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Berberine AND cyp 450

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https://www.readbyqxmd.com/read/27070564/in-vivo-and-in-vitro-study-on-drug-drug-interaction-of-lovastatin-and-berberine-from-pharmacokinetic-and-hepg2-cell-metabolism-studies
#1
Hanming Cui, Jialong Wang, Qiuyan Zhang, Mengmeng Dang, Hui Liu, Yu Dong, Lu Zhang, Fang Yang, Jianhua Wu, Xiaolin Tong
BACKGROUND: We assumed that the pharmacokinetics of lovastatin could be changed by the induction effect of berberine. METHODS: An UPLC-MS/MS method was developed and validated for the pharmacokinetics tudy of lovastatin to investigate the in vivo drug-drug interactions between lovastatin and berberine. SD male rats were random divided into lovastatin group and berberine induced prior to lovastatin group for the in vivo pharmacokinetic studies. Meanwhile HepG2 cells were induced by berberine for three days to study the metabolism of lovastatin...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/24583342/palmatine-activates-ahr-and-upregulates-cyp1a-activity-in-hepg2-cells-but-not-in-human-hepatocytes
#2
Jiri Vrba, Marika Havlikova, Denisa Gerhardova, Jitka Ulrichova
The protoberberine alkaloid palmatine is present in preparations from medicinal plants such as Coptis chinensis and Corydalis yanhusuo. This study examined whether palmatine affects the expression of cytochromes P450 (CYPs) 1A1 and 1A2 in primary cultures of human hepatocytes and human hepatoma HepG2 cells grown as monolayer or spheroids. Gene reporter assays showed that palmatine significantly activated the aryl hydrocarbon receptor (AhR) and increased the activity of CYP1A1 gene promoter in transiently transfected HepG2 cells...
June 2014: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/24528081/preferential-induction-of-cyp1a1-over-cyp1b1-in-human-breast-cancer-mcf-7-cells-after-exposure-to-berberine
#3
Chun-Jie Wen, Lan-Xiang Wu, Li-Juan Fu, Dong-Ya Shen, Xue Zhang, Yi-Wen Zhang, Jing Yu, Hong-Hao Zhou
Estrogens are considered the major breast cancer risk factor, and the carcinogenic potential of estrogens might be attributed to the DNA modification caused by derivatives formed during metabolism. 17β-estradiol (E2), the main steroidal estrogen present in women, is metabolized via two major pathways: formation of the 2-hydroxyestradiol (2-OH E2) and 4-hydroxyestradiol (4-OH E2) through the action of Cytochrome P450 (CYP) 1A1 and 1B1, respectively. Previous reports suggested that 2-OH E2 have putative protective effects, while 4-OH E2 is genotoxic and has potent carcinogenic activity...
2014: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/23886934/inhibition-of-cyp1-by-berberine-palmatine-and-jatrorrhizine-selectivity-kinetic-characterization-and-molecular-modeling
#4
Sheng-Nan Lo, Yu-Ping Chang, Keng-Chang Tsai, Chia-Yu Chang, Tian-Shung Wu, Yune-Fang Ueng
Cytochrome P450 (P450, CYP) 1 family plays a primary role in the detoxification and bioactivation of polycyclic aromatic hydrocarbons. Human CYP1A1, CYP1A2, and CYP1B1 exhibit differential substrate specificity and tissue distribution. Berberine, palmatine, and jatrorrhizine are protoberberine alkaloids present in several medicinal herbs, such as Coptis chinensis (Huang-Lian) and goldenseal. These protoberberines inhibited CYP1A1.1- and CYP1B1.1-catalyzed 7-ethoxyresorufin O-deethylation (EROD) activities, whereas CYP1A2...
November 1, 2013: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/23299247/cyp450-1a2-and-multiple-ugt1a-isoforms-are-responsible-for-jatrorrhizine-metabolism-in-human-liver-microsomes
#5
Hui Zhou, Rong Shi, Bingliang Ma, Yueming Ma, Changhong Wang, Dazheng Wu, Xinhong Wang, Nengneng Cheng
Jatrorrhizine, one of the protoberberine alkaloids derived from the plant Coptis chinensis, is expected to be developed as a new gastric prokinetic drug, but its metabolic characteristics in humans remain unknown. This study characterized the phase I and phase II metabolites, metabolic kinetics, and cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes responsible for the metabolism of jatrorrhizine in human liver microsomes (HLMs). Chemical inhibition in HLMs and metabolism by recombinant human CYP or UGT enzymes were employed to determine the key metabolic enzyme subtypes...
April 2013: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/23001793/stereoselective-interaction-between-tetrahydropalmatine-enantiomers-and-cyp-enzymes-in-human-liver-microsomes
#6
Si-Yuan Sun, Yu-Qing Wang, Li-Ping Li, Lu Wang, Su Zeng, Hui Zhou, Hui-Di Jiang
Tetrahydropalmatine (THP), with one chiral center, is an alkaloid that possesses analgesic and many other pharmacological actives. The aim of the present study is to investigate stereoselective metabolism of THP enantiomers in human liver microsomes (HLM) and elucidate which cytochrome P450 (CYP) isoforms contribute to the stereoselective metabolism in HLM. Additionally, the inhibitions of THP enantiomers on activity of CYP enzymes are also investigated. The results demonstrated that (+)-THP was preferentially metabolized by HLM...
January 2013: Chirality
https://www.readbyqxmd.com/read/22855269/clinical-evidence-of-herbal-drugs-as-perpetrators-of-pharmacokinetic-drug-interactions
#7
REVIEW
Robert Hermann, Oliver von Richter
The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular highly prevalent in patient populations already exposed to complex treatment algorithms and polypharmacotherapy, frequently involving narrow therapeutic index drugs. Accordingly, the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years. However, review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive...
September 2012: Planta Medica
https://www.readbyqxmd.com/read/22517372/stereoselective-metabolism-of-tetrahydropalmatine-enantiomers-in-rat-liver-microsomes
#8
Ming Zhao, Li-Ping Li, Dong-Li Sun, Si-Yuan Sun, Shan-Ding Huang, Su Zeng, Hui-Di Jiang
Tetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)-THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Cl(int)) ratios of (+)-THP to (-)-THP were 2...
May 2012: Chirality
https://www.readbyqxmd.com/read/22342832/modulations-of-cytochrome-p450-expression-in-diabetic-mice-by-berberine
#9
Waranya Chatuphonprasert, Nobuo Nemoto, Tsutomu Sakuma, Kanokwan Jarukamjorn
Berberine, an isoquinoline alkaloid isolated from medicinal plants such as Berberis aristata, Coptis chinesis, Coptis japonica, Coscinium fenestatun, and Hydrastis Canadensis, is widely used in Asian countries for the treatment of diabetes, hypertension, and hypercholesterolemia. Interaction between berberine and the cytochrome P450 enzymes (CYPs) has been extensively reported, but there are only a few reports of this interaction in the diabetic state. In this study, the effect of berberine on the mRNA of the CYPs in primary mouse hepatocytes and in streptozotocin (STZ)-induced diabetic mice was investigated...
March 5, 2012: Chemico-biological Interactions
https://www.readbyqxmd.com/read/21920422/dose-response-of-berberine-on-hepatic-cytochromes-p450-mrna-expression-and-activities-in-mice
#10
Ying Guo, Chad Pope, Xingguo Cheng, Honghao Zhou, Curtis D Klaassen
ETHNOPHARMACOLOGICAL RELEVANCE: Berberine is an isoquinoline alkaloid isolated from the root and bark of plants such as goldenseal, Berberis, and Chinese goldthread. Berberine-containing crude drugs have been used as an antimicrobial remedy against gastrointestinal infections for thousands of years. It is also widely used in Asian countries for diabetes, hypertension, and hypercholesterolemia therapy. AIM OF THE STUDY: Potential drug-drug interactions are of concern because of the wide usage of berberine...
October 31, 2011: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/21870106/repeated-administration-of-berberine-inhibits-cytochromes-p450-in-humans
#11
RANDOMIZED CONTROLLED TRIAL
Ying Guo, Yao Chen, Zhi-Rong Tan, Curtis D Klaassen, Hong-Hao Zhou
PURPOSE: Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interactions between berberine-containing products and cytochromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses. METHODS: A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t...
February 2012: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/21787170/cyp2d-plays-a-major-role-in-berberine-metabolism-in-liver-of-mice-and-humans
#12
Ying Guo, Feng Li, Xiaochao Ma, Xingguo Cheng, Honghao Zhou, Curtis D Klaassen
Berberine is a widely used plant extract for gastrointestinal infections, and is reported to have potential benefits in treatment for diabetes and hypercholesterolemia. It has been suggested that interactions between berberine-containing products and cytochromes P450 (CYPs) exist, but little is known about which CYPs mediate the metabolism of berberine in vivo. In this study, berberine metabolites in urine and feces of mice were analyzed, and the role that CYPs play in producing these metabolites were characterized in liver microsomes from mice (MLM) and humans (HLM), as well as recombinant human CYPs...
November 2011: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/21755496/development-of-a-whole-cell-screening-system-for-evaluation-of-the-human-cyp1a2-mediated-metabolism
#13
Chih-Chieh Chu, Kao-Lu Pan, Hsien-Tsung Yao, John Tsu-An Hsu
Cytochrome P450 1A2 (CYP1A2) is an important member of cytochrome P450 involved in drug metabolism. In this study, a cell line, Huh7-1A2-I-E, with high expression level of CYP1A2 is established based on Huh7 cells. To achieve this, we constructed a recombinant lentiviral vector, pLenti-1A2-I-E, containing a single promoter encoding CYP1A2 followed by an internal ribosome entry site (IRES) to permit the translation of enhanced green fluorescence protein (EGFP). Such a design has greatly facilitated the selection of stable cell lines because the translations of CYP1A2 and EGFP proteins would be based on a single bi-cistronic mRNA...
December 2011: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/21678521/the-in-vitro-inhibition-of-human-cyp1a2-cyp2d6-and-cyp3a4-by-tetrahydropalmatine-neferine-and-berberine
#14
Yong Zhao, Bent Håvard Hellum, Aihua Liang, Odd Georg Nilsen
The purpose of this study was to investigate the in vitro inhibition potential of the three purified herbal constituents tetrahydropalmatine (Tet), neferine (Nef) and berberine (Ber) towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. In vitro incubations were performed with phenacetin, dextromethorphan and testosterone, respectively, as CYP substrates and their metabolites were determined by validated HPLC methods. Positive control inhibitors were run for each CYP in all incubation series...
February 2012: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/21419197/protopine-and-allocryptopine-increase-mrna-levels-of-cytochromes-p450-1a-in-human-hepatocytes-and-hepg2-cells-independently-of-ahr
#15
Jiri Vrba, Eva Vrublova, Martin Modriansky, Jitka Ulrichova
The isoquinoline alkaloids protopine and allocryptopine are present in phytopreparations from medicinal plants, such as Fumaria officinalis. Since nothing is known about effects of the alkaloids on the expression of xenobiotic-metabolizing enzymes, we examined whether protopine or allocryptopine affect the expression of cytochromes P450 (CYPs) 1A1 and 1A2 in primary cultures of human hepatocytes and human hepatoma HepG2 cells. In HepG2 cells, protopine and allocryptopine significantly increased CYP1A1 mRNA levels after 24h exposure at concentrations from 25 and 10 μM, respectively, as shown by real-time PCR...
June 10, 2011: Toxicology Letters
https://www.readbyqxmd.com/read/21351505/-in-vitro-o-demethylation-of-rotundine-by-recombinant-human-cyp-isoenzymes
#16
Chun-zheng Li, Qing-hui Lin, Xiao-mei Zhuang, Jian-wei Xie, Hua Li
Rotundine (1 micromol L(-1)) was incubated with a panel of rCYP enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remained parent drug in incubates was quantitatively analyzed by an Agilent LC-MS. CYP2C19, 3A4 and 2D6 were identified to be the isoenzymes involved in the metabolism of rotundine. The individual contributions of CYP2C19, 3A4 and 2D6 to the rotundine metabolism were assessed using the method of total normalized rate to be 31.46%, 60.37% and 8.17%, respectively. The metabolites of rotundine in incubates were screened with ESI-MS at selected ion mode, and were further identified using MS2 spectra and precise molecular mass obtained from an Agilent LC/Q-TOF-MSMS, as well as MS(n) spectra of LC-iTrap-MS(n)...
March 2010: Yao Xue Xue Bao, Acta Pharmaceutica Sinica
https://www.readbyqxmd.com/read/20641061/identification-of-cytochrome-p450-cyp-isoforms-involved-in-the-metabolism-of-corynoline-and-assessment-of-its-herb-drug-interactions
#17
Zhong-Ze Fang, Yan-Yan Zhang, Guang-Bo Ge, Si-Cheng Liang, Dong-Xue Sun, Liang-Liang Zhu, Pei-Pei Dong, Yun-Feng Cao, Ling Yang
Corynoline, an isoquinoline alkaloid isolated from the genus Corydalis, has been demonstrated to show multiple pharmacological effects including inhibition of acetylcholinesterase, inhibition of cell adhesion, fungitoxic and cytotoxic activity. The present study focused on its metabolism and metabolism-based herb-drug interactions. After corynoline was incubated with human liver microsomes (HLMs) in the presence of NADPH, two metabolites (M-1 and M-2) were formed. Chemical inhibition experiments and assays with recombinant CYP isoforms showed that CYP2C9 was mainly involved in the formation of M-1 and CYP3A4 mainly catalysed the production of M-2...
February 2011: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/19283771/oxidative-demethylenation-and-subsequent-glucuronidation-are-the-major-metabolic-pathways-of-berberine-in-rats
#18
Yitong Liu, Haiping Hao, Hongguang Xie, Hua Lv, Changxiao Liu, Guangji Wang
Present study was designed to explore roles of metabolic clearance in the disposition of berberine (BBR) in rats, with a focus on oxidative metabolism and subsequent glucuronidation. Plasma from rats after intravenous administration of BBR was collected to identify and quantify BBR and its major metabolites. The major circulating metabolites of BBR were oxidative metabolites M1 (via demethylation) and M2 (via demethylenation) and their corresponding glucuronides, with M2-glucuronide approximately 24-fold higher than M1-glucuronide...
November 2009: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/17418998/effect-of-berberine-on-hepatocyte-proliferation-inducible-nitric-oxide-synthase-expression-cytochrome-p450-2e1-and-1a2-activities-in-diethylnitrosamine-and-phenobarbital-treated-rats
#19
Xuan Zhao, Jun-Jie Zhang, Xin Wang, Xiu-Yun Bu, Ya-Qing Lou, Guo-Liang Zhang
This study investigated the effect of berberine on the early phase of hepatocarcinogenesis stimulated by diethylnitrosamine (DEN, 150 mg/kg, 4 weeks) plus phenobarbital (PB, 75 mg/kg, 7 days) in rats. The expressions of proliferating cell nuclear antigen (PCNA) and inducible nitric oxide synthase (iNOS) were evaluated by immunohistochemistry. The activities of CYP isoenzymes were analyzed using different probe drugs including chlorzoxazone (CYP2E1) and phenacetin (CYP1A2) by high-performance liquid chromatography (HPLC) in vivo or in vitro...
November 2008: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/14757125/cytochrome-p450-isoenzymes-involved-in-rat-liver-microsomal-metabolism-of-californine-and-protopine
#20
Liane D Paul, Dietmar Springer, Roland F Staack, Thomas Kraemer, Hans H Maurer
Studies are described on the cytochrome P450 (CYP) isoenzyme dependence of the main metabolic steps of the Eschscholtzia californica alkaloids californine and protopine using rat liver microsomes. Preparations of E. californica are in use as phytopharmaceuticals and as herbal drugs of abuse. CYP isoenzyme dependences were studied using specific chemical inhibitors for CYP1A2, CYP2D1, and CYP3A2 (alpha-naphthoflavone, quinine, and ketoconazole, respectively). CYP2C11 was inhibited by specific antibodies for lack of specific chemical inhibitors...
February 6, 2004: European Journal of Pharmacology
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