Impact of Curcuma longa extract on the expression level of brain transporters in in vivo model

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Introduction: Blood brain barrier and multidrug resistance phenomenon are subjects of many investigations. Mainly, because of their functions in protecting the central nervous system (CNS) by blocking the delivery of toxic substances to the brain. This special function has some disadvantages, like drug delivery to the brain in neurodegenerative diseases

Objective: The aim of this study was to examine how natural and synthetic substances affect the expression levels of genes (Mdr1a, Mdr1b, Mrp1, Mrp2, Oatp1a4, Oatp1a5 and Oatp1c1) that encode transporters in the blood-brain barrier.

Methods: cDNA was synthesized from total RNA isolated from rat hippocampus. The expression level of genes was determined using real-time PCR (RT-PCR) method.

Results: Our findings showed that verapamil, as a synthetic substance, caused the greatest reduction of mRNA level of genes studied. The standardized extract of Curcuma longa reduced the expression level for Mrp1 and Mrp2, whereas the increase of mRNA level was observed for Mdr1b, Oatp1a5 and Oatp1c1.

Conclusions: These results suggests that herbal extracts may play an important role in overcoming the blood brain barrier during pharmacotherapy.

1. Sarrazin JL, Bonneville F, Martin-Blondel G. Brain infections. Diagn Interv Imaging 2012; 93(6):473-90. doi:

2. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55(4):475-82. doi:

3. Saatman KE, Duhaime AC, Bullock R, Maas AIR, Valadka A, Manley GT, et al. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25(7):719-38. doi:

4. McFaline-Figueroa JR, Lee EQ. Brain Tumors. Am J Med 2018; 131(8):874-882. doi:

5. Seifert HA, Offner H. The splenic response to stroke: from rodents to stroke subjects. J Neuroinflammation 2018; 5:195. doi:

6. Florendo M, Figacz A, Srinageshwar B, Sharma A, Swanson D, Dunbar GL, et al. Use of polyamidoamine dendrimers in brain diseases. Molecules 2018; 23(9):2238. doi:

7. Chen M, Du ZY, Zheng X, Li DL, Zhou RP, Zhang K. Use of curcumin in diagnosis, prevention, and treatment of Alzheimer’s disease. Neural Regen Res 2018; 13(4):742-752. doi:

8. Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer’s disease: An overview. Ann Indian Acad Neurol 2008; 11(1):13–19. doi:

9. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37(1):13-25. doi:

10. Daneman R, Prat A. The blood–brain barrier. Cold Spring Harb Perspect Biol 2015; 7(1):a020412. doi:

11. Moretti R, Chhor V, Titomanlio L, Fleiss B, Gressens P. Brain edema in developing brain diseases. In: Brain edema. From molecular mechanisms to clinical practice. London 2017:393-429.

12. Tajes M, Ramos-Fernández E, Weng-Jiang X, Bosch-Morató M, Guivernau B, Eraso-Pichot A, et al. The blood-brain barrier: structure, function and therapeutic approaches to cross it. Mol Membr Biol 2014; 31(5):152-67. doi:

13. Schenk GJ, Kooij G, Reijerkerk A, de Vries H. Disease influence on BBB transport in inflammatory disorders. In: Hammarlund-Udenaes M, de Lange E, Thorne R. (eds.). Drug delivery to the brain. AAPS advances in the pharmaceutical sciences. New York 2014, 10:573-589.

14. Bogacz A, Deka-Pawlik D, Bartkowiak-Wieczorek J, Karasiewicz M, Kujawski R, Kowalska A, et al. The effect of herbal materials on the P-glycoprotein activity and function. Herba Pol 2013; 59(4):129-141. doi:

15. Young AB. Four decades of neurodegenerative disease research: How far we have come! J Neurosci 2009; 29(41):12722-12728. doi:

16. Zhang F, Lin Y, Kannan S, Kanan RM. Targeting specific cells in the brain with nanomedicines for CNS therapies. J Control Release 2016; 240:212–226. doi:

17. Mrozikiewicz PM, Bogacz A, Bartkowiak-Wieczorek J, Kujawski R, Mikołajczak PL, et al. Screening for impact of popular herbs improving mental abilities on the transcriptional level of brain transporters. Acta Pharm 2014; 64(2):223-32. doi:

18. Urquhart BL, Kim RB. Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol 2009; 65(11):1063-70. doi:

19. Patel M, Souto EB, Singh KK. Advances in brain drug targeting and delivery: limitations and challenges of solid lipid nanoparticles. Expert Opin Drug Deliv 2013; 10(7):889-905. doi:

20. Zhang R, Jie J, Zhou Y, Cao Z, Li W. Longterm effects of Panax ginseng on disposition of fexofenadine in rats in vivo. Am J Chin Med 2009; 37:657-667. doi:

21. Zhang J, Zhou F, Wu X, Gu Y, Ai H, Zheng Y, et al. 20(S)-ginsenoside Rh2 noncompetitively inhibits P-glycoprotein in vitro and in vivo: a case for herb–drug interactions. Drug Metab Dispos 2010; 38:2179–2187. doi:

22. Garrovo Ch, Rosati A, Bartoli F, Decorti G. St John’s wort modulation and developmental expression of multidrug transporters in the rat. Phytother Res 2006; 20:468-473. doi:

23. Scambia G, Ranelletti FO, Panici PB, De Vincenzo R, Bonanno G, Ferrandina G, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemoth Pharm 1994; 34:459-464. doi:

24. Yuan J, Liu W, Zhu H, Zhang X, Feng Y, Chen Y, et al. Curcumin attenuates blood-brain barrier dis ruption after subarachnoid hemorrhage in mice. J Surg Res 2017; 207:85-91. doi:

25. Wang YF, Gu YT, Qin GH, Zhong L, Meng YN. Curcumin ameliorates the permeability of the blood-brain barrier during hypoxia by upregulating heme oxygenase-1 expression in brain microvascular endothelial cells. J Mol Neurosci 2013; 51(2):344-351. doi:

26. Klinger NV, Mittal S. Therapeutic potential of curcumin for the treatment of brain tumors. Oxid Med Cell Longev 2016; 2016:9324085. doi:

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