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Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine

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Abstract

Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministrated with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration–time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P < 0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P < 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

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References

  1. Zhang MF, Shen YQ. Antidiarrheal and anti-inflammatory effects of berberine. Zhongguo Yao Li Xue Bao. 1989;10:174–6.

    CAS  PubMed  Google Scholar 

  2. Yang J, Ljn J. Advance on study in anti-tumor mechanism of berberine (Ber). Zhongguo Zhong Yao Za Zhi. 2007;32:881–3. 934.

    CAS  PubMed  Google Scholar 

  3. Lee KZ. Clinical trials of berberine chloride as pharmaceutical agent of type II diabetes. Hubei J Tradit Chin Med. 2006;28:38–41.

    Google Scholar 

  4. Yuan YH. Clinical trial of berberine as pharmaceutical agent of type 2 diabetes. Mod J Integr Tradit Chin West Med. 1999;8:1777–81.

    Google Scholar 

  5. Qu QM, Zhang MF. The pharmacokinetics of berberine. Chin Acad Med Mag Organ. 2002;12:31–5.

    Google Scholar 

  6. Pappenheimer JR. Physiological regulation of transepithelial impedance in the intestinal mucosa of rats and hamsters. J Membr Biol. 1987;100:137–48.

    Article  CAS  PubMed  Google Scholar 

  7. Coyne CB, Kelly MM, Boucher RC, Johnson LG. Enhanced epithelial gene transfer by modulation of tight junctions with sodium caprate. Am J Respir Cell Mol Biol. 2000;23:602–9.

    CAS  PubMed  Google Scholar 

  8. Lindmark T, Kimura Y, Artursson P. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther. 1998;284:362–9.

    CAS  PubMed  Google Scholar 

  9. Tomita M, Hayashi M, Awazu S. Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells. J Pharm Sci. 1996;85:608–11.

    Article  CAS  PubMed  Google Scholar 

  10. Sharma P, Varma MVS, Chawla HPS, et al. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Biochem Pharmacol. 2000;59:665–72.

    Article  Google Scholar 

  11. Lindmark T, Soderholm JD, Olaison G, Alvan G, Ocklind G, Artursson P. Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate. Pharm Res. 1997;14:930–5.

    Article  CAS  PubMed  Google Scholar 

  12. Salartash K, Gonze MD, Leone-Bay A, Baughman R, Sternbergh III WC, Money SR. Oral low-molecular weight heparin and delivery agent prevents jugular venous thrombosis in the rat. J Vasc Surg. 1999;30:526–31.

    Article  CAS  PubMed  Google Scholar 

  13. Dos Santos I, Fawaz F, Lagueny AM, Bonini F. Improvement of norfloxacin oral bioavailability by EDTA and sodium caprate. Int J Pharm. 2003;260:1–4.

    Article  PubMed  Google Scholar 

  14. Sasaki K, Yonebayashi S, Yoshida M, Shimizu K, Aotsuka T, Takayama K. Improvement in the bioavailability of poorly absorbed glycyrrhizin via various non-vascular administration routes in rats. Int J Pharm. 2003;265:95–102.

    Article  CAS  PubMed  Google Scholar 

  15. Ling W, Rui LC, Hua JX. In situ intestinal absorption behaviors of tanshinone IIA from its inclusion complex with hydroxypropyl-beta-cyclodextrin. Biol Pharm Bull. 2007;30:1918–22.

    Article  PubMed  Google Scholar 

  16. Hillgren KM, Kato A, Borchardt RT. In vitro systems for studying intestinal drug absorption. Med Res Rev. 1995;15:83–109.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang M, Lv XY, Li J, Xu ZG, Chen L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res. 2008;2008:704045.

    PubMed  Google Scholar 

  18. Zhang M, Lv XY, Li J, Xu ZG, Chen L. Alteration of 11beta-hydroxysteroid dehydrogenase type 1 in skeletal muscle in a rat model of type 2 diabetes. Mol Cell Biochem. 2009;324:147–55.

    Article  CAS  PubMed  Google Scholar 

  19. Barthe L, Woodley JF, Kenworthy S, Houin G. An improved everted gut sac as a simple and accurate technique to measure paracellular transport across the small intestine. Eur J Drug Metab Pharmacokinet. 1998;23:313–23.

    CAS  PubMed  Google Scholar 

  20. Xu MG, Wang JM, Chen L, Wang Y, Yang Z, Tao J. Berberine-induced mobilization of circulating endothelial progenitor cells improves human small artery elasticity. J Hum Hypertens. 2008;22:389–93.

    Article  CAS  PubMed  Google Scholar 

  21. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93:2559–65.

    Article  CAS  PubMed  Google Scholar 

  22. Zhou JY, Zhou SW, Zhang KB, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biol Pharm Bull. 2008;31:1169–76.

    Article  CAS  PubMed  Google Scholar 

  23. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2003;92:173–6.

    Article  CAS  PubMed  Google Scholar 

  24. Maeng HJ, Yoo HJ, Kim IW, et al. P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. J Pharm Sci. 2002;91:2614–21.

    Article  CAS  PubMed  Google Scholar 

  25. Pan GY, Wang GJ, Sun J-G. Inhibitory action of berberine on glucose absorption. Acta Pharm Sin. 2003;38:911–4.

    CAS  Google Scholar 

  26. Lo YL, Huang JD. Effects of sodium deoxycholate and sodium caprate on the transport of epirubicin in human intestinal epithelial Caco-2 cell layers and everted gut sacs of rats. Biochem Pharmacol. 2000;59:665–72.

    Article  CAS  PubMed  Google Scholar 

  27. Aungst BJ. Intestinal permeation enhancers. J Pharm Sci. 2000;89:429–42.

    Article  CAS  PubMed  Google Scholar 

  28. Lee YS, Kim WS, Kim KH. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55:2256–64.

    Article  CAS  PubMed  Google Scholar 

  29. Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab. 2008;294:E148–56.

    Article  CAS  PubMed  Google Scholar 

  30. Yin J, Hu R, Chen M, et al. Effects of berberine on glucose metabolism in vitro. Metabolism. 2002;51:1439–43.

    Article  CAS  PubMed  Google Scholar 

  31. Chao AC, Nguyen JV, Broughall M, Griffin A, Fix JA, Daddona PE. In vitro and in vivo evaluation of effects of sodium caprate on enteral peptide absorption and on mucosal morphology. Int J Pharm. 1999;191:15–24.

    Article  CAS  PubMed  Google Scholar 

  32. Uchiyama T, Sugiyama T, Quan YS, et al. Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside. J Pharm Pharmacol. 1999;51:1241–50.

    Article  CAS  PubMed  Google Scholar 

  33. Yamamoto A, Okagawa T, Kotani A. Effects of different absorption enhancers on the permeation of ebiratide, an ACTH analogue, across intestinal membranes. J Pharm Pharmacol. 1997;49:1057–61.

    CAS  PubMed  Google Scholar 

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Acknowledgment

Thanks to Pharmaceutical Sciences Department of Jilin University for the help of HPLC and LC–MS technique. The subject supported by administration of traditional Chinese medicine of Jilin province (2004-076) and National Natural Science Foundation of China (30572218).

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Authors and Affiliations

  1. Department of Pharmacology, Norman Bethune Medical College, Jilin University, Changchun, Jilin, 130021, China

    Xiao-Yan Lv, Jing Li, Ming Zhang, Chun-Mei Wang, Zheng Fan & Li Chen

  2. Department of Cadre Ward, First Affiliated Hospital of Jilin University, Changchun, Jilin, 130021, China

    Chun-yan Wang

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  1. Xiao-Yan Lv
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  2. Jing Li
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  3. Ming Zhang
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  4. Chun-Mei Wang
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  7. Li Chen
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Correspondence to Chun-yan Wang or Li Chen.

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Lv, XY., Li, J., Zhang, M. et al. Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine. AAPS PharmSciTech 11, 372–382 (2010). https://doi.org/10.1208/s12249-010-9386-z

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  • DOI: https://doi.org/10.1208/s12249-010-9386-z

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