Hepatoprotective Activity of Aqueous and Ethanol Extract of <i>Lippia adoensis</i> Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Yared Wasihun; Eyasu Makonnen; Mekbeb Afewerk; Wondwossen Ergete

doi:doi:10.11648/j.plm.20170101.12

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Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Yared Wasihun, Eyasu Makonnen, Mekbeb Afewerk, Wondwossen Ergete

Published in Pathology and Laboratory Medicine (Volume 1, Issue 1)

Received: 27 June 2016 Accepted: 9 March 2017 Published: 10 March 2017

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Abstract

Liver disease is one of the fatal diseases. Medicinal plants may serve as one ofthe best sources of remedies for treatment of liver disease. Identification of a potential therapeutic agent for protection of liver from hepatotoxins provides a useful way for the prevention of liver related illnesses. The aim of the present study was, therefore, to investigate the hepatoprotective activity of 80% ethanolic and aqueous extract of leaves of Lippia adoensis againstcarbontetrachloride induced liver injury in mice. Mice were pretreated with extract of Lippia adoensis (200 & 400 mg/kg bw. po) for 7 days and then challenged with CCl₄ (0.2 ml/100 gm p. o) on the 7^th day. Serum biomarkers (AST, ALT, ALP and total bilirubin, total protein and albumin) were estimated in all the study groups. Histopathological examination was also carried out for all groups of mice. CCl₄ significantly (P < 0.001) increased the AST, ALT, ALP and total bilirubin levels and decreased the level of total protein and albumin indicating hepatic damage. Pretreatment with theextract of Lippia adoensis (200 & 400 mg/kg) produced significant (P < 0.001) hepatoprotective effects as evidenced by decreased serum enzymes (AST, ALT, ALP) and serum bilirubin and increase the level of total protein and albumin as well as by histopathological findings of the liver. Histopathological examination of the liver tissues of CCl₄ group represented the presence of marked foci of mononuclear inﬁltration in the hepatic parenchyma tissue, sinusoid and around central vein, as well as disorganization of hepatic plates, whilepretreatment with extract of Lippia adoensis overcome most of these changes to normal histological architecture of the liver. Body weights of Lippia adoensis extract treated groups increased significantly (P < 0.001) as compared to carbontetrachloride treated group. The absolute and relative liver weights of extracts treated mice decreased significantly (P < 0.001) as compared to those treated with CCl4. The results obtained from both ethanolic and aqueous extract of Lippia adoensis were comparable with those of the standard drug, Silymarin. It can be concluded from the present study that bothethanolic and aqueous extracts of Lippia adoensis have hepatoprotective effect.

Published in	Pathology and Laboratory Medicine (Volume 1, Issue 1)
DOI	10.11648/j.plm.20170101.12
Page(s)	5-13
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Lippia adoensis, Aqueous Extract, Ethanol Extract, Hepatoprotective, CCl₄, Silymarin, AST, ALT, ALP, Bilirubin, Protein, Albumin and Mice

References

[1]	Abegaz, B., Asfaw, N. and Lwande, W. Constituents of essential oil from wild and cultivated Lippia adoensis, J. Essent. Oil Res.1993; 5: 487-491.
[2]	Alaezi CM, Adisa JO, Okorochi EC and Okechi OO. A progressive Nuclear stain substitute for haematoxylin And eosin staining technique in the Demonstration of invasive ductal Carcinoma. GJSR Journal.2014; 2 (2): 51-55.
[3]	Amita Jain, Rashmi Ranade, Prem Pritam, Neelu Joshi, Sirisha Lakshmi Vavilala, Ankita Jain. A comparative study of antioxidant activity, total phenolic and flavonoid contents in different parts of Helicteres isora. L. American journal of life sciences.2014; 2 (5): 292-302.
[4]	Andréia Assunção Soares, Anacharis Babeto de Sá-Nakanishi, Adelar Bracht, Sandra Maria Gomes da Costa, Eloá Angélica Koehnlein, Cristina Giatti Marques de Souza and Rosane Marina Peralta. Hepatoprotective effects of mushrooms. Molecules.2013; 18: 7609-7630.
[5]	Asres K and Bucar F. Lippia adoensisvar. Adoensis: studies on the essential oil composition and antioxidant activity, Ethiop. Pharm. J.2002; 20:32-38.
[6]	Asres, K, Bibbons, W, David, P. and Polo, M. Alkaloids of Ethiopian Calpurniaaurea, subsp. aurea, Phytochemistry. 1986; 25 (6): 1443-1447.
[7]	Bhaargavi, Vuyyuri, G. S. L. Jyotsna, and Reshma Tripurana. "A review on hepatoprotective activity." International Journal of Pharmaceutical Sciences & Research. 2014; 5 (3): 690-702.
[8]	Bhaskara KL and Mukalel SL. Curative efficacy of methanolic extract of Monochoria vaginalis against Carbontetra chloride (CCl4) induced liver fibrosis. Journal of Pharmacy and Biological Sciences (IOSR-JPBS). 2014; 9 (1): 71-76.
[9]	Bimlesh Kumar, Harleen Kaur Sandhar, Sunil Prasher, Prashant Tiwari, Manoj Salhan, Pardeep Sharma. Phytochemistry and Pharmacology. Internationale Pharmaceutica Sciencia.2011; 1 (1): 25-41.
[10]	Cheng, Jianhui, Zuofa Zhang, Zhiguo Zheng, Guoying Lv, Liangyan Wang, Bing Tian, and Yuejin Hua. "Antioxidative and Hepatoprotective Activities of Deinoxanthin-Rich Extract from Deinococcus radiodurans R1 against Carbon Tetrachloride-Induced Liver Injury in Mice. " Tropical Journal of Pharmaceutical Research 2014; 13 (4): 581-586.
[11]	Comfort JA, Augusta AE, Gbadebo EA, Margaret OOand Emmanuel NM. N-Nitrosation of dimethylamine hydrochloride and its toxicology in the wistar rats fed different levels of dietary protein. European Journal of Experimental Biology. 2013; 3 (2): 94-103.
[12]	David EK, Naga PC, William ML. Hepatic histological findings in suspecteddrug-induced liver injury. Hepatology.2014; 59 (2): 661–670. doi:10.1002/hep.26709.
[13]	Douhri B., Idaomar M, Skalisenhaj N, Ennabili A, Abrini J. Hepatoprotective effect of Origanum elongatum. European journal of medicinal plants 2014; 4 (1): 14-28.
[14]	El Sohafy, Samah M., Saleh I. Alqasoumi, Aly M. Metwally, Abdallah A. Omar, Masouda M. Amer, Mohammed I. Abou Shoer, S. A. El Toumy, and Maged S. Abdel-Kader. "Evaluation of the hepatoprotective activity of some plants belonging to the tribe Cynareae growing in Egypt. " Journal of Medicinal Plants Research. 2013; 7 (7): 324-328.
[15]	Farhan H, Rammal H, Hijazi A, Hamad H, Daher A, Reda M, Badran B. In vitro antioxidant activity of ethanolic and aqueous extracts from crude malva parviflora. Grown in lebanon. Asian J Pharm Clin Res.2012; 5 (3): 234-238.
[16]	Francesco Visioli, Catalina Alarcón, Cristina Andres, Michael Aviram, Conceição Calhau, Alfredo Cassano, Massimo D’Archivio, Ana Faria, Gaëlle Favé, Vincenzo Fogliano, Rafael Llorach. Polyphenols and human health. Critical Reviews in Food Science and Nutrition.2011; 51: 524–546.
[17]	Gayathiri S, Vetriselvan S, Shankar J, Ishwin S, Hemah D, Shereenjeet K, Yaashini A. Hepatoprotective activity of aqueous extract of hippophae rhamnoides. International journal of biological & pharmaceutical research. 2012; 3 (4): 531-537.
[18]	Isha I. Sait, Jyoti Harindran, A. Abdul Vahab, Jeena J. L, Nasli S. Jolly John. Potential hepatoprotective effect and antioxidant role of methanol extract of morinda tinctoria in carbon tetrachloride induced hepatotoxicity in albino rats. Int J Pharm 2014; 4 (1): 363-368.
[19]	Iyanda A A and Adeniyi F A. Buffer conditions for measuring alkaline phosphatase activity in Indices of Hepatorenal Function. J Phys Pharm Adv. 2014; 4 (1): 310-317.
[20]	Jamilah M Hashemi. Hibiscus Sabdariffa Calyx Extract alleviate hepato toxicity induced by carbon tetrachloride on male albino rats. NatSci. 2014; 12 (6): 111-120.
[21]	Kadejo OA, James DB, Sallau BA, Ozigi A A. In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats. Asian Pac J Trop Biomed. 2013; 3 (5): 395-400.
[22]	Kanwal Z, Muhammad IS, Muhammad AM. Effect of Momordica charantia (bitter melon) on serum glucose level and various protein parameters in acetaminophen intoxicated rabbits. J Intercult Ethnopharmacol.2012; 1 (1): 7-12.
[23]	Kutaiba Ibrahim Alzand, Mohamed Ali Abdullah, Mukul Tailang. Structural elucidation and biological activity of the flavonoid from the roots of cudrania tricuspidata. World Journal of Pharmaceutical Research. 2014; 3 (10): 981-997.
[24]	Li Yin, Lei Wei, Rao Fu, Lisheng Ding, Yiran Guo, Lin Tang and Fang Chen. Antioxidant and hepatoprotective activity of veronica ciliata fisch Extracts against carbon tetrachloride-induced liver injury in mice. Molecules.2014; 19: 7223-7236.
[25]	Maliha AAM. Phenoli. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transminases. Journal of Food and Nutrition Sciences.2014; 2 (5): 207-214.
[26]	Manuj Kr. Bharali, Hage Konya, Luk Bahadur Chetry. Protective effect of Oroxylum indicum on acetaminophen induced liver injury in rat. International Current Pharmaceutical Journal, January 2014, 3 (2): 223-227.
[27]	Mary Tolulope Olaleye, Ayodeji Emmannuel Amobonye, Kayode Komolafe, Afolabi Clement Akinmoladun. Protective eﬀects of Parinari curatellifolia ﬂavonoids against acetaminophen-induced hepatic necrosis in rats. Saudi Journal of Biological Sciences.2014; 21: 486–492.
[28]	Mohamed STS, Madhusudhana C, Chetty S, Ramkanth V. S. T, Rajan KM. Hepatoprotective herbs. Int. J. Res. Pharm Sci. 2010; 1: 1-5.
[29]	Muhammad Imran, Muhammad Ali, Muhammad Ali, Mohammad Saleem and Muhammad Hanif. Hepatoprotective effect of leaves of aqueous ethanol extract ofCestrum nocturnum. Bangladesh J Pharmacol 2014; 9: 167-170.
[30]	NorlailyMohd Ali, HamidahMohd Yusof, Kamariah Long, Swee Keong Yeap, Wan Yong Ho. Antioxidant and Hepatoprotective Eﬀect of Aqueous Extract of Germinated and Fermented Mung Bean on Ethanol-Mediated Liver Damage. Bio Med Research International. 2013; 9.
[31]	Riot Sishu, Mariamawit Yonathan, Ameha Seyoum and Kaleab Asres. Radical scavenging activity of volatile oils of herbs traditionally used to spice cooking butter in Ethiopia. Ethiopian Pharmaceutical Journal.2005; 23: 7-14.
[32]	Sabreena Rashid, Zahoor A Kaloo, Seema Singh & Iram Bashir. Medicinal importance of Genus Rheum onhepatoprotective, International Journal of Advanced Research. 2014; 2 (7): 261-267.
[33]	Sagar D, Varsha Z, Dinesh D, Shital P. Hepatoprotective activity of Alcoholic leafextract of Alianthus exelssa root against carbon tetrachloride toxicity induced in albino rat. Int. J. PharmTech Res. 2012; 4 (2).
[34]	Sampath Kumar GV, Sri Vidya VVL, Ch. Sandhya. Hepatoprotective activity of borreria hispida l. Roots against carbon tetrachloride induced hepatotoxicity in albino wistar rats. International Journal of Biological & Pharmaceutical Research. 2013; 4 (12): 1277-1282.
[35]	Senthilkumar, Ravichandran, Rahul Chandran, and Thangaraj Parimelazhagan. "Hepatoprotective effect of Rhodiola imbricata rhizome against paracetamol-induced liver toxicity in rats. " Saudi journal of biological sciences.2014; 21 (5): 409-416.
[36]	Showket Hussain Bhat, Rajni Shrivastava, Mohd Yousuf Malla, Mohd Iqbal, Tahira Anjum, Abrar Hussain Mir, Manik Sharma. Hepatoprotective activity of argemone mexicanalinn against toxic effects of carbon tetrachloride in rats. World Journal of Pharmaceutical Research.2014; 3 (3): 4037-4048.
[37]	Singh, A, BhatTK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clinic Toxicology.2011; S4:001. doi:10.4172/2161-0495. S4-001.
[38]	Snehal Gite, Supriya Yadav, Smita Nilegaonkar, Vaishali Agte. Evaluation of hepatoprotective potential of functional food formulations using in vitro and in vivo models of CCl4 radical induced toxicity. International Journal of Interdisciplinary and Multidisciplinary Studies (IJIMS), 2014: 1 (10) 6-13.
[39]	Sundaram R, Murugesan G. Hepatoprotective and antioxidant activity of a mangrove plant Lumnitzera racemosa. Asian Pac J Trop Biomed. 2011; 1 (5): 348-352.
[40]	Sunita Shailajan, Mayuresh Joshi, Bhavesh Tiwari. Hepatoprotective activity of Parmelia perlata (Huds.) Ach. against CCl4 induced liver toxicity. Journal of Applied Pharmaceutical Science. 2014; 4 (02): 070-074.
[41]	Tadewos H, Abadi G, Henok K. Evaluation of physico-chemical, microbial and organoleptic properties of cow milk in smoked container with olive (Olea africana) and added leaves of Lippia adoensis. American Journal of Food Science and Nutrition.2014; 1 (2): 29-37.
[42]	Toshihiro, A., Gebreyesus, T., Hiroshi, H. and Toshitake, T. Co-occurrence of C- 24 Epimeric 24-ethylsterols Possessing and Lacking a 25 bond in Kalanchoe petitiana, Phytochemistry.1992; 31: 163-166.
[43]	Tulay Ozcan, Akpinar BA, Yilmaz EL, and Delikanli B. Phenolics in Human Health. International Journal of Chemical Engineering and Applications.2014; 5 (5): 393-396.

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APA Style

Yared Wasihun, Eyasu Makonnen, Mekbeb Afewerk, Wondwossen Ergete. (2017). Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathology and Laboratory Medicine, 1(1), 5-13. https://doi.org/10.11648/j.plm.20170101.12

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ACS Style

Yared Wasihun; Eyasu Makonnen; Mekbeb Afewerk; Wondwossen Ergete. Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathol. Lab. Med. 2017, 1(1), 5-13. doi: 10.11648/j.plm.20170101.12

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AMA Style

Yared Wasihun, Eyasu Makonnen, Mekbeb Afewerk, Wondwossen Ergete. Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathol Lab Med. 2017;1(1):5-13. doi: 10.11648/j.plm.20170101.12

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@article{10.11648/j.plm.20170101.12,
  author = {Yared Wasihun and Eyasu Makonnen and Mekbeb Afewerk and Wondwossen Ergete},
  title = {Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice},
  journal = {Pathology and Laboratory Medicine},
  volume = {1},
  number = {1},
  pages = {5-13},
  doi = {10.11648/j.plm.20170101.12},
  url = {https://doi.org/10.11648/j.plm.20170101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.plm.20170101.12},
  abstract = {Liver disease is one of the fatal diseases. Medicinal plants may serve as one ofthe best sources of remedies for treatment of liver disease. Identification of a potential therapeutic agent for protection of liver from hepatotoxins provides a useful way for the prevention of liver related illnesses. The aim of the present study was, therefore, to investigate the hepatoprotective activity of 80% ethanolic and aqueous extract of leaves of Lippia adoensis againstcarbontetrachloride induced liver injury in mice. Mice were pretreated with extract of Lippia adoensis (200 & 400 mg/kg bw. po) for 7 days and then challenged with CCl4 (0.2 ml/100 gm p. o) on the 7th day. Serum biomarkers (AST, ALT, ALP and total bilirubin, total protein and albumin) were estimated in all the study groups. Histopathological examination was also carried out for all groups of mice. CCl4 significantly (P Lippia adoensis (200 & 400 mg/kg) produced significant (P 4 group represented the presence of marked foci of mononuclear inﬁltration in the hepatic parenchyma tissue, sinusoid and around central vein, as well as disorganization of hepatic plates, whilepretreatment with extract of Lippia adoensis overcome most of these changes to normal histological architecture of the liver. Body weights of Lippia adoensis extract treated groups increased significantly (P Lippia adoensis were comparable with those of the standard drug, Silymarin. It can be concluded from the present study that bothethanolic and aqueous extracts of Lippia adoensis have hepatoprotective effect.},
 year = {2017}
}

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TY - JOUR
T1 - Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice
AU - Yared Wasihun
AU - Eyasu Makonnen
AU - Mekbeb Afewerk
AU - Wondwossen Ergete
Y1 - 2017/03/10
PY - 2017
N1 - https://doi.org/10.11648/j.plm.20170101.12
DO - 10.11648/j.plm.20170101.12
T2 - Pathology and Laboratory Medicine
JF - Pathology and Laboratory Medicine
JO - Pathology and Laboratory Medicine
SP - 5
EP - 13
PB - Science Publishing Group
SN - 2640-4478
UR - https://doi.org/10.11648/j.plm.20170101.12
AB - Liver disease is one of the fatal diseases. Medicinal plants may serve as one ofthe best sources of remedies for treatment of liver disease. Identification of a potential therapeutic agent for protection of liver from hepatotoxins provides a useful way for the prevention of liver related illnesses. The aim of the present study was, therefore, to investigate the hepatoprotective activity of 80% ethanolic and aqueous extract of leaves of Lippia adoensis againstcarbontetrachloride induced liver injury in mice. Mice were pretreated with extract of Lippia adoensis (200 & 400 mg/kg bw. po) for 7 days and then challenged with CCl4 (0.2 ml/100 gm p. o) on the 7th day. Serum biomarkers (AST, ALT, ALP and total bilirubin, total protein and albumin) were estimated in all the study groups. Histopathological examination was also carried out for all groups of mice. CCl4 significantly (P Lippia adoensis (200 & 400 mg/kg) produced significant (P 4 group represented the presence of marked foci of mononuclear inﬁltration in the hepatic parenchyma tissue, sinusoid and around central vein, as well as disorganization of hepatic plates, whilepretreatment with extract of Lippia adoensis overcome most of these changes to normal histological architecture of the liver. Body weights of Lippia adoensis extract treated groups increased significantly (P Lippia adoensis were comparable with those of the standard drug, Silymarin. It can be concluded from the present study that bothethanolic and aqueous extracts of Lippia adoensis have hepatoprotective effect.
VL - 1
IS - 1
ER -

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Author Information

Yared Wasihun

Department of Pharmacy, College of Medicine and Health Sciences, Ambo University, Ambo, Ethiopia
Eyasu Makonnen

Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, AddisAbaba, Ethiopia
Mekbeb Afewerk

Department of Anatomy, School of Medicine, College of Health Sciences, Addis Ababa University, AddisAbaba, Ethiopia
Wondwossen Ergete

Department of Pathology, School of Medicine, College of Health Sciences, Addis Ababa University, AddisAbaba, Ethiopia

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Yared Wasihun, Eyasu Makonnen, Mekbeb Afewerk, Wondwossen Ergete. (2017). Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathology and Laboratory Medicine, 1(1), 5-13. https://doi.org/10.11648/j.plm.20170101.12

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Yared Wasihun; Eyasu Makonnen; Mekbeb Afewerk; Wondwossen Ergete. Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathol. Lab. Med. 2017, 1(1), 5-13. doi: 10.11648/j.plm.20170101.12

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AMA Style

Yared Wasihun, Eyasu Makonnen, Mekbeb Afewerk, Wondwossen Ergete. Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Pathol Lab Med. 2017;1(1):5-13. doi: 10.11648/j.plm.20170101.12

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@article{10.11648/j.plm.20170101.12,
  author = {Yared Wasihun and Eyasu Makonnen and Mekbeb Afewerk and Wondwossen Ergete},
  title = {Hepatoprotective Activity of Aqueous and Ethanol Extract of Lippia adoensis Leaf Against Carbon Tetrachloride-Induced Hepatotoxicity in Mice},
  journal = {Pathology and Laboratory Medicine},
  volume = {1},
  number = {1},
  pages = {5-13},
  doi = {10.11648/j.plm.20170101.12},
  url = {https://doi.org/10.11648/j.plm.20170101.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.plm.20170101.12},
  abstract = {Liver disease is one of the fatal diseases. Medicinal plants may serve as one ofthe best sources of remedies for treatment of liver disease. Identification of a potential therapeutic agent for protection of liver from hepatotoxins provides a useful way for the prevention of liver related illnesses. The aim of the present study was, therefore, to investigate the hepatoprotective activity of 80% ethanolic and aqueous extract of leaves of Lippia adoensis againstcarbontetrachloride induced liver injury in mice. Mice were pretreated with extract of Lippia adoensis (200 & 400 mg/kg bw. po) for 7 days and then challenged with CCl4 (0.2 ml/100 gm p. o) on the 7th day. Serum biomarkers (AST, ALT, ALP and total bilirubin, total protein and albumin) were estimated in all the study groups. Histopathological examination was also carried out for all groups of mice. CCl4 significantly (P Lippia adoensis (200 & 400 mg/kg) produced significant (P 4 group represented the presence of marked foci of mononuclear inﬁltration in the hepatic parenchyma tissue, sinusoid and around central vein, as well as disorganization of hepatic plates, whilepretreatment with extract of Lippia adoensis overcome most of these changes to normal histological architecture of the liver. Body weights of Lippia adoensis extract treated groups increased significantly (P Lippia adoensis were comparable with those of the standard drug, Silymarin. It can be concluded from the present study that bothethanolic and aqueous extracts of Lippia adoensis have hepatoprotective effect.},
 year = {2017}
}

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