Toxicology and Environmental Health Sciences

, Volume 10, Issue 5, pp 268–277 | Cite as

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

  • Rajesh KrithikaEmail author
  • Ramtej Jayaram Verma
Original article



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.


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


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.


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.


S.nigrum CCl4 Hypolipidemic Hypoglycaemic 


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  1. 1.
    Perumpail, B. J. et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J. Gastroenterol. 23, 8263–8276 (2017).CrossRefGoogle Scholar
  2. 2.
    Recknagel, R. O. Carbon tetrachloride hepatotoxicity. Pharmacol. Rev. 19, 145–208 (1967).Google Scholar
  3. 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).CrossRefGoogle Scholar
  4. 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).Google Scholar
  5. 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. 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. 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).CrossRefGoogle Scholar
  8. 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).CrossRefGoogle Scholar
  9. 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).CrossRefGoogle Scholar
  10. 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).CrossRefGoogle Scholar
  11. 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).CrossRefGoogle Scholar
  12. 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).CrossRefGoogle Scholar
  13. 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).CrossRefGoogle Scholar
  14. 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).CrossRefGoogle Scholar
  15. 15.
    Ploa, G. L. & Hewitt W. R. in Principles and Methods of Toxicology (edn Wallace, H. A.) 599–628 (Raven Press, New York, 1989).Google Scholar
  16. 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).CrossRefGoogle Scholar
  17. 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).Google Scholar
  18. 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).CrossRefGoogle Scholar
  19. 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).CrossRefGoogle Scholar
  20. 20.
    Iritani, N. & Fukuda, E. Effect of corn oil feeding on triglyceride synthesis in the rat. J. Nutr. 110, 1138–1143 (1980b).CrossRefGoogle Scholar
  21. 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).CrossRefGoogle Scholar
  22. 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).Google Scholar
  23. 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. 24.
    Soni, B., Visavadiya, N. P. & Madamwar, D. Ameliorative action of cyanobacterial phycoerythrin on CCl4–induced toxicity in rats. Toxicolog. 248, 59–65 (2008).CrossRefGoogle Scholar
  25. 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).CrossRefGoogle Scholar
  26. 26.
    Rothschild, M. A., Oratz, M. & Schreiber, S. S. Effects of carbon tetrachloride on albumin synthesis. J. Clin. Invest. 51, 2310–2314 (1972).CrossRefGoogle Scholar
  27. 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).CrossRefGoogle Scholar
  28. 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).CrossRefGoogle Scholar
  29. 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).CrossRefGoogle Scholar
  30. 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. 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).Google Scholar
  32. 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).Google Scholar
  33. 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).Google Scholar
  34. 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).Google Scholar
  35. 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).Google Scholar
  36. 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).Google Scholar
  37. 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).Google Scholar
  38. 38.
    Seifter, S., Dayton, S., Novic, B. & Muntwyler, E. The estimation of glycogen with anthrone reagent. Arch. Biochem. 25, 191–200 (1950).Google Scholar
  39. 39.
    Dubowski, K. M. An O–toluidine method for body–fluid glucose determination. Clin. Chem. 8, 215–235 (1962).Google Scholar
  40. 40.
    Malloy, H. T. & Evelyn, K. A. The determination of bilirubin with photoelectric colorimeter. J. Biol. Chem. 119, 481–490 (1937).Google Scholar

Copyright information

© Korean Society of Environmental Risk Assessment and Health Science and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Zoology, Biomedical Technology and Human GeneticsUniversity School of Sciences, Gujarat UniversityAhmedabadIndia

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