Role of P-glycoprotein in restricting the brain penetration of tanshinone IIA, a major active constituent from the root of Salvia miltiorrhiza Bunge, across the blood-brain barrier

Xenobiotica

Volumn 37, Issue 6, 2007, Pages 635-678

  Chen, X ^a   Zhou, Z W ^b   Xue, C C ^c   Li, X X ^b   Zhou, S F ^d  

^a First Affiliated Hospital   (China)

^b NANCHANG UNIVERSITY   (China)

^c RMIT UNIVERSITY   (Australia)

^d QUEENSLAND UNIVERSITY OF TECHNOLOGY   (Australia)

Author keywords

Blood brain barrier; Mdr1a knockout mice; P glycoprotein; Pharmacokinetics of tanshinone IIA; Tanshinone IIA

Indexed keywords

CRYPTOTANSHINONE; GLYCOPROTEIN P; GLYCOPROTEIN P INHIBITOR; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; QUINIDINE; QUINOLINIC ACID; TANSHINONE; VERAPAMIL;

ADJUVANT THERAPY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; BRAIN MICROCIRCULATION; BRAIN PERFUSION; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG TRANSPORT; DRUG UPTAKE; ENDOTHELIUM CELL; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; NONHUMAN; PLANT ROOT; PROTEIN FUNCTION; RAT; SALVIA MILTIORRHIZA; TRANSPORT KINETICS;

ANIMALS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; CELLS, CULTURED; ENDOTHELIAL CELLS; INFARCTION, MIDDLE CEREBRAL ARTERY; MALE; MICE; MICE, KNOCKOUT; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; P-GLYCOPROTEIN; PHENANTHRENES; PLANT ROOTS; QUINIDINE; QUINOLINIC ACID; RATS; RATS, SPRAGUE-DAWLEY; SALVIA MILTIORRHIZA; VERAPAMIL;

MUS; RATTUS; SALVIA MILTIORRHIZA;

EID: 34447118246     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.1080/00498250701411258     Document Type: Article

References (103)

1. Adams JD, Wang R, Yang J, Lien EJ. 2006. Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chinese Medicine 1:1-15.
2. Altar CA, Dugich-Djordjevic M, Armanini M, Bakhit C. 1991. Medial-to-lateral gradient of neostriatal NGF receptors: Relationship to cholinergic neurons and NGF-like immunoreactivity. Journal of Neuroscience 11:828-836.
3. Anonymous. 1977. Danshen in ischemic stroke. Chinese Medical Journal 3:224-226.
4. Arboix M, Paz OG, Colombo T, D'Incalci M. 1997. Multidrug resistance-reversing agents increase vinblastine distribution in normal tissues expressing the P-glycoprotein but do not enhance drug penetration in brain and testis. Journal of Pharmacology and Experimental Therapeutics 281:1226-1230.
5. Banks WA. 1999. Physiology and pathology of the blood-brain barrier: Implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J Neurovirol 5:538-555.
6. Begley DJ. 2004. ABC transporters and the blood-brain barrier. Current Pharmaceutical Design 10:1295-1312.
7. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. 1996. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27:1616-1622.
8. Bi HC, Law FC, Zhong GP, Xu CS, Pan Y, Ding L, Chen X, Zhao LZ, Xu Q, Huang M. 2007. Study of tanshinone IIA tissue distribution in rat by liquid chromatography-tandem mass spectrometry method. Biomedical Chromatography 21:473-479.
9. Borst P, Elferink RO. 2002. Mammalian ABC transporters in health and disease. Annual Review of Biochemistry 71:537-592.
10. Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72:248-254.
11. Brown RC, Egleton RD, Davis TP. 2004. Mannitol opening of the blood-brain barrier: Regional variation in the permeability of sucrose, but not 86Rb+ or albumin. Brain Research 1014:221-227.
12. Cecchelli R, Dehouck B, Descamps L, Fenart L, Buee-Scherrer VV, Duhem C, Lundquist S, Rentfel M, Torpier G, Dehouck MP. 1999. In vitro model for evaluating drug transport across the blood-brain barrier. Advanced Drug Delivery Reviews 36:165-178.
13. Chang HM, Chen KP, Choang TF, Chow HF, Chui Y, Hon PM, Lau Tan FW, Yang Y, Zhong ZP, Lee M, et al. 1990. Structure elucidation and total synthesis of new tanshinones isolated from Salvia miltiorriza Bunge (Danshen). Journal of Organic Chemistry 55:3537-3543.
14. Chang PN, Mao JC, Huang SH, Ning L, Wang ZJ, On T, Duan W, Zhu YZ. 2006. Analysis of cardioprotective effects using purified Salvia miltiorrhiza extract on isolated rat hearts. Journal of Pharmacological Sciences 101:245-249.
15. Chen TH, Hsu YT, Chen CH, Kao SH, Lee HM. 2007. Tanshinone IIA from Salvia miltiorrhiza induces heme oxygenase-1 expression and inhibits lipopolysaccharide-induced nitric oxide expression in RAW 264.7 cells. Mitochondrion 7:101-105.
16. Cheng TO. 2006a. Danshen: A popular Chinese cardiac herbal drug. Journal of the American College of Cardiology 47:1498.
17. Cheng TO. 2006b. Danshen: What every cardiologist should know about this Chinese herbal drug. International Journal of Cardiology 110:411-412.
18. Collett A, Tanianis-Hughes J, Carlson GL, Harwood MD, Warhurst G. 2005. Comparison of P-glycoprotein-mediated drug-digoxin interactions in Caco-2 with human and rodent intestine: Relevance to in vivo prediction. European Journal of Pharmaceutical Sciences 26:386-393.
19. Couture L, Nash JA, Turgeon J. 2006. The ATP-binding cassette transporters and their implication in drug disposition: A special look at the heart. Pharmacological Reviews 58:244-258.
20. Dallas S, Miller DS, Bendayan R. 2006. Multidrug resistance-associated proteins: Expression and function in the central nervous system. Pharmacological Reviews 58:140-161.
21. Danheiser RL, Casebier DS, Loebach JL. 1992. Total synthesis of dan shen diterpenoid quinones. Tetrahedron Letters 33:1149-1152.
22. de Boer AG, Gaillard PJ. 2007. Drug targeting to the brain. Annual Review of Pharmacology and Toxicology 47:323-355.
23. de Boer AG, van der Sandt IC, Gaillard PJ. 2003. The role of drug transporters at the blood-brain barrier. Annual Review of Pharmacology and Toxicology 43:629-656.
24. Deeken JF, Loscher W. 2007. The blood-brain barrier and cancer: Transporters, treatment, and Trojan horses. Clinical Cancer Research 13:1663-1674.
25. Deeley RG, Westlake C, Cole SP. 2006. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiological Reviews 86:849-899.
26. Desrayaud S, Guntz P, Scherrmann JM, Lemaire M. 1997. Effect of the P-glycoprotein inhibitor, SDZ PSC 833, on the blood and brain pharmacokinetics of colchicine. Life Sciences 61:153-163.
27. Don MJ, Shen CC, Syu WJ, Ding YH, Sun CM. 2006. Cytotoxic and aromatic constituents from Salvia miltiorrhiza. Phytochemistry 67:497-503.
28. Dong JC, Xu LN. 1996. [Beneficial effects of acetylsalvianolic acid A on focal cerebral ischemic rats subjected to middle cerebral artery thrombosis]. Yao Xue Xue Bao 31:6-9.
29. Drion N, Lemaire M, Lefauconnier JM, Scherrmann JM. 1996. Role of P-glycoprotein in the blood-brain transport of colchicine and vinblastine. Journal of Neurochemistry 67:1688-1693.
30. El Hafny B, Cano N, Piciotti M, Regina A, Scherrmann JM, Roux F. 1997. Role of P-glycoprotein in colchicine and vinblastine cellular kinetics in an immortalized rat brain microvessel endothelial cell line. Biochemical Pharmacology 53:1735-1742.
31. Fabis MJ, Scott GS, Kean RB, Koprowski H, Hooper DC. 2007. Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models. Proceedings of the National Academy of Sciences USA 104:5656-5661.
32. Gaillard PJ, van Der Meide PH, de Boer AG, Breimer DD. 2001. Glucocorticoid and type 1 interferon interactions at the blood-brain barrier: Relevance for drug therapies for multiple sclerosis. Neuroreport 12:2189-2193.
33. Girardin F. 2006. Membrane transporter proteins: A challenge for CNS drug development. Dialogues Clinical Neuroscience 8:311-321.
34. Golden PL, Pollack GM. 2003. Blood-brain barrier efflux transport. J Pharm Sci 92:1739-1753.
35. Gu M, Zhang G, Su Z, Ouyang F. 2004. Identification of major active constituents in the fingerprint of Salvia miltiorrhiza Bunge developed by high-speed counter-current chromatography. Journal of Chromatography. A. 1041:239-243.
36. Gumbleton M, Audus KL. 2001. Progress and limitations in the use of in vitro cell cultures to serve as a permeability screen for the blood-brain barrier. Journal of Pharmaceutical Sciences 90:1681-1698.
37. Hao H, Wang G, Cui N, Li J, Xie L, Ding Z. 2006. Pharmacokinetics, absorption and tissue distribution of tanshinone IIA solid dispersion. Planta Medica 72:1311-1317.
38. Hao H, Wang G, Cui N, Li J, Xie L, Ding Z. 2007. Identification of a novel intestinal first pass metabolic pathway: NQO1 mediated quinone reduction and subsequent glucuronidation. Current Drug Metabolism 8:137-149.
39. Hawkins BT, Davis TP. 2005. The blood-brain barrier/neurovascular unit in health and disease. Pharmacological Reviews 57:173-185.
40. Hermann DM, Kilic E, Spudich A, Kramer SD, Wunderli-Allenspach H, Bassetti CL. 2006. Role of drug efflux carriers in the healthy and diseased brain. Annals of Neurology 60:489-498.
41. +-dependent nucleoside transporter in microglia. Journal of Pharmacology and Experimental Therapeutics 292:366-374.
42. Horn TF, Engelmann M. 2001. In vivo microdialysis for nonapeptides in rat brain - A practical guide. Methods 23:41-53.
43. Huang KJ, Wang H, Xie WZ, Zhang HS. 2007. Investigation of the effect of tanshinone IIA on nitric oxide production in human vascular endothelial cells by fluorescence imaging. Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy, in press.
44. Imanshahidi M, Hosseinzadeh H. 2006. The pharmacological effects of Salvia species on the central nervous system. Phytotherapy Research 20:427-437.
45. Jang SI, Jeong SI, Kim KJ, Kim HJ, Yu HH, Park R, Kim HM, You YO. 2003. Tanshinone IIA from Salvia miltiorrhiza inhibits inducible nitric oxide synthase expression and production of TNF-alpha, IL-1beta and IL-6 in activated RAW 264.7 cells. Planta Medica 69:1057-1059.
46. Jang SI, Kim HJ, Kim YJ, Jeong SI, You YO. 2006. Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells: Possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. European Journal of Pharmacology 542:1-7.
47. Ji XY, Tan BK, Zhu YZ. 2000. Salvia miltiorrhiza and ischemic diseases. Acta Pharmacologica Sinica 21:1089-1094.
48. Jonker JW, Wagenaar E, van Deemter L, Gottschlich R, Bender HM, Dasenbrock J, Schinkel AH. 1999. Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug. British Journal of Pharmacology 127:43-50.
49. Katoh M, Suzuyama N, Takeuchi T, Yoshitomi S, Asahi S, Yokoi T. 2006. Kinetic analyses for species differences in P-glycoprotein-mediated drug transport. Journal of Pharmaceutical Sciences 95:2673-2683.
50. Lam BY, Lo AC, Sun X, Luo HW, Chung SK, Sucher NJ. 2003. Neuroprotective effects of tanshinones in transient focal cerebral ischemia in mice. Phytomedicine 10:286-291.
51. Lee J, Li JH, Oya S, Snyder JK. 1992. Asymmetric synthesis of tanshindiol A. Journal of Organic Chemistry 57:5301-5312.
52. Lee SY, Choi DY, Woo ER. 2005. Inhibition of osteoclast differentiation by tanshinones from the root of Salvia miltiorrhiza Bunge. Archives of Pharmacal Research 28:909-913.
53. Lemaire M, Bruelisauer A, Guntz P, Sato H. 1996. Dose-dependent brain penetration of SDZ PSC 833, a novel multidrug resistance-reversing cyclosporin, in rats. Cancer Chemotherapy and Pharmacology 38:481-486.
54. Letrent SP, Pollack GM, Brouwer KR, Brouwer KL. 1999. Effects of a potent and specific P-glycoprotein inhibitor on the blood-brain barrier distribution and antinociceptive effect of morphine in the rat. Drug Metabolism and Disposition 27:827-834.
55. Li P, Wang GJ, Li J, Hao HP, Zheng CN. 2006a. Identification of tanshinone IIA metabolites in rat liver microsomes by liquid chromatography-tandem mass spectrometry. Journal of Chromatography. A. 1104:366-369.
56. Li P, Wang GJ, Li J, Hao HP, Zheng CN. 2006b. Simultaneous determination of tanshinone IIA and its three hydroxylated metabolites by liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry 20:815-822.
57. Lin JH, Yamazaki M. 2003. Role of P-glycoprotein in pharmacokinetics: Clinical implications. Clinical Pharmacokinetics 42:59-98.
58. Liu AH, Li L, Xu M, Lin YH, Guo HZ, Guo DA. 2006. Simultaneous quantification of six major phenolic acids in the roots of Salvia miltiorrhiza and four related traditional Chinese medicinal preparations by HPLC-DAD method. Journal of Pharmaceutical and Biomedical Analysis 41:48-56.
59. Loscher W, Potschka H. 2005. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2:86-98.
60. Ma L, Zhang X, Guo H, Gan Y. 2006. Determination of four water-soluble compounds in Salvia miltiorrhiza Bunge by high-performance liquid chromatography with a coulometric electrode array system. Journal of Chromatography. B. 833:260-263.
61. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: Aplication to proliferation and cytotoxicity assays. Journal of Immunological Methods 65:55-63.
62. Pardridge WM. 2007. Blood-brain barrier delivery. Drug Discovery Today 12:54-61.
63. The Phamacopoeia Commission of PRC. 2005. Pharmacopoeia of the People's Republic of China version 2005 Vol. 1. Beijing: Beijing Chemical Industry Press.
64. Roux F, Couraud PO. 2005. Rat brain endothelial cell lines for the study of blood-brain barrier permeability and transport functions. Cellular and Molecular Neurobiology 25:41-58.
65. Schinkel AH, Wagenaar E, van Deemter L, Mol CA, Borst P. 1995. Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. Journal of Clinical Investigation 96:1698-1705.
66. Schinkel AH, Wagenaar E, Mol CA, van Deemter L. 1996. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. Journal of Clinical Investigation 97:2517-2524.
67. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O, et al. 1997. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proceedings of the National Academy of Sciences USA 94:4028-4033.
68. Shanghai Cooperative Group for the Study of Tanshinone IIA. 1984. Therapeutic effect of sodium tanshinone IIA sulfonate in patients with coronary heart disease. A double blind study. Shanghai Cooperative Group for the Study of tanshinone IIA. Journal of Traditional Chinese Medicine 4:20-24.
69. Siegal T, Zylber-Katz E. 2002. Strategies for increasing drug delivery to the brain: Focus on brain lymphoma. Clinical Pharmacokinetics 41:171-186.
70. Song M, Hang TJ, Zhang Zh X, Du R, Chen J. 2005. Determination of cryptotanshinone and its metabolite in rat plasma by liquid chromatography- tandem mass spectrometry. Journal of Chromatography. B. 827:205-209.
71. Song S, Suzuki H, Kawai R, Sugiyama Y. 1999. Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metabolism and Disposition 27:689-694.
72. Sugihara N, Toyama K, Michihara A, Akasaki K, Tsuji H, Furuno K. 2006. Effect of benzo[a]pyrene on P-glycoprotein-mediated transport in Caco-2 cell monolayer. Toxicology 223:156-165.
73. Sze FK, Yeung FF, Wong E, Lau J. 2005. Does Danshen improve disability after acute ischaemic stroke? Acta Neurologica Scandinavica 111:118-125.
74. Takahashi K, Ouyang X, Komatsu K, Nakamura N, Hattori M, Baba A, Azuma J. 2002. Sodium tanshinone IIA sulfonate derived from Danshen (Salvia miltiorrhiza) attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac cells. Biochemical Pharmacology 64:745-749.
75. Takasato Y, Rapoport SI, Smith QR. 1984. An in situ brain perfusion technique to study cerebrovascular transport in the rat. American Journal of Physiology: Heart and Circulatory Physiology 247:H484-493.
76. Tamai I, Senmaru M, Terasaki T, Tsuji A. 1995. Na(+)- and Cl(-)-dependent transport of taurine at the blood-brain barrier. Biochemical Pharmacology 50:1783-1793.
77. Tang F, Wu X, Wang T, Wang P, Li R, Zhang H, Gao J, Chen S, Bao L, Huang H, et al. 2007. Tanshinone II A attenuates atherosclerotic calcification in rat model by inhibition of oxidative stress. Vascular Pharmacology 46:427-438.
78. Tao YY, Liu CH. 2004. [Progress of research on mechanism of salvia miltiorrhiza and its chemical ingredients against liver fibrosis]. Zhong Xi Yi Jie He Xue Bao 2:145-148.
79. Tatsuta T, Naito M, Oh-hara T, Sugawara I, Tsuruo T. 1992. Functional involvement of P-glycoprotein in blood-brain barrier. Journal of Biological Chemistry 267:20383-20391.
80. Taylor EM. 2002. The impact of efflux transporters in the brain on the development of drugs for CNS disorders. Clinical Pharmacokinetics 41:81-92.
81. Terasaki T, Ohtsuki S. 2005. Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: An overview of biology and methodology. NeuroRx 2:63-72.
82. Tian Q, Zhang J, Chan E, Duan W, Zhou SF. 2005. Multidrug resistance proteins (MRPs) and implication in drug development. Drug Development Research 51:1-18.
83. Wang L, Xiong ZY, Wang G. 2004. [Systematic assessment on randomized controlled trials for treatment of stable angina pectoris by compound salvia pellet]. Zhongguo Zhong Xi Yi Jie He Za Zhi 24:500-504.
84. Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J, Wang W. 2005. Potential anticancer activity of tanshinone IIA against human breast cancer. International Journal of Cancer 116:799-807.
85. Wang J, Wang X, Jiang S, Yuan S, Lin P, Zhang J, Lu Y, Wang Q, Xiong Z, Wu Y, et al. 2007a. Growth inhibition and induction of apoptosis and differentiation of tanshinone IIA in human glioma cells. Journal of Neurooncology 82:11-21.
86. Wang X, Morris-Natschke SL, Lee KH. 2007b. New developments in the chemistry and biology of the bioactive constituents of Tanshen. Medicinal Research Reviews 27:133-148.
87. Wei YJ, Li SL, Li P. 2007. Simultaneous determination of seven active components of Fufang Danshen tablet by high performance liquid chromatography. Biomedical Chromatography 21:1-9.
88. WHO. 1991. World Health Orginization program on traditional medicines: Guidelines for the assessment of herbal medicines. Geneva: World Health Orginization.
89. Wu B, Liu M, Zhang S. 2004. Dan Shen agents for acute ischaemic stroke. Cochrane Database of Systematic Reviews CD004295.
90. Xia WJ, Yang M, Fok TF, Li K, Chan WY, Ng PC, Ng HK, Chik KW, Wang CC, Gu GJ, et al. 2005. Partial neuroprotective effect of pretreatment with tanshinone IIA on neonatal hypoxia-ischemia brain damage. Pediatric Research 58:784-790.
91. Yang LJ, Jeng CJ, Kung HN, Chang CC, Wang AG, Chau GY, Don MJ, Chau YP. 2005. Tanshinone IIA isolated from Salvia miltiorrhiza elicits the cell death of human endothelial cells. Journal of Biomedical Science 12:347-361.
92. Yang M, Liu A, Guan S, Sun J, Xu M, Guo D. 2006. Characterization of tanshinones in the roots of Salvia miltiorrhiza (Dan-shen) by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Rapid Communications in Mass Spectrometry 20:1266-1280.
93. Yang L, Zou X, Liang Q, Chen H, Feng J, Yan L, Wang Z, Zhou D, Li S, Yao S, et al. 2007. Sodium tanshinone IIA sulfonate depresses angiotensin II-induced cardiomyocyte hypertrophy through MEK/ERK pathway. Experimental and Molecular Medicine 39:65-73.
94. Yu WG, Xu LN. 1994. [Effect of acetylsalvianolic acid A on platelet function]. Yao Xue Xue Bao 29:412-416.
95. Yu WG, Xu LN. 1997. [Acetylsalvianolic acid A - A new thromboxane synthetase inhibitor]. Yao Xue Xue Bao 32:467-469.
96. Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Liu PQ, Duan W, Zhou SF. 2007. Role of P-glycoprotein in the intestinal absorption of tanshinone IIA, the major active ingredient in the roots of Salvia miltiorrhiza. Current Drug Metabolism, in press.
97. Zhang HS, Wang SQ. 2007. Nrf2 is involved in the effect of tanshinone IIA on intracellular redox status in human aortic smooth muscle cells. Biochemical Pharmacology 73:1358-1366.
98. Zhang J, Huang M, Guan S, Bi HC, Pan Y, Duan W, Chan SY, Chen X, Hong YH, Bian JS, et al. 2006. A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza. Journal of Pharmacology and Experimental Therapeutics 317:1285-1294.
99. Zhao BL, Jiang W, Zhao Y, Hou JW, Xin WJ. 1996. Scavenging effects of Salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochemistry and Molecular Biology International 38:1171-1182.
100. Zhou S, Paxton JW, Kestell P, Tingle MD. 2001. Reversible binding of the novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid to plasma proteins and its distribution into blood cells in various species. Journal of Pharmacy and Pharmacology 53:463-471.
101. Zhou L, Zuo Z, Chow MS. 2005a. Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. Journal of Clinical Pharmacology 45:1345-1359.
102. Zhou S, Feng X, Kestell P, Paxton JW, Baguley BC, Chan E. 2005b. Transport of the investigational anti-cancer drug 5,6-dimethylxanthenone-4- acetic acid and its acyl glucuronide by human intestinal Caco-2 cells. European Journal of Pharmaceutical Sciences 24:513-524.
103. Zhu Y.-P. 1998. Chinese materia medica: Chemistry, pharmacology and applications Amsterdam, The Netherlands: Harwood Academic Publishers.