Deglycosylation of Liquiritin Strongly Enhances its Inhibitory Potential Towards UDP‐Glucuronosyltransferase (UGT) Isoforms

The detailed mechanisms on licorice–drug interaction remain to be unclear. The aim of the present study is to investigate the inhibition of important UGT isoforms by two important ingredients of licorice, liquiritin, and liquiritigenin. The results showed that liquiritigenin exhibited stronger inhibition towards all the tested UGT isoforms than liquiritin. Data fitting using Dixon and Lineweaver–Burk plots demonstrated the competitive inhibition of liquiritigenin towards UGT1A1 and UGT1A9‐mediated 4‐MU glucuronidation reaction. The inhibition kinetic parameters (K_i) were calculated to be 9.1 and 3.2 μM for UGT1A1 and UGT1A9, respectively. Substrate‐dependent inhibition behaviour was also observed for UGT1A1 in the present study. All these results will be helpful for understanding the deep mechanism of licorice–drug interaction. However, when translating these in vitro parameters into in vivo situations, more complex factors should be considered, such as substrate‐dependent inhibition of UGT isoforms, the contribution of UGT1A1 and UGT1A9 towards the metabolism of drugs, and many factors affecting the abundance of ingredients in the licorice. Copyright © 2012 John Wiley & Sons, Ltd.     

Strong Specific Inhibition of UDP‐glucuronosyltransferase 2B7 by Atractylenolide I and III

Drug‐metabolizing enzymes inhibition‐based drug–drug interaction remains to be the key limiting factor for the research and development of efficient herbal components to become clinical drugs. The present study aims to determine the inhibition of uridine 5′‐diphospho‐glucuronosyltransferases (UGTs) isoforms by two important efficient herbal ingredients isolated from Atractylodes macrocephala Koidz, atractylenolide I and III. In vitro recombinant UGTs‐catalysed glucuronidation of 4‐methylumbelliferone was used to determine the inhibition capability and kinetics of atractylenolide I and III towards UGT2B7, and in silico docking method was employed to explain the possible mechanism. Atractylenolide I and III exhibited specific inhibition towards UGT2B7, with negligible influence towards other UGT isoforms. Atractylenolide I exerted stronger inhibition potential than atractylenolide III towards UGT2B7, which is attributed to the different hydrogen bonds and hydrophobic interactions. Inhibition kinetic analysis was performed for the inhibition of atractylenolide I towards UGT2B7. Inhibition kinetic determination showed that atractylenolide I competitively inhibited UGT2B7, and inhibition kinetic parameter (Ki) was calculated to be 6.4 μM. In combination of the maximum plasma concentration of atractylenolide I after oral administration of 50 mg/kg atractylenolide I, the area under the plasma concentration‐time curve ration AUC_i/AUC was calculated to be 1.17, indicating the highly possible drug–drug interaction between atractylenolide I and drugs mainly undergoing UGT2B7‐catalysed metabolism. Copyright © 2015 John Wiley & Sons, Ltd.     

The Inhibitory Effect of 20(S)‐Protopanaxatriol (ppt) Towards UGT1A1 and UGT2B7

Ginseng, a commonly used natural product, has been frequently reported to induce herb–drug interaction with many clinical drugs. The intestinal bacterial metabolites of ginsenosides have been widely regarded as the substance basis for ginseng–drug interactions. To date, little is known about the inhibitory effect of intestinal bacterial metabolites of ginsenosides towards UDP‐glucuronosyltransferases (UGTs). In vitro investigation of the inhibition of 20(S)‐protopanaxatriol (ppt) towards UGT1A1 and UGT2B7 was carried out. The results showed that ppt exhibited strong noncompetitive inhibition towards UGT1A1 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters (K_i) were calculated to be 8.8 and 2.2 μM for UGT1A1 and UGT2B7, respectively. Using the maximum plasma concentration of ppt, the alteration of area under the concentration–time curve was calculated to be 20% and 70% respectively for UGT1A1‐mediated and UGT2B7‐mediated metabolism. However, given that the varied contribution of these two UGT isoforms towards drug metabolism and the influence of herb complexity and individual difference, the explanation of these results should be paid more caution. Copyright © 2012 John Wiley & Sons, Ltd.     

Comparison of Inhibition Capability of Scutellarein and Scutellarin Towards Important Liver UDP‐Glucuronosyltransferase (UGT) Isoforms

Scutellarin is an important bioactive flavonoid extracted from Erigeron breviscapus (Vant.) Hand‐Mazz, and scutellarein is the corresponding aglycone of scutellarin. The present study aims to compare the inhibition potential of scutellarin and scutellarein towards several important UDP‐glucuronosyltransferase (UGT) isoforms, including UGT1A1, UGT1A6, UGT1A9 and UGT2B7. It was demonstrated that scutellarein exerted stronger inhibition towards the tested UGT isoforms than scutellarin. Furthermore, the inhibition kinetic type and parameters (K_i) were determined for the scutellarein's inhibition towards these UGT isoforms. Competitive inhibition of scutellarein towards all these UGT isoforms was demonstrated, and the K_i values were calculated to be 0.02, 5.0, 5.8 and 35.9 μM for UGT1A1, 1A6, 1A9 and 2B7, respectively. Using in vivo maximum plasma concentration of scutellarein in rat, the in vitro–in vivo extrapolation was performed to predict in vivo situation, indicating the most possible in vivo adverse effects due to the inhibition of scutellarein towards UGT1A1. All these results remind us to monitor the utilization of scutellarin and scutellarein, and the herbs containing these two components. Copyright © 2013 John Wiley & Sons, Ltd.     

The Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B

Praeruptorin A (PA) and B (PB) are two important compounds isolated from Bai‐hua Qian‐hu and have been reported to exert multiple biochemical and pharmacological activities. The present study aims to determine the inhibition of PA and PB on the activity of important phase II drug‐metabolizing enzymes uridine 5'‐diphospho‐glucuronosyltransferase (UGTs) isoforms. In vitro UGT incubation system was used to determine the inhibition potential of PA and PB on the activity of various UGT isoforms. In silico docking was performed to explain the inhibition difference between PA and PB towards the activity of UGT1A6. Inhibition behaviour was determined, and in vitro–in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (K_i) and in vivo exposure level of PA. Praeruptorin A (100 μM) exhibited the strongest inhibition on the activity of UGT1A6 and UGT2B7, with 97.8% and 90.1% activity inhibited by 100 μM of PA, respectively. In silico docking study indicates the significant contribution of hydrogen bond interaction towards the stronger inhibition of PA than PB towards UGT1A6. Praeruptorin A noncompetitively inhibited the activity of UGT1A6 and competitively inhibited the activity of UGT2B7. The inhibition kinetic parameter (K_i) of PA towards UGT1A6 and UGT2B7 was calculated to be 1.2 and 3.3 μM, respectively. The [I]/K_i value was calculated to be 15.8 and 5.8 for the inhibition of PA on UGT1A6 and UGT2B7, indicating high inhibition potential of PA towards these two UGT isoforms in vivo. Therefore, closely monitoring the interaction between PA and drugs mainly undergoing UGT1A6 or UGT2B7‐catalyzed metabolism is very necessary. Copyright © 2016 John Wiley & Sons, Ltd.     

Investigation of UDP-glucuronosyltransferases (UGTs) inhibitory properties of carvacrol

UDP‐glucuronosyltransferases (UGTs), the most important phase II drug metabolizing enzymes (DMEs), could metabolize many drugs and various endogenous substances including bilirubin, steroid hormones, thyroid hormones, bile acids and fat‐soluble vitamins. Evaluation of the inhibitory effects of compounds on UGTs is clinically important because inhibition of UGT isoforms could not only result in serious drug–drug interactions (DDIs), but also induce metabolic disorders of endogenous substances. The aim of the present study was to investigate the inhibitory effects of carvacrol on major UGT isoforms. The results showed that carvacrol could inhibit the activity of UGT1A9 with negligible effects on other UGT isoforms. When 4‐methylumbelliferone (4‐MU) was used as a nonspecific probe substrate and recombinant UGT enzymes were utilized as an enzyme resource, the inhibition of UGT1A9 was best fit to the competitive type and the inhibition kinetic parameter (K_i) was calculated to be 5.7 µ m . Furthermore, another specific probe substrate, propofol, was employed to determine the inhibitory kinetics of UGT1A9, and the results demonstrated that the inhibitory type was noncompetitive. The inhibition kinetic parameter (K_i) was determined to be 25.0 µ m . Because this substrate‐dependent inhibition of UGT1A9 might confuse the in vitro–in vivo extrapolation, these in vitro inhibition kinetic parameters should be interpreted with special caution. Copyright © 2011 John Wiley & Sons, Ltd.     

Tyrosinase inhibitory constituents from the stems of Maackia fauriei

Bioassay‐guided investigation of the stems of Maackia fauriei led to the isolation of seven flavonoid constituents, formononetin (1), genistein (2), daidzein (3), texasin (4), tectorigenin (5), odoratin (6) and mirkoin (7). Their structures were elucidated on the basis of spectral studies as well as by comparison with literature data. Tyrosinase inhibition activities were carried out on the isolated compounds. Among these, mirkoin (7) was identified as a potent tyrosinase inhibitor. It inhibited mushroom tyrosinase with an IC₅₀ value of 0.005 mm , which is ten times more active than kojic acid (IC₅₀ = 0.045 mm ). The inhibition kinetics, analysed by Lineweaver‐Burk plots, indicated mirkoin (7) to be a competitive inhibitor of tyrosinase when l ‐tyrosinase was used as a substrate. The results suggest that hydroxyl groups at C‐4′ in the B ring of flavonoids play an important role in the tyrosinase inhibition activities. Interestingly, compounds 4–7 were isolated for the first time from this plant. Copyright © 2009 John Wiley & Sons, Ltd.     

Inhibition of UDP‐Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis

Structure–activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine‐Diphosphate) UDP‐glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (K_i) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb–drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9‐mediated metabolism. In conclusion, in silico‐in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis. Copyright © 2015 John Wiley & Sons, Ltd.     

Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs

The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed by time‐dependent and nicotinamide adenine dinucleotide phosphate‐dependent and reversible inhibition by Lineweaver–Burk plot assessments. Inhibition mechanisms were also assessed by computerized interaction prediction by using the Discovery Studio CDOCKER software (Accelrys, San Diego, CA, USA). Tetrahydropalmatine showed a mechanism‐based inhibition of both CYP1A2 and CYP2D6, and Ber of CYP2D6. Neferine and Ber both showed a nonmechanistic inhibition of CYP1A2. All compounds showed a similar and significant mechanism‐based inhibition of CYP3A4. Tetrahydropalmatine and Ber demonstrated both reversible and irreversible inhibition of CYP2D6 and CYP3A4. Tetrahydropalmatine and Ber displayed H‐bond and several Pi‐bond connections with specific amino acid residues of CYP1A2, CYP2D6 and CYP3A4, giving further knowledge to the identified reversible and irreversible herb–drug interactions. Tetrahydropalmatine and Ber should be considered for herb–drug interactions in clinical therapy until relevant clinical studies are available. Copyright © 2015 John Wiley & Sons, Ltd.     

甘草次酸C3、C11、C30衍生物的合成及其体外抗肿瘤活性研究

目的对甘草次酸C3、C11、C30进行结构改造及其体外抗肿瘤活性研究。方法甘草次酸经锌汞齐还原为11-脱氧_甘草次酸,然后C。羧基与卤代烃发生酯化反应,C3-羟基与甲基磺酰氯在0℃冰浴条件下发生甲基磺酰化反应,最后在104℃回流条件下与叠氮钠发生消除反应,从而得到目标产物;通过SRB法对上述合成的甘草次酸衍生物进行体外抗肿瘤活性研究。结果设计并合成了7个目标产物5g-5g,利用IR、MS和1H-NMR确证了结构;抗肿瘤活性筛选结果表明5a对MCF-7的抑制率比母体显著提高,5a、5c、5e对A549的抑制率均比母体有所提高。结论结构改造合理,对进一步开展甘草次酸衍生物的结构改造和抗肿瘤活性研究具有一定的参考价值。     

人尿苷二磷酸葡糖醛酸转移酶(UGT)亚型参与反式-白藜芦醇体外代谢的研究

目的:研究参与反式-白藜芦醇(trans-resveratrol,TR)Ⅱ相代谢的主要尿苷二磷酸葡糖醛酸转移酶(UGTs)亚型。方法:在体外对反式-白藜芦醇与12种主要的人重组UGT亚型进行温孵,采用液相色谱-质谱法测定其葡萄糖醛酸代谢产物,对其结构做初步分析,并考察不同UGT亚型对白藜芦醇代谢产物生成速率的影响。结果:在体外代谢系统中,白藜芦醇被UGT催化生成2种单葡萄糖醛酸代谢产物M-1和M-2,初步推断其为白藜芦醇-4’和3-葡萄糖醛酸化物,亚型UGT1A1,1A3,1A8,1A9,1A10都参与了催化产生代谢产物M-1和M-2,UGT1A6,1A7仅对M-2的生成有贡献。随着底物浓度的升高,UGT1A1,1A10催化底物产生M-1和M-2及1A8催化底物产生M-2的速率都减慢,出现了底物抑制现象。结论:UGT1A1,1A8,1A9,1A10参与了代谢产物M-1的产生,其中UGT1A9的贡献最大,UGT1A1,1A6,1A7,1A8,1A9,1A10参与了代谢产物M-2的产生,其中1A1和1A9贡献最大,UGT1A3也有少量参与2种代谢物的产生,其他亚型几乎都不参与反式-白藜芦醇的Ⅱ相代谢反应。     

Inhibition of UDP‐Glucuronosyltransferase (UGT) Isoforms by Arctiin and Arctigenin

Arctiin is the major pharmacological ingredient of Fructus Arctii, and arctigenin is the metabolite of arctiin formed via the catalysis of human intestinal bacteria. The present study aims to investigate the inhibition profile of arctiin and arctigenin on important phase II drug‐metabolizing enzymes UDP‐glucuronosyltransferases (UGTs), indicating the possible herb–drug interaction. In vitro screening experiment showed that 100 μM of arctiin and arctigenin inhibited the activity of UGT1A3, 1A9, 2B7, and 2B15. Homology modeling‐based in silico docking of arctiin and arctigenin into the activity cavity of UGT2B15 showed that hydrogen bonds and hydrophobic interactions contributed to the strong binding free energy of arctiin (?8.14 kcal/mol) and arctigenin (?8.43 kcal/mol) with UGT2B15. Inhibition kinetics study showed that arctiin and arctigenin exerted competitive and noncompetitive inhibition toward UGT2B15, respectively. The inhibition kinetic parameters (K_i) were calculated to be 16.0 and 76.7 μM for the inhibition of UGT2B15 by arctiin and arctigenin, respectively. Based on the plasma concentration of arctiin and arctigenin after administration of 100 mg/kg of arctiin, the [I]/K_i values were calculated to be 0.3 and 0.007 for arctiin and arctigenin, respectively. Based on the inhibition evaluation standard ([I]/K_i < 0.1, low possibility; 0.1 < [I]/K_i < 1, medium possibility; [I]/K_i > 1, high possibility), arctiin might induce drug–drug interaction with medium possibility. Based on these results, clinical monitoring the utilization of Fructus Arctii is very important and necessary. Copyright © 2016 John Wiley & Sons, Ltd.     

Inhibitory effects of antrodins A–E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease

Antrodia cinnamomea is a highly valued folk medicine used for liver cancer, a disease often caused by the long term infection of hepatitis C virus (HCV). In the present study, the maleic and succinic acid constituents (antrodins A–E) of this medicinal fungus, the in vivo metabolites of antrodin C and the analogue of one of the metabolites were tested for their inhibitory activity on HCV protease. Most of the compounds showed potent inhibitory activity, with antrodin A being the most potent (IC₅₀ = 0.9 µg/mL). Antrodin A was isolated as one of the constituents of A. cinnamomea and was also detected as an in vivo metabolite of the major constituent antrodin C. The mode of inhibition for antrodin A on HCV protease was revealed by a Lineweaver‐Burk plot as competitive inhibition. These results strongly support the use of this folk medicine for liver cancer and HCV infection which is a global problem. Copyright © 2008 John Wiley & Sons, Ltd.     

Selective Antibacterial Activity of Patchouli Alcohol Against Helicobacter pylori Based on Inhibition of Urease

The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration‐dependent fashion with IC₅₀ values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver‐Burk plots indicated that the type of inhibition was non‐competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA‐inactivated urease assay showed DL‐dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection. Copyright © 2014 John Wiley & Sons, Ltd.     

In Vitro Characterization of Glucuronidation of Vanillin: Identification of Human UDP‐Glucuronosyltransferases and Species Differences

Vanillin is a food flavoring agent widely utilized in foods, beverages, drugs, and perfumes and has been demonstrated to exhibit multiple pharmacological activities. Given the importance of glucuronidation in the metabolism of vanillin, the UDP‐glucuronosyltransferase conjugation pathway of vanillin was investigated in this study. Vanillin glucuronide was identified by high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) and a hydrolysis reaction catalyzed by β‐glucuronidase. The kinetic study showed that vanillin glucuronidation by HLMs and HIMs followed Michaelis‐Menten kinetics and the kinetic parameters were as follows: 134.9 ± 13.5 μM and 81.3 ± 11.3 μM for K_m of HLMs and HIMs, 63.8 ± 2.0 nmol/min/mg pro and 13.4 ±2.0 nmol/min/mg pro for V_max of HLMs and HIMs. All UDP‐glucuronosyltransferase (UGT) isoforms except UGT1A4, 1A9, and 2B7 showed the capability to glucuronidate vanillin, and UGT1A6 exerted the higher V_max/K_m values than other UGT isoforms for the glucuronidation of vanillin when assuming expression of isoforms is similar in recombinant UGTs. Kinetic analysis using liver microsomes from six studied speices indicated that vanillin had highest affinity for the monkey liver microsomes enzyme (K_m = 25.6 ± 3.2 μM) and the lowest affinity for the mice liver microsomes enzyme (K_m = 149.1 ± 18.4 μM), and intrinsic clearance was in the following order: monkey > dog > minipig > mice > rat ~ human. These data collectively provided important information for understanding glucuronidation of vanillin. Copyright © 2012 John Wiley & Sons, Ltd.     

甘草酸、甘草次酸的抗肿瘤机制及其作为药物递送载体的研究进展

甘草Glycyrrhizae Radix et Rhizoma是中医临床常用中药之一,具有补脾益气、清热解毒、祛痰止咳、缓急止痛、调和诸药等功能。其主要活性成分为皂苷、黄酮、多糖等。其中,皂苷类成分甘草酸、甘草次酸不仅对肝癌、肺癌、乳腺癌等多种癌症具有抑制作用,还能与化疗药物联用增加药效,同时可被开发用作药物递送的载体材料以解决药物低水溶性、低生物利用度、高毒副作用等问题。研究发现,甘草酸、甘草次酸的增溶作用可能与其两亲性结构有关,有望进一步探索它们作为药物跨膜运输载体的特性。基于甘草的抗肿瘤机制,系统地对甘草酸、甘草次酸在药物递送系统方面的应用进行综述,为开发甘草酸、甘草次酸作为药物递送系统辅料的深入研究提供参考。     

促透剂对良肤乳膏中丹皮酚、白鲜碱、梣酮和甘草次酸的体外透皮吸收及皮肤滞留量的影响

目的:研究不同促透剂对良肤乳膏中有效成分体外透皮吸收及皮肤滞留量的影响,筛选有效的促透剂.方法:选择氮酮、油酸、卡必醇、肉豆蔻酸异丙酯4种促透剂,采用改良的Franz扩散池法,以离体小鼠皮肤为透皮屏障,采用HPLC同时测定接受液和皮肤中有效成分的含量,考察不同促透剂对良肤乳膏中丹皮酚、白鲜碱、梣酮及甘草次酸的累积透过量、透皮吸收速率、时滞及皮肤滞留量的影响.结果:3% IPM对良肤乳膏中有效成分的促透效果较其他促透剂好,对丹皮酚、白鲜碱、梣酮、甘草次酸的促透倍数依次为1.52,1.24,1.73,3.21倍(P<0.05),并且对甘草次酸的皮肤滞留量增加倍数为1.96倍(P<0.05),对其他成分的滞留量影响不显著.结论:不同促透剂对良肤乳膏中不同有效成分的透皮吸收和皮肤滞留量的影响有差异,其中3% IPM既能促进良肤乳膏中4种有效成分的体外透皮吸收,又能增加甘草次酸的皮肤滞留量,可作为良肤乳膏的促透剂.     

3种乳化体系乳膏中黄芩苷、苦参碱、甘草次酸和大黄素的体外经皮渗透的影响研究

研究烷基糖苷、司盘-吐温和A6/25 3种乳化体系对乳膏中黄芩苷、苦参碱、甘草次酸和大黄素的体外经皮渗透的影响。以改良的Franz扩散池和离体小鼠皮进行体外渗透实验,采用HPLC同时测定3种不同乳化体系乳膏中4种中药单体的累积透过量与皮肤滞留量,并考察不同中药成分在相同乳化体系乳膏及不同乳化体系乳膏对相同中药成分的累积透过量、皮肤滞留量及透皮吸收速率的影响。结果表明,不同中药成分在相同乳化体系的累积透过量及透皮吸收速率大小为苦参碱黄芩苷甘草次酸大黄素。不同乳化体系乳膏对相同中药成分的累积透过量及透皮吸收速率的影响除甘草次酸和大黄素无显著性差异外,司盘-吐温乳化体系的累积透过量及透皮吸收速率较大。各中药成分在3种乳化体系中累积透过量及透皮吸收速率规律具有一致性。而不同乳化体系对相同中药成分的累积透过量、皮肤滞留量及透皮吸收速率的影响并无一致性规律。     

芍药苷对甘草酸及甘草次酸大鼠体内药动学的影响

 目的 研究芍药苷对甘草酸及其活性代谢产物甘草次酸吸收动力学的影响。方法 将大鼠单独或与芍药苷联合灌胃给予甘草酸后,不同时间点采集血样,建立药物浓度-时间曲线,药动学参数采用Topfit 2.0软件计算分析。结果 与单独给药相比,联合给药后甘草酸达峰浓度 (ρ_max) 与AUC分别降低至单独给药的9%和33%,达峰时间 (t_max) 显著延长,清除率(CL)增加,分布更为广泛;甘草次酸仅出现半衰期 (t_1/2) 显著延长,而其他药动学参数无明显变化。结论 芍药苷对甘草酸的吸收速度和程度均有显著性抑制,对甘草次酸吸收动力学影响较小。
     

注射用丹参多酚酸中主要成分的降解动力学分析

目的:探索注射用丹参多酚酸中主要活性成分(丹酚酸B和迷迭香酸)在不同pH和温度下的降解规律.方法:采用HPLC测定迷迭香酸、丹酚酸B含量,研究二者在不同pH(1～13)和温度(60,70,80,90℃)下含量变化,通过化学动力学法计算降解动力学参数.结果:丹酚酸B与迷迭香酸在不同pH和温度下降解反应均属于一级动力学反应,降解速率随pH及温度的升高而增加.丹酚酸B和迷迭香酸在水溶液中的降解活化能(Ea)分别为48.54,49.83 kJ· mol-1,在注射用丹参多酚酸中则分别为95.19,83.56 kJ· mol-1.结论:丹酚酸B与迷迭香酸在碱性条件及高温条件下易降解,与对照品相比较,二者在注射用丹参多酚酸中更为稳定.