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Hepatotoxicity and nephrotoxicity of saponin-enriched extract of Asparagus cochinchinensis in ICR mice

Abstract

The inhibitory effects of Asparagus cochinchinensis against inflammatory response induced by lipopolysaccharide (LPS), substance P and phthalic anhydride (PA) treatment were recently reported for some cell lines and animal models. To evaluate the hepatotoxicity and nephrotoxicity of A. cochinchinensis toward the livers and kidneys of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed in male and female ICR mice after oral administration of 150, 300 and 600 mg/kg body weight/day saponin-enriched extract of A. cochinchinensis (SEAC) for 14 days. The saponin, total flavonoid and total phenol levels were found to be 57.2, 88.5 and 102.1 mg/g in SEAC, respectively, and the scavenging activity of SEAC gradually increased in a dose-dependent manner. Moreover, body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ between the vehicle and SEAC treated group. Furthermore, no significant alterations were measured in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the SEAC treated group relative to the vehicle treated group. Moreover, the specific pathological features induced by most toxic compounds were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that SEAC does not induce any specific toxicity in the livers and kidneys of male and female ICR mice at doses of 600 mg/kg body weight/day.

References

  1. 1.

    Xiong D, Yu LX, Yan X, Guo C, Xiong Y. Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice. Am J Chin Med 2011; 39(3): 719–726.

    PubMed  Article  Google Scholar 

  2. 2.

    Xiao PG. Modern Chinese material medica, Chemical Industry Press, Beijing, 2002; p 150.

    Google Scholar 

  3. 3.

    Kim H, Lee E, Lim T, Jung J, Lyu Y. Inhibitory effect of Asparagus cochinchinensis on tumor necrosis factor-alpha secretion from astrocytes. Int J Immunopharmacol 1998; 20(4-5): 153–162.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Lee DY, Choo BK, Yoon T, Cheon MS, Lee HW, Lee AY, Kim HK. Anti-inflammatory effects of Asparagus cochinchinensis extract in acute and chronic cutaneous inflammation. J Ethnopharmacol 2009; 121(4): 28–34.

    PubMed  Article  Google Scholar 

  5. 5.

    Luo J, Long QD, Li CX, Li L, Huang NH, Nie M, Tang PX. Comparison of antitussive, expectorant and anti-asthmatic effect between ALWB and ACM. J GuiYang Med Coll 1998; 23: 132–134.

    Google Scholar 

  6. 6.

    Sung JE, Lee HA, Kim JE, Go J, Seo EJ, Yun WB, Kim DS, Son HJ, Lee CY, Lee HS, Hwang DY. Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation. Lab Anim Res 2016; 32(3): 34–45.

    PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 1965; 16(3): 144–158.

    CAS  Google Scholar 

  8. 8.

    Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 1999; 64: 555–559.

    CAS  Article  Google Scholar 

  9. 9.

    Helaly FM, Soliman HSM, Soheir AD, Ahmed AA. Controlled release of migration of molluscicidal saponin from different types of polymers containing Calendula officinalis. Adv Polym Techn 2001; 20(3): 305–311.

    CAS  Article  Google Scholar 

  10. 10.

    Oh H, Ko EK, Kim DH, Jang KK, Park SE, Lee HS, Kim YC. Secoiridoid glucosides with free radical scavenging activity from the leaves of Syringa dilatata. Phytother Res 2003; 17(3): 417–419.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Cragg GM, Newman DJ. Drug discovery and development from natural products: the way forward, 11th NAPRECA, Symposium Book of Proceedings, Antananarivo, 2005; pp 56–69.

    Google Scholar 

  12. 12.

    Newman DJ. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J Med Chem 2008; 51(3): 2589–2599.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Efange SMN. Natural products: a continuing source of inspiration for the medical chemist. In: Advances in phytomedicine (Wootton JC, ed), 5nd ed, Elsevier Science, Amsterdam, 2002; pp 61–69.

    Google Scholar 

  14. 14.

    Parasuraman S. Toxicological screening. J Pharmacol Pharmacother 2011; 2(2): 74–79.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Bruneton J. Pharmacognosie, Phytochimie, Plantes Medicinales, ditions Technique & Documentation, Paris, 1995; p 1120.

    Google Scholar 

  16. 16.

    Francis G, Kerem Z, Makkar HP, Becker K. The biological action of saponins in animal systems: a review. Br J Nutr 2002; 88(3): 587–605.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Sparg SG, Light ME, van Staden J. Biological activities and distribution of plant saponins. J Ethnopharmacol 2004; 94(2-3): 219–243.

    Google Scholar 

  18. 18.

    Sahu NP, Banerjee S, Mondal NB, Mandal D. Steroidal saponins. In: Fortschritte der Chemie Organischer Naturstoffe/progress in the chemistry of organic natural products, fortschritte der chemie organischer naturstoffe/progress in the chemistry of organic natural products, vol 89, Springer, Vienna, 2008; pp 45–141.

    Google Scholar 

  19. 19.

    Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev 2010; 9(2): 425–474.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Alaoui K, Belabbes M, Cherrah Y, Hassar M, Charrouf Z, Amarouch H, Roquebert J. Acute and chronic toxicity of saponins from Argania spinosa. Ann Pharm Fr 1998; 56(3): 213–219.

    CAS  PubMed  Google Scholar 

  21. 21.

    Witthawaskul P, Panthong A, Kanjanapothi D, Taesothikul T, Lertprasertsuke N. Acute and subacute toxicities of the saponin mixture isolated from Schefflera leucantha Viguier. J Ethnopharmacol 2003; 89(3): 115–121.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Wisloff H, Uhlig S, Scheie E, Loader J, Wilkins A, Flaoyen A. Toxicity testing of saponin-containing Yucca schidigera Roetzl. juice in relation to hepato-and nephrotoxicity of Narthecium ossifragum (L.) Huds. Toxicon 2008; 51(3): 140–150.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Cho YM, Imai T, Ito Y, Takami S, Hasumura M, Yamazaki T, Hirose M, Nishikawa A. A 13-week subchronic toxicity study of dietary administered saponin-rich and isoflavones-containing soybean extract in F344 rats. Food Chem Toxicol 2009; 47(3): 2150–2156.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Bissell DM, Gores GJ, Laskin DL, Hoofnagle JH. Drug-induced liver injury: mechanisms and test systems. Hepatology 2001; 33(3): 1009–1013.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41(3): 1313–1321.

    PubMed  Article  Google Scholar 

  26. 26.

    Giannini E, Botta F, Fasoli A, Ceppa P, Risso D, Lantieri PB, Celle G, Testa R. Progressive liver functional impairment is associated with an increase in AST/ALT ratio. Dig Dis Sci 1999; 44(3): 1249–1253.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol 1998; 93(3): 44–48.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Yoon SH, Park EJ, Oh KH, Chung YG, Kwon OJ. The effect of Lithospermi radix on benzo (a) pyrene-induced hepatotoxicity. J Korean Soc Food Sci Nutr 1993; 22(3): 144–148.

    CAS  Google Scholar 

  29. 29.

    Hayes AW. Principles and methods of toxicology, Raven Press, New York, 1982; pp 447–474.

    Google Scholar 

  30. 30.

    Kim DH, Deung YK, Lee YM, Yoon YS, Kwon KR, Park DB, Park YK, Lee KJ. The liver protecting effect of pomegranate (Punica granatum) seed oil in mice treated with CC14. Korean J Electron Microscopy 2006; 36(3): 173–182.

    Google Scholar 

  31. 31.

    Michael B, Yano B, Sellers RS, Perry R, Morton D, Roome N, Johnson JK, Schafer K, Pitsch S. Evaluation of organ weights for rodent and non-rodent toxicity studies: a review of regulatory guidelines and a survey of current practices. Toxicol Pathol 2007; 35(3): 742–750.

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Singhal PC, Sharma P, Sanwal V, Prasad A, Kapasi A, Ranjan R, Franki N, Reddy K, Gibbons N. Morphine modulates proliferation of kidney fibroblasts. Kidney Int 1998; 53(3): 350–357.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Falconer IR, Hardy SJ, Humpage AR, Froscio SM, Tozer GJ, Hawkins PR. Hepatic and renal toxicity of the blue-green alga (cyanobacterium) Cylindrospermopsis raciborskii in male Swiss albino mice. Environ Toxicol 1999; 14(3): 143–150.

    CAS  Article  Google Scholar 

  34. 34.

    Horiguchi H, Oguma E, Kayama F, Sato M, Fukushima M. Dexamethasone prevents acute cadmium-induced hepatic injury but exacerbates kidney dysfunction in rabbits. Toxicol Appl Pharmacol 2001; 174(4): 225–234.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Bonventre JV, Vaidya VS, Schmouder R, Feig P, Dieterle F. Nextgeneration biomarkers for detecting kidney toxicity. Nat Biotechnol 2010; 28(3): 436–440.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Ezejiofor AN, Orish CN, Orisakwe OE. Effect of aqueous leaves extract of Costus afer Ker Gawl (Zingiberaceae) on the liver and kidney of male albino Wistar rat. Anc Sci Life 2013; 33(3): 4–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Diwan FH, Abdel-Hassan IA, Mohammed ST. Effect of saponin on mortality and histopathological changes in mice. East Mediterr Health J 2000; 6(2-3): 345–351.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by grants to Professor Dae Youn Hwang from the Korea Institute of Planning Evaluation for Technology of Food, Agriculture, Forestry and Fisheries (Grant no. 114034-03-1-HD030).

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Correspondence to Dae Youn Hwang.

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Sung, J.E., Choi, J.Y., Kim, J.E. et al. Hepatotoxicity and nephrotoxicity of saponin-enriched extract of Asparagus cochinchinensis in ICR mice. Lab Anim Res 33, 57–67 (2017). https://doi.org/10.5625/lar.2017.33.2.57

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Keywords

  • Asparagus cochinchinensis
  • hepatotoxicity
  • nephrotoxicity
  • saponin
  • histopathology