Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
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Biological Activities of Ursi Fel's Component Ursodeoxycholic Acid and Its Derivatives

웅담 성분 Ursodeoxycholic Acid 유도체들의 생물활성

  • Cha, Bae Cheon (Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University)
  • 차배천 (상지대학교 보건과학대학 제약공학과)
  • Received : 2017.02.06
  • Accepted : 2017.03.14
  • Published : 2017.03.31
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Abstract

Ursi Fel's component ursodeoxycholic acid (UDCA), a traditional medicine, is used for the treatment of hepatic diseases. UDCA derivatives prepared by conjugation with antioxidant moiety such as maltol, sesamol, eugenol, mesitol and 3,4-(methylenedeoxy)aniline were expected to have various biological activity caused by synergistic effect of UDCA. Therefore, in this study, it was conducted the study of the manufacture of the UDCA derivatives and their biological activity. As a result, UDCA derivatives showed weak antioxidant activity in TBA method in vitro compared to original agents. SJ-505, SJ-502 and SJ-504 showed the effect of reducing ALT, AST, sorbitol dehydrogenase and ${\gamma}-glutamyltransferase$ in $CCl_4-induced$ liver injury experiment in vivo, even if the effects are weaker than UDCA and silymarin of the control group.

Keywords

References

  1. Halliwell, B. (1991) Drug antioxidant effects. A basis for drug selection? Drugs 42: 569-605. https://doi.org/10.2165/00003495-199142040-00003
  2. Ceratti, P. A. (1994) Oxy-radicals and cancer. Lancet. 344: 862-863. https://doi.org/10.1016/S0140-6736(94)92832-0
  3. Schwarz, K. B. (1996) Oxidative stress during viral infection: A review. Free Radic. Biol. Med. 21: 641-649. https://doi.org/10.1016/0891-5849(96)00131-1
  4. Moon, J. O. and Park, J. H. (1997) Screening of the hepatoprotective drugs from folk medicines. Kor. J. Pharmacogn. 28: 156-161.
  5. Kang, J. K., Jung, E. Y. and Nam, S. Y. (2001) Single dose oral toxicity study of a new hepatotherapeutic agent GODEX (HEPADIF-S) in rats. J. Appl. Pharmacol. 9: 140-142.
  6. Yamaguchi, S., Qian, Z. Z. and Nohara, T. (1998) Bile acids of Fel Ursi. Chem. Pharm. Bull. 46: 1653-1655. https://doi.org/10.1248/cpb.46.1653
  7. Zhang, H. Y., Chen, Y. D. and Zhuang, G. L. (1996) Pharmacological action of bear bile extract in mice. Chinese Trad. Herb. Drugs 27: 10-12.
  8. Jin, Z. G., Zhang, T. Y., Liang, W. B. and Liang, C. G. (1997) Effects of bear bile injection on blood lipid. Chinese Trad. Herb. Drugs 28: 4-5.
  9. Kitami, K. and Kanai, S. (1982) Effect of ursodeoxycholic acid on the bile flow in the rat. Life Sci. 31: 1973-1985. https://doi.org/10.1016/0024-3205(82)90036-4
  10. Ward, A., Brogden, R. N., Heel, R. C., Speight, T. M. and Avery, G. S. (1984) Urosodeoxycholic acid: A review of its pharmacological properties and therapeutic efficacy. Drugs 27: 95-131. https://doi.org/10.2165/00003495-198427020-00001
  11. Lanzini, A. and Northfield, T. C. (1988) Effect of ursodeoxycholic acid on biliary lipid coupling and on cholesterol absorption during fasting and eating in subjects with cholesterol gallstones. Gastroenterology 95: 408-416. https://doi.org/10.1016/0016-5085(88)90498-2
  12. Roslyn, J. J., Abedin, M. Z., Strichartz, S. D., Abdou, M. S. and Palant, C. E. (1989) Regulation of gallbladder ion transport: role of bile lipids. Surgery 105: 207-212.
  13. Kawamura, T., Koizume, F. and Ishimori, A. (1989) Effect of ursodeoxycholic acid on water immersion restraint stress ulcer of rats. Nippon Shokakibyo Gakkai Zasshi 86: 2373-2378.
  14. Chen, X., Xu, J., Zhang, C., Yu, T., Wang, H., Zhao, M., Duan, Z. H., Zhang, Y., Xu, J. M. and Xu, D. X. (2011) The protective effects of ursodeoxycholic acid on isoniazid plus rifampicin induced liver injury in mice. Eur. J. Pharmacol. 659: 53-60. https://doi.org/10.1016/j.ejphar.2011.03.007
  15. Park, S. Y., Woo, J. S., Jung, Y, J., Won, T. J., Huh, Y. J., Lee, C. W., Kim, H. S., Joo, S. S., Lee, D. I. and Hwang, K. W. (2008) Anti-inflammatory effects of UDCA on splenocytes exposed to PMA/ ionomycin. Biomol. Ther. 16: 126-131. https://doi.org/10.4062/biomolther.2008.16.2.126
  16. Cho, T. S., Lee, J. C., Cho, S. I. and Lee, S. M. (1998) A study on anti-stress activities of cholic acid derivatives. J. Appl. Pharmacol. 6: 232-241 .
  17. Tschirne, A., Haehling, S. von., Palus, S., Doehner, W., Anker, S. D. and Springer, J. (2012) Ursodeoxycholic acid treatment in a rat model of cancer cachexia. J. Cachexia Sarcopenia Muscle 3: 31-36. https://doi.org/10.1007/s13539-011-0044-4
  18. Liu, H., Xu, H. W., Zhang, Y. Z., Huang, Y., Han, G. Q., Liang, T. J., Wei, L. L., Qin, C. Y. and Qin, C. K. (2015) Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice. World J. Gastroenterol. 21: 10367-10374. https://doi.org/10.3748/wjg.v21.i36.10367
  19. Oh, A. R., Bae, J. S., Lee, J. H., Shin, E. J., Oh, B. C., Park, S. C. and Cha, J. Y. (2016) Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice. BMB Rep. 49: 105-110. https://doi.org/10.5483/BMBRep.2016.49.2.173
  20. Ren, J., Wang, Y., Wang, J., Lin, J., Wei, K. and Huang, R. (2013) Synthesis and antitumor activity of N-sulfonyl-3,7-dioxo-$5{\beta}$-cholan-24-amides, ursodeoxycholic acid derivatives. Steroids 78: 53-58. https://doi.org/10.1016/j.steroids.2012.09.009
  21. Sharma, R., Prichard, D., Majer, F., Byne, A. M., Kelleher, D., Long, A. and Gilmer, J. F. (2011) Ursodeoxycholic acid amides as novel glucocorticoid receptor modulators. J. Med. Chem. 54: 122-130. https://doi.org/10.1021/jm100860s
  22. Choi, Y. H., Im, E. O., Suh, H. S., Jin, Y. S., Yoo, Y. H. and Kim, N. D. (2003) Apoptosis and modulation of cell cycle control by synthetic derivatives of ursodeoxycholic acid and chenodeoxycholic acid in human prostate cancer cells. Cancer Lett. 199: 157-167. https://doi.org/10.1016/S0304-3835(03)00351-3
  23. Konishi, T. (2000) Basic studies on the utility of ursodeoxycholic acid derivatives for clinical medicine. Yakugaku Zasshi 120: 1-15. https://doi.org/10.1248/yakushi1947.120.1_1
  24. Masugi, F. and Nakamura, T. (1977) Measurement of thiobarbituric acid value in liver homogenate solubilized with sodium dodecylsulphate and variation of the values affected by vitamin E and drugs. Vitamin 51: 21-29.
  25. Reitman, S. and Frankel, S. (1957) Estimation of glutamate oxaloacetate transaminase in the serum of liver disease patients. Am. J. Clin. Path. 28: 56-63. https://doi.org/10.1093/ajcp/28.1.56
  26. Han, B. H., Park, M. H. and Han, Y. N. (1985) Studies on the antioxidant components of Korean Ginseng(V) : The mechanism of antioxidant activity of maltol and phenolic acid. Korean Biochem. J. 4: 337-340.
  27. Kanimozhi, P. and Prasad, N. R. (2009) Antioxidant potential of sesamol and its role on radiation-induced DNA damage in whole-body irradiated Swiss albino mice. Environ. Toxicol. Pharmacol. 28: 192-197. https://doi.org/10.1016/j.etap.2009.04.003
  28. Nam, H. and Kim, M. M. (2013) Eugenol with antioxidant activity inhibits MMP-9 related to metastasis in human fibrosarcoma cells. Food Chem. Toxicol. 55: 106-112. https://doi.org/10.1016/j.fct.2012.12.050
  29. Cha, B. C. (2000) Synthesis of mefenamic acid derivatives and antioxidative and anticoagulant activities. J. Appl. Pharmacol. 8: 349-353.
  30. Ma, X. and Cao, X. (2014) Separation of ursodeoxycholic acid by silylation crystallization. Bioresour. Bioprocess. 1: 5-12. https://doi.org/10.1186/s40643-014-0005-9
  31. Lapenna, D., Ciofani, G., Festi, D., Neri, M., Pierdomenico, S. D., Giamberardino, M. A. and Cuccurullo, F. (2002) Antioxidant properties of ursodeoxycholic acid. Biochem. Pharmacol. 64: 1661-1667. https://doi.org/10.1016/S0006-2952(02)01391-6
  32. Jnaneshwari, S., Hemshekhar, M., Thushara, R. M., Sundaram, M. S., Santhosh, M. S., Sunitha, K., Shankar, R. L., Kemparaju, K. and Girish, K. S. (2014) Sesamol ameliorates cyclophosphamide-induced hepatotoxicity by modulating oxidative stress and inflammatory mediators. Anticancer Agents Med. Chem. 14: 975-983.