Skip to main content
SpringerLink
Log in

Evaluation of the toxicological properties and hepatoprotective effects of PAI-N002, a mixture of herbal extracts, in rats

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

The short-term toxicity of PAI-N002, a mixture of Schizandra chinensis, Astragalus membranaceus, Artemisia capillaris, and Coriolus versicolor extracts (1 : 1 : 1 : 1), was evaluated in rats. This study also investigated the protective effect of PAI-N002 on liver injury induced by the co-administration of ethanol and carbon tetrachloride (EC) in rats. PAI-N002 was virtually non-toxic to rats after a single oral administration, with LD50 values > 5,000 mg/kg. The subacute toxicity study showed that 2-week repeated oral dose of PAI-N002 did not cause any adverse effects on clinical signs, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross findings, and organ weights in rats given up to 1,000 mg/kg/day. When rats with EC-induced hepatotoxicity were treated with PAI-N002 at 250 mg/kg/day for 28 days, PAI-N002 treatment significantly improved EC-induced hepatic injury, as evidenced by the decline of serum AST and ALT activities and decreased histopathological alterations. PAI-N002 also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the levels of the antioxidant glutathione and the activities of the antioxidant enzymes catalase, superoxide dismutase, and glutathione-S-transferase. These results indicate that the short-term treatment of rats with PAI-N002 has no harmful effects and that PAI-N002 has hepatoprotective and antioxidant properties in EC-induced chronic liver injury in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barnes, P. M., Powell-Griner, E., McFann, K. & Nahin, R. L. Complementary and alternative medicine use among adults: United States, 2002. Adv Data 343:1–19 (2004).

    PubMed  Google Scholar 

  2. Mahady, G. B. Global harmonization of herbal health claims. J Nutr 131:1120S–1123S (2001).

    CAS  PubMed  Google Scholar 

  3. Seeff, L. B., Lindsay, K. L., Bacon, B. R., Kresina, T. F. & Hoofnaqle, J. H. Complementary and alternative medicine in chronic liver disease. Hepatology 34: 595–603 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Lee, K. J. & Jeong, H. G. Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity. Food Chem Toxicol 40:517–525 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Fogden, E. & Neuberger, J. Alternative medicines and the liver. Liver Int 23:213–220 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Hanje, A. J., Fortune, B., Song, M., Hill, D. & McClain, C. The use of selected nutrition supplements and complementary and alternative medicine in liver disease. Nutr Clin Pract 21:255–272 (2006).

    Article  PubMed  Google Scholar 

  7. Muriel, P. & Rivera-Espinoza, Y. Beneficial drugs for liver diseases. J Appl Toxicol 28:93–103 (2008).

    Article  CAS  PubMed  Google Scholar 

  8. Sinclair, S. Chinese herbs: a clinical review of Astragalus, Ligusticum and Schizandrae. Altern Med Rev 3:38–344 (1998).

    Google Scholar 

  9. Zhu, M., Lin, K., Yeung, R. & Li, R. Evaluation of the protective effects of Schisandra chinensis on phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmacol 67:61–68 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Kim, I. S. & Choi, S. Y. Physicochemical properties and antioxidative activities of Omija (Schizandra chinensis Bailon). Korean J Food Nutr 21:35–42 (2008).

    Article  Google Scholar 

  11. Yan, F. et al. Synergistic hepatoprotective effect of Schisandrae lignans with Astragalus polysaccharides on chronic liver injury in rats. Phytomedicine 16:805–813 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Liu, X. et al. Studies on biologically active principles of Huangqi, root of Astragalus membranaceus, isolation and detection of constituents scavenging superoxide anion. J Clin Pharm Sci 2:80–84 (1993).

    CAS  Google Scholar 

  13. Toda, S. & Shirataki, Y. Inhibitory effects of Astragali Radix, a crude drug in oriental medicines, on lipid peroxidation and protein oxidative modification by copper. J Ethnopharmacol 68:331–333 (1999).

    Article  CAS  PubMed  Google Scholar 

  14. Gui, S. Y. et al. Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats. J Ethnopharmacol 103:154–159 (2006).

    Article  PubMed  Google Scholar 

  15. Kiso, Y., Sasaki, K., Oshima, Y. & Hikino, H. Liverprotective drugs V. Validity of the oriental medicines. 42. Structure of arcapillin, an antihepatoxic principle of Artemisia capillaries herba. Heterocycles 19:1615–1517 (1982).

    Article  CAS  Google Scholar 

  16. Lee, S. G. The therapeutic effect of Artemisia Capillaris extract on hepatic damage induced by carbon tetrachloride in rats. J Vet Clin 22:206–213 (2005).

    Google Scholar 

  17. Wei, W. S. et al. Effects of Coriolus versicolor polysaccharides on superoxide dismutase activities in mice. Zhongguo Yao Li Xue Bao 17:174–178 (1996).

    CAS  PubMed  Google Scholar 

  18. Fisher, M. & Yang, L. X. Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res 22:1737–1754.

  19. Bent, S. Herbal medicine in the United States: review of efficacy, safety, and regulation. J Gen Intern Med 23:854–859 (2008).

    Article  PubMed  Google Scholar 

  20. Pradhan, S. C. & Girish, C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 124:491–504 (2006).

    CAS  PubMed  Google Scholar 

  21. De Smet, P. A. Herbal remedies. N Engl J Med 347: 2046–2056 (2002).

    Article  PubMed  Google Scholar 

  22. Deng, J. F. Clinical and laboratory investigations in herbal poisonings. Toxicology 181:571–576 (2002).

    Article  PubMed  Google Scholar 

  23. Jin, T. Y. Toxicological research on Yun Zhi polysac-charopeptide (PSP): In International Symposium on Traditional Chinese Medicine and Cancer: Development and Clinical Validation-Advances Research in PSP (Yan, Q. Y. ed), Hong Kong Association for Health Care Ltd, 76–79 (1999).

  24. Kordali, S., Aslan, I., Calmasur, O. & Cakir, A. Toxicity of essential oils isolated from three Artemisia species and some of their major components to granary weevil, Sitophilus granaries (L.) (Coleoptera: Curculionidae). Ind Crop Prod 23:162–170 (2006).

    Article  CAS  Google Scholar 

  25. Yu, S. Y. et al. Subchronic toxicity studies of Radix Astragali extract in rats and dogs. J Ethnopharmacol 110:352–355 (2007).

    Article  PubMed  Google Scholar 

  26. Molander, D. W., Wroblewsk, F. & La Due, J. S. Transaminase compared with cholinesterase and alkaline phosphatase an index of hepatocellular integrity. Clin Res Proc 3:20–24 (1995).

    Google Scholar 

  27. Zimmerman, H. J. & Seeff, L. B. Enzymes in hepatic disease: In Diagnostic Enzymology (Goodley, E. L. ed.), Lea and Febiger, Philadelphia, 1–38 (1970).

    Google Scholar 

  28. Johansen, J. S., Harris, A. K., Rychly, D. J. & Ergul, A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovas Diabetol 4:5 (2005).

    Article  Google Scholar 

  29. Valko, M. et al. Free radicals and antioxidants in normal physiological function and human disease. Int J Biochem Cell Biol 39:44–84 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Lieber, C. S. Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. Adv Pharmacol 38:601–628 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Weber, L. W. D., Bull, M. & Stampfl, A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 33:105–136 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Williams, A. C. & Christopher, W. Relationship between reactive oxygen species production and lipid peroxidation in human sperm suspensions and their association with sperm function. Fertil Steril 83:929–936 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Wilcox, J. K., Ash, S. L. & Catignani, G. L. Antioxidants and prevention of chronic disease. Crit Rev Food Nutr 44:275–295 (2004).

    Article  Google Scholar 

  34. Yang, Y. S. et al. Protective effects of Pycnogenol® on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. Food Chem Toxicol 46:380–387 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Lin, S., Fujii, M. & Hou, D. X. Molecular mechanisms of apoptosis induced by schzandrae-derived lignans in human leukemia HL-60 cells. Food Chem Toxicol 46:590–597 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Seo, H. C. et al. Extraction and identification of antioxidant components from Artemisia capillaris herba. Plants Foods Hum Nutr 58:1–12 (2003).

    Article  Google Scholar 

  37. Polese, J. M. The Pocket Guide to Mushrooms. Cologne. Germany, 1–382 (1999).

  38. Erman, F., Balkan, J., Cevikbas, U., Kocak-Toker, N. & Uysal, M. Betaine or taurine administration prevents fibrosis and lipid peroxidation induced by rat liver by ethanol plus carbon tetrachloride intoxication. Amino Acids 27:199–205 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Berton, T. R. et al. The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis. Mol Carcinog 23:175–184 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Moron, M. S., Depierre, J. W. & Mannervik, B. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochem Biophys Acta 582:67–78 (1979).

    CAS  PubMed  Google Scholar 

  41. Aebi, H. Catalase in vitro. In: Packer, L. (Ed.), Methods in Enzymology, vol. 105. Academic Press, San Diego, 121–126 (1984).

    Google Scholar 

  42. McCord, J. M. Mutant mice, Cu, Zn superoxide dismutase, and motor neuron degeneration. Science 266: 1586–1587 (1994).

    CAS  PubMed  Google Scholar 

  43. Habig, W. H., Jakoby, W. B., Guthenberg, C., Mannervik, B. & Vander Jagt, D. L. 2-Propylthiouracil does not replace glutathione for the glutathione transferases. J Biol Chem 259:7409–7410 (1984).

    CAS  PubMed  Google Scholar 

  44. Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. Protein measurement with folin phenol reagent. J Biol Chem 193:265–275 (1951).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, Korea

    Sung-Hwan Kim, Jeong-Hyeon Lim, In-Sik Shin, Changjong Moon, Soo-Hyun Park, Sung-Ho Kim & Jong-Choon Kim

  2. PHARMAPEX Co., Suwon, Gyeonggi, 443-270, Korea

    Jung-Sik Lee & Eun-Hye Kwon

Authors
  1. Sung-Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeong-Hyeon Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. In-Sik Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Changjong Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soo-Hyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sung-Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jung-Sik Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eun-Hye Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jong-Choon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jong-Choon Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, SH., Lim, JH., Shin, IS. et al. Evaluation of the toxicological properties and hepatoprotective effects of PAI-N002, a mixture of herbal extracts, in rats. Mol. Cell. Toxicol. 6, 239–246 (2010). https://doi.org/10.1007/s13273-010-0033-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-010-0033-2

Keywords

Search

Navigation