共查询到20条相似文献，搜索用时 31 毫秒
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Cytochrome P450 1 enzyme inhibition and anticancer potential of chromene amides from Amyris plumieri
Badal S Williams SA Huang G Francis S Vedantam P Vendantam P Dunbar O Jacobs H Tzeng TJ Gangemi J Delgoda R 《Fitoterapia》2011,82(2):230-236
Cytochrome P450 (CYP) enzyme inhibitory properties of six chromenylated amide compounds (CAs) from Amyris plumieri are described. Inhibition of CYP microsomes (CYP1A1, CYP1A2, CYP1B1, CYP2D6, CYP3A4 and CYP2C19) was monitored using a fluorescent assay. Potent inhibition was found against CYP1A1 with IC50 and Ki for CA1 (acetamide), being the lowest at 1.547 ± 1.0 μM and 0.37 μM respectively, displaying non-competitive kinetics. The selectivity for CYP1A1 was increased in CA3 (butanamide), which also exhibited cytotoxicity against breast cancer cells, MCF7 with an IC50 of 47.46 ± 1.62 μM. Structure-activity relationship studies provide insight at a molecular level for CAs with implications in chemoprevention and chemotherapy. 相似文献
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This study investigated the effect of tanshinones on rat liver microsomal CYP3A2 and 2C11 activity and explored the structure-activity relationship of tanshinones with CYP3A activity. Cryptotanshinone, tanshinone I and tanshinone IIA were competitive CYP3A2 inhibitors (Ki = 199-243 μM) and CYP2C11 inhibitors (Ki = 91-118 μM). Dihydrotanshinone was not only a noncompetitive inhibitor of CYP3A2 (Ki = 110 μM), but also a competitive CYP2C11 inhibitor (Ki = 55 μM). The structural difference between dihydrotanshinone and tanshinone I at C-15 position of furan ring resulted in the different modes of inhibition on CYP3A activity. 相似文献
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The present study was aimed to investigate the possible interaction of the standardized extract of Acorus calamus (AC) with Cytochrome P450 enzyme, quantitative determination of the α-asarone in the AC rhizome was performed by RP-HPLC method. In vitro interaction of the plant extract was evaluated by CYP450-carbon monoxide complex (CYP450-CO) assay. Effect on individual isoforms such as CYP3A4 and CYP2D6 isozymes were analyzed through fluorescence product formation and respective IC50 values were determined. CYP450-CO assay showed moderate interaction potential. Extract showed higher IC50 values (46.84 ± 1.83-32.99 ± 2.21 μg/ml) comparing to the standard inhibitors and lower IC50 value than α-asarone (65.16 ± 2.37-42.15 ± 2.45 μg/ml). 相似文献
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Fourteen acridone alkaloids isolated from Lunasia amara Blanco were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for cytochrome P450 2D6 (CYP2D6). Among the 14 compounds, 5-hydroxygraveroline (1), 8-methoxyifflaiamine (2), lunamarine (3), and lunine (12) increased their inhibitory activity with increasing preincubation time. Then, we further examined the possibility of mechanism-based inhibition on 5-hydroxygraveroline (1) and lunamarine (3), which showed the potent inhibition. Further investigations on 1 and 3 showed that the characteristic time- and concentration-dependent inhibition, which required a catalytic step with NADPH, was not protected by nucleophiles, and was decreased by the presence of a competitive inhibitor. Thus, 1 and 3 were concluded as mechanism-based inactivators of CYP2D6. 相似文献
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Shuang–Huang–Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the in vitro metabolism in Sprague–Dawley rat liver microsomes of forsythoside A were investigated. The observations from Sprague–Dawley rat liver microsomes in the presence of β-NADPH or UDPGA that forsythoside A may be the substrates of CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3, UGT1A1 and UGT1A9; Chlorogenic acid may be the substrates of CYP3A4, CYP2C9, CYP1A2, CYP2C19, UGT1A6, UGT1A3 and UGT1A1; Baicalin may be the substrates of CYP3A4, CYP2C19, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; Baicalein may be the substrates of CYP3A4, CYP2E1 and UGT1A6. It was also found that the residue of forsythoside A in SHL, FF + LJF and FF + SR was greatly increased compared with that in FF in Sprague–Dawley rat liver microsomes in the presence of β-NADPH or UDPGA, which indicated that the metabolism of forsythoside A in SHL may be influenced by chlorogenic acid in LJF acting on the CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3 and UGT1A1; baicalin in SR acting on the CYP3A4, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; baicalein acting on the CYP3A4 and UGT1A6 respectively. 相似文献
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Berberine was reported to protect against the intestinal injury and improve the survival rate in sepsis, and glutamine deficiency was considered to be correlated with mortality in sepsis. We found that berberine pretreatment ameliorated lipopolysaccharide-induced direct intestinal injury and mucosal hypoplasia and attenuated impairments of intestinal glutamine transport and glutaminase activity, B0AT1 mRNA and protein expressions, and glutaminase protein expression. These findings showed the first time that berberine pretreatment could improve intestinal recovery and attenuate the impairment of glutamine transport and glutaminase activity in rat sepsis. This might be one of the mechanisms for the beneficial effect of berberine on sepsis. 相似文献
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Binbing Ling Jane Alcorn Bernard Laarveld Andrew A. Olkowski 《Journal of pest science》2009,82(3):273-281
Richardson ground squirrels (Spermophilus richardsonii) are prominent pests on the prairies of North America. Rodenticides have been used for their control for several decades, but this pest continues to thrive. In this study we considered the possibility that this apparent lack of success in controlling this pest may be associated with systemic adaptation of Richardson ground squirrels to toxins. Accordingly, we examined the hepatic cytochrome P450 (CYP) enzyme system (phase I biotransformation) in Richardson ground squirrels selected from fields where rodenticides were used (exposed) and from fields where no toxins were distributed (naïve). We found that the content and activity of individual components of the CYP system including CYP, cytochrome b5, and NADPH–CYP reductase in liver microsomes were higher in exposed Richardson ground squirrels than in naïve Richardson ground squirrels. In vitro CYP-mediated activities for generic substrates representing major groups of reactions were found to be highly variable among individuals. However, systemic activity was comparable among the naïve and exposed Richardson ground squirrels. These findings indicate that Richardson ground squirrels may readily develop resistance to toxins by enhancing the functional capacity of enzymes responsible for detoxification. Therefore, it is important to carefully monitor the efficiency of toxicological methods of Richardson ground squirrels control and to revise management strategies accordingly. 相似文献
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Chao DC Lin LJ Kao ST Huang HC Chang CS Liang JA Wu SL Hsiang CY Ho TY 《Fitoterapia》2011,82(4):696-703
Zuo-Jin-Wan (ZJW) has been used to treat hepatocellular carcinoma in Asia. This study was to determine whether ZJW and its components blocked activator protein 1 (AP-1) and nuclear factor-κB (NF-κB) activities as well as tumor promotion in hepatoblastoma HepG2 cells. ZJW and its components, Coptis chinensis and Evodia rutaecarpa, inhibited AP-1 and NF-κB activities, and suppressed anchorage-independent growth of HepG2 cells. The major alkaloidal ingredients, berberine and evodiamine, inhibited AP-1 activities and/or NF-κB activation, and further suppressed hepatocellular transformation. In conclusion, ZJW and its constituents, berberine and evodiamine, suppressed tumor promotion primarily through AP-1 and/or NF-κB pathways in HepG2 cells. 相似文献
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Six different isoquinoline alkaloids (sanguinarine, chelerythrine, berberine, coptisine, allocryptopine, and protopine) were extracted by butanol and octanol from aqueous solution, pH 4.5. The samples were analyzed by HPLC. Butanol extraction was non-selective, alkaloids passed into organic phase in 83–98%. Octanol extraction provided more selective yields: sanguinarine 99%, chelerythrine 94%, berberine 18%, coptisine 16%, allocryptopine 7.5%, protopine 7%. Further, we tested octanol treatment of extract from Dicranostigma lactucoides. The octanol extraction yields were also selective: sanguinarine 98%, chelerythrine 92%, chelirubine 92.5%, protopine 6% and allocryptopine 3.5%. 6-Butoxy-5,6-dihydrosanguinarine and 6-butoxy-5,6-dihydrochelerythrine were prepared and their NMR and MS data are reported and discussed. 相似文献
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Cerný D Lekić N Váňová K Muchová L Hořínek A Kmoníčková E Zídek Z Kameníková L Farghali H 《Fitoterapia》2011,82(5):786-791
This work studied a relationship between HO-1/CO system and lipid peroxidation with consequent effects on liver functions and NOS-2. We focused on curcumin pretreatment in rat toxic model of d-galactosamine and lipopolysaccharide. Hepatocyte viability, lipid peroxidation, antioxidant status, ALT and AST were evaluated. HO-1 and NOS-2 expressions and respective enzyme activity were determined. Curcumin caused decreases in ALT and AST levels as well as in lipid peroxidation. Furthermore, curcumin pretreatment increased liver HO-1 (2.4-fold, p = 0.001), but reduced NOS-2 (4.1-fold, p = 0.01) expressions. In conclusion, the tuning of CO/NO pathways is important in shedding light on curcumin's cytoprotective effects in this model. 相似文献
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Berberine is one of the main alkaloids of Rhizoma coptidis which has been used for patients with gastrointestinal disorders. The major aim of this study was to investigate the effect of berberine on tight junction. Caco-2 cells were treated with various concentration of berberine. We observed the integrity of tight junction by measuring the transepithelial electrical resistance (TEER), and also studied the effect of berberine on morphology of tight junction and tight junction protein. These findings showed the first time that berberine could reduce epithelial gut permeability, and might help explain the possible mechanisms of anti-diarrhea activity of berberine. 相似文献
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Majtan J Klaudiny J Bohova J Kohutova L Dzurova M Sediva M Bartosova M Majtan V 《Fitoterapia》2012,83(4):671-677
Methylglyoxal (MGO) is a major antibacterial component of manuka honey. Another antibacterial component found in Revamil honey, peptide defensin1, was not identified in manuka honey. The primary aim of the study was to evaluate the content of defensin1 in honeys of different botanical origins and to investigate a presumed effect of reactive MGO on defensin1 and a dominant protein of honey MRJP1 in manuka honey. Immunoblotting of honey samples showed that defensin1 was a regular but quantitatively variable component of honeys. One of the reasons of varying contents of defensin1 in different honeys seems to be constitutive but varying defensin1 expression in individual honeybees in bee populations that we documented on samples of nurse and forager bees by RT-PCR. Comparative analyses of honeys revealed a size modification of defensin1, MRJP1 and probably also α-glucosidase in manuka honey. We further showed that (i) the treatment of purified defensin1 in solution containing high amount of MGO caused a time-dependent loss of its antibacterial activity and (ii) increasing MGO concentrations in a non-manuka honey were connected with a gradual increase in the molecular weight of MRJP1. Obtained results demonstrate that MGO abrogates the antibacterial activity of defensin1 and modifies MRJP1 in manuka honey. We assume that MGO could also have negative effects on the structure and function of other proteins/peptides in manuka honey, including glucose oxidase, generating hydrogen peroxide. 相似文献