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[PMID]: 29472517
[Au] Autor:Chan JKW; Bittner S; Bittner A; Atwal S; Shen WJ; Inayathullah M; Rajada J; Nicolls MR; Kraemer FB; Azhar S
[Ad] Address:VA Palo Alto Health CareSystem.
[Ti] Title:Nordihydroguaiaretic acid, a lignan from Larrea tridentata (Creosote bush) protects against ALIOS diet-induced metabolic dysfunction in mice.
[So] Source:J Pharmacol Exp Ther;, 2018 Feb 22.
[Is] ISSN:1521-0103
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:To determine the effects of NDGA on metabolic and molecular changes in response to feeding mice typical American fast food or Western diet, mice were fed with ALIOS diet and subjected to metabolic analysis. Male C57BL/6J mice were randomly assigned to: ALIOS, ALIOS + NDGA, or control diet and maintained on the specific diet for 8 weeks. Mice fed ALIOS diet, showed increased body, liver and epididymal fat pad weight, plasma ALT and AST levels (a measure of liver injury), and liver triglyceride (TG) content. Co-administration of NDGA normalized body and epididymal fat pad weight, ALT and AST levels, and liver TG. NDGA treatment also improved insulin sensitivity but not glucose intolerance in ALIOS diet fed mice. In ALIOS diet fed mice, NDGA supplementation induced PPARα (the master regulator of fatty acid oxidation) and mRNA levels of Cpt1c and Cpt2, key genes involved in fatty acid oxidation as compared to ALIOS diet. NDGA significantly reduced liver ER stress response CHOP protein, as compared to chow or ALIOS diet and also ameliorated ALIOS diet-induced elevation of apoptosis signaling protein, CASP3. Likewise, NDGA downregulated the ALIOS-diet induced mRNA levels of Pparg, Fasn, and Dgat2. NDGA treatment of ALIOS fed mice upregulated the hepatic expression of antioxidant enzymes, GPX4 and PRDX3 proteins. In conclusion, we provide evidence that NDGA improves metabolic dysregulation by simultaneously modulating PPARα transcription factor and key genes involved in fatty acid oxidation, key antioxidant and lipogenic enzymes, and apoptosis and ER stress signaling pathways.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180227
[Lr] Last revision date:180227
[St] Status:Publisher

  2 / 258 MEDLINE  
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[PMID]: 29427244
[Au] Autor:García JE; Gómez L; Mendoza-de-Gives P; Rivera-Corona JL; Millán-Orozco J; Ascacio JA; Medina MA; Mellado M
[Ad] Address:Department of Animal Nutrition, Autonomous Agrarian University Antonio Narro, 25315, Saltillo, Coahuila, Mexico.
[Ti] Title:Anthelmintic efficacy of hydro-methanolic extracts of Larrea tridentata against larvae of Haemonchus contortus.
[So] Source:Trop Anim Health Prod;, 2018 Feb 09.
[Is] ISSN:1573-7438
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:An in vitro study was conducted to determine the anthelminthic activity of hydro-methanolic extracts of Larrea tridentata on sheathed and exsheathed larvae of Haemonchus contortus. Larvae of the parasite were incubated at 20-25 °C in hydro-methanolic extracts at concentrations of 12.5, 25, 50, 100, and 200 mg/mL for 24, 48, or 72 h. Ivermectin and water were the positive and negative controls, respectively. Total phenolic compounds of leaves of L. tridentata were 97.88 ± 10.45 mg/g of dry matter. Other compounds detected in this shrub by HPLC-mass spectrometry were sesamin, galocatechin, peonidin 3-O rutinoside, methyl galangin, epigallocatechin 7-O-glucuronide, and epigalocatechin. Mortality rate of sheathed and exsheathed H. contortus was low (16-34%) with doses ≤ 100 mg/mL of the extracts. At 200 mg/ml, the hydro-methanolic extracts of L. tridentata killed 32.1 and 68.4% of sheathed and exsheathed larvae, respectively, regardless of incubation time. The effective concentration of the L. tridentata extract for 50% larvae mortality (EC ) after 24 h of incubation was 36 mg/mL (CI = 6-94). Microscopic observations revealed damage to the cuticle of this parasite exposed to extracts of L. tridentata. These in vitro results provided evidence that L. tridentata extracts possess anti-Haemonchus contortus properties, particularly during the exsheathed stage of this nematode. It would be necessary to assess the safety of this shrub in vivo and also to carry out in vivo efficacy studies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180210
[Lr] Last revision date:180210
[St] Status:Publisher
[do] DOI:10.1007/s11250-018-1535-5

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[PMID]: 29385086
[Au] Autor:Ahn J; Pei Y; Chae HS; Kim SH; Kim YM; Choi YH; Lee J; Chang M; Song YS; Rodriguez R; Oh DC; Kim J; Choi S; Joo SH; Chin YW
[Ad] Address:College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea. jm212224@snu.ac.kr.
[Ti] Title:Spiroketones and a Biphenyl Analog from Stems and Leaves of Larrea nitida and Their Inhibitory Activity against IL-6 Production.
[So] Source:Molecules;23(2), 2018 Jan 31.
[Is] ISSN:1420-3049
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:Bioactivity-guided fractionation for the stems of leaves of Cav., using interleukin-6 (IL-6) inhibitory assay in human mast cells (HMC-1), led to the isolation of three new compounds with an unprecedented skeleton in nature ( - ) and three known compounds ( - ). Their structures were elucidated through extensive spectroscopic analysis. The three new compounds were elucidated as two new spiroketones, nitidaones A ( ), and B ( ) and one new biphenyl analog, nitidaol ( ). The known compounds were identified as nordihydroguaiaretic acid ( ), 7,3',4'-tri- -methylquercetin ( ) and ayanin ( ). All the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells. Of them, compounds , - showed potent anti-inflammatory activity, with IC values of 12.8, 17.5, 14.9, 22.9, and 17.8 µM, respectively.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180131
[Lr] Last revision date:180131
[St] Status:In-Process

  4 / 258 MEDLINE  
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[PMID]: 29223919
[Au] Autor:Hernández-Zamudio G; Sáenz-Mata J; Moreno-Reséndez A; Castañeda-Gaytán G; Ogaz A; Carballar-Hernández S; Hernández-Cuevas L
[Ad] Address:Departamento de Agroecología de la Coordinación de Carreras Agronómicas, Universidad Autónoma Agraria Antonio Narro, Unidad Laguna, Torreón, Coahuila, México.
[Ti] Title:Dinámica de la diversidad temporal de los hongos micorrícicos arbusculares de Larrea tridentata (Sesse & Mocino ex DC) Coville en un ecosistema semiárido. [Temporal diversity dynamics of the arbuscular mycorrhizal fungi of Larrea tridentata (Sesse & Mocino ex DC) Coville in a semi-arid ecosystem].
[So] Source:Rev Argent Microbiol;, 2017 Dec 06.
[Is] ISSN:0325-7541
[Cp] Country of publication:Argentina
[La] Language:spa
[Ab] Abstract:Arbuscular mycorrhizal fungi (AMF) of arid and semiarid ecosystems are important for the development of plants that grow under biotic stress in wild or in agro-ecosystems. There is little information on the temporal diversity of these organisms in perennial plants from arid ecosystems in northern Mexico. On this study, the mycorrhizal colonization and the temporal diversity of AMF in the rhizosphere of Larrea tridentata, perennial plant abundant in the Chihuahuan Desert region were explored. Samples of the rhizosphere and roots of fifteen plants in each of the three sampling dates during the 2015 year were obtained. A total of 17 species of HMA belonging to 12 genera and 7 families within the phylum Glomeromycota in all three sampling dates were found. Funneliformis geosporum was the dominant species belonging to the family Glomeraceae which possess the highest genera number on L. tridentata. The highest mycorrhization percentage was in February with 83.22, followed by September and May with 75.27 and 65.27%, respectively. A maximum of 16 AM fungal species were isolated and identified from L. tridentata rhizosphere in February, 15 species in May and 12 species in September. Statistical analysis showed significant differences between sampling dates in the spores number.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 171210
[Lr] Last revision date:171210
[St] Status:Publisher

  5 / 258 MEDLINE  
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[PMID]: 28857321
[Au] Autor:Alonso MR; Peralta I; Monti D; Martino R; Anesini C
[Ad] Address:Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
[Ti] Title:Stability of an Aqueous Extract of Larrea divaricata Cav. during a Simulated Digestion Process.
[So] Source:Phytother Res;31(11):1708-1714, 2017 Nov.
[Is] ISSN:1099-1573
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Larrea divaricata Cav. (Zygophyllaceae) is a South American plant widely distributed in Argentina that is used in folk medicine to treat inflammatory diseases. The aqueous extract is known to have well-documented biological activities such as antitumour, immunomodulatory, antimicrobial, antiinflammatory and antioxidant. However, its stability in gastrointestinal fluids is unknown. The latter is an important factor to assure the bioavailability of plant extracts intended to be administered via the oral route. The aim of this work was to study the stability of a lyophilized aqueous extract of L. divaricata compressed as a pill. To this end, the main polyphenol compound found in the extract, that is, the nordihydroguaiaretic acid, the total polyphenols and flavonoids content and the antioxidant activity such as diphenylpicrylhydrazyl scavenger activity and reducing power were assayed after subjecting the extract to different incubation times in simulated digestive fluids. The HPLC and spectroscopic methods were employed. Although the levels of polyphenols and flavonoids decreased upon incubation in gastric and intestinal fluids, the extract maintained its antioxidant activity related to the presence of nordihydroguaiaretic acid. These results are promising and encourage the potential use of the extract by the oral route as a supplement or phytomedicine with antioxidant activity. Copyright © 2017 John Wiley & Sons, Ltd.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1709
[Cu] Class update date: 171107
[Lr] Last revision date:171107
[St] Status:In-Process
[do] DOI:10.1002/ptr.5897

  6 / 258 MEDLINE  
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[PMID]: 28793307
[Au] Autor:Bashyal B; Li L; Bains T; Debnath A; LaBarbera DV
[Ad] Address:Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
[Ti] Title:Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.
[So] Source:PLoS Negl Trop Dis;11(8):e0005832, 2017 Aug.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.
[Mh] MeSH terms primary: Antiprotozoal Agents/pharmacology
Entamoeba histolytica/drug effects
Giardia lamblia/drug effects
Larrea/chemistry
Naegleria fowleri/drug effects
Plant Extracts/pharmacology
[Mh] MeSH terms secundary: Antiprotozoal Agents/chemistry
Antiprotozoal Agents/isolation & purification
Humans
Masoprocol/isolation & purification
Masoprocol/pharmacology
Naphthols/isolation & purification
Naphthols/pharmacology
Plant Extracts/chemistry
Plant Extracts/isolation & purification
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Antiprotozoal Agents); 0 (Naphthols); 0 (Plant Extracts); 0 (demethoxyisoguaiacin); 7BO8G1BYQU (Masoprocol)
[Em] Entry month:1709
[Cu] Class update date: 170901
[Lr] Last revision date:170901
[Js] Journal subset:IM
[Da] Date of entry for processing:170810
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005832

  7 / 258 MEDLINE  
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[PMID]: 28417450
[Au] Autor:García EM; Cherry N; Lambert BD; Muir JP; Nazareno MA; Arroquy JI
[Ad] Address:CITSE - Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Universidad Nacional de Santiago del Estero, Santiago del Estero, Argentina.
[Ti] Title:Exploring the biological activity of condensed tannins and nutritional value of tree and shrub leaves from native species of the Argentinean Dry Chaco.
[So] Source:J Sci Food Agric;97(14):5021-5027, 2017 Nov.
[Is] ISSN:1097-0010
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Tropical tree or shrub leaves are an important source of nutrients for ruminants and a potential source of biologically active compounds that may affect ruminal metabolism of nutrients. Therefore, eight woody species from the native flora of Argentinean Dry Chaco, rich in secondary compounds such as condensed tannins (CT), were assessed for their nutritional value, CT fractions and in vitro true digestibility of dry matter, as well as biological activity (BA). RESULTS: Differences among species were found in contents of total phenol, protein-precipitating phenols (PPP), bound proteins to PPP (BP) and BP/PPP (P < 0.0001). The BP/PPP ratio reveals differences among species in potential BA as indicated by protein precipitation. The major CT of each species were isolated and purified for use as a standard. Although Schinopsis balansae had the most (P ≤ 0.05) total CT (19.59% DM), Caesalpinia paraguariensis had greater (P ≤ 0.05) BA with the most PPP (530.21% dry matter). Larrea divaricata, at 0.97, followed by Acacia aroma, at 0.89, had CT with the highest (P ≤ 0.05) BP/PPP ratios, followed by Prosopis alba (0.59). CONCLUSION: There were differences in nutritive value and bioactivity among species. Those with the greatest CT were not necessarily those with the most BA. Caesalpinia paraguariensis, S. balansae and L. divaricata were the most promising species as native forage CT sources. Cercidiurm praecox (20.87% CP; 18.14% acid detergent fiber) and Prosopis nigra (19.00% CP; 27.96% acid detergent fiber) showed the best (P ≤ 0.05) nutritive values. According to their nutritive traits, these species might be complementary in grass-based ruminant diets. © 2017 Society of Chemical Industry.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1704
[Cu] Class update date: 171018
[Lr] Last revision date:171018
[St] Status:In-Process
[do] DOI:10.1002/jsfa.8382

  8 / 258 MEDLINE  
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[PMID]: 28226316
[Au] Autor:Alonso MR; Anesini C
[Ad] Address:Facultad de Farmacia y Bioquímica, Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA), Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.
[Ti] Title:Clinical Evidence of Increase in Hair Growth and Decrease in Hair Loss without Adverse Reactions Promoted by the Commercial Lotion ECOHAIR®.
[So] Source:Skin Pharmacol Physiol;30(1):46-54, 2017.
[Is] ISSN:1660-5535
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:BACKGROUND/AIMS: Hair exerts protection, sensory functions, thermoregulation, and sexual attractiveness. Hair loss (alopecia) is caused by several diseases, drug intake, hormone imbalance, stress, and infections (Malassesia furfur). Drugs usually used in alopecia produce irreversible systemic and local side effects. An association of extracts of Coffea arabica and Larrea divaricata (ECOHAIR®) is successfully being commercialized in Argentina for hair growth. The aim of this study was to provide scientific support for the efficacy and innocuousness of ECOHAIR® in patients with noncicatricial alopecia during a 3-month treatment. METHODS: The efficacy was determined through the assessment of an increase in hair volume, improvement in hair looks, growth of new hair, and a decrease in hair loss by the test of hair count and hair traction. The capacity to decrease the amount of dandruff was also evaluated as well as the adverse local effects caused by the treatment. RESULTS: ECOHAIR® spray improved the overall hair volume and appearance; it increased its thickness, induced hair growth, and decreased hair loss. Besides, no adverse local reactions were observed upon treatment with the product. CONCLUSION: This study provides scientific support for the clinical use of ECOHAIR® as a treatment to be used in noncicatricial alopecia.
[Mh] MeSH terms primary: Alopecia/drug therapy
Coffea
Larrea
Plant Extracts/therapeutic use
[Mh] MeSH terms secundary: Adult
Aged
Female
Hair/drug effects
Hair/growth & development
Humans
Male
Middle Aged
Phytotherapy
Treatment Outcome
Young Adult
[Pt] Publication type:CLINICAL TRIAL; CLINICAL TRIAL, PHASE IV; JOURNAL ARTICLE
[Nm] Name of substance:0 (Plant Extracts)
[Em] Entry month:1703
[Cu] Class update date: 170327
[Lr] Last revision date:170327
[Js] Journal subset:IM
[Da] Date of entry for processing:170223
[St] Status:MEDLINE
[do] DOI:10.1159/000455958

  9 / 258 MEDLINE  
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[PMID]: 28198919
[Au] Autor:Gómez-Cansino R; Guzmán-Gutiérrez SL; Campos-Lara MG; Espitia-Pinzón CI; Reyes-Chilpa R
[Ad] Address:Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, 04510 México, DF, México.
[Ti] Title:Natural Compounds from Mexican Medicinal Plants as Potential Drug Leads for Anti-Tuberculosis Drugs.
[So] Source:An Acad Bras Cienc;89(1):31-43, 2017 Jan-Mar.
[Is] ISSN:1678-2690
[Cp] Country of publication:Brazil
[La] Language:eng
[Ab] Abstract:In Mexican Traditional Medicine 187 plant species are used in the treatment of respiratory conditions that may be associated with tuberculosis. In this contribution, we review the ethnobotany, chemistry and pharmacology of 63 species whose extracts have been assayed for antimycobacterial activity in vitro. Among these, the most potent is Aristolochia brevipes (MIC= 12.5 µg/mL), followed by Aristolochia taliscana, Citrus sinensis, Chrysactinia mexicana, Persea americana, and Olea europaea (MIC<64 µg/mL). Other potent extracts (inhibition > 95%, 50 µg/mL) include: Amphipterygium adstringens, Larrea divaricata, and Phoradendron robinsoni. Several active compounds have been identified, the most potent are: Licarin A (isolated from A. taliscana), and 9-amino-9-methoxy-3,4-dihydro-2H-benzo[h]-chromen-2-one (transformation product of 9-methoxytariacuripyrone isolated from Aristolochia brevipes), both with MIC= 3.125 µg/mL, that is 8-fold less potent than the reference drug Rifampicin (MIC= 0.5 µg/mL). Any of the compounds or extracts here reviewed has been studied in clinical trials or with animal models; however, these should be accomplished since several are active against strains resistant to common drugs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1702
[Cu] Class update date: 170419
[Lr] Last revision date:170419
[St] Status:In-Data-Review

  10 / 258 MEDLINE  
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[PMID]: 28058783
[Au] Autor:Jeong H; Kim S; Lee J; Park JY; Zhou W; Liu X; Kim SD; Song YS; Jang CY; Oh SR; Choi S; Chang M
[Ad] Address:Graduate School of Biological Sciences, Sookmyung Women's University, 100, Chungparo 47-gil, Seoul, 140-742, Korea.
[Ti] Title:Characterization of Phase I and Phase II Hepatic Metabolism and Reactive Intermediates of Larrea nitida Cav. and Its Lignan Compounds.
[So] Source:Phytother Res;31(1):140-151, 2017 Jan.
[Is] ISSN:1099-1573
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Larrea nitida Cav. (LNC), which belongs to the family Zygophyllaceae, is widely indigenous and used in South America to treat various pathological conditions. It contains the antioxidant and antiinflammatory but toxic nordihydroguaiaretic acid (NDGA) as well as O-methylated metabolite of NDGA (MNDGA) as bioactive compounds. The hepatic metabolism-based toxicological potential of extracts of LNC (LNE), NDGA, and MNDGA has not previously been reported. The present study aimed to characterize the phase I and phase II hepatic metabolism and reactive intermediates of LNE, NDGA, and MNDGA and their effects on the major drug-metabolizing enzymes in vitro and ex vivo. A methanol extract of LNC collected from Chile as well as NDGA and MNDGA isolated from LNE were subjected to metabolic stability assays in liver microsomes in the presence of the cofactors reduced nicotinamide dinucleotide phosphate (NADPH) and/or uridine 5'-diphosphoglucuronic acid (UDPGA). Cytochrome P450 (CYP) inhibition assays were performed using CYP isozyme-specific model substrates to examine the inhibitory activities of LNE, NDGA, and MNDGA, which were expressed as % inhibition and IC values. Ex vivo CYP induction potential was investigated in the liver microsomes prepared from the rats intraperitoneally administered with LNE. Glutathione (GSH) adduct formation was monitored by LC-MS analysis of the microsomal incubation samples with either NDGA or MNDGA and an excess of GSH to determine the formation of electrophilic reactive intermediates. Both NDGA and MNDGA were stable to NADPH-dependent phase I metabolism, but labile to glucuronide conjugation. LNE, NDGA, and MNDGA showed significant inhibitory effects on CYP1A2, 2C9, 2D6, and/or 3A4, with IC values in the micromolar range. LNE was found to be a CYP1A2 inducer in ex vivo rat experiments, and mono- and di-GSH adducts of both NDGA and MNDGA were identified by LC-MS analysis. Our study suggests that hepatic clearance is the major elimination route for the lignans NDGA and MNDGA present in LNE. These lignans may possess the ability to modify biomacromolecules via producing reactive intermediates. In addition, LNE, NDGA, and MNDGA are found to be inhibitors for various CYP isozymes such as CYP2C9 and 3A4. Thus, the consumption of LNC as an herbal preparation or NDGA may cause metabolism-driven herb-drug interactions. Copyright © 2016 John Wiley & Sons, Ltd.
[Mh] MeSH terms primary: Larrea/chemistry
Lignans/chemistry
Liver/metabolism
Microsomes, Liver/drug effects
[Mh] MeSH terms secundary: Animals
Female
Herb-Drug Interactions
Humans
Lignans/pharmacology
Rats
[Pt] Publication type:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Name of substance:0 (Lignans)
[Em] Entry month:1704
[Cu] Class update date: 170817
[Lr] Last revision date:170817
[Js] Journal subset:IM
[Da] Date of entry for processing:170107
[St] Status:MEDLINE
[do] DOI:10.1002/ptr.5742


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