Skip to main content
SpringerLink
Log in

Hypolipidemic and Hypoglycemic Effects of Hydroalcoholic Extract of Solanum nigrum Linn. in CCl4-induced Hepatotoxicity in Mice

  • Original article
  • Published:
Toxicology and Environmental Health Sciences Aims and scope Submit manuscript

Abstract

Objective

Carbon tetrachloride (CCl4) toxicity is the model commonly exploited to produce hepatic damage. This model is used to screen drugs with hepatoprotective activity on various experimental animals and to validate their liver protecting property. Carbon tetrachloride gets accumulated in hepatic parenchymal cells and is metabolically activated by cytochrome P450-dependent monooxygenases to generate free radicals which covalently bind with tissue macromolecules like carbohydrates and proteins causing disturbances in cellular homeostasis. This may lead to the initiation of lipid peroxidation a sequence of chain reactions in cellular membranes which ultimately may result in steatosis. The present study was an attempt to study the anti-hepatotoxic, hypolipidemic and hypoglycaemic effect of S. nigrum against CCl4 - induced hepatotoxicity in female mice.

Methods

The hypolipidemic, hypoglycaemic and hepatoprotective activity of hydroalcoholic extract of S. nigrum was evaluated by various biochemical parameters and by histopathological examination.

Results

Carbon tetrachloride administration caused a significant increase in liver total lipids, triglyceride (TG), cholesterol and free fatty acid content. Similarly serum low density lipoproteins (LDL-C), very low density lipoprotein levels (VLDL-C) and bilirubin were elevated after toxin administration, while serum high density lipoproteins (HDL-C) was lowered as compared to vehicle control. It was observed that oral administration of the toxin caused a significant increase in blood glucose level, while a significant decrease was observed in the glycogen and protein content of the liver and albumin content of serum as compared to vehicle control.

Conclusion

Oral administration of S. nigrum effectively mitigated the changes induced by CCl4 in a dose - dependent manner. Our results indicated S. nigrum exerts hepatoprotective property by stabilizing tissue macromolecules resulting in maintenance of cellular hemeostasis.

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. Perumpail, B. J. et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J. Gastroenterol. 23, 8263–8276 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Recknagel, R. O. Carbon tetrachloride hepatotoxicity. Pharmacol. Rev. 19, 145–208 (1967).

    CAS  PubMed  Google Scholar 

  3. Weber, L. W. D., Boll, 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 

  4. Patel, A., Biswas, S., Shoja, M. H., Ramalingayya, G. V. & Nandakumar, K. Protective Effects of Aqueous Extract of Solanum nigrum Linn. Leaves in Rat Models of Oral Mucositis. Sci. World J. 2014, doi: 10.1155/ 2014/345939 (2014).

  5. Mushtaq, A. & Ahmad, M. Hepatoprotective Activity of Aqueous–Ethanolic Extract of Solanum nigrum Against Nimesulide Intoxicated Albino rats. Eur. J. Zool. Res. 2, 19–25 (2013).

    Google Scholar 

  6. Sah, A. K., Rambhade, A., Gohate, A., Rambhade, S. K. & Goswami, R. B. Hepatoprotective activity of Phyllanthus Niruri herbs and Solanum nigrum stem bark against paracetamol–induced hepatotoxicity. Am. J. Pharm Tech Res. 2, 1–10 (2012).

    Google Scholar 

  7. Raju, K. et al. Effect of dried fruits of Solanum nigrum Linn. against CCl4–induced hepatic damage in rats. Biol. Pharma. Bull. 26, 1618–1619 (2003).

    Article  CAS  Google Scholar 

  8. Lin, H. M. et al. Hepatoprotective effects of Solanum nigrum Linn extract against CCl4–induced oxidative damage in rats. Chem–Biol. Interact. 171, 283–293 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Arulmozhi, V., Krishnaveni, M., Karthishwaran, K., Dhamodharan, G. & Mirunalini, S. Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity. Pharmacogn. Mag. 6, 42–50 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lee, S. J., Ko, J. H., Lim, K. & Lim, K. T. 150 kda glycoprotein isolated from Solanum nigrum Linne enhances activities of detoxicant enzymes and lowers plasmic cholesterol in mouse. Pharmacol. Res. 51, 399–408 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Sohrabipour, S., Kharazmi, F., Soltani, N. & Kamalinejad, M. Effect of the administration of Solanum nigrum fruit on blood glucose, lipid profiles, and sensitivity of the vascular mesenteric bed to phenylephrine in streptozotocin–induced diabetic rats. Med. Sci. Monitor Basic Res. 19, 133–140 (2013).

    Article  Google Scholar 

  12. Fang, H. L. & Lin, W. C. Corn oil enhancing hepatic lipid peroxidation induced by CCl4 does not aggravate liver fibrosis in rats. Food Chem. Toxicol. 46, 2267–2273 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Hsieh, C. C., Fang, H. L. & Lina, W. C. Inhibitory effect of Solanum nigrum on thioacetamide–induced liver fibrosis in mice. J. Ethnopharmacol. 119, 117–121 (2008).

    Article  PubMed  Google Scholar 

  14. Attia, M. N. T. & Ali, M. A. Hepatoprotective activity of allicin against carbon tetrachloride induced hepatic injury in rats. J. Biol. Sci. 6, 457–468 (2006).

    Article  CAS  Google Scholar 

  15. Ploa, G. L. & Hewitt W. R. in Principles and Methods of Toxicology (edn Wallace, H. A.) 599–628 (Raven Press, New York, 1989).

  16. Pappas, Jr. N. J. Source of increased serum aspartate and alanine aminotransferase: cycloheximide effect on carbon tetrachloride hepatotoxicity. Clin. Chim. Acta. 154, 181–190 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. Chander, R., Kapoor, N. K. & Dhawan, B. N. Picroliv affects gamma–glutamyl cycle in liver and brain of Mastomys natalensis infected with Plasmodium berghei. Ind. J. Exp. Biol. 32, 324–327 (1994).

    CAS  Google Scholar 

  18. Lee, S. J. & Lim, K. T. Glycine–and proline–rich glycoprotein regulates the balance between cell proliferation and apoptosis for ACF formation in 1,2–dimethylhydrazine–treated A/J mice. Mol. Cellular Biochem. 325, 187–197 (2009).

    Article  CAS  Google Scholar 

  19. Wang, M. Y., Anderson, G., Nowicki, D. & Jensen, J. Hepatic protection by noni fruit juice against CCl4–induced chronic liver damage in female SDrats. Plant Food Hum. Nutr. 63, 141–145 (2008).

    Article  CAS  Google Scholar 

  20. Iritani, N. & Fukuda, E. Effect of corn oil feeding on triglyceride synthesis in the rat. J. Nutr. 110, 1138–1143 (1980b).

    Article  CAS  PubMed  Google Scholar 

  21. Boll, M., Weber, L. W. D., Becker, E. & Stampfl, A. Pathogenesis of carbon tetrachloride–induced hepatocyte injury: Bioactivation of CCl4 by cytochrome P450 and effects on lipid homeostasis. Z. Naturforsch. 56, 111–121 (2001).

    Article  CAS  Google Scholar 

  22. Subbarao, V. V. & Gupta, M. L. Effect of Liv–52 and carbon tetrachloride on the liver protein and nucleic acids. IRCS Med. Sci. 7, 499–500 (1979).

    CAS  Google Scholar 

  23. Gupta, A. K., Ganguly, P., Majumder, U. K. & Ghosal, S. Improvement of lipid and antioxidant status in hyperlipidaemic rats treated with steroidal saponins of Solanium nigrum and Solanum xanthocarpum. PharmacologyOnLin. 1, 1–14 (2009).

    Google Scholar 

  24. Soni, B., Visavadiya, N. P. & Madamwar, D. Ameliorative action of cyanobacterial phycoerythrin on CCl4–induced toxicity in rats. Toxicolog. 248, 59–65 (2008).

    Article  CAS  Google Scholar 

  25. Bishayee, A., Sarkar, A. & Chatterjee, M. The hepatoprotective activity of carrot (Daucas carota L.) against carbon tetrachloride intoxication in mouse liver. J. Ethnopharmacol. 47, 69–74 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Rothschild, M. A., Oratz, M. & Schreiber, S. S. Effects of carbon tetrachloride on albumin synthesis. J. Clin. Invest. 51, 2310–2314 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yadav, N. P., Pal, A., Shanker, K., Bawankule, D. U. & Gupta, A. K. Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4–induced hepatotoxicity in Rattus norvegicus. Phytomedicin. 15, 1053–1061 (2008).

    Article  CAS  Google Scholar 

  28. Agbor, G. A., Oben, J. E., Nkegoum, B., Takala, J. P. & Ngogang, J. Y. Hepatoprotective activity of Hibiscus cannabinus (Linn.) against carbon tetrachloride and paracetamol–induced liver damage in rats. Pak. J. Biol. Sci. 8, 1397–1401 (2005).

    Article  Google Scholar 

  29. Reitman, S. & Frankel, S. A colorimetric method for the determination of serum glutamic oxaloacetic acid and glutamic pyruvate transaminases. Am. J. Clin. Pathol. 28, 56–63 (1957).

    Article  CAS  PubMed  Google Scholar 

  30. Fringes, C. S., Fendley, T. W., Dunn, R. T. & Queen, C. A. Improved determination of total serum lipids by the sulpho vanillin reaction. Clin. Chem. 18, 673–674 (1972).

    Google Scholar 

  31. Zlatkis, A., Zak, B. & Boyle, G. J. A new method for the determination of serum cholesterol. Int. J. Lab. Clin. Med. 41, 486–492 (1953).

    CAS  Google Scholar 

  32. Folch, J., Lees, M. & Stanley, G. H. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).

    CAS  Google Scholar 

  33. Foster, L. B. & Dunn, R. T. Stable reagents for determination of serum triglycerides by a colorimetric hantzsch condensation method. Clin. Chem. 19, 338–340 (1973).

    CAS  PubMed  Google Scholar 

  34. Hron, W. T. & Menahan, L. A. A sensitive method for the determination of free fatty acids in plasma. J. Lip. Res. 22, 377–382 (1981).

    CAS  Google Scholar 

  35. Friedewald, W. T., Levy, R. I. & Fredrickson, D. S. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without the use of preparative centrifuge. Clin. Chem. 18, 499–502 (1972).

    CAS  PubMed  Google Scholar 

  36. 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 

  37. Miyada, D. S., Baysinger, V., Notrica, S. & Nakumura, R. M. Albumin quantification by dye binding and salt fractionation techniques. Clin. Chem. 18, 52–56 (1972).

    CAS  PubMed  Google Scholar 

  38. Seifter, S., Dayton, S., Novic, B. & Muntwyler, E. The estimation of glycogen with anthrone reagent. Arch. Biochem. 25, 191–200 (1950).

    CAS  PubMed  Google Scholar 

  39. Dubowski, K. M. An O–toluidine method for body–fluid glucose determination. Clin. Chem. 8, 215–235 (1962).

    CAS  PubMed  Google Scholar 

  40. Malloy, H. T. & Evelyn, K. A. The determination of bilirubin with photoelectric colorimeter. J. Biol. Chem. 119, 481–490 (1937).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Zoology, Biomedical Technology and Human Genetics, University School of Sciences, Gujarat University, Ahmedabad, 380009, India

    Rajesh Krithika & Ramtej Jayaram Verma

Authors
  1. Rajesh Krithika
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramtej Jayaram Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh Krithika.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Krithika, R., Verma, R.J. Hypolipidemic and Hypoglycemic Effects of Hydroalcoholic Extract of Solanum nigrum Linn. in CCl4-induced Hepatotoxicity in Mice. Toxicol. Environ. Health Sci. 10, 268–277 (2018). https://doi.org/10.1007/s13530-018-0375-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13530-018-0375-z

Keywords

Search

Navigation