Abstract
Aim:
(+)-Catechin and puerarin are polyphenol and flavonoid, respectively, in green tea and foodstuffs. They exhibit potent antioxidant activity and are widely used for treating cardiocerebrovascular diseases. The aim of this work was to investigate the potential interactions between (+)-catechin and puerarin following concurrent oral administration in rats, and their absorption mechanisms in Caco-2 cell monolayers.
Methods:
Pharmacokinetic studies were conducted in male rats received (+)-catechin (140 mg/kg, po) and/or puerarin (200 mg/kg, po). The cell uptake and transport behavior in Caco-2 cell monolayers and the interactions of the two compounds were analyzed.
Results:
When (+)-catechin and puerarin were administered concurrently, the AUC0-12 h and Cmax values of puerarin were 2.48-fold and 3.91-fold, respectively, as large as those of puerarin alone; the AUC0-12 h and Cmax values of (+)-catechin were decreased to 57.62% and 77.55%, respectively, compared with those of (+)-catechin alone. In Caco-2 cell monolayers, (+)-catechin (300 and 600 μmol/L) significantly increased the cell uptake and transport of puerarin, whereas puerarin (300 and 600 μmol/L) significantly decreased the cellular uptake and transport of (+)-catechin. Furthermore, both cyclosporine A (P-glycoprotein inhibitor) and MK-571 (MRP-2 inhibitor) significantly increased the cellular uptake and transport of (+)-catechin and puerarin.
Conclusion:
Concurrent oral administration of (+)-catechin and puerarin significantly increased the absolute oral bioavailability of puerarin, but decreasing that of (+)-catechin. The competitive efflux of (+)-catechin and puerarin by P-glycoprotein and MRP-2 might lead to this interaction during their absorption process in the small intestine.
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References
Mak JC . Potential role of green tea catechins in various disease therapies: progress and promise. Clin Exp Pharmacol Physiol 2012; 39: 265–73.
Bell JR, Donovan JL, Wong R, Waterhouse AL, German JB, Walzem RL, et al. (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Pharmacogn Rev 2000; 71: 103–8.
Morel I, Lescoat G, Cogrel P, Sergent O, Pasdeloup N, Brissot P, et al. Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol 1993; 45: 13–9.
Li M . Pueraria lobata (Willd.) Ohwi (Gegen, Kudzu). Dietary Chinese Herbs: Springer; 2015. P 235–45.
Hsu FL, Liu IM, Kuo DH, Chen WC, Su HC, Cheng JT . Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats. J Nat Prod 2003; 66: 788–92.
Yan LP, Chan SW, Chan AS, Chen SL, Ma XJ, Xu HX . Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats. Life Sci 2006; 79: 324–30.
Xuan B, Zhou YH, Yang RL, Li N, Min ZD, Chiou GC . Improvement of ocular blood flow and retinal functions with puerarin analogs. J Ocul Pharmacol Ther 1999; 15: 207–16.
Song X, Chen P, Chai X . Effects of puerarin on blood pressure and plasma renin activity in spontaneously hypertensive rat. Acta Pharmacol Sin 1988; 9: 55–8.
Benlhabib E, Baker JI, Keyler DE, Singh AK . Effects of purified puerarin on voluntary alcohol intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol. J Med Food 2004; 7: 180–6.
Song Y, Manson JE, Buring JE, Sesso HD, Liu S . Associations of dietary flavonoids with risk of type 2 diabetes, and markers of insulin resistance and systemic inflammation in women: a prospective study and cross-sectional analysis. J Am Coll Nutr 2005; 24: 376–84.
Yang CS, Landau JM . Effects of tea consumption on nutrition and health. J Nutr 2000; 130: 2409–12.
Geng Z, Zongdao C, Yimin W . Physicochemical properties of lotus (Nelumbo nucifera Gaertn) and kudzu (Pueraria hirsute Matsum) starches. Inter J Food Sci Tech 2007; 42: 1449–55.
Rice-Evans CA, Miller NJ, Paganga G . Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Bio Med 1996; 20: 933–56.
Tijburg L, Mattern T, Folts J, Weisgerber U, Katan M . Tea flavonoids and cardiovascular diseases: a review. Critl Rev Food Sci 1997; 37: 771–85.
Wan H, Zhu H, Tian M, Hu X, Yang J, Zhao C, et al. Protective effect of chuanxiongzine-puerarin in a rat model of transient middle cerebral artery occlusion-induced focal cerebral ischemia. Nucl Med Commun 2008; 29: 1113–22.
Guerra M, Speroni E, Broccoli M, Cangini M, Pasini P, Minghetti A, et al. Comparison between Chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin: antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. Life Sci 2000; 67: 2997–3006.
Das N . Studies on flavonoid metabolism: Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol 1971; 20: 3435–45.
Zhang QH, Wang WB, Li J, Chang YX, Wang YF, Zhang J, et al. Simultaneous determination of catechin, epicatechin and epicatechin gallate in rat plasma by LC–ESI-MS/MS for pharmacokinetic studies after oral administration of Cynomorium songaricum extract. J Chromatogr B Analyt Technol Biomed Life Sci 2012; 880: 168–71.
Zhao L, Liu A, Sun M, Gu J, Wang H, Wang S, et al. Enhancement of oral bioavailability of puerarin by polybutylcyanoacrylate nanoparticles. J Nanomater 2011; 2011: 6.
Wong Jl, Zheng Z . The clinical research of Song Ling Xue Mai Kang ameliorating the compliance and endothelial function of artery in hypertensive patients. J Tradit Chin Med Univ Hunan 2011; 8: 27.
Shen Z, Theander O . Flavonoid glycosides from needles of Pinus massoniana. Phytochemistry 1985; 24: 155–8.
Qiao HY, Zhu WL, Luo R, Ke ZH, Hao XF, Ke X, et al. UPLC fingerprint and components identification of Songling Xuemaikang capsules by LC-MS/MS. West China J Pharm Sci 2013; 1: 30.
Palleria C, Di Paolo A, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci 2013; 18: 601–10.
Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS . Piperine enhances the bioavailability of the tea polyphenol (−)-epigallocatechin-3-gallate in mice. J Nutr 2004; 134: 1948–52.
Baba S, Osakabe N, Natsume M, Muto Y, Takizawa T, Terao J . In vivo comparison of the bioavailability of (+)-catechin,(−)-epicatechin and their mixture in orally administered rats. J Nutr 2001; 131: 2885–91.
Jiang L, Dai J, Huang Z, Du Q, Lin J, Wang Y . Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 915–916: 8–12.
Manach C, Texier O, Morand C, Crespy V, Régérat F, Demigné C, et al. Comparison of the bioavailability of quercetin and catechin in rats. Free Radical Biol Med 1999; 27: 1259–66.
König J, Müller F, Fromm MF . Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacogn Rev 2013; 65: 944–66.
Liang XL, Zhao LJ, Liao ZG, Zhao GW, Zhang J, Chao YC, et al. Transport properties of puerarin and effect of Radix Angelicae Dahuricae extract on the transport of puerarin in Caco-2 cell model. J Ethnopharmacol 2012; 144: 677–82.
Song L, Zhang N, Xu DS . Absorption mechanism of paeoniflorin across Caco-2 monolayer model. Chin Tradit and Herbal Drugs 2008; 39: 41.
Wang R, Kuo C, Lien L, Lien E . Structure–activity relationship: analyses of P-glycoprotein substrates and inhibitors. J Clin Pharm Ther 2003; 28: 203–28.
Kitagawa S, Nabekura T, Takahashi T, Nakamura Y, Sakamoto H, Tano H, et al. Structure-activity relationships of the inhibitory effects of flavonoids on P-glycoprotein-mediated transport in KB-C2 cells. Biol Pharm Bull 2005; 28: 2274–8.
Saxena V, Hussain MD . Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer. Int J Nanomed 2012; 7: 713–21.
Acknowledgements
We are thankful for the financial support of the National S&T Major Project of China (Grant No 2012ZX09304004001) and the National Natural Science Foundation of China (No 81473169).
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Supplementary Figure S1 is available at Acta Pharmacologica Sinica's website.
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Supplementary Figure S1
(A) A blank plasma spiked with 5 μL of 1000 ng/mL puerarin (final concentration, 50 ng/mL). (DOC 20 kb)
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Su, Hf., Lin, Q., Wang, Xy. et al. Absorptive interactions of concurrent oral administration of (+)-catechin and puerarin in rats and the underlying mechanisms. Acta Pharmacol Sin 37, 545–554 (2016). https://doi.org/10.1038/aps.2015.164
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DOI: https://doi.org/10.1038/aps.2015.164
