Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

General Research Article

Evaluation of Hepatoprotective Activity of Clerodendrum paniculatum Leaf on Carbon Tetrachloride-Induced Liver Toxicity Model in Swiss Albino Rats and Its Characterization by GC-MS

Author(s): Remya Kopilakkal and Balamurali M. Musuvathi*

Volume 20, Issue 7, 2020

Page: [1097 - 1109] Pages: 13

DOI: 10.2174/1871530320666200312152331

Price: $65

Abstract

Background: Clerodendrum paniculatum has ethnomedicinal importance in treatment of disorders like wound, typhoid, jaundice, malaria and anemia.

Objective: To evaluate the antioxidant and hepatoprotective activity of Clerodendrum paniculatum leaves against carbon tetrachloride (CCl4) induced rat model and identification of its bioactive constituents by Gas Chromatography Mass Spectroscopy (GC MS).

Methods: Successive solvent extraction was carried out. Total phenolic, flavonoid content and antioxidant activity by 2,2- diphenyl-1-picryl hydrazyl (DPPH), nitric oxide and 2-Azino-bis [3-ethyl benzothiazoline- 6-sufonic acid] (ABTS method) were done. Ethyl acetate extract was selected for hepatoprotective study in carbon tetrachloride intoxicated model followed by the measurement of liver function marker enzymes such as SGOT (Serum Glutamate Oxaloacetate Transaminase), SGPT (Serum Glutamate Pyruvate Transaminase), and ALP (Alkaline Phosphatase). Biochemical parameters like bilirubin and protein were measured. Histopathologic liver sections were carried out. Bioactive constituents were evaluated by GC MS.

Results: By DPPH and ABTS method, ethyl acetate extract showed IC50 as 70.14±0.92 μg/ml,2958.24±2.460 μg/ml, respectively. The alcoholic extract showed maximum IC50 (197.22 ±7.16 μg/ml) by Nitric oxide radical scavenging method. Hepatoprotective study reveals that intoxicated animal groups have elevated levels of enzymes and bilirubin and suppress the production of protein. The extract pre-treatment showed a significant decrease in enzymes and increased production of total protein in a dose-dependent manner. Histopathologic studies also support the hepatoprotective activity. GC MS analysis revealed the presence of seven major bioactive constituents with ethyl palmitate as the major one.

Conclusion: The results support the proof for the hepatoprotective potential of the CPLE extract with potent antioxidant activity and enhanced liver enzyme level. The observed activity could be due to the presence of bioactive compounds as identified by GC MS analysis.

Keywords: Antioxidant activity, Clerodendrum paniculatum, DPPH, nitric oxide, reducing power, ABTS, hepatoprotective activity, CCl4, GC-MS.

Graphical Abstract
[1]
Pham-Huy, L.A.; He, H.; Pham-Huy, C. Free radicals, antioxidants in disease and health. Int. J. Biomed. Sci., 2008, 4(2), 89-96.
[PMID: 23675073]
[2]
Gutteridge, J.M. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin. Chem., 1995, 41(12 Pt 2), 1819-1828.
[http://dx.doi.org/10.1093/clinchem/41.12.1819] [PMID: 7497639]
[3]
Javier, M.; Maria, D.A.; Amadeo, G.V.; Alfonso, P.; Gabriwl, C.; Fernando, F.; Juana, M.; Pilar, Z. Phenolic composition, antioxi-dant activity and in vitro availability of four different berries. J. Chem., 2016.
[4]
Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J., 2012, 5(1), 9-19.
[http://dx.doi.org/10.1097/WOX.0b013e3182439613] [PMID: 23268465]
[5]
Gan, R.Y.; Kuang, L.; Xu, X.R.; Zhang, Y.; Xia, E.Q.; Song, F.L.; Li, H.B. Screening of natural antioxidants from traditional Chinese medicinal plants associated with treatment of rheumatic disease. Molecules, 2010, 15(9), 5988-5997.
[http://dx.doi.org/10.3390/molecules15095988] [PMID: 20877204]
[6]
Kasprzak, K.S. Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Radic. Biol. Med., 2002, 32(10), 958-967.
[http://dx.doi.org/10.1016/S0891-5849(02)00809-2] [PMID: 12008111]
[7]
Jacob, R.A.; Sotoudeh, G. Vitamin C function and status in chronic disease. Nutr. Clin. Care, 2002, 5(2), 66-74.
[http://dx.doi.org/10.1046/j.1523-5408.2002.00005.x] [PMID: 12134712]
[8]
Mujeeb, M.; Alam Khan, S.; Aeri, V.; Ali, B. Hepatoprotective activity of the ethanolic extract of Ficuscarica Linn. Leaves in Carbon tetrachloride induced hepatotoxicity in rats. Iran. J. Pharm. Res., 2011, 10(2), 301-306.
[PMID: 24250358]
[9]
Montemayor, C.D.; Perez, C.; Aranda, R.S.; Minsky, N.W. Mod-els of hepatoprotective activity assessment. MedicinaUniversitar-ia., 2015, 17(69), 222-228.
[10]
Mroueh, M.; Saab, Y.; Rizkallah, R. Hepatoprotective activity of Centaurium erythraea on acetaminophen-induced hepatotoxicity in rats. Phytother. Res., 2004, 18(5), 431-433.
[http://dx.doi.org/10.1002/ptr.1498] [PMID: 15174008]
[11]
Feroz, A.; Nahida, T. Experimental models used for the study of antihepatotoxic agents. J. Acute Dis., 2012, 1(2), 85-89.
[http://dx.doi.org/10.1016/S2221-6189(13)60021-9]
[12]
Meyer, S.A.; Kulkarni, A.P. Introduction to biochemical toxicology, 3rd; New York,. , 2001; pp. 487-490.
[13]
Rao, G.M.; Rao, C.V.; Pushpangadan, P.; Shirwaikar, A. Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn. J. Ethnopharmacol., 2006, 103(3), 484-490.
[http://dx.doi.org/10.1016/j.jep.2005.08.073] [PMID: 16213120]
[14]
Roth, R.A.; Ganey, P.E. Intrinsic versus idiosyncratic drug-induced hepatotoxicity--two villains or one? J. Pharmacol. Exp. Ther., 2010, 332(3), 692-697.
[http://dx.doi.org/10.1124/jpet.109.162651] [PMID: 20019161]
[15]
Russmann, S.; Kullak-Ublick, G.A.; Grattagliano, I. Current concepts of mechanisms in drug-induced hepatotoxicity. Curr. Med. Chem., 2009, 16(23), 3041-3053.
[http://dx.doi.org/10.2174/092986709788803097] [PMID: 19689281]
[16]
Gogoi, N.; Gogoi, A.; Neog, B.; Baruah, D.; Singh, K.D. evalua-tion of antioxidant and hepatoprotective activity of fruit rind ex-tract of Garcinia dulcis (Roxburg). Pharmacognosy Res., 2017, 9(3), 266-272.
[http://dx.doi.org/10.4103/0974-8490.210330] [PMID: 28827968]
[17]
Nizar, T.; Walid, E.; Hedia, H.; Yassine, Y.; Abdelhamid, K.; Ali, F.; Nizar, N. Screening of natural antioxidants from selected me-dicinal plants. Int. J. Food Prop., 2013, 16(5), 1117-1126.
[http://dx.doi.org/10.1080/10942912.2011.576360]
[18]
Shajiselvin, C.D.; Rakhi, A.R. Evaluation of hypolipidemic effect of various extracts of whole plant of Clerodendrum paniculatum in rat fed with high fat diet. European J Biomed. Pharm. Sci., 2014, 1(1), 87-96.
[19]
Chethana, G.S.; Hari, V.; Gopinath, S.M. Review on Clerodendruminerme. J Pharm. Sci. Innov., 2013, 2(2), 38-40.
[http://dx.doi.org/10.7897/2277-4572.02220]
[20]
Kirtikar, K.R.; Basu, B.D. Indian Medicinal Plants, 1st ed; , 1918, p. 877.
[http://dx.doi.org/10.5962/bhl.title.137025]
[21]
Prasad, M.P.; Sushant, S.; Chikkaswamy, B.K. Phytochemical analysis, antioxidant potential, antibacterial activity and molecu-lar characterization of Clerodendrum species. Int J. Mol. Biol., 2012, 3(3), 71-76.
[http://dx.doi.org/10.9735/0976-0482.3.3.71-76]
[22]
Khandelwal, K.R.; Varunda, S. Practical pharmacognosy, techniques and experiments , 3.1-3.5.
[23]
Trease, G.E.; Evans, W.C. Pharmacognosy 2002.
[24]
Krishanthi, P.M.; Rathinam, X.; Kassi, M.; Ayyalu, D.; Surash, R.; Sadassivam, K.; Sreeramanan, S. A comparative study on the antioxidant acivity of methanolic leaf extracts ofFicusreligi-osaL,Chromolaenaodorata (L.) King &Rabinson,Cynodondactylon(L.) Pers. AndTridaxprocumbens L. Asian Pac. J. Trop. Med., 2010, 3(5), 348-350.
[http://dx.doi.org/10.1016/S1995-7645(10)60084-3]
[25]
Basu, P.; Maier, C. Invitro antioxidant activities and polyphenol contents of seven commercially available fruits. Pharmacognosy Res., 2016, 8(4), 258-264.
[http://dx.doi.org/10.4103/0974-8490.188875] [PMID: 27695265]
[26]
Subedi, L.; Timalsena, S.; Duwadi, P.; Thapa, R.; Paudel, A.; Parajuli, K. Antioxidant activity and phenol and flavonoid contents of eight medicinal plants from Western Nepal. J. Tradit. Chin. Med., 2014, 34(5), 584-590.
[http://dx.doi.org/10.1016/S0254-6272(15)30067-4] [PMID: 25417410]
[27]
Irsha, M.; Zafaryab, M.D. Man Singh; Moshahid, M.A. Com-parative analysis of the antioxidant activity of Cassia fistula ex-tracts. Int. J. Med. Chem., 2012, 1-6.
[http://dx.doi.org/10.1155/2012/157125]
[28]
Duo, Q.D.; Ankawijaya, A.E.; Tran-Nguyen, P.L.; Huynh, L.H.; Soetaredjo, F.E.; Ismadji, S.; Hsu, J.Y. Effects of extraction sol-vent on total phenol content, total flavonoid content, and antiox-idant activity of Limnophila aromatic. Yao Wu Shi Pin Fen Xi, 2014, 22, 296-302.
[29]
Ameida, M.M.B.; Sousa, P.H.M.; Arriaga, A.M.C.; Prado, G.M.P.; Magalhaes, C.E.; Maia, G.A.; Lemos, T.L.G. Bioactive compounds and antioxidant activity of fresh exotic fruits from northeastern Brazil. Int. Food Res. J., 2011, 44, 2155-2159.
[http://dx.doi.org/10.1016/j.foodres.2011.03.051]
[30]
Govindan, P.; Muthukrishnan, S. Evaluation of total phenolic content and free radical scavenging activity of Boerhaviadiffusa. J Acute Med., 2013, 3(3), 103-109.
[http://dx.doi.org/10.1016/j.jacme.2013.06.003]
[31]
Venkatachalam, U.; Muthukrishnan, S. Free radical scavenging activity of ethanolic extract of Desmodiumgangeticum. J Acute Med., 2012, 2(2), 36-42.
[http://dx.doi.org/10.1016/j.jacme.2012.04.002]
[32]
Mondal, A.; Maity, T.K.; Pal, D.; Sannigrahi, S.; Singh, J. Isolation and in vivo hepatoprotective activity of Melothria heterophylla (Lour.) Cogn. against chemically induced liver injuries in rats. Asian Pac. J. Trop. Med., 2011, 4(8), 619-623.
[http://dx.doi.org/10.1016/S1995-7645(11)60159-4] [PMID: 21914539]
[33]
Balasubramanian, T.; Tapan, K.C. Hepatoprotective and antioxi-dant effects of Stereospermumsuaveolens on carbon tetrachloride induced hepatic damage in rats. J. Complement. Integr. Med., 2010, 7(1), 22.
[34]
Ecobichon, D.J. The basis of toxicology testing; CRC Press: New York, 1997, pp. 43-86.
[35]
Azeem, A.K.; Mathew, M. Hepatoprotective effect of Averrhoea-carambola fruit extract on Carbon tetrachloride induced hepato-toxicity in mice. Asian Pac. J. Trop. Med., 2010, 3(8), 610-613.
[http://dx.doi.org/10.1016/S1995-7645(10)60148-4]
[36]
Gnanadesignan, M.; Ravikumar, S. hepatoprotective and antioxi-dant properties of marine halophyte Luminetzeraracemosa bark extract in carbon tetrachloride induced hepatotoxicity. Asian Pac. J. Trop. Med., 2011, 4(6), 462-465.
[http://dx.doi.org/10.1016/S1995-7645(11)60126-0] [PMID: 21771699]
[37]
Li, C.; Yi, L.T.; Geng, D.; Han, Y.Y.; Weng, L.J. Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice. Pharm. Biol., 2015, 53(5), 767-772.
[http://dx.doi.org/10.3109/13880209.2014.941506] [PMID: 25431325]
[38]
Zhou, D.; Ruan, J.; Cai, Y.; Xiong, Z.; Fu, W.; Wei, A. Antioxidant and hepatoprotective activity of ethanol extract of Arachniodes exilis (Hance). Ching. J. Ethnopharmacol., 2010, 129(2), 232-237.
[http://dx.doi.org/10.1016/j.jep.2010.03.016] [PMID: 20347029]
[39]
Zarezade, V.; Moludi, J.; Mostafazadeh, M.; Mohammadi, M.; Veisi, A. Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats. Avicenna J. Phytomed., 2018, 8(1), 51-62.
[PMID: 29387574]
[40]
Saraswat, B.; Visen, P.; Patnaik, G.K.; Dhawan, B.N. Anticholes-tatic effect of Picroliv, active hepatoprotective principle of Picro-rhizakurrooa against Ccl4 induced cholestasis. Indian J Exp. Bio., 1993, 31, 316-318.
[PMID: 8359830]
[41]
Vidya, S.M.; Krishna, V.; Manjunatha, B.K.; Mankani, K.L.; Ahmed, M.; Singh, S.D. Evaluation of hepatoprotective activity of Clerodendrum serratum L. Indian J. Exp. Biol., 2007, 45(6), 538-542.
[PMID: 17585689]
[42]
Jiang, Y.; Fan, X.; Wang, Y.; Tan, H.; Chen, P.; Zeng, H.; Huang, M.; Bi, H. Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem. Biol. Interact., 2015, 231, 83-89.
[http://dx.doi.org/10.1016/j.cbi.2015.02.022] [PMID: 25753323]
[43]
Xu, M.L.; Wang, L.L. Protective effects of aqueous extract of cortex dictamni on myocardial ischemia perfusion injury in rats. Acta Labor Animalis Scientia Sinica., 2013, 21, 47-52.
[44]
Liu, Y.J.; Du, J.L.; Cao, L.P.; Jia, R.; Shen, Y.J.; Zhao, C.Y. Xu,p.; Yin, G.J. Anti-inflammatory and protective effect of Ganodermalucidum polysaccharides on Ccl4 induced hepatocyte damage in common carp (Cyprinuscarpio L.). Int. Immunopharmacol., 2015, 25(1), 112-120.
[http://dx.doi.org/10.1016/j.intimp.2015.01.023] [PMID: 25639226]
[45]
u. L.; Xin,H.; Zheng,G.; Su,Y.; Ling,C. Hepatoprotective activity of the total saponins from Actiinidavalvatadunn root against car-bon tetrachloride induced liver damage in mice Evid; Based Compl. Alt. Med, 2012.
[46]
Gupta, R.K.; Hussain, T.; Panigrahi, G.; Das, A.; Singh, G.N.; Sweety, K.; Faiyazuddin, M.; Rao, C.V. Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals. Asian Pac. J. Trop. Med., 2011, 4(12), 964-968.
[http://dx.doi.org/10.1016/S1995-7645(11)60227-7] [PMID: 22118032]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy