Mentha pulegium Aqueous Extract Exhibits Antidiabetic and Hepatoprotective Effects in Streptozotocin-Induced Diabetic Rats

Author(s): Omar Farid, Naoufel Ali Zeggwagh, Fadwa EL Ouadi, Mohamed Eddouks*.

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 19 , Issue 3 , 2019

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Graphical Abstract:


Objective: The aim of this work was to evaluate the antihyperglycemic activity of aerial parts aqueous extract (A.P.A.E) of Mentha pulegium (M. pulegium) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rat. The glucose tolerance was evaluated in normal rats. Moreover, the histological sections and morphometric analysis at the liver and pancreas have been carried out in this investigation both in normal and STZ-diabetic rats.

Methods: The effect of A.P.A.E of M. pulegium (20 mg/kg) on blood glucose levels was investigated in normal and diabetic rats (n=6). Histopathological changes in liver and pancreas were examined under phase contrast microscope and a preliminary screening for various bioactive constituents was realized according to standard methods.

Key Findings: Both single and repeated oral administration of A.P.A.E (20 mg/kg) caused a significant reduction in blood glucose levels in STZ-diabetic rats (p<0.0001). The morphometric analysis and histological sections realized in pancreas and liver have showed the beneficial effect of the A.P.A.E in cellular population. According to oral glucose tolerance test (OGTT), the aqueous extract has revealed an improvement of glucose tolerance in normal rat. Furthermore, the preliminary phytochemical screening of A.P.A.E of M. pulegium has demonstrated the presence of various metabolite compounds including polyphenols, flavonoids, terpenoids tannins, cyanidins, sesquiterpenes, and glycosides.

Conclusion: We conclude that the A.P.A.E of M. pulegium (20 mg/kg) exhibits a potent antihyperglycemic activity in STZ diabetic rats.

Keywords: Mentha pulegium, blood glucose, phytochemical screening, antihyperglycemic activity, streptozotocin-induced diabetic rats, oral glucose tolerance test (OGTT).

International Diabetes Federation. IDF Diabetes Atlas, 7th ed; International Diabetes Federation: Brussels, Belgium, 2015.
Mohan, H. Textbook of pathology, 5th ed; Jaypee Brothers Medical Publishers: New Delhi, 2005, p. 842.
Lyra, R.; Oliveira, M.; Lins, D.; Cavalcanti, N. Prevention of type 2 diabetess mellitus. Arq. Bras. Endocrinol. Metabol, 2006, 50(2), 239-249.
Baradaran, A.; Madihi, Y.; Merrikhi, A.; Rafieian-Kopaei, M.; Nasri, H. Serum lipoprotein (a) in diabetic patients with various renal function not yet on dialysis. Pak. J. Med. Sci., 2013, 29(1), 354-357.
Moller, D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature, 2001, 414(6865), 821-827.
Bahmani, M.; Golshahi, H.; Saki, K.; Rafieian-Kopaei, M.; Delfan, B.; Mohammadi, T. Medicinal plants and secondary metabolites for diabetes mellitus control. Asian Pac. J. Trop. Biomed., 2014, 4(2), S687-S692.
Alarcon-Aguilara, F.J.; Roman-Ramos, R.; Perez-Gutierrez, S.; Aguilar-Contreras, A.; Contreras-Weber, C.C.; Flores-Saenz, J.L. Study of the anti-hyperglycemic effect of plants used as antidiabetics. J. Ethnopharmacol., 1998, 61(2), 101-110.
Blumenthal, M. The Complete German Commission E Monographs, Therapeutic Guide to Herbal Medicines; American Botanical Council: Austin, 1999.
European Pharmacopoeia, 4th ed; Council of Europe: Strasbourg, 2002.
Naghibi, F.; Mosaddegh, M.; Motamed, S.M.; Ghorbani, A. Labiatae family in folk medicine in iran: from ethnobotany to pharmacology. Iran. J. Pharm. Res., 2005, 2, 63-79.
Dorman, H.J.; Kosar, M.; Kahlos, S.K.; Holm, Y.; Hiltunen, R. Antioxidant prosperities and composition of aqueous extracts from Menthaspecies, hybrids, varieties and cultivars. J. Agric. Food Chem., 2003, 51, 4563-4569.
Chalchat, J.C.; Gorunovic, M.S.; Maksimovic, Z.A.; Petrovic, S.D. Essential oil of wild growing Mentha pulegium L. from Yugoslavia. J. Essent. Oil Res., 2000, 12, 598-600.
Kamkar, A.; Javan, A.J.; Asadi, F.; Kamalinejad, M. The antioxidative effect of Iranian Mentha pulegium extracts and essential oilin sunflower oil. Food Chem. Toxicol., 2010, 48, 1796-1800.
Sarikurkcu, C.; Eryigit, F.; Cengiz, M.; Tepe, B.; Cakir, A.; Mete, E. Screening of the antioxidant activity of the essential oil and methanol extract of Mentha pulegium L. from Turkey. Spectrosc. Lett., 2012, 45(5), 352-358.
Mahboubi, M.; Haghi, G. Antimicrobial activity and chemical composition of Mentha pulegium L. essential oil. J. Ethnopharmacol., 2008, 119, 325-327.
Boukhebti, H.; Chaker, A.N.; Belhadj, H.; Sahli, F.; Ramdhani, M.; Laouer, H.; Harzallah, H. Chemical composition and antibacterial activity of Mentha pulegium L. and Mentha spicata L. essential oils. Der. Pharm. Lett., 2011, 3, 267-275.
Ait-ouazzou, A.; Loran, S.; Arakrak, A.; Laglaoui, A.; Rota, C.; Herrera, A.; Pagan, R.; Conchello, P. Evaluation of the chemical composition andantimicrobial activity of Mentha pulegium, Juniperusphoenicea, and Cyperus longus essential oils from Morocco. Food Res. Int., 2012, 45, 313-319.
Teixeira, B.; Marques, A.; Ramos, C.; Batista, I.; Serrano, C.; Matos, O.; Neng, R.N.; Nogueira, M.; Jose, F.; Saraive, J.A. European pennyroyal (Mentha pulegium) from Portugal: Chemical composition of essential oil and antioxidant and antimicrobial properties ofextracts and essential oil. Ind. Crops Prod., 2012, 36, 81-87.
Gulluce, M.; Sahin, F.; Sokmen, M.; Ozer, H.; Daferera, D.; Sokmen, A.; Polissiou, M.; Adiguzel, A.; Ozkan, H. Antimicrobial and antioxidant properties of the essential oilsand methanol extract from Mentha longifolia L. ssp. longifolia. Food Chem., 2007, 103, 1449-1456.
Moreno, L.; Bello, R.; Primo-Yufera, E.; Esplugues, J. Pharmacological properties of methanol extract from Mentha suaveolens Ehrh. Phytother. Res., 2002, 16, 10-13.
Mimica-Dukic, N.; Bozin, B. Mentha L. Species (Lamiaceae) as promising sources of bioactive secondary metabolites. Curr. Pharm. Des., 2008, 14, 3141-3150.
Eddouks, M.; Maghrani, M.; Lemhadri, A.; Ouahidi, M.L.; Jouad, H. Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). J. Ethnopharmacol., 2002, 82(2), 97-103.
Farid, O.; Khallouki, F.; Hajji, L.; Eddouks, M. Aqueous extract of Anabasis aretioides ameliorates streptozotocin-induced diabetes mellitus in rats. J. Nat. Prod., 2017, 7, 4.
Wagner, H.; Bladt, X.S.; Gain, Z.; Suie, E.M. Plant drug analysis; Springer Verlag: Berlin, Germany, 1996, p. 360.
Khatun, A.; Rahman, M.; Kabir, S.; Akter, M.N.; Chowdhury, S.A. Phytochemical and pharmacological properties of the methanolic extract of Ardisia humilis Vahl. (Myrsinaceae). Int. J. Res. Ayurveda Pharm., 2013, 4(1), 38-41.
Farnsworth, N.R. Biological and phytochemical screening of plants. J. Pharm. Sci., 1966, 55, 225-276.
Wall, M.E.; Wani, M.C.; Brown, D.M.; Fullas, F.; Olwald, J.B.; Josephson, F.F.; Thornton, N.M.; Pezzuto, J.M.; Beecher, C.W.; Farnsworth, N.R.; Cordell, G.A.; Kinghorn, A.D. Effect of tannins on screening of plant extracts for enzyme inhibitory activity and techniques for their removal. Phytomedicine, 1996, 3, 281-285.
Eddouks, M.; Maghrani, M.; Zeggwagh, N.A.; Michel, J.B. Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats. J. Ethnopharmacol., 2005, 97(2), 391-395.
Farid, O.; Hebi, M.; Ajebli, M. EL Hidani, A.; Eddouks M. Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats. J. Basic Clin. Physiol. Pharmacol, 2017, 1, 28(3), 275-282.
Meddah, B.; Ducroc, R.; Faouzi, M.E.A.; Eto, B.; Mahraoui, L.; Andaloussi, A.B.; Martineau, L.C.; Cherrah, Y.; Haddad, P.S. Nigella sativa inhibits intestinal glucose absorption and improves glucosetolerance in rats. J. Ethnopharmacol., 2009, 121, 419-424.
Burcelin, R.; Eddouks, M.; Maury, J.; Kande, J.; Assan, R.; Girard, J. Excessive glucose production, rather than insulin resistance, accounts for hyperglycaemia in recent-onset streptozotocin-diabetic rats. Diabetologia, 1995, 38, 283-290.
Lukic, M.L.; Stosic-Grujicic, S.; Shahin, A. Effector mechanisms in low-dose streptozotocin-induced diabetes. Dev. Comp. Immunol., 1998, 6, 119-128.
Tominaga, M.; Kimura, M.; Sugiyama, K.; Abe, T.; Igarashi, K.; Igarashi, M.; Eguchi, H.; Sekikawa, A.; Ogawa, A.; Manaka, H.; Sasaki, H. Effects of Seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotocininduced diabetic rats. Diabetes Res. Clin. Pract., 1995, 29, 11-17.
Attele, A.; Zhou, Y.P.; Xie, J.T.; Wu, J.A.; Zhang, L.; Dey, L.; Pugh, W.; Rue, P.A.; Polonsky, K.S.; Yuan, C.S. Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes, 2002, 51, 1851-1858.
Hu, X.; Sato, J.; Oshida, Y.; Xu, M.; Bajotto, G.; Sato, Y. Effect of Gosha-jinki-gan (Chinese herbal medicine: Niu-Chesen-Qi-Wan) on insulin resistance in streptozotocin-induced diabeticrats. Diabetes Res. Clin. Pract., 2003, 59, 111-130.
Deshpande, A.M.; Bhuniya, D.; De, S.; Dave, B.; Vyavahare, V.P.; Kurhade, S.H.; Kandalkar, S.R.; Naik, K.P.; Kobal, B.S.; Kaduskar, R.D.; Basu, S.; Jain, V.; Patil, P.; Joshi, S.C.; Bhat, G.; Raje, A.A.; Reddy, S.; Gundu, J.; Madgula, V.; Tambe, S.; Shitole, P.; Umrani, D.; Chugh, A.; Palle, V.P.; Mookhtiar, K.A. Discovery of liver-directed glucokinase activator having anti-hyperglycemic effect without hypoglycemia. Eur. J. Med. Chem., 2017, 133, 268-286.
Chakravarthy, B.K.; Saroj, G.; Gambhir, S.S.; Gode, K.D. Pancreatic beta cell regeneration-a novel antidiabetic mechanism of Pterocarpus marsupium roxb. Indian J. Pharmacol., 1980, 12, 123-128.
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.
Links, M.R.; Taylor, J.; Kruger, M.C.; Naidoo, V.; Taylor, JR.N. Kafirin microparticle encapsulated Sorghum condensed tannins exhibit potential as an anti-hyperglycaemic agent in a small animal model. J. Func. Foods, 2016, 20.
Cheng, J.T.; Liu, I.M.; Chi, T.C.; Su, H.C.; Chang, C.G. Metformin-like effects of queifu di huang wan, a Chinese herbalmixture, on streptozotocin-induced diabetic rat. Horm. Metab. Res., 2001, 33, 727-732.
Ugochukwu, N.H.; Babady, N.E. Antihyperglycemic effect of aqueous and ethanolic extracts of Gongroema latifolium leaves on glucose ad glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats. Life Sci., 2003, 73, 1925-1938.
Lee, K.T.; Jung, T.W.; Lee, H.J.; Kim, S.G.; Shin, Y.S.; Whang, W.K. The antidiabetic effect of genosenoside Rb2 via activation of AMPK. Arch. Pharm. Res., 2011, 34, 1201-1208.
Bahmani, M.; Saki, K.; Rafieian-Kopaei, M.; Karamati, S.A.; Eftekhari, Z.; Jelodari, M. The most common herbal medicines affecting Sarcomastigophora branches: A review study. Asian Pac. J. Trop. Biomed., 2014, 4(12), 930-937.
Eddouks, M.; Lemhadri, A.; Zeggwagh, N.A.; Michel, J-B. Potent hypoglycaemic activity of the aqueous extract of Chamaemelu nobile in normal and streptozotocin-induced diabetic rats. Diabetes Res. Clin. Pract., 2005, 67, 189-195.
Mata, A.T.; Proença, C.; Ferreira, A.R.; Serralheiro, M.L.; Nogueira, J.M.F. Arau´ jo. M.E.M. Antioxidant and antiacetylcholinesterase activities of five plants used as Portuguese food spices. Food Chem., 2007, 103, 778-786.
Badisa, R.B.; Tzakou, O.; Couladis, M.; Pilarinou, E. Cytotoxic activities of some Greek Labiatae herbs. Phytother. Res., 2003, 17(5), 472-476.
Romero-Jimenez, M.; Campos-Sanchez, J.; Analla, M.; Munoz-Serrano, A.; Alonso-Moraga, A. Genotoxicityand anti-genotoxicity of some traditional medicinal herbs. Mutat. Res., 2005, 585(1-2), 147-155.
Bouchra, C.; Achouri, M.; Idrissi-Hassani, L.M.; Hmamouchi, M. Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr. J. Ethnopharmacol., 2003, 89, 165-169.
Sivropoulou, A.; Kokkini, S.; Lanaras, T.; Arsenakis, M. Antimicrobial activity of mint essential oils. J. Agric. Food Chem., 1995, 43(9), 2384-2388.
Aruoma, O.I. Free radicals, oxidative stress, and antioxidants in human health and disease. J. Am. Oil Chem. Soc., 1998, 75(2), 199-212.
Scalbert, A.; Manach, C.; Morand, C.; Rémésy, C.; Jiménez, L. Dietary polyphenols and the prevention of diseases. Crit. Rev. Food Sci. Nutr., 2005, 45(4), 287-306.
Ingold, K.U. Inhibition of oil oxidation by 2,6-di-butyl-4-substitutedphenols. J. Phys. Chem., 1960, 64, 1636-1642.
Revathy, J.; Srinivasan, S.; Abdullah, S.H.S.; Muruganathan, U. Antihyperglycemic effect of hesperetin, a citrus flavonoid, extenuates hyperglycemia and exploring the potential role in antioxidant and antihyperlipidemic in streptozotocin-induced diabetic rats. Biomed. Pharmacother., 2018, 97, 98-106.
Tunçdemir, M.; Ertürküner, S.P.; Ozçelik, D. Investigation of lipid peroxidation and antiapoptotic effects of zinc aganist liver damage in diabetic rats. Hum. Exp. Toxicol., 2017, 36, 813-822.
Zia-ur-rehman. M.; Mirajab, K.; Mushtaq, A. Potential for Pakistani traditional medicinal plants to combat diabetes. J. Tradit. Chin. Med., 2014, 34(4), 488-490.

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Year: 2019
Page: [292 - 301]
Pages: 10
DOI: 10.2174/1871530318666181005102247
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