Creative Commons License 2019 Volume 6 Issue 3

Goji Berry (Lycium barbarum L.) Extract Alleviate Acute Hepatotoxicity Induced by Methotrexate in Rats

Manal M.S. Mansoury

Methotrexate (Metho) is widely used in the treatment of autoimmune and malignancy diseases. Goji berry (G. berries), Lycium barbarum L., fruit extract has immune-modulating, antioxidant and antitumor effects. This study assessed whether G. berries fruits' extract alleviated the hepatotoxicity induced by Metho in rats. Forty rats were randomly segregated into four groups (G); GI (Cont), GII (Metho); rats on the 21th day injected interperitoneal (ip) with Metho (20 mg/kg), GIII (G. berries 200 mg/kg +Metho) and GIV (G. berries 400 mg/kg + Metho). Rats in GIII and GIV given G. berries 200 and 400 mg/kg orally once a day and on the 21th day rats were injected with Metho i.p as in GII. Blood and hepatic tissues samples were collected after 5 days of Metho injection. Serum liver enzyme activities, interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were measured. Liver oxidative stress indices (superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO)) levels were measured in the homogenate liver tissues. Liver sections were examined under microscope to detect the changes in liver tissues. The results showed that there were significant (p< 0.001) increases in serum liver enzyme activities and anti-inflammatory cytokine (IL-1β and TNF-α) levels, as well as hepatic oxidative stress, as marked by significant (p< 0.001) increases in hepatic MDA and NO levels, with significant (p< 0.001) decreases in SOD and CAT activities in Metho group compared with Cont group. Examined hepatic sections showed hydropic degeneration of hepatocytes, congestion of hepatoportal blood vessels, portal infiltration with mononuclear cells. Administration of G. berries extract (200 mg/kg) and (400 mg/kg) revealed significant (p< 0.001) reduction in serum liver enzyme activities and anti-inflammatory cytokines levels, and elevating the hepatic antioxidant status compared with Metho injected rats, as well as overcoming the tissue changes, the majority of the cells tend to be normal especially in the pretreated group with G. berries 400 mg/kg + Metho. In conclusion, the results revealed that G. berries has acute hepatoprotective effect; this could be explained by its ability to restore the antioxidant status and suppress inflammatory responses.


Farvell, G.C., and Liddle, C.2002. Hepatoxicity in the twenty first century. Seminar on liver diseases,22: 109 – 206.

Usha, K., Kasturi, M.and Hemalatha, P.2007. Hepatoprotective effect of Hygrophila spinosa and Cassia occidentalis on carbon tetrachloride induced liver damage in experimental rats. Indian Journal of Clinical Biochemistry, 22(2): 132 – 5.

Adewusi, E.A. and Afolayan, A.J.2010. A review of natural products with hepatoprotective activity. Journal of Medicinal Plants Research. 4 (13): 1318 – 34.

Gesine, P. 2007. Artificial and bio-artificial liver support. Organogesis, 3(1): 20-24.

Singh, A., Bhat, T.K.and Sharma, O.P. 2011. Clinical Biochemistry of Hepatotoxicity. J. Clinic. Toxicol., 4: 80-89.

Kumar, C.H., Ramesh, A., Kumar, J.S.and Ishaq, B.M.2011. A review on hepatoprotective activity of medicinal plants. International Journal of Pharmaceutical Sciences and Research, 2(3): 501.

Goyal, S.N., Mahajan, U.B., Chandrayan, G., Kumawat, V.S., Kamble, S., Patil, P., Agrawal, Y.O., Patil, C.R. and Ojha, S. 2016. Protective effect of oleanolic acid on oxidative injury and cellular abnormalities in doxorubicin induced cardiac toxicity in rats. Am. J. of Translational Res., 8(1): 60-69.

Lakshmi, B.V.S., Muvvala, S. and Shashank, P. 2014. Protective effect of Vitis vinifera in doxorubicin-induced oxidative stress in rats-A preliminary study.Inter. J. of Adv. in Pharmacy Med. and Bioallied Sci., 2:7-14.

Anum Munir, Shaukat Iqbal Malik, Sehar Aslam, Azhar Mehmood, Saeed Amjad, K. A. Malik,Muhammad Younis, Abbas Husain Shah, G Mujtaba Shah, 2018. “Medicinal plants are effective inhibitors of type I and II diabetes”, Pharmacophore, 9(5), 1-7.

Bath, R.K., Brar, N.K., Forouhar, F.A.and Wu, G.Y. 2014. A review of methotrexate-associated hepatotoxicity. J. Dig. Dis.,15:517-24.

Tornero Molina, J., Ballina García, F.J., Calvo Alén, J., Caracuel Ruiz, M.Á., Carbonell Abelló, J.and López Meseguer, A.2015. Recommendations for the use of methotrexate in rheumatoid arthritis: up and down scaling of the dose and administration routes. Reumatol. Clin., 6:11:18.

Te, H.S., Schiano, T.D., Kuan, S.F., Hanauer, S.B., Conjeevaram, H.S.and Baker, A.L.2000. Hepatic effects of long-term methotrexate use in the treatment of inflammatory bowel disease. Am. J. Gastroenterol., :95:3150-6.

Sotoudehmanesh, R., Anvari, B., Akhlaghi, M., Shahraeeni, S.and Kolahdoozan, S.2010. Methotrexate hepatotoxicity in patients with rheumatoid arthritis. Middle East J. Dig. Dis., 2:104-9.

Sulaiman, S.R., Ali, A.J. and Mohammed, T.A. 2015. In vitro antiplasmodial and effects of sub-chronic administration of Trichilia emetic leaves extracts. International Research Journal of Natural Sciences, 3(2): 1-15.

Ramalingam, P., Subramaniyan, V., Srinivasan, P., Jobu, G.E.and Morvin, Y. 2016. Quantitative traditional knowledge of medicinal plants used to treat livestock dieseases from Kudavasal taluk of Thiruvarur district, Tamil Nadu, India. Revista Brasileira de Farmacognosia, 26(1): 109-121.

Vuayalakshmi, S., Ranjitha, J., Devi, R. and Bhagiyalakshmi, M.2013. Pharmacological profile of Cassia occidentalis L – A Review. International journal of pharmacy and pharmaceutical science,5 (3): 29 – 33.

Shivjeet, S., Sandeep, K.S. and Ashutosh, Y. 2013. Review on cassia species: pharmacological, traditional and medicinal aspects in various countries. American Journal of Phytomedicine and Clinical Therapeutics, 1: 291- 312.

Benchennouf, A., Grigorakis, S., Loupassaki, S., Kokkalou, E. 2017. Phytochemical analysis and antioxidant activity of Lycium barbarum (Goji) cultivated in Greece. Pharmaceutical biology. 55, 596-602.

Yang, R.-f., Zhao, C., Chen, X., Chan, S.-w., Wu, J.-y. 2015. Chemical properties and bioactivities of Goji (Lycium barbarum) polysaccharides extracted by different methods. Journal of Functional Foods. 17, 903-909.

Zhang, Q., Chen, W., Zhao, J., Xi, W. 2016. Functional constituents and antioxidant activities of eight Chinese native goji genotypes. Food Chemistry. 20, 230-236.

Quality control methods for medicinal plants materials. eneva: World Health Organization;1998.

BoKang, C., Su, L., XiaoJun, L., Jun,W. ShuHong, L., QiBo, W. and ShengPing, L. 2011.Effects of Lycium Barbarum aqueous and ethanol extracts on high-fat-diet induced oxidative stress in rat liver tissue Molecules, 16, 9116-9128.

Khalifa, M.M.A., Bakr, A.G. and Osman, A.T. 2017. Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. Biomed Pharmacother., 95:529-535.

Holt, M.; Ju, C. Drug-induced liver injury. Handb. Exp. Pharmacol. 2010, 196, 3–27.

Danan, G. and Teschke, R. 2016. RUCAM in drug and herb induced liver injury: The update. Int. J. Mol. Sci., 17:14.

Sunilson, J. A.J., Muthappan, M., Amitava, D., Suraj,R. Varatharajan, R. and Promwichit, P. 2009. Hepatoprotective activity of Coccinia grandis leaves against carbon tetrachloride induced hepatic injury in rats. International Journal of pharmacology, 5(3): 222-227.

Stirnimann, G., Kessebohm, K. and Lauterburg, B. 2010. Liver injury caused by drugs: An update. Swiss Méd. Wkly., 140, 18.

Pereira C., Barros L and Ferreira I.C. 2016. Extraction, identification, fractionation and isolation of phenolic compounds in plants with hepatoprotective effects. J. Sci. Food Agric., 96:1068-84.

Kpemissi, M., Metowogo, K., Lawson-Evi, P., Eklu-Kadégbékou, K., Aklikokou, A.K. and Gbéassor, M. 2015. Hepatoprotective and antioxidant effects of Acanthospermum hispidum (DC) leaves on carbon tetrachloride-induced acute liver damage in rat. Int. J. Biol. Chem. Sci., 9(5): 2263 -71.

Jahovic, N., Sener, G., Ersoy, Y., Arbac, S.and Yˇegen, B.C.2004. Amelioration of methotrexati-induced enteritis by melatonin in rats. Cell Biochem. Funct., 22: 169- 78.

ALL, C., Ertan, B., Ergul, B.K.and Bulent, K.2006.N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats. Med. Sci. Monit.., 12 (8): BR247- 8.

Jahovic, N., Cevik, H., Sehirli, A.O., Yˇegen, B.C.and Sener, G.2003. Melatonin prevents methotraxate- induced hepatorenal oxidative injury in rats. J. Pineal. Res., 34: 282- 7.

Ducruet, J., Rébénaque, P., Diserens, S., Kosińska-Cagnazzo, A., Héritier, I. and Andlauer, W. 2017. Amber ale beer enriched with goji berries–The effect on bioactive compound content and sensorial properties. Food Chemistry, 226, 109-118.

Benchennouf, A., Grigorakis, S., Loupassaki, S.and Kokkalou, E. 2017. Phytochemical analysis and antioxidant activity of Lycium barbarum (Goji) cultivated in Greece. Pharmaceutical biology, 55, 596-602.

Khafaga A. F. and El-Sayed Y. S. 2018. Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation Life Sci., 196 9–17.

Mehrzadi, S., Fatemi, I., Esmaeilizadeh, M., Ghaznavi, H., Kalantar, H. and Goudarzi, M. 2018. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed. Pharmacother., 97 233–239.

Amagase, H., Sun B., Borek, C. 2009. Lycium barbarum (goji) juice improves in vivo antioxidant biomarkers in serum of healthy adults. Nutrition Research, 29(1):19–25.

Bucheli, P., Vidal, K., Shen, L., Gu, Z., Zhang, C., Miller, L.E.and Wang, J. 2011. Goji berry effects on macular characteristics and plasma antioxidant levels. Optom. Vis. Sci., 88(2): 257-262.

Entomology and Applied Science Letters is an international double-blind peer reviewed publication which publishes scientific research & review articles related to insects that contain information of interest to a wider audience, e.g. papers bearing on the theoretical, genetic, agricultural, medical and biodiversity issues. Emphasis is also placed on the selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance. In addition to full-length research articles and reviews, the journal publishes interpretive articles in a Forum section, Short Communications, and Letters to the Editor. The journal publishes reports on all phases of medical entomology and medical acarology, including the systematics and biology of insects, acarines, and other arthropods of public health and veterinary significance.

Announcement and Advertisement
Announcements regarding scientific activities such as conferences, symposium, are published for free. Advertisements can be either published or placed on website as banners.
open access
Entomology and Applied Science Letters supports the submission of entomological papers that contain information of interest to a wider reader groups e. g. papers bearing on taxonomy, phylogeny, biodiversity, ecology, systematic, agriculture, morphology. The selection of comprehensive, revisionary or integrated systematics studies of broader biological or zoogeographical relevance is also important. Distinguished entomologists drawn from different parts of the world serve as honorary members of the Editorial Board. The journal encompasses all the varied aspects of entomological research.