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研究生:謝硯如
研究生(外文):Yen-Ju Hsieh
論文名稱:白花藤中磯松素的含量分析及其在大白鼠的藥物動力學研究
論文名稱(外文):Herbal analysis of plumbagin content in Plumbago zeylanica L. and its pharmacokinetics in rats
指導教授:蔡東湖蔡東湖引用關係
指導教授(外文):Tung-Hu Tsai
學位類別:博士
校院名稱:國立陽明大學
系所名稱:傳統醫藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:90
中文關鍵詞:磯松素藥物動力學液相層析串聯質譜儀
外文關鍵詞:plumbaginpharmacokineticsliquid chromatography coupled with tandem mass spectrometry
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磯松素是分離自白花藤中的一個主要的活性成分,是一種廣泛分佈於灌木林或草原間的半攀緣性植物。在過去的文獻中,多數著重在白花藤的含量分析,在近代的研究則著重在藥理藥效學上的評估,如抗癌、抗發炎及中樞系統方面的研究。但是對於磯松素在生物體內的動向則是鮮少被注意。因此首先,建立一套可靠的液相層析串聯質譜儀分析方法,有效地去偵測在白花藤植物中磯松素的含量。其次,利用液相層析串聯質譜儀結合清醒老鼠的自動採樣系統,以探討其口服生物可利用率。此外,使用微透析採樣技術和高效能液相層析儀來監測游離態的磯松素在大白鼠體內的藥物動力學變化,並探討P糖蛋白抑制劑和葡萄糖醛酸反應抑制劑對於血液和膽汁排除上所扮演的角色。最後,測定尿液和糞便中藥物的含量,以瞭解口服給藥後未被吸收的磯松素含量,並進一步探討尿液中可能的代謝產物。
結果發現:分別以水,50 %乙醇和95 %乙醇萃取後,磯松素其含量分別為 0.2 ± 0.04, 3.9 ± 0.71 及 13.4 ± 1.30 g/kg。而在清醒且可自由活動的大白鼠模式下,所測得的磯松素口服生物可利用率為38.7 ± 5 %。游離態的磯松素可以在血液和膽汁中被偵測。磯松素在血液和膽汁的濃度對時間曲線下面積分別為59.9 ± 7.1 and 31.2 ± 1.8 min・µg/mL,顯示出在膽汁中所測得的未結合態磯松素濃度大於在血漿所測得的未結合態磯松素的濃度。此外經由計算後所得到的膽汁到血液的分佈係數約為1.7,由這個結果我們推測磯松素可能有經過腸肝循環。在併用P糖蛋白抑制劑後磯松素在膽汁中排出減少,但是對於血液的影響不大,推測磯松素的肝膽排除作用可能受到P糖蛋白的調控。併用葡萄糖醛酸反應抑制劑後在膽汁中所測得的磯松素量增加,但對於血液的磯松素含量影響不大,推測磯松素在體內可能經過葡萄糖醛酸反應後而排出。84小時內磯松素的糞便排除量為口服給予劑量的49.2 %,而120小時內在尿液中的累積量則為口服給予劑量的12 %。在經由液相層析串聯質譜儀進一步推測磯松素可能進行了第一相脂肪族氫氧化反應和第二相的葡萄糖醛酸反應。
綜合上述,本研究建立了一套可靠的分析方法,並且進一步瞭解磯松素在大白鼠體內的吸收、分佈、代謝及排泄,故磯松素的成分分析和藥物動力學研究,提供了有價值的臨床應用資訊。
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is an herbal ingredient which is isolated from the root of Plumbago zeylanica L. In previous reports, there is information on the separations of plumbagin from P. zeylanica L. and its analytical method. Also in recent years, some studies investigated pharmacological functions such as anti-cancer, anti-inflammation and central nervous system effects. However, the absorption, distribution, metabolism, and elimination of plumbagin are still unknown.
First of all, a reliable liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method was developed to determine the contents of plumbagin from P. zeylanica L. Secondly, an automated blood sampling system for serial blood sampling from conscious and freely moving rats coupled with LC-MS/MS method was used to evaluate the oral bioavailability of plumbagin. Thirdly, microdialysis sampling techniques coupled with high performance liquid chromatography and ultraviolet spectrometry was developed to simultaneously assess the unbound plumbagin in rat blood and bile. Moreover, the roles of P-glycoprotein transport and glucuronidation metabolism on the pharmacokinetics of plumbagin were also estimated by using cyclopsorin A and probenecid to inhibit respective pathways. Finally, the elimination of plumbagin in urine and feces were measured to determine the unabsorbed part and possible metabolites of plumbagin after oral administration.
The results indicate that mass fractions of plumbagin in Plumbago zeylanica L. for H2O, 50 % ethanol (v/v) and 95 % ethanol (v/v) were 0.2 ± 0.04, 3.9 ± 0.71 and 13.4 ± 1.30 g/kg, respectively. The oral bioavailability of plumbagin was 38.7 ± 5 %. Unbound plumbagin appeared in blood and bile microdialysate. The AUC of plumbagin in blood and bile were 59.9 ± 7.1 and 31.2 ± 1.8 min・µg/mL, respectively. Furthermore, the bile-to-blood distribution ratio (AUCbile/AUCblood) of plumbagin was 1.7. These results suggest that plumbagin can be excreted in the bile. In combination with P-glycoprotein inhibitor, the concentration of plumbagin in bile declined, but not in blood. This data supports the idea that excretion of plumbagin in bile is regulated by P-glycoprotein. In combination with glucuronidation inhibitor, the concentration of plumbagin in bile increased, but not in blood. The result supports that plumbagin excreted through the glucuronidation pathway. 49.2 % of plumbagin appeared in feces within 84 hours, and 12 % of plumbagin appeared in urine 120 hours after oral administration, approximately. Furthermore, possible metabolites of plumbagin were found in rat urine and they were produced by the metabolism of plumbagin in liver with phase I aliphatic hydroxylation (MW 203) and phase II glucuronidation (MW 363 and 539) in urine, as identified by LC-MS/MS.
In conclusion, this study developed a reliable LC-MS/MS to determine the absorption, distribution, metabolism and elimination of plumbagin in the rat. Herbal analysis of Plumbago zeylanica L. and pharmacokinetics of plumbagin will provide some valuable information for future clinical application.
Abstract 1
摘要 3
1. Introduction 5
1-1. Introduction of plumbagin from Plumbago zeylanica L. 5
1-1-1. Herbal analysis of plumbagin 5
1-1-2. Pharmacological effects of plumbagin 7
1-1-3. Pharmacokinetics of plumbagin 8
1-2. Pharmacokinetic study 8
1-3. Automated blood sampling (ABS) system 9
1-3-1. Introduction of automated blood sampling (ABS) system 9
1-3-2. Applications of automated blood sampling (ABS) system 10
1-4. Microdialysis module 10
1-4-1. Introduction of microdialysis 10
1-4-2. Pros and cons for microdialysis 11
1-4-3. Application of in vivo microdialysis 11
1-5. Rationale 12
1-6. Aim of study 13
2. Materials and Methods 14
2-1. Materials and methods 14
2-2. Animals 14
2-3. Microdialysis installation 15
2-4. Analytical instruments 16
2-4-1. LC-MS/MS condition 16
2-4-1-1. Plumbagin analysis in Plumbago zeylanica L. 16
2-4-1-2. Plumbagin analysis in biological samples 17
2-4-1-3. In vitro microsome analysis 18
2-4-2. LC-UV condition 19
2-5. Method validation 19
2-5-1. Calibration curves 20
2-5-2. Recovery 21
2-6. Drug administration 22
2-6-1. Freely moving rats 22
2-6-2. Microdialysis experiments 22
2-6-3. Metabolic experiments 22
2-6-3-1. Enzymatic hydrolysis 23
2-6-3-2. In vitro liver microsome analysis 23
2-7. Sample preparation 23
2-7-1. Herbal extraction 23
2-7-2. Plasma sample extraction 24
2-7-3. The urine and fecal samples extraction 24
2-8. Pharmacokinetic applications 24
2-9. Statistics 25
3. Results 26
3-1. Identification and herbal analysis of plumbagin 26
3-1-1. LC-MS/MS 26
3-1-2. Method validation 26
3-1-3. Recovery 27
3-1-4. Herbal analysis 27
3-2. Pharmacokinetics of plumbagin 27
3-2-1. LC-MS/MS 27
3-2-2. Method validation 28
3-2-3. Pharmacokinetics application 29
3-3. Pharmacokinetics of unbound plumbagin 29
3-3-1. Chromatograms of dialysate 29
3-3-2. Method validation 29
3-3-3. In vitro recovery of plumbagin from microdialysis probe 30
3-3-4. Pharmacokinetic study of unbound plumbagin 30
3-4. Metabolism of plumbagin 31
3-4-1. Chromatograms of rat urine and feces 31
3-4-2. Method validation 32
3-4-3. Glucuronidation of urinary sample 32
3-4-4. Fecal excretion 33
4. Discussion 35
4-1. Analytical methods 35
4-1-1. New analytical method development 35
4-1-2. Herbal analysis of plumbagin 36
4-2. Pharmacokinetics application of plumbagin 37
4-2-1. LC-MS/MS 37
4-2-2. Recovery 37
4-2-3. Bioavailability 38
4-2-4. Automated blood sampling system 39
4-3. Pharmacokinetics of unbound plumbagin 39
4-3-1. Calibration of the microdialysis probes 39
4-3-2. Pharmacokinetics 40
4-4. Metabolism of plumbagin 43
4-4-1. Glucuronidation of urinary sample 43
4-4-2. Fecal excretion 43
4-4-3. Urinary excretion 44
4-5. Reference summaries for the related studies 44
5. Conclusion 45
References 46
研究成果 89
Ahmad I, Mehmood Z, and Mohammad F (1998) Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol 62: 183-193.
Ahmad A, Banerjee S, Wang Z, Kong D, and Sarkar FH (2008) Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-kB and Bcl-2. J Cellular Biochem 105: 1461–1471.
Aziz MH, Dreckschmidt NE, and Verma AK (2008) Plumbagin, a medicinal plant–derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res 68: 9024-9032.
Baber N, Halliday L, Sibeon R, Littler T, and Orme ML (1978) The interaction
between indomethacin and probenecid. A clinical and pharmacokinetic study. Clin
Pharmacol Ther 24: 298-307.
Bianchi L, De Micheli E, Bricolo A, Ballini C, Fattori M, Venturi C, Pedata F, Tipton KF, and Della Corte L (2004) Extracellular levels of amino acids and choline in human high grade gliomas: an intraoperative microdialysis study. Neurochemical Res 29: 325-334.
Bopaiah CP and Pradhan N (2001) Central nervous system stimulatory action from the root extract of Plumbago zeylanica in rats. Phytother Res 15: 153-156.
Bressolle F, Bromet-Petit M, and Audran M (1996) Validation of liquid chromatographic and gas chromatographic methods. Applications to pharmacokinetics. J Chromatogr B 686: 3-10.
Carneheim C and Stahle L (1991) Microdialysis of lipophilic compounds: a methodological study. Pharmacol Toxicol 69: 378-380.
Chan-Bacab MJ and Peña-Rodríguez LM (2001) Plant natural products with leishmanicidal activity. Nat Prod Rep 18: 674-688.
Chandrasekaran B and Nagarajan B (1981) Metabolism of echitamine and plumbagin in rat. J Biosci 3: 395-400.
Cheng CL, Chou CH, and Hu OY (2005) Determination of lamotrigine in small volumes of plasma by high-performance liquid chromatography. J Chromatogr B 817: 199-206.
Chiu NY and Chang KH (1986) The illustrated medicinal plants of Taiwan. SMC, Taipei, pp.172-173.
Chu XY, Kato Y, and Sugiyama Y (1999) Possible involvement of P-glycoprotein in biliary excretion of CPT-11 in rats. Drug Metab Dispos 27: 440-441.
Dai Y, Hou LF, Chan YP, Cheng L, and But PP (2004) Inhibition of immediate allergic reactions by ethanol extract from Plumbago zeylanica stems. Biol Pharm Bull 27: 429-432.
Davies MI (1999) A review of microdialysis sampling for pharmacokinetic applications. Anal Chim Acta 379: 227-282.
Didry N, Dubreuil L, Trotin F, and Pinkas M (1998) Antimicrobial activity of aerial parts of Drosera peltata Smith on oral bacteria. J Ethnopharmacol 60: 91-96.
Dinda B, Hajra AK, and Chel G (1997) Naphthoquinones of Plumbago. species: a review. J. Indian Chem Soc 74: 974-979.
Ding Y, Chen ZJ, Liu S, Che D, Vetter M, and Chang CH (2005) Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone. J Pharm Pharmacol 57: 111-116.
DiStefano JJ (1982) Noncompartmental vs. compartmental analysis: some bases for
choice. Am J Physiol 243: 1-6.
Durga R, Sridhar P, and Polasa H (1990) Effects of plumbagin on antibiotic resistance in bacteria. Indian J Med Res 91: 18-20.
Evrard PA, Ragusi C, Boschi G, Verbeeck RK, and Scherrmann JM (1998) Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition. Brain Res 786: 122-127.
Fromm MF, Kim RB, Stein CM, Wilkinson GR, and Roden DM (1999) Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99: 552-557.
Gillespie WR (1991) Noncompartmental versus compartmental modelling in clinical pharmacokinetics. Clin Pharmacokinet 20: 253-262.
Gomathinayagam R, Sowmyalakshmi S, Mardhatillah F, Kumar R, Akbarsha MA, and Damodaran C (2008) Anticancer mechanism of plumbagin, a natural compound, on non-small cell lung cancer cells. Anticancer Res 28: 785-792.
Gunaherath GMKB, Gunatilaka AAL, Sultanbawa MUS, and Balasubramaniam S (1983) 1,2(3)-Tetrahydro-3,3'-biplumbagin: a naphthalenone and other constituents from Plumbago zeylanica. Phytochemistry 22: 1245-1248.
Gunaratna PC, Kissinger PT, Kissinger CB, and Gitzen JF (2004) An automated blood sampler for simultaneous sampling of systemic blood and brain microdialysates for drug absorption, distribution, metabolism, and elimination studies. J Pharmacol Toxicol Methods 49: 57-64.
Gupta MM, Verma RK, Uniyal GC, and Jain SP (1993) Determination of plumbagin by normal phase high performance liquid chromatography. J Chromatogr 637: 209-212.
Hart KT (1958) Study of hydrolysis of urinary metabolites of 2-methyl- 1,4-naphthoquinone. Proc Soc Exp Biol Med 97: 848-851.
Hazra B, Sarkar R, Bhattacharyya S, Ghosh PK, Chel G, and Dinda B (2002) Synthesis of plumbagin derivatives and their inhibitory activities against Ehrlich ascites carcinoma in vivo and Leishmania donovani Promastigotes in vitro. Phytother Res 16: 133-137.
Holmang A, Mimura K, Bjorntorp P, and Lonnroth P (1997) Interstitial muscle insulin and glucose levels in normal and insulin-resistant Zucker rats. Diabetes 46: 1799-1804.
Hsieh YJ, Lin LC, and Tsai TH (2005) Determination and identification of plumbagin from the roots of Plumbago zeylanica L. by liquid chromatography with tandem mass spectrometry. J Chromatogr A 1083: 141-145.
Hsieh YJ, Lin LC, and Tsai TH (2006) Measurement and pharmacokinetic study of plumbagin in a conscious freely moving rat using liquid chromatography/tandem mass spectrometry. J Chromatogr B 844: 1-5.
Hsu YL, Cho CY, Kuo PL, Huang YT, and Lin CC (2006) Plumbagin (5-hydroxy-2-
methyl-1,4-naphthoquinone) induces apoptosis and cell cycle arrest in A549 cells through p53 accumulation via c-Jun NH2-terminal kinase-mediated phosphorylation at serine 15 in vitro and in vivo. J Pharmacol Exp Ther 318: 484-494.
Iyengar MA and Pendse GS (1966) Plumbago zeylanica L. (Chitrak). A gastrointestinal flora normaliser. Planta Med 14: 337-351.
Mossa1 JS, El-Feraly FS, and Muhammad I (2004) Antimycobacterial constituents from Juniperus procera, Ferula communis and Plumbago zeylanica and their in vitro synergistic activity with isonicotinic acid hydrazide. Phytother Res 18: 934–937.
Nair S, Nair RR, Srinivas P, Srinivas G, and Pillai MR (2008) Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway. Mol Carcinog 47: 22-33.
Jamali F and Kunz-Dober CM (1999) Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery. Br J Clin Pharmacol 47: 391-396.
Kavimani S, Ilango R, Madheswaran M, Jayakar B, Gupta M, and Majumdar UK (1996) Antitumor activity of plumbagin against Dalton´s ascitic lymphoma. Indian J Pharm Sci 58: 194-196.
Kawiak A, Piosik J, Stasilojc G, Gwizdek-Wisniewska A, Marczak L, Stobiecki
M, Bigda J, and Lojkowska E (2007) Induction of apoptosis by plumbagin through
reactive oxygen species-mediated inhibition of topoisomerase II. Toxicol Appl Pharmacol 223: 267-276.
Khramov AN and Stenken JA (1999) Enhanced microdialysis. extraction efficiency of ibuprofen in vitro by facilitated. transport with β-cyclodextrin. Anal Chem 71: 1257-1264.
Kirtikar KR and Basu BD (1993) Indian Medicinal Plants Shiva Publishers: Dehradun, India, pp.1466-1468.
Krishnaswamy M and Purushothaman KK (1980) Plumbagin: a study of its anticancer, antibacterial & antifungal properties. Indian J Exp Biol 18: 876-877.
Kusuhara H, Suzuki H, and Sugiyama Y (1998) The role of P-glycoprotein and
canalicular multispecific organic anion transporter in the hepatobiliary excretion of
drugs. J Pharm Sci 87: 1025-1040.
Kuo PL, Hsu YL, and Cho CY (2006) Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther 5: 3209-3221.
Lee C and Sarna SK (1997) Central regulation of gastric emptying of solid nutrient meals by corticotropin releasing factor. Neurogastroenterol Motil 9: 221-229.
Leis S, Drenkhahn S, Schick C, Arnolt C, Schmelz M, Birklein F, and Bickel A (2004) Catecholamine release in human skin: a microdialysis study. Exp Neurology 188: 86-93.
Li HL (1998) Flora of Taiwan, second ed. Editorial Committee of the Flora of Taiwan, pp.79-82.
Li A, May MP, and Bigelow JC (2006) Identification of a metabolite of atrazine, N-ethyl-6-methoxy-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, upon incubation with rat liver microsomes. J Chromatogr B 836: 129-132.
Lin LC and Chou CJ (2003) Metroterpenes and C-glucosylflavonoids from the aerial parts of Plumbago zeylanica. Chin Pharm J 55: 77-81.
Lin LC, Yang LL, and Chou CJ (2003) Cytotoxic naphthoquinones and plumbagic acid glucosides from Plumbago zeylanica. Phytochemistry 62: 619-622.
Lin LC, Yang KY, Chen YF, Wang SC, and Tsai TH (2005) Measurement of daphnoretin in plasma of freely moving rat by liquid chromatography. J Chromatogr A 1073: 285-289.
Marston A and Hostettmann K (1984) High-performance liquid. chromatography of some naturally occurring naphthoquinones. J Chromatogr 295: 526-529.
Mays DC, Dixon KF, Balboa A, Pawluk LJ, Bauer MR, Nawoot S, and Gerber N
(1991) A nonprimate animal model applicable to zidovudine pharmacokinetics in
humans: inhibition of glucuronidation and renal excretion of zidovudine by
probenecid in rats. J Pharmacol Exp Ther 259: 1261-1270.
McDowall RD (1989) Sample preparation for biomedical analysis. J Chromatogr 492: 3-58.
Meijer DKF, Smit JW, and MulleR M (1997) Hepatobiliary elimination of cationic
drugs: the role of P-glycoproteins and other ATP-dependent transporters. Adv Drug
Deliv Rev 25: 159-200.
Nguyen AT, Malonne H, Duez P, Vanhaelen-Fastre R, Vanhaelen M, and Fontaine J (2004) Cytotoxic constituents from Plumbago zeylanica. Fitoterapia 75: 500-504.
Ofner B, Boukhabza A, Pacha W, Amsterdam CV, and Wintersteiger R (1997) Determination of SDZ ICM 567 in blood and muscle microdialysis samples by microbore liquid chromatography with ultraviolet and fluorescence detection. J Chromatogr B 700: 191-200.
Oyedapo OO (1996) Studies on bioactivity of the root extract of Plumbago zeylanica. International Journal of Pharmacognosy 34: 365-369.
de Paiva SR, Lima LA, Figueiredo Mr, and Kaplan MA (2004) Plumbagin quantification in roots of Plumbago scandens L. obtained by different extraction techniques. An Acad Bras Cienc 76: 499-504.
Powolny AA and Singh SV (2008) Plumbagin-induced apoptosis in human prostate cancer cells is associated with modulation of cellular redox status and generation of reactive oxygen species. Pharm Res 25: 2171-2180.
Quellec AL, Dupin S, Genissel P, Saivin S, Marchand B, and Houin G (1995) Microdialysis probes calibration: gradient and tissue dependent changes in no net flux and reverse dialysis methods. J Pharmacol Toxicol Methods 33: 11-16.
Sargenti SR and Vichnewski W (2000) Sonication. and liquid chromatography as a rapid technique. for extraction and fractionation of plant material. Phytochem Anal 11: 69-73.
Savina PM and Brouwer KL (1992) Probenecid-impaired biliary excretion of acetaminophen glucuronide and sulfate in the rat. Drug Metab Dispos. 20: 496-501.
Sandur SK, Ichikawa H, Sethi G, Ahn KS, and Aggarwal BB (2006) Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents. J Biol Chem 281: 17023-17033.
Sanyal U, Bhattacharyy S, Patra A, and Hazra B (2003) Liquid chromatographic separation of derivatives of diospyrin, a bioactive bisnaphthoquinonoid plant-product, and analogous naphthyl compounds. J Chromatogr A 1017: 225-232.
Shargel L and Yu ABC (1993) Aplied Biopharmaceutics and Pharmacokinetics, third ed. Prentice-Hall, New York, pp.15-33.
Shen Z, Dong Z, Cheng P, Li L, Chen Z, and Liu J (2003) Effects of plumbagin on platelet aggregation and platelet-neutrophil interactions. Planta Med 69: 605-609.
Simonsen HT, Nordskjold JB, Smitt UW, Nyman U, Palpu P, Joshi P, and Varughese G (2001) In vitro screening of Indian medicinal plants for antiplasmodial activity. J Ethnopharmacol 74: 195-204.
Srinivas P, Gopinath G, Banerji A, Dinakar A, and Srinivas G (2004) Plumbagin induces reactive oxygen species, which mediate apoptosis in human cervical cancer cells. Mol Carcinog 40: 201-211.
Stensen W and Jensen E (1994) High performance liquid chromatographic separations of naphtoquinones and their derivatives. J Chromatogr A 659: 87-93.
Sugie S, Okamoto K, Rahman KM, Tanaka T, Kawai K, Yamahara J, and Mori H (1998) Inhibitory effects of plumbagin and juglone on azoxymethane-induced intestinal carcinogenesis in rats. Cancer Lett 127: 177-183.
Suraveratum N, Krungkral SR, Leangaramgul P, Prapunwattana P, and Krungkai J (2000) Purification and characterization of Plasmodium falciparum succinate dehydrogenase. Mol Biochem Parasitol 105: 215-222.
Tsai TH (2001) Pharmacokinetics of pefloxacin and its interaction with cyclosporin A,
a P-glycoprotein modulator, in rat blood, brain and bile, using simultaneous microdialysis. Br J Pharmacol 132: 1310-1316.
Tsai TH (2002) Determination of naringin in rat blood, brain, liver, and bile using microdialysis and its interaction with cyclosporin A, a p-glycoprotein modulator. J Agric Food Chem 50: 6669-6674.
Tanigawara Y (2000) Role of P-glycoprotein in drug disposition. Ther Drug Monit
22: 137-140.
Tezuka M, Takahashi C, Kuroyanagi M, Satake M, Yoshihira K, and Natori S (1973) New naphthoquinones from Diospyros. Phytochemistry 12: 175-183.
Thompson RM, Gerber N, Seibert RA, and Desiderio DM (1972) Identification of 2-methyl-1,4-naphthohydroguinone monoglucuronide as a metabolite of 2-methyl- 1,4-naphthoquinone (menadione) in rat bile. Res Commun Chem Pathol Pharmacol 4: 543-552.
Tikkanen L, Matsushima T, Natori S, and Yoshihira K (1983) Mutagenicity of natural naphthoquinones and benzoquinones in the Salmonella/microsome test. Mutat Res 124: 25-34.
Wang YC and Huang TL (2005) High-performance liquid chromatography for quantification of plumbagin, an anti-Helicobacter pylori compound of Plumbago zeylanica L. J Chromatogr A 1094: 99-104.
Wang YC and Huang TL (2005) Anti-Helicobacter pylori activity of Plumbago zeylanica L. FEMS Immunol Med Microbiol 43: 407-412.
Wang YC and Huang TL (2005) Screening of anti-Helicobacter pylori herbs deriving from Taiwanese folk medicinal plants. FEMS Immunol Med Microbiol 43: 295-300.
Wang CC, Chiang YM, Sung SC, Hsu YL, Chang JK, and Kuo PL (2008) Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Lett 259: 82-98.
Watanabe T, Miyauchi S, Sawada Y, Iga T, Hanano M, Inaba M, and Sugiyama Y (1992) Kinetic analysis of hepatobiliary transport of vincristine in perfused rat liver.
Possible roles of P-glycoprotein in biliary excretion of vincristine. J Hepatol 16: 77-88.
Yamaoka K, Nakagawa T, and Uno T (1978) Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 6: 165-175.
Zou AP and Cowley AW Jr (1997) Nitric oxide in renal cortex and medulla. An in vivo microdialysis study. Hypertension 29: 194-198.
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