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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (1): 49-56.doi: 10.3736/jcim20110109

• Original Experimental Research • Previous Articles     Next Articles

Effects of Phyllanthus acidus (L.) Skeels fruit on carbon tetrachloride-induced acute oxidative damage in livers of rats and mice

Nilesh Kumar Jain(), Santram Lodhi, Avijeet Jain, Alok Nahata, Abhay K. Singhai   

  1. Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar 470003, India
  • Received:2010-09-03 Accepted:2010-10-08 Online:2011-01-20 Published:2011-01-15
  • Supported by:
    All India Council for Technical Education (AICTE), New Delhi, India

Objective: The present study was undertaken with a view to validate the traditional use of Phyllanthus acidus (L.) Skeels fruit as a hepatoprotective agent.
Methods: The 70% ethanolic extract of P. acidus fruit (100, 200 and 400 mg/kg, p.o.), and reference drug silymarin (100 mg/kg, p.o.) were given to rats of different groups respectively once a day for 5 d and the carbon tetrachloride (CCl4) (2 mL/kg, subcutaneously) was given on days 2 and 3. Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) were assessed along with liver histopathological examination. The effects on oxidative stress markers such as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also assessed in liver tissue homogenate to evaluate in vivo antioxidant activity. In addition, the effects on hexobarbitone-induced sleeping time were observed and the free radical-scavenging potential was determined by using 2,2-diphenyl-1-picrylhydrazil (DPPH) in mice.
Results: P. acidus extracts and silymarin exhibited a significant hepatoprotective effect as evident from the decreases of serum AST, ALT and ALP levels and LPO and increases in the levels of TP, GSH, SOD, CAT, and GPx compared with control group (P<0.01 or P<0.05). The biochemical results were supplemented with results of histopathological sections of the liver tissues. P. acidus extracts considerably shortened the duration of hexobarbitone-induced sleeping time in mice compared with control group (P<0.01) and showed remarkable DPPH-scavenging activity.
Conclusion: The present findings suggest that the hepatoprotective effect of P. acidus against CCl4-induced oxidative damage may be related to its antioxidant and free radical-scavenging potentials.

Key words: Phyllanthus, plant extracts, carbon tetrachloride, oxidative stress, liver function tests, animal experimentation, rats, mice

Figure 1

Histological observations of rat livers with CCl4-induced hepatotoxicityA: Liver section of normal control rats; B: Liver section of CCl4 control rats; C: Liver section of rats treated with CCl4 and silymarin; D: Liver section of rats treated with CCl4 and P. acidus ethanolic extracts."

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[1] Gonzalez CA . Nutrition and cancer: the current epidemiological evidence[J]. Br J Nutr, 2006,96(Suppl 1):S42-S45
doi: 10.1079/BJN20061699
[2] Jamshidzadeh A, Fereidooni F, Salehi Z, Niknahad H . Hepatoprotective activity of Gundelia tourenfortii[J]. J Ethnopharmacol, 2005,101(1-3):233-237
doi: 10.1016/j.jep.2005.04.013
[3] Wills PJ, Asha VV . Protective effect of Lygodium flexuosum(L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats[J]. J Ethnopharmacol, 2006,108(3):320-326
doi: 10.1016/j.jep.2006.05.032
[4] Calixto JB, Santos AR, Cechinel Filho V, Yunes RA . Protective effect of Lygodium flexuosum(L.) A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential[J]. Med Res Rev, 1998,18(4):225-258
doi: 10.1002/(ISSN)1098-1128
[5] Thyagarajan S, Jayaram S . Natural history of Phyllanthus amarus in the treatment of hepatitis B[J]. Indian J Med Microbiol, 1992,10(2):64-80
[6] Gulati RK, Agarwal S, Agrawal SS . Hepatoprotective studies on Phyllanthus emblica Linn. and quercetin[J]. Indian J Exp Biol, 1995,33(4):261-268
[7] Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C . The protective effects of Phyllanthus emblica Linn. extract on ethanol induced rat hepatic injury[J]. J Ethnopharmacol, 2006,107(3):361-364
doi: 10.1016/j.jep.2006.03.035
[8] Harish R, Shivanandappa T . Antioxidant activity and hepatoprotective potential of Phyllanthus niruri[J]. Food Chem, 2006,95(2):180-185
doi: 10.1016/j.foodchem.2004.11.049
[9] Bhattacharjee R, Sil PC . Protein isolate from the herb, Phyllanthus niruri L.(Euphorbiaceae), plays hepatoprotective role against carbon tetrachloride induced liver damage via its antioxidant properties[J]. Food Chem Toxicol, 2007,45(5):817-826
doi: 10.1016/j.fct.2006.10.029
[10] Council of Scientific and Industrial Research . The wealth of India: a dictionary of Indian raw materials and industrial products[M]. New Delhi: Publications and Information Directorate, Council of Scientific and Industrial Research, 1998
[11] Kirtikar KR, Basu BD . Indian medicinal plants[M]. Allahabad: Lalit Mohan Basu, 1987
[12] Christophe W. Ethnopharmacology of medicinal plants: Asia and the Pacific[M]. New Jersey: Humana Press, 2006
[13] Direkbusarakom S, Herunsalee A, Yoshimizu M, Ezura Y . Antiviral activity of several Thai traditional herb extracts against fish pathogenic viruses[J]. Fish Pathol, 1996,31(4):209-213
doi: 10.3147/jsfp.31.209
[14] Meléndez PA, Capriles VA . Antibacterial properties of tropical plants from Puerto Rico[J]. Phytomedicine, 2006,13(4):272-276
doi: 10.1016/j.phymed.2004.11.009
[15] Ingkaninan K, Temkitthawon P, Chuenchom K, Yuyaem T, Thongnoi W . Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating and neurotonic remedies[J]. J Ethnopharmacol, 2003,89(2-3):261-264
doi: 10.1016/j.jep.2003.08.008
[16] Sousa M, Ousingsawat J, Seitz R, Puntheeranurak S, Regalado A, Schmidt A, Grego T, Jansakul C, Amaral MD, Schreiber R, Kunzelmann K . An extract from the medicinal plant Phyllanthus acidus and its isolated compounds induce airway chloride secretion: a potential treatment for cystic fibrosis[J]. Mol Pharmacol, 2007,71(1):366-376
[17] Mahidol C, Prawat H, Prachyawarakorn V, Ruchirawat S . Investigation of some bioactive Thai medicinal plants[J]. Phytochem Rev, 2002,1(3):287-297
doi: 10.1023/A:1026085724239
[18] Unander DW, Webster GL, Blumberg BS . Usage and bioassays in Phyllanthus(Euphorbiaceae). Ⅳ. Clustering of antiviral uses and other effects[J]. J Ethnopharmacol, 1995,45(1):1-18
doi: 10.1016/0378-8741(94)01189-7
[19] Lee CY, Peng WH, Cheng HY, Chen FN, Lai MT, Chiu TH . Hepatoprotective effect of Phyllanthus in Taiwan on acute liver damage induced by carbon tetrachloride[J]. Am J Chin Med, 2006,34(3):471-482
doi: 10.1142/S0192415X06004004
[20] Gopal N, Sengottuvelu S . Hepatoprotective activity of Clerodendrum inerme against CCl4 induced hepatic injury in rats[J]. Fitoterapia, 2008,79(1):24-26
doi: 10.1016/j.fitote.2007.07.006
[21] Harborne JB . Phytochemical methods: a guide to modern technique of plant analysis(3rd ed)[M]. London: Chapman & Hill, 1998
[22] .[ OTHER] .Organisation for Economic Co-operation and Development. OECD series on testing and assessment: Number 24: Guidance document on acute oral toxicity testing. OTHER].Organisation for Economic Co-operation and Development. OECD series on testing and assessment: Number 24: Guidance document on acute oral toxicity testing.
[23] Jain A, Soni M, Deb L, Jain A, Rout SP, Gupta VB, Krishna KL . Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves[J]. J Ethnopharmacol, 2008,115(1):61-66
doi: 10.1016/j.jep.2007.09.009
[24] Reitman S, Frankel S . A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases[J]. Am J Clin Pathol, 1957,28(1):56-63
doi: 10.1093/ajcp/28.1.56
[25] Kind PR, King EJ . Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine[J]. J Clin Path, 1954,7(4):322-326
doi: 10.1136/jcp.7.4.322
[26] Mallay HT, Evelyn KA . Estimation of serum bilirubin level with the photoelectric colorimeter[J]. J Biol Chem, 1937,119:481-484
[27] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ . Protein measurement with the Folin phenol reagent[J]. J Biol Chem, 1951,193(1):265-271
[28] Ohkawa H, Ohishi N, Yagi K . Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction[J]. Anal Biochem, 1979,95(2):351-358
doi: 10.1016/0003-2697(79)90738-3
[29] Ellman GL . Tissue sulfhydryl groups[J]. Arch Biochem Biophys, 1959,82(1):70-77
doi: 10.1016/0003-9861(59)90090-6
[30] Beauchamp C, Fridovich I . Superoxide dismutase: improved assays and an assay applicable to acrylamide gels[J]. Anal Biochem, 1971,44(1):276-287
doi: 10.1016/0003-2697(71)90370-8
[31] Sinha AK . Colorimetric assay of catalase[J]. Anal Biochem, 1972,47(2):389-394
doi: 10.1016/0003-2697(72)90132-7
[32] Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG . Selenium: biochemical role as a component of glutathione peroxidase[J]. Science, 1973,179(73):588-590
doi: 10.1126/science.179.4073.588
[33] Blois MS . Antioxidant determination by the use of a stable free radical[J]. Nature, 1958,181:1199-1200
doi: 10.1038/1811199a0
[34] Van Puyvelde L, Kayonga A, Brioen P, Costa J, Ndimubakunzi A, De Kimpe N, Schamp N . The hepatoprotective principle of Hypoestes triflora leaves[J]. J Ethnopharmacol, 1989,26(2):121-127
doi: 10.1016/0378-8741(89)90059-7
[35] Suja SR, Latha PG, Pushpangadan P, Rajasekharan S . Evaluation of hepatoprotective effects of Helminthostachys zeylanica(L.) Hook against carbon tetrachloride-induced liver damage in Wistar rats[J]. J Ethnopharmacol, 2004,92(1):61-66
doi: 10.1016/j.jep.2004.01.019
[36] Clawson GA . Mechanisms of carbon tetrachloride hepatotoxicity[J]. Pathol Immunopathol Res, 1989,8(2):104-112
doi: 10.1159/000157141
[37] Rajesh MG, Latha MS . Preliminary evaluation of the antihepatotoxic activity of Kamilari, a polyherbal formulation[J]. J Ethnopharmacol, 2004,91(1):99-104
doi: 10.1016/j.jep.2003.12.011
[38] Recknagel RO, Glende Jr EA, Britton RS. Free radical damage and lipid peroxidation. In: Meeks RG, Harrison SD, Bull RJ. Hepatotoxicology[M]. Boca Raton: CRC Press, 1991
[39] Shenoy KA, Somayaji SN, Bairy KL . Hepatoprotective effects of Ginkgo biloba against carbon tetrachloride induced hepatic injury in rats[J]. Indian J Pharmacol, 2001,33(4):260-266
[40] Sanmugapriya E, Venkataraman S . Studies on hepatoprotective and antioxidant actions of Strychnos potatorum Linn. seeds on CCl4-induced acute hepatic injury in experimental rats[J]. J Ethnopharmacol, 2006,105(1-2):154-160
doi: 10.1016/j.jep.2005.10.028
[41] Anand KK, Singh B, Saxena AK, Chandan BK, Gupta VN, Bhardwaj V . 3,4,5-Trihydroxy benzoic acid(gallic acid), the hepatoprotective principle in the fruits of Terminalia belerica — bioassay guided activity[J]. Pharmacol Res, 1997,36(4):315-321
doi: 10.1006/phrs.1997.0236
[42] Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK, Suri KA, Suri J, Bhadauria M, Singh B . Hepatoprotective potential of Aloe barbadensis Mill. against carbon tetrachloride induced hepatotoxicity[J]. J Ethnopharmacol, 2007,111(3):560-566
doi: 10.1016/j.jep.2007.01.008
[43] Lake BG, Harris RA, Phillips JC, Gangolli SD . Studies on the effects of L-ascorbic acid on acetaminophen-induced hepatotoxicity. 1. Inhibition of the covalent binding of acetaminophen metabolites to hepatic microsomes in vitro[J]. Toxicol Appl Pharmacol, 1981,60(2):229-240
doi: 10.1016/0041-008X(91)90227-6
[44] Carini R, Comoglio A, Albano E, Poli G . Lipid peroxidation and irreversible damage in the rat hepatocyte model. Protection by the silybin-phospholipid complex IdB 1016[J]. Biochem Pharmacol, 1992,43(10):2111-2115
doi: 10.1016/0006-2952(92)90168-I
[45] Fraga CG, Martino VS, Ferraro GE, Coussio JD, Boveris A . Flavonoids as antioxidants evaluated by in vitro and in situ liver chemiluminescence[J]. Biochem Pharmacol, 1987,36(5):717-720
doi: 10.1016/0006-2952(87)90724-6
[46] Laughton MJ, Halliwell B, Evans PJ, Hoult JR . Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA[J]. Biochem Pharmacol, 1989,38(17):2859-2865
doi: 10.1016/0006-2952(89)90442-5
[47] Sanz MJ, Ferrandiz ML, Cejudo M, Terencio MC, Gil B, Bustos G, Ubeda A, Gunasegaran R, Alcaraz MJ . Influence of a series of natural flavonoids on free radical generating systems and oxidative stress[J]. Xenobiotica, 1994,24(7):689-699
doi: 10.3109/00498259409043270
[48] Jose JK, Kuttan R . Antioxidant activity of Emblica officinalis[J]. J Clin Biochem Nutr, 1995,19(2):63-70
doi: 10.3164/jcbn.19.63
[49] Ghosal S, Tripathi VK, Chauhan S . Active constituents of Emblica officinalis: PartⅠ. The chemistry and antioxidative effect of two new hydrolysable tannins, emblicanin A and B[J]. Indian J Chem, 1996,35(9):941-948
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