症相关信号通路。筛选出槲皮素、大黄素、β-谷甾醇、大黄素甲醚、芹菜素5个关键化学成分,c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、TNF-α、细胞肿瘤抗原p53(cellular tumor antigen p53,P53)、白介素-6(interleukin-6,IL-6)和表皮生长因子受体(epidermal growth factor receptor,EGFR)5个关键靶点。分子对接结果显示,上述化合物与靶点的结合能均为负值。实验验证结果显示,何首乌-虎杖能显著抑制AD细胞模型5个关键靶点的表达。结论何首乌-虎杖可能通过调节核心靶点JNK、TNF-α、P53、IL-6抑制炎症反应、抑制细胞凋亡,从而发挥治疗CSVD作用。
