Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistoc...Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.展开更多
Background:Yuanhu Zhitong Prescription(元胡止痛方,YZP),a well-known herbal prescription for an analgesic effect,is recorded in the China Pharmacopoeia,consisting of Yanhusuo(Rhizoma Corydalis)and Baizhi(Radix Angelica...Background:Yuanhu Zhitong Prescription(元胡止痛方,YZP),a well-known herbal prescription for an analgesic effect,is recorded in the China Pharmacopoeia,consisting of Yanhusuo(Rhizoma Corydalis)and Baizhi(Radix Angelicae Dahuricae).Objective:To explore the influence of 70%EtOH extracts from Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)and YZP on the CYP450s,especially the differences between the single drug and prescription.Materials and methods:Cocktail probe drugs method was used to evaluate Cytochrome P450 activities in rat liver microsomes,including CYP1A2,CYP2D1,CYP2C11,CYP2C6 and CYP3A1,after rats repeatedly administrated with the extracts of Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)and YZP for 7 days.Results:Yanhusuo(Rhizoma Corydalis)extracts significantly increased the activities of CYP1A2,2C6 and 3A1,and inhibited that of 2D1.Baizhi(Radix Angelicae Dahuricae)extracts significantly increased the activities of CYP1A2 and inhibited that of 2D1 and 2C11.YZP extracts exhibited the same effect with single drugs.Conclusion:These results might partly interpret the TCM compatibility.Moreover,co-administration of prescriptions containing Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)or YZP should consider a potential herb(drug)-drug interaction medicated by the induction of CYP1A2,2C6 and 3A1 and inhibition of CYP2D1 and 2C11 enzymes.展开更多
Tobacco smoking is a global public health threat causing several illnesses including cardiovascular disease(Myocardial infarction), cerebrovascular disease(Stroke), peripheral vascular disease(Claudication), chronic o...Tobacco smoking is a global public health threat causing several illnesses including cardiovascular disease(Myocardial infarction), cerebrovascular disease(Stroke), peripheral vascular disease(Claudication), chronic obstructive pulmonary disease, asthma, reduced female infertility, sexual dysfunction in men, different types of cancer and many other diseases. It has been estimated in 2015 that approximately 1.3 billion people smoke, around the globe. Use of medications among smokers is more common, nowadays. This review is aimed to identify the medications affected by smoking, involving Cytochrome P450(CYP)and uridine diphosphate-glucuronosyltransferases(UGTs) enzymes and Nicotine. Polycyclic aromatic hydrocarbons(PAHs) of tobacco smoke have been associated with the induction of CYP enzymes such as CYP1A1, CYP1A2 and possibly CYP2E1 and UGT enzymes. The drugs metabolized by CYP1A1,CYP1A2, CYP2E1 and UGT enzymes might be affected by tobacco smoking and the smokers taking medications metabolized by those enzymes, may need higher doses due to decreased plasma concentrations through enhanced induction by PAHs of tobacco smoke. The prescribers and the pharmacists are required to be aware of medications affected by tobacco smoking to prevent the toxicityassociated complications during smoking cessation.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
Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfu...Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfusion technique, then brain tissues were postfixed, paraffin-embedded and cut into series sections, which were labeled by the improved strept-avidin-biotin complex DAB-nickel enhancer (SABC-DAB-Ni) immunohistochemistry and hematoxylin & eosin (H & E) stain techniques.Results The immunohistochemical results indicated that P450 2C-11 enzyme was localized in diverse numbers of neurons as well as some neuroglial cells, with focal or defuse distribution in many brain regions such as cerebrum, thalamus, olfactory bulb, hypothalamus, brain-stem, hippocampus, cerebellum, interpositus nucleus, caudate-putamen, and globus pallidus. In contrast, no positive findings of P450 4A-2, 3 and 8 enzymes were obtained in the same animals. With high magnification, 2C-11 protein was able to be roughly observed on the endoplasmic reticulum of the rat neurons.Conclusions P450 2C-11 protein, rather than P450 4A-2, 3 and 8, may be a candidate of brain P450 enzymes in the normal male rats.展开更多
OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large over...OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered.展开更多
OBJECTIVE： Consuming botanical dietary supplements or herbal drugs along with prescription drugs may lead to potential pharmacokinetic-pharmacodynamic（PK-PD） herb-drug interactions（HDI）. The present study focuses...OBJECTIVE： Consuming botanical dietary supplements or herbal drugs along with prescription drugs may lead to potential pharmacokinetic-pharmacodynamic（PK-PD） herb-drug interactions（HDI）. The present study focuses on the importance of and novel approach for assessing HDI in integrative medicine with case examples of two frequently-used Ayurvedic Rasayana botanicals.METHODS： The aqueous extracts of Asparagus racemosus（ARE） and Gymnema sylvester（GSE） were prepared as per Ayurvedic Pharmacopoeia of India. Chemoprofiling of these extracts was done using high-performance liquid chromatography（HPLC）. Additionally, ARE was characterized for the presence of shatavarins IV and I using HPLC ＆ mass spectroscopy respectively. Effects of ARE and GSE were investigated on rat liver microsome using testosterone probe drug assay. The changes in formation of metabolite（6-β hydroxy testosterone） were monitored on incubation of testosterone alone, testosterone with ketoconazole, ARE and GSE using HPLC. Half inhibitory concentration（IC50） was used to predict plausible HDI.RESULTS： ARE and GSE showed no inhibition with IC50 values 〉1 000 μg/m L while the standard inhibitor ketoconazole completely abolished CYP3A4-dependent activity at 0.531 μg/m L and IC50 was found to be 0.036 μg/m L.CONCLUSION： ARE and GSE prepared as per Ayurvedic Pharmacopoeia of India were found to be safe for CYP3A4-mediated inhibitory HDI in rats. Our in vitro study suggests the need of further in vivo investigation for HDI in order to provide clinical relevance.展开更多
文摘Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines.
基金National Key Research and Development Program of China[2017YFC1702104,2017YFC1702303]National Natural Science Foundation of China[Grant No.81830111 and 81774201]the Youth Innovation Team of Shaanxi Universities and Shaanxi Provincial Science and Technology Department Project[No.2016SF-378]。
文摘Background:Yuanhu Zhitong Prescription(元胡止痛方,YZP),a well-known herbal prescription for an analgesic effect,is recorded in the China Pharmacopoeia,consisting of Yanhusuo(Rhizoma Corydalis)and Baizhi(Radix Angelicae Dahuricae).Objective:To explore the influence of 70%EtOH extracts from Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)and YZP on the CYP450s,especially the differences between the single drug and prescription.Materials and methods:Cocktail probe drugs method was used to evaluate Cytochrome P450 activities in rat liver microsomes,including CYP1A2,CYP2D1,CYP2C11,CYP2C6 and CYP3A1,after rats repeatedly administrated with the extracts of Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)and YZP for 7 days.Results:Yanhusuo(Rhizoma Corydalis)extracts significantly increased the activities of CYP1A2,2C6 and 3A1,and inhibited that of 2D1.Baizhi(Radix Angelicae Dahuricae)extracts significantly increased the activities of CYP1A2 and inhibited that of 2D1 and 2C11.YZP extracts exhibited the same effect with single drugs.Conclusion:These results might partly interpret the TCM compatibility.Moreover,co-administration of prescriptions containing Yanhusuo(Rhizoma Corydalis),Baizhi(Radix Angelicae Dahuricae)or YZP should consider a potential herb(drug)-drug interaction medicated by the induction of CYP1A2,2C6 and 3A1 and inhibition of CYP2D1 and 2C11 enzymes.
文摘Tobacco smoking is a global public health threat causing several illnesses including cardiovascular disease(Myocardial infarction), cerebrovascular disease(Stroke), peripheral vascular disease(Claudication), chronic obstructive pulmonary disease, asthma, reduced female infertility, sexual dysfunction in men, different types of cancer and many other diseases. It has been estimated in 2015 that approximately 1.3 billion people smoke, around the globe. Use of medications among smokers is more common, nowadays. This review is aimed to identify the medications affected by smoking, involving Cytochrome P450(CYP)and uridine diphosphate-glucuronosyltransferases(UGTs) enzymes and Nicotine. Polycyclic aromatic hydrocarbons(PAHs) of tobacco smoke have been associated with the induction of CYP enzymes such as CYP1A1, CYP1A2 and possibly CYP2E1 and UGT enzymes. The drugs metabolized by CYP1A1,CYP1A2, CYP2E1 and UGT enzymes might be affected by tobacco smoking and the smokers taking medications metabolized by those enzymes, may need higher doses due to decreased plasma concentrations through enhanced induction by PAHs of tobacco smoke. The prescribers and the pharmacists are required to be aware of medications affected by tobacco smoking to prevent the toxicityassociated complications during smoking cessation.
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).
文摘Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfusion technique, then brain tissues were postfixed, paraffin-embedded and cut into series sections, which were labeled by the improved strept-avidin-biotin complex DAB-nickel enhancer (SABC-DAB-Ni) immunohistochemistry and hematoxylin & eosin (H & E) stain techniques.Results The immunohistochemical results indicated that P450 2C-11 enzyme was localized in diverse numbers of neurons as well as some neuroglial cells, with focal or defuse distribution in many brain regions such as cerebrum, thalamus, olfactory bulb, hypothalamus, brain-stem, hippocampus, cerebellum, interpositus nucleus, caudate-putamen, and globus pallidus. In contrast, no positive findings of P450 4A-2, 3 and 8 enzymes were obtained in the same animals. With high magnification, 2C-11 protein was able to be roughly observed on the endoplasmic reticulum of the rat neurons.Conclusions P450 2C-11 protein, rather than P450 4A-2, 3 and 8, may be a candidate of brain P450 enzymes in the normal male rats.
基金National Natural Science Foundation of China(Research Method and Key Technology of Intracorporal Process of Therapeutic Material Basis Based on Concurrent Multiple Metabolism,No.81274042)Special Fund for Scientific Research in the Public Interest(Research on the Treament of Cerebral Infarction With the Combination of Chinese and Western Medicine and the Literature Analysis,No.201407013)
文摘OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered.
基金BSDT’s Ayurvedic College, Synapse Laboratory Pvt. Ltd., National Toxicology Center, & National Centre for Cell Science, Pune for extending their kind support to carry out this work
文摘OBJECTIVE： Consuming botanical dietary supplements or herbal drugs along with prescription drugs may lead to potential pharmacokinetic-pharmacodynamic（PK-PD） herb-drug interactions（HDI）. The present study focuses on the importance of and novel approach for assessing HDI in integrative medicine with case examples of two frequently-used Ayurvedic Rasayana botanicals.METHODS： The aqueous extracts of Asparagus racemosus（ARE） and Gymnema sylvester（GSE） were prepared as per Ayurvedic Pharmacopoeia of India. Chemoprofiling of these extracts was done using high-performance liquid chromatography（HPLC）. Additionally, ARE was characterized for the presence of shatavarins IV and I using HPLC ＆ mass spectroscopy respectively. Effects of ARE and GSE were investigated on rat liver microsome using testosterone probe drug assay. The changes in formation of metabolite（6-β hydroxy testosterone） were monitored on incubation of testosterone alone, testosterone with ketoconazole, ARE and GSE using HPLC. Half inhibitory concentration（IC50） was used to predict plausible HDI.RESULTS： ARE and GSE showed no inhibition with IC50 values 〉1 000 μg/m L while the standard inhibitor ketoconazole completely abolished CYP3A4-dependent activity at 0.531 μg/m L and IC50 was found to be 0.036 μg/m L.CONCLUSION： ARE and GSE prepared as per Ayurvedic Pharmacopoeia of India were found to be safe for CYP3A4-mediated inhibitory HDI in rats. Our in vitro study suggests the need of further in vivo investigation for HDI in order to provide clinical relevance.
