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

References

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