Effect of Terebinthus atlanticus on Glucose Metabolism in Diabetic Rats

Author(s): Fadwa El-Ouady, Lhoussaine Hajji, Mohamed Eddouks*

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
Formerly Current Drug Targets - Cardiovascular & Hematological Disorders

Volume 20 , Issue 1 , 2020

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Graphical Abstract:


Background: Terebinthus atlanticus (Anacardiaceae) is an important source of essential oil and phenolic compounds justifying its use in traditional medicine.

Objective: The present work aimed to evaluate the antidiabetic and the antioxidant activities of the aqueous extract of the leaves of Terebinthus atlanticus (T. atlanticus).

Methods: The current study evaluated the effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of the leaves of T. atlanticus (PALAE) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rats. Furthermore, the effect of PALAE on glucose tolerance and histopathological examination of the liver was carried out.

Results: A single oral administration of PALAE reduced blood glucose levels in normal (p<0.05), and STZ diabetic rats (p<0.0001), 6 and 4 hours after administration, respectively. Furthermore, this extract had an optimal effect (p<0.0001) in both normal and STZ diabetic rats at the 15th and 7th day of treatment. This extract was also shown to prevent significantly the increase on blood glucose levels 120 min after glucose administration, in both normal (p<0.05), and diabetic (p<0.01) treated rats when compared to the control group. In addition, the histopathological analysis highlighted the positive effect of T. atlanticus on pancreas and liver.

Conclusion: The study demonstrates the antihyperglycemic effect of the aqueous T. atlanticus extracts in diabetic rats which should be mediated through the amelioration of the oxidative stress as well as an improvement in liver histology.

Keywords: Glucose tolerance, histopathological changes, streptozotocin, T. atlanticus, diabetes mellitus, gastrointestinal disorders.

Aboelsoud, N H Herbal medicine in ancient Egypt. J. Med. Plants Res, 2010, 4(2), 082-086.
UNESCO. Culture and Health, Orientation texts-World.Decade for Cultural Development Documents CLT/DEC. PROParis: France, 1996, 29.
Bailey, C.J.; Day, C. Traditional plant medicines as treatments for diabetes. Diabetes Care, 1989, 12(8), 553-564.
[http://dx.doi.org/10.2337/diacare.12.8.553] [PMID: 2673695]
Ghosh, R.; Sharatchandra, Kh.; Rita, S.; Thokchom, I.S. Hypoglycemic activity of Ficus hispida (bark) in normal and diabetic albino rats. Indian J. Pharmacol., 2004, 4, 222-225.
Khelil, A.; Kellal, A. Possibilité de culture et délimitationdes zones à vocation pistachier en Algérie. Fruits, 1980, 35, 177-185.
Moghtader, M. Comparative survey on the essential oilcomposition from the leaves and fruits of Pistacia mutica FischerKerman Province. MEJSR, 2010, 5, 291-297.
Saffarzadeh, A.; Vincze, L.; Csapo, J. Determination of the chemical composition of acorn (Quercus branti), Pistacia atlantica and Pistacia khinjuk seed as non-conventional feedstuffs. Acta Agric Kaposvar., 1999, 3(3), 59-69.
Monjause, A. Connaissance du bétoum Pistacia atlanticaDesf. Biologie et foret. Rev. For. Fr., 1980, 4, 357-363.
Quézel, P.; Santa, S. Nouvelle flore de l’Algérie et des régions désertiques méridionales. Tome 2. Centre national de la recherche scientifique, 1963.
Ozenda, P. Flore du Sahara. 2ème éd. Centre national de la recherche scientifique, 1983.
Yousfi, M. Étude des fractions lipidiques et phénoliques du Pistachier de l’atlas (Pistacia atlantica), de la gale et du champignon inonotus hispidus associé. Edition Marseille., 2006, 3, 219.
Benhamou, N.; Atik Bekkara, F.; Kadifkova Panovska, T. Antioxidant and antimicrobial activities of the Pistacia lentiscus and Pistacia atlantica extracts. Afr. J. Pharm. Pharmacol., 2008, 2, 22-28.
Gourine, N.; Bombarda, I.; Yousfi, M.; Gaydou, E.M. Chemotypes of Pistacia atlantica leaf essential oils from Algeria. Nat. Prod. Commun., 2010, 5(1), 115-120.
[http://dx.doi.org/10.1177/1934578X1000500128] [PMID: 20184035]
Eddouks, M.; Ajebli, M.; Hebi, M. Ethnopharmacological survey of medicinal plants used in Daraa-Tafilalet region (Province of Errachidia), Morocco. J. Ethnopharmacol., 2017, 198, 516-530.
[http://dx.doi.org/10.1016/j.jep.2016.12.017] [PMID: 28003130]
Giner-Larza, E.M.; Máñez, S.; Giner-Pons, R.M.; Carmen Recio, M.; Ríos, J.L. On the anti-inflammatory and anti-phospholipase A(2) activity of extracts from lanostane-rich species. J. Ethnopharmacol., 2000, 73(1-2), 61-69.
[http://dx.doi.org/10.1016/S0378-8741(00)00276-2] [PMID: 11025140]
Dedoussis, G.V.Z.; Kaliora, A.C.; Psarras, S.; Chiou, A.; Mylona, A.; Papadopoulos, N.G.; Andrikopoulos, N.K. Antiatherogenic effect of Pistacia lentiscus via GSH restoration and downregulation of CD36 mRNA expression. Atherosclerosis, 2004, 174(2), 293-303.
[http://dx.doi.org/10.1016/j.atherosclerosis.2004.02.011] [PMID: 15136059]
Hamdan, I.I.; Afifi, F.U. Studies on the in vitro and in vivo hypoglycemic activities of some medicinal plants used in treatment of diabetes in Jordanian traditional medicine. J. Ethnopharmacol., 2004, 93(1), 117-121.
[http://dx.doi.org/10.1016/j.jep.2004.03.033] [PMID: 15182916]
Ghalem, BR.; Mohamed, B. Essential oil from gum of Pistacia atlantica Desf.: screening of antimicrobial activity. African. J Pharm Pharmacol, 2009, 3(3), 087-091.
Peksel, A.; Arisan-Atac, I.; Yanardag, R. Evaluation of antioxidant and antiacetylcholinesterase activities of the extracts of Pistachia atlantica Desf. Leaves. J. Food Biochem., 2010, 34, 451-476.
Mahmoudvand, H.; Saedi Dezaki, E.; Ezatpour, B.; Sharifi, I.; Kheirandish, F.; Rashidipour, M. In Vitro and In Vivo Antileishmanial Activities of Pistacia vera Essential Oil. Planta Med., 2016, 82(4), 279-284.
[http://dx.doi.org/10.1055/s-0035-1558209] [PMID: 26829519]
Rouhi-Boroujeni, H.; Heidarian, E.; Deris, F. Rafieian –Kopaei M. Extract of Pistachia atlantica L. on hyperlipidemia and biomarkers of oxidative stress in rats fed a high- fat diet and hypoglycemic effect in diabetic rats induced with alloxan. IIOAB J., 2017, 8(2), 58-64.
Ajebli, M.; Eddouks, M. Pharmacological and Phytochemical Study of Mentha suaveolens Ehrh in Normal and Streptozotocin-induced Diabetic Rats. Nat. Prod. J., 2018, 8, 1-15.
Hebi, M.; Eddouks, M. Glucose Lowering Activity of Anvillea Radiata Coss & Durieu in Diabetic Rats. Cardiovasc. Hematol. Disord. Drug Targets, 2018, 18(1), 71-80.
[http://dx.doi.org/10.2174/1871529X18666180223100427] [PMID: 29473527]
Hebi, M.; Farid, O.; Ajebli, M.; Eddouks, M. Potent antihyperglycemic and hypoglycemic effect of Tamarix articulata Vahl. in normal and streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2017, 87, 230-239.
[http://dx.doi.org/10.1016/j.biopha.2016.12.111] [PMID: 28061406]
Hashemnia, M.; Oryan, A.; Hamidi, A.R.; Mohammadalipour, A. Blood glucose levels and pathology of organs in alloxan-induced diabetic rats treated with hydro-ethanol extracts of Allium sativum and Capparis spinosa. Afr. J. Pharm. Pharmacol., 2012, 6(21), 1559-1564.
Cohen, P.; Goedert, M. GSK3 inhibitors: development and therapeutic potential. Nat. Rev. Drug Discov., 2004, 3(6), 479-487.
[http://dx.doi.org/10.1038/nrd1415] [PMID: 15173837]
Kolterman, O.G.; Gray, R.S.; Shapiro, G.; Scarlett, J.A.; Griffin, J.; Olefsky, J.M. The acute and chronic effects of sulfonylurea therapy in type II diabetic subjects. Diabetes, 1984, 33(4), 346-354.
[http://dx.doi.org/10.2337/diab.33.4.346] [PMID: 6423429]
Lebovitz, H.E.; Feinglos, M.N.; Bucholtz, H.K.; Lebovitz, F.L. Potentiation of insulin action: a probable mechanism for the anti-diabetic action of sulfonylurea drugs. J. Clin. Endocrinol. Metab., 1977, 45(3), 601-604.
[http://dx.doi.org/10.1210/jcem-45-3-601] [PMID: 903405]
Simonson, D.C.; Ferrannini, E.; Bevilacqua, S.; Smith, D.; Barrett, E.; Carlson, R.; DeFronzo, R.A. Mechanism of improvement in glucose metabolism after chronic glyburide therapy. Diabetes, 1984, 33(9), 838-845.
[http://dx.doi.org/10.2337/diab.33.9.838] [PMID: 6432610]
Wolff, S.P. Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br. Med. Bull., 1993, 49(3), 642-652.
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a072637] [PMID: 8221029]
Sathishsekar, D.; Subramanian, S. Antioxidant properties of Momordica Charantia (bitter gourd) seeds on Streptozotocin induced diabetic rats. Asia Pac. J. Clin. Nutr., 2005, 14(2), 153-158.
[PMID: 15927932]
Abdollahi, M.; Zuki, A.B.Z.; Goh, Y.M.; Rezaeizadeh, A.; Noordin, M.M. The effects of Momordiaca charantia on the liver in streptozotocin-induced diabetes in neonatal rats. Afr. J. Biotechnol., 2010, 9(31), 5004-5012.
Dawei, G.; Li, Q. Yusheng Fan JP. Antioxidant phenyl propanoid esters of triterpenes from dioclea lasiophylla. Biol., 2004, 42, 36-38.
Yoshikawa, M.; Shimada, H.; Nishida, N.; Li, Y.; Toguchida, I.; Yamahara, J.; Matsuda, H. Antidiabetic principles of natural medicines. II. Aldose reductase and alpha-glucosidase inhibitors from Brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtaceae): Structures of myrciacitrins I and II and myrciaphenones A and B. Chem. Pharm. Bull. (Tokyo), 1998, 46(1), 113-119.
[http://dx.doi.org/10.1248/cpb.46.113] [PMID: 9468642]
Pan, H.Z.; Chang, D.; Feng, L.G.; Xu, F.J.; Kuang, H.Y.; Lu, M.J. Oxidative damage to DNA and its relationship with diabetic complications. Biomed. Environ. Sci., 2007, 20(2), 160-163.
[PMID: 17624192]
Maritim, A.C.; Sanders, R.A.; Watkins, J.B. III Diabetes, oxidative stress, and antioxidants: a review. J. Biochem. Mol. Toxicol., 2003, 17(1), 24-38.
[http://dx.doi.org/10.1002/jbt.10058] [PMID: 12616644]
Chung, S.S.M.; Ho, E.C.M.; Lam, K.S.L.; Chung, S.K.; Chung, S.K. Contribution of polyol pathway to diabetes-induced oxidative stress. J. Am. Soc. Nephrol., 2003, 14(8)(Suppl. 3), S233-S236.
[http://dx.doi.org/10.1097/01.ASN.0000077408.15865.06] [PMID: 12874437]
MIN D.B. Lipid oxidation of edible oil.Akoh, C.C.; Min, D.B., Eds.; Food Lipids Chemistry. Nutrition and Biotechnol, 1998, 283-296.
Ceriello, A. Postprandial hyperglycemia and diabetes complications. Diabetes, 2005, 54(1), 1-7.
Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 2001, 414(6865), 821-827.
[http://dx.doi.org/10.1038/414821a] [PMID: 11742415]
Chakravarthy, B.K.; Saroj, G.; Gambhir, S.S.; Gode, K.D. Pancreatic beta cell regeneration-a novel antidiabetic mechanism of Pterocarpus marsupium roxb. Int. J. Pharmacol., 1980, 12, 123-128.
Hashemnia, M.; Nikousefat, Z.; Yazdani-Rostam, M. Antidiabetic effect of Pistacia atlantica and Amygdalus scoparia in streptozotocin-induced diabetic mice. Comp. Clin. Pathol., 2015, 24(6), 1301-1306.
Ansari, S.H.; Ali, M.; Quadry, J.S. Tree new tetracyclic triterpenoids from Pistacia integerrima galls. Pharmazie, 1993, 49, 356-357.
Monaco, P.; Previtera, L.; Mangoni, L. Terpenes in Pistacia plants: A possible defence role for monoterpenes against gall-forming aphids. Phytochemistry, 1982, 21, 2408-2410.
Caputo, R.; Mangoni, L.; Monaco, P.; Palumbo, G. Triterpenes of galls of Pistacia terebinthus galls produced by Pemphigus utricularius. Phytochemistry, 1975, 14, 809-811.
Caputo, R.; Mangoni, L.; Monaco, P.; Palumbo, G.; Aynehchim, Y.; Bagheri, M. Triterpenes from bled resin of Pistacia vera. Phytochemistry, 1978, 17, 815-817.
Kawashty, S.A.; Mosharrafa, S.A.; El-Gibali, M.; Saleh, N.A.M. The flavonoids of four Pistacia species in Egypt. Biochem. Syst. Ecol., 2000, 28(9), 915-917.
[http://dx.doi.org/10.1016/S0305-1978(99)00113-1] [PMID: 10913855]
Shi, Q.; Zuo, C. Chemical components of the leaves of Pistacia chinensis Bge. Zhongguo Zhongyao Zazhi, 1992, 17(7), 422-423, 446.
[PMID: 1445648]
Zhao, X.; Sun, H.; Hou, A.; Zhao, Q.; Wei, T.; Xin, W. Antioxidant properties of two gallotannins isolated from the leaves of Pistacia weinmannifolia. Biochim. Biophys. Acta, 2005, 1725(1), 103-110.
[http://dx.doi.org/10.1016/j.bbagen.2005.04.015] [PMID: 15925448]
Yousfi, M.; Djeridane, A.; Bombarda, I.; Duhem, B.; Gaydou, E.M.; Gaydou, E.M. Isolation and characterization of a new hispolone derivative from antioxidant extracts of Pistacia atlantica. Phytother. Res., 2009, 23(9), 1237-1242.
[http://dx.doi.org/10.1002/ptr.2543] [PMID: 19274680]
Latha, R.C.; Daisy, P. Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats. Chem. Biol. Interact., 2011, 189(1-2), 112-118.
[http://dx.doi.org/10.1016/j.cbi.2010.11.005] [PMID: 21078310]
Punithavathi, V.R.; Prince, P.S.M.; Kumar, R.; Selvakumari, J. Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur. J. Pharmacol., 2011, 650(1), 465-471.
[http://dx.doi.org/10.1016/j.ejphar.2010.08.059] [PMID: 20863784]
Gandhi, G.R.; Jothi, G.; Antony, P.J.; Balakrishna, K.; Paulraj, M.G.; Ignacimuthu, S.; Stalin, A.; Al-Dhabi, N.A. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway. Eur. J. Pharmacol., 2014, 745, 201-216.
[http://dx.doi.org/10.1016/j.ejphar.2014.10.044] [PMID: 25445038]
Ahmed, Z.B.; Yousfi, M.; Viaene, J.; Dejaegher, B.; Demeyer, K.; Mangelings, D.; Vander Heyden, Y. Potentially antidiabetic and antihypertensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting. J. Pharm. Biomed. Anal., 2018, 149, 547-556.
[http://dx.doi.org/10.1016/j.jpba.2017.11.049] [PMID: 29190580]
Furman, B.L.; Candasamy, M.; Bhattamisra, S.K.; Veettil, S.K. Reduction of blood glucose by plant extracts and their use in the treatment of diabetes mellitus; discrepancies in effectiveness between animal and human studies. J. Ethnopharmacol., 2020, 247, 112264
[http://dx.doi.org/10.1016/j.jep.2019.112264] [http://dx.doi.org/10.1016/j.jep.2004.03.033] [PMID: 15182916]
Aganga, A.A.; Mosase, K.W. Tannins content, nutritive value and dry matter digestibility of Lonchocarous capussa, Ziziphus mucropata, Sclerocarya birrea, Kirkia acuminata and Rhus lancea seeds. Anim. Feed Sci. Technol., 2001, 91, 107-113.

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Year: 2020
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DOI: 10.2174/1871529X19666190902124018

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