DOI QR코드

DOI QR Code

Therapeutic Effect of Whole Bear Bile and Its Components against Croton Oil-Induced Rectal Inflammation in Rats

  • Park, Jeong-Sook (Chungbuk National University College of Pharmacy) ;
  • Yoo, Dong-Ho (Chungbuk National University College of Pharmacy) ;
  • Lee, In-Jeong (Chungbuk National University College of Pharmacy) ;
  • Roh, Eun-Mi-Ri (Chungbuk National University College of Pharmacy) ;
  • Kim, Young-Soo (Chungbuk National University College of Pharmacy) ;
  • Han, Kun (Chungbuk National University College of Pharmacy)
  • Published : 2010.01.31

Abstract

Bear bile has been used as a therapeutic for cerebral and coronary thrombosis, convulsion, hepatitis, jaundice, and abscess in traditional oriental medicine. In recent decades, the effects of bile acids on cancer, cholestasis, and liver injury have been investigated in many studies. In this study, we investigated the anti-inflammatory effects of whole bear bile (WBB) and its two major components, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), on rectal inflammation in rats. Bile acids in WBB were quantitatively analyzed by HPLC. Rectal inflammation was induced in male Sprague-Dawley rats by insertion of croton oil-saturated cotton tips. WBB, UDCA or CDCA solution was orally administered to rats one hour after induction of rectal inflammation. Rats were sacrificed 4 or 24 hours after induction of rectal inflammation. The evaluation included measurement of weight and thickness of rectum and histopathologic examination of rectal tissue. Furthermore, we examined the inhibitory effect of WBB, UDCA or CDCA against NO production in LPS-stimulated RAW 264.7 cells. The contents of UDCA and CDCA in WBB were $39.26{\mu}g/mg$ and $47.11{\mu}g/mg$, respectively. WBB treatment significantly reduced the weight and thickness of rectum compared with UDCA or CDCA treatment. The inhibition of NO production by WBB, UDCA and CDCA in LPS-stimulated RAW 264.7 cells was much higher than that by the control. And, WBB treatment suppressed the induction of NO synthase in rectum homogenates. These results suggest that the anti-inflammatory effect of WBB is related to the suppression of NO synthase induction and the inhibition of NO production by UDCA, CDCA and other bile acids of WBB.

Keywords

References

  1. Archer, S. (1993). Measurement of nitric oxide in biological models. FASEB J. 7, 349-360. https://doi.org/10.1096/fasebj.7.2.8440411
  2. Beuers, U., Boyer, J. L. and Paumgartner, G. (1998). Ursodeoxycholic acid in cholestasis: Potential mechanisms of action and therapeutic applications. Hepatology 28, 1449-1453. https://doi.org/10.1002/hep.510280601
  3. Earnest, D. L., Holubec, H., Wali, R. K., Jolley, C. S., Bissonette, M., Bhattacharyya, A. K., Roy, H., Khare, S. and Brasitus, T. A. (1994). Chemoprevention of azoxymethaneinduced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid. Cancer Res. 54, 5071-5074.
  4. Fried, R. H., Murakami, C. S., Fisher, L. D., Willson, R. A., Sullivan, K. M. and McDonald, G. B. (1992). Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver. Ann. Intern. Med. 116, 624-629. https://doi.org/10.7326/0003-4819-116-8-624
  5. Hattori, Y., Murakami, Y., Hattori, S., Kuroda, H., Kasai, K. and Shimoda, S. (1996). Ursodeoxycholic acid inhibits the induction of nitric oxide synthase. Eur. J. Pharmacol. 300, 147-150. https://doi.org/10.1016/0014-2999(96)00012-X
  6. Invernizzi, P., Salzman, A. L., Szabo, C., Ueta, I., O'Connor, M. and Setchell, K. D. (1997). Ursodeoxycholate inhibits induction of NOS in human intestinal epithelial cells and in vivo. Am. J. Physiol. 273, G131-G138.
  7. Katsuyama, K., Shichiri, M., Kato, H., Imai, T., Marumo, F. and Hirata, Y. (1999). Differential inhibitory actions by glucocorticoid and aspirin on cytokine-induced nitric oxide production in vascular smooth muscle cells. Endocrinology 140, 2183-2190. https://doi.org/10.1210/en.140.5.2183
  8. Korhonen, R., Lahti, A., Kankaanranta, H. and Moilanen, E. (2005). Nitric oxide production and signaling in inflammation. Curr. Drug Targets Inflamm. Allergy 4, 471-479. https://doi.org/10.2174/1568010054526359
  9. Loder, P. B., Kamm, M. A., Nicholls R. J. and Phillips, R. K. (1994). Hemorrhoids: pathology, pathophysiology and aetiology. Br. J. Surg. 81, 946-954. https://doi.org/10.1002/bjs.1800810707
  10. Milsom, J. W. (1992). Hemorrhoidal disease. In Fundamentals of Anorectal Surgery (D. E. Beck, S. D. Wexner, Eds), pp. 192-214. McGraw-Hill, New York.
  11. Mingrone, G. and Greco, A. V. (1980). Reversed phase high performance liquid chromatographic separation and quantification of individual human bile acids. J. Chromatogr. 183, 277-286. https://doi.org/10.1016/S0378-4347(00)81707-7
  12. Needleman, P. and Isakson, P. C. (1997). The discovery and function of COX-2. J. Rheumatol. 49, 6-8.
  13. Podda, M., Ghezzi, C., Battezzati, P. M., Crosignani, A., Zuin, M. and Roda, A. (1990). Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis. Gastroenterology 98, 1044-1050. https://doi.org/10.1016/0016-5085(90)90032-V
  14. Poupon, R. E., Poupon, R. and Balkau, B. (1994). Ursodiol for the long-term treatment of primary biliary cirrhosis. N. Engl. J. Med. 330, 1342-1347. https://doi.org/10.1056/NEJM199405123301903
  15. Seybold, V. S., Jia, Y. P. and Abrahams, L. G. (2003). Cyclooxygenase-2 contributes to central sensitization in rats with peripheral inflammation. Pain 105, 47-55. https://doi.org/10.1016/S0304-3959(03)00254-9
  16. Sola, S., Garshelis, D. L., Amaral, J. D., Noyce, K. V., Coy, P. L., Steer, C. J., Iaizzo, P. A. and Rodrigues, C. M. (2006). Plasma levels of ursodeoxycholic acid in black bears, Ursus americanus: Seasonal changes. Comp. Biochem. Physiol. 143, 204-208.
  17. Tanaka, H., Makino, Y., Miura, T., Hirano, F., Okamoto, K., Komuro, K., Sato, Y. and Makino I. (1990). Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of INF-TEX>$\gamma$-induced MHC class II gene expression via a glucocorticoid receptor dependent pathway. J. Immunol. 156, 1601-1608.
  18. Weitzel, C., Stark, D., Kullmann, F., Schölmerich, J., Holstege, A. and Falk, W. (2005). Ursodeoxycholic acid induced activation of the glucocorticoid receptor in primary rat hepatocytes. Eur. J. Gastroenterol. Hepatol. 17, 169-177. https://doi.org/10.1097/00042737-200502000-00007

Cited by

  1. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective vol.2016, 2016, https://doi.org/10.1155/2016/4305074
  2. Transcriptional regulation of cholesterol and bile acid metabolism after dietary soyabean meal treatment in Atlantic salmon (Salmo salar L.) vol.109, pp.04, 2013, https://doi.org/10.1017/S0007114512002024