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Cardiovascular & Hematological Disorders-Drug Targets

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ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Research Article

Antihyperglycemic Effect of Rhamnus alaternus L. Aqueous Extract in Streptozotocin-induced Diabetic Rats

Author(s): Smail Amtaghri, Omar Farid, Nadia Lahrach, Miloudia Slaoui and Mohamed Eddouks*

Volume 22, Issue 4, 2022

Published on: 27 January, 2023

Page: [245 - 255] Pages: 11

DOI: 10.2174/1871529X23666230123123317

Price: $65

Abstract

Background: Traditionally, the aerial parts of Rhamnus alaternus L. have been widely used in Mediterranean countries, including Morocco, to cure diabetes.

Aim: This study aimed to evaluate the antidiabetic effect of Rhamnus alaternus aqueous extract in streptozotocin(STZ)-induced diabetic rats.

Objective: This work aimed to evaluate the antihyperglycemic effect of Rhamnus alaternus aqueous extract (RAAE) in normal and diabetic rats. Then the phytochemical composition, antioxidant capacity, and potential toxicity of RAAE were also assessed.

Methods: The effects of acute (6 h) and subchronic (7 days) oral administration of RAAE (20 mg/kg) on blood glucose levels and lipid profiles were evaluated in normal and diabetic rats. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity, using the DPPH method, were evaluated. Additionally, the toxicity of the aqueous extract (5 mg/kg) was also studied and the LD50 value was determined.

Results: RAAE (20 mg/kg) over 7 days of oral administration significantly decreased the blood glucose levels both in normal and diabetic rats. In diabetic rats, this extract also improved oral glucose tolerance. In addition, RAAE possessed significant antioxidant activity. According to preliminary phytochemical research, RAAE contains several chemical compounds, including alkaloids, polyphenols, flavonoids, cyanidins, anthraquinones, and sterols. On the other hand, the quantitative phytochemical study of the aqueous extract revealed a considerable amount of total phenolic compounds (497.93 ± 3.38 mg GAE/1g of RAAE), flavonoids (100.42 ± 0.32 mg RE/ g of RAAE), and tannins (14.32 ± 0.37 mg CE/1g of RAAE).

Conclusion: We conclude that RAAE exerts a significant antihyperglycemic effect in STZ-induced diabetic rats at a low dose. Indeed, more research is still required to support the use of this plant in the Moroccan population's diabetes care.

[1]
Umar, A.; Ahmed, Q.U.; Muhammad, B.Y.; Dogarai, B.B.S.; Soad, S.Z.B.M. Anti-hyperglycemic activity of the leaves of Tetracera scandens Linn. Merr. (Dilleniaceae) in alloxan induced diabetic rats. J. Ethnopharmacol., 2010, 131(1), 140-145.
[http://dx.doi.org/10.1016/j.jep.2010.06.016] [PMID: 20600771]
[2]
Wild, S.; Roglic, G.; Green, A.; Sicree, R.; King, H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care, 2004, 27(5), 1047-1053.
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[3]
Dewanjee, S.; Das, A.K.; Sahu, R.; Gangopadhyay, M. Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes. Food Chem. Toxicol., 2009, 47(10), 2679-2685.
[http://dx.doi.org/10.1016/j.fct.2009.07.038] [PMID: 19660513]
[4]
Selamoglu, Z. The natural products and healthy life. J. Trad. Med. Clin. Naturopathy, 2018, 7(2), 1-2.
[5]
Selamoglu, Z. Polyphenolic compounds in human health with pharmacological properties. J. Trad. Med. Clin. Naturopathy, 2017, 2076(4), 137.
[6]
Selamoglu, Z. Biotechnological approaches on anticancer activity of flavonoids. Mod. Approach. Drug Des., 2017, 1(2), 510.
[7]
Ben Ammar, R.; Kilani, S.; Abdelwahed, A.; Hayder, N.; Mahmoud, A.; Chibani, J.; Ghedira, K. In vitro mutagenicity, antimutagenicity and free radical scavenging activities of Rhamnus alaternus L.(Rhamnaceae) extracts. Pak. J. Biol. Sci., 2005, 8(3), 439-445.
[http://dx.doi.org/10.3923/pjbs.2005.439.445]
[8]
Bas, J.M.; Oliveras, J.; Gómez, C. Myrmecochory and short-term seed fate in Rhamnus alaternus: Ant species and seed characteristics. Acta Oecol., 2009, 35(3), 380-384.
[http://dx.doi.org/10.1016/j.actao.2009.02.003]
[9]
Ben Ammar, R.; Kilani, S.; Bouhlel, I.; Ezzi, L.; Skandrani, I.; Boubaker, J.; Ben Sghaier, M.; Naffeti, A.; Mahmoud, A.; Chekir-Ghedira, L.; Ghedira, K. Antiproliferative, antioxidant, and antimutagenic activities of flavonoid-enriched extracts from (Tunisian) Rhamnus alaternus L.: combination with the phytochemical composition. Drug Chem. Toxicol., 2008, 31(1), 61-80.
[http://dx.doi.org/10.1080/01480540701688725] [PMID: 18161508]
[10]
Boukef, K. Rhamnus alaternus. Essaydali, 2001, 81, 34-35.
[11]
Mati, E.; de Boer, H. Ethnobotany and trade of medicinal plants in the Qaysari Market, Kurdish Autonomous Region, Iraq. J. Ethnopharmacol., 2011, 133(2), 490-510.
[http://dx.doi.org/10.1016/j.jep.2010.10.023] [PMID: 20965241]
[12]
Lardos, A. The botanical materia medica of the Iatrosophikon—A collection of prescriptions from a monastery in Cyprus. J. Ethnopharmacol., 2006, 104(3), 387-406.
[http://dx.doi.org/10.1016/j.jep.2005.12.035] [PMID: 16459038]
[13]
Guarrera, P.M. Household dyeing plants and traditional uses in some areas of Italy. J. Ethnobiol. Ethnomed., 2006, 2(1), 9.
[http://dx.doi.org/10.1186/1746-4269-2-9] [PMID: 16457717]
[14]
Ben Ammar, R.; Kilani, S.; Bouhlel, I.; Skandrani, I.; Naffeti, A.; Boubaker, J.; Ben Sghaier, M.; Bhouri, W.; Mahmoud, A.; Chekir-Ghedira, L.; Ghedira, K. Antibacterial and cytotoxic activities of extracts from (Tunisian) Rhamnus alaternus (Rhamnaceae). Ann. Microbiol., 2007, 57(3), 453-460.
[http://dx.doi.org/10.1007/BF03175089]
[15]
Ammar, R.B.; Sghaier, M.B.; Boubaker, J.; Bhouri, W.; Naffeti, A.; Skandrani, I.; Bouhlel, I.; Kilani, S.; Ghedira, K.; Chekir-Ghedira, L. Antioxidant activity and inhibition of aflatoxin B1-, nifuroxazide-, and sodium azide-induced mutagenicity by extracts from Rhamnus alaternus L. Chem. Biol. Interact., 2008, 174(1), 1-10.
[http://dx.doi.org/10.1016/j.cbi.2008.04.006] [PMID: 18511029]
[16]
Ammar, R.B.; Bouhlel, I.; Valenti, K.; Sghaier, M.B.; Kilani, S.; Mariotte, A.M.; Dijoux-Franca, M.G.; Laporte, F.; Ghedira, K.; Chekir-Ghedira, L. Transcriptional response of genes involved in cell defense system in human cells stressed by H2O2 and pre-treated with (Tunisian) Rhamnus alaternus extracts: Combination with polyphenolic compounds and classic in vitro assays. Chem. Biol. Interact., 2007, 168(3), 171-183.
[http://dx.doi.org/10.1016/j.cbi.2007.04.002] [PMID: 17512922]
[17]
Tacherfiout, M.; Petrov, P.D.; Mattonai, M.; Ribechini, E.; Ribot, J.; Bonet, M.L.; Khettal, B. Antihyperlipidemic effect of a Rhamnus alaternus leaf extract in Triton-induced hyperlipidemic rats and human HepG2 cells. Biomed. Pharmacother., 2018, 101, 501-509.
[http://dx.doi.org/10.1016/j.biopha.2018.02.106] [PMID: 29501772]
[18]
Stocker, P.; Yousfi, M.; Djerridane, O.; Perrier, J.; Amziani, R.; El Boustani, S.; Moulin, A. Effect of flavonoids from various Mediterranean plants on enzymatic activity of intestinal carboxylesterase. Biochimie, 2004, 86(12), 919-925.
[http://dx.doi.org/10.1016/j.biochi.2004.09.005] [PMID: 15667942]
[19]
Bhouri, W.; Sghaier, M.B.; Kilani, S.; Bouhlel, I.; Dijoux-Franca, M.G.; Ghedira, K.; Ghedira, L.C. Evaluation of antioxidant and antigenotoxic activity of two flavonoids from Rhamnus alaternus L. (Rhamnaceae): Kaempferol 3-O-β-isorhamninoside and rhamnocitrin 3-O-β-isorhamninoside. Food Chem. Toxicol., 2011, 49(5), 1167-1173.
[http://dx.doi.org/10.1016/j.fct.2011.02.011] [PMID: 21338653]
[20]
Moussi, K.; Nayak, B.; Perkins, L.B.; Dahmoune, F.; Madani, K.; Chibane, M. HPLC-DAD profile of phenolic compounds and antioxidant activity of leaves extract of Rhamnus alaternus L. Ind. Crops Prod., 2015, 74, 858-866.
[http://dx.doi.org/10.1016/j.indcrop.2015.06.015]
[21]
Ajebli, M.; Eddouks, M. Buxus sempervirens L. Improves Streptozotocin-induced Diabetes Mellitus in Rats. Cardiovasc. Hematol. Disord. Drug Targets, 2017, 17(2), 142-152.
[PMID: 28925906]
[22]
Ajebli, M.; Eddouks, M. Pharmacological and phytochemical study of Mentha suaveolens Ehrh in normal and streptozotocin-induced diabetic rats. Nat. Prod. J., 2018, 8(3), 213-227.
[http://dx.doi.org/10.2174/2210315508666180327120434]
[23]
Bouhlali, E.D.T.; Alem, C.; Zegzouti, Y.F. Antioxidant and anti-hemolytic activities of phenolic constituents of six moroccan date fruit (Phoenix dactylifera L.) syrups. Biotechnol Indian J, 2016, 12(1), 45-52.
[24]
Kim, D.O.; Jeong, S.W.; Lee, C.Y. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem., 2003, 81(3), 321-326.
[http://dx.doi.org/10.1016/S0308-8146(02)00423-5]
[25]
Broadhurst, R.B.; Jones, W.T. Analysis of condensed tannins using acidified vanillin. J. Sci. Food Agric., 1978, 29(9), 788-794.
[http://dx.doi.org/10.1002/jsfa.2740290908]
[26]
Blois, M.S. Antioxidant determinations by the use of a stable free radical. Nature, 1958, 181(4617), 1199-1200.
[http://dx.doi.org/10.1038/1811199a0]
[27]
Hebi, M.; Eddouks, M. Evaluation of the antioxidant activity of Stevia rebaudiana. Phytotherapie, 2016, 14(1), 17-22.
[http://dx.doi.org/10.1007/s10298-015-0999-y]
[28]
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]
[29]
Ajebli, M.; Eddouks, M. Flavonoid-enriched extract from desert plant warionia saharae improves glucose and cholesterol levels in diabetic rats. Cardiovasc. Hematol. Agents Med. Chem., 2019, 17(1), 28-39.
[http://dx.doi.org/10.2174/1871525717666190121143934] [PMID: 30666919]
[30]
OECD, T.N. Acute oral toxicity: Acute toxic class method. Test Guideline, 2001, 423.
[31]
Twaij, H.A.A.; Kery, A.; Al-Khazraji, N.K. Some pharmacological, toxicological and phytochemical investigations on Centaurea phyllocephala. J. Ethnopharmacol., 1983, 9(2-3), 299-314.
[http://dx.doi.org/10.1016/0378-8741(83)90037-5] [PMID: 6677820]
[32]
El Allaoui, A.; Rhazi Filali, F.; Oumokhtar, B.; Ibijbijen, J. Evaluation of the acute toxicity of the dye (Rhodamine B) used in the manufacture of traditional sausages in the city of Meknes in Morocco. La Science en Liberté, 2011, 3, 1-15.
[33]
Kapuriya, P.B.; Sadariya, K.A.; Bhavsar, S.K.; Thaker, A.M. Antidiabetic activity of aqueous extracts of Linum usitatissimum in streptozotocin induced diabetic rats. The Pharma. Innov. J., 2018, 7(7), 149-154.
[34]
Gauthier, E.L. Streptozotocin: Uses, mechanism of action and side effects; Nova Science Publishers, Incorporated, 2014.
[35]
Sreejesh, P.G.; Thampi, B.H.; Sreekumaran, E. Hypoglycaemic effect of glibenclamide: A critical study on the basis of creatinine and lipid peroxidation status of streptozotocin-induced diabetic rat. Indian J. Pharm. Sci., 2017, 79(5), 768-777.
[36]
Schmatz, R.; Perreira, L.B.; Stefanello, N.; Mazzanti, C.; Spanevello, R.; Gutierres, J.; Bagatini, M.; Martins, C.C.; Abdalla, F.H.; Daci da Silva Serres, J.; Zanini, D.; Vieira, J.M.; Cardoso, A.M.; Schetinger, M.R.; Morsch, V.M. Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie, 2012, 94(2), 374-383.
[http://dx.doi.org/10.1016/j.biochi.2011.08.005] [PMID: 21864646]
[37]
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]
[38]
Rochette, L.; Zeller, M.; Cottin, Y.; Vergely, C. Diabetes, oxidative stress and therapeutic strategies. Biochim. Biophys. Acta, Gen. Subj., 2014, 1840(9), 2709-2729.
[http://dx.doi.org/10.1016/j.bbagen.2014.05.017] [PMID: 24905298]
[39]
Zeouk, I.; Ouedrhiri, W.; Jiménez, I.A.; Lorenzo-Morales, J.; Bazzocchi, I.L.; Bekhti, K. Intra-combined antioxidant activity and chemical characterization of three fractions from Rhamnus alaternus extract: Mixture design. Ind. Crops Prod., 2020, 144, 112054.
[http://dx.doi.org/10.1016/j.indcrop.2019.112054]
[40]
Benzaid, C.; Tichati, L.; Trea, F.; Rouabhia, M.; Ouali, K. Rhamnus alaternus aqueous extract enhances the capacity of system redox defence and protects hepatocytes against aluminum chloride toxicity in rats. Clinical Phytoscience, 2021, 7(1), 67.
[http://dx.doi.org/10.1186/s40816-021-00302-3]
[41]
Corbi, G.; Conti, V.; Komici, K.; Manzo, V.; Filippelli, A.; Palazzo, M.; Vizzari, F.; Davinelli, S.; Di Costanzo, A.; Scapagnini, G.; Ferrara, N.; Casamassima, D. Phenolic plant extracts induce sirt1 activity and increase antioxidant levels in the rabbit’s heart and liver. Oxid. Med. Cell. Longev., 2018, 2018, 2731289.
[http://dx.doi.org/10.1155/2018/2731289] [PMID: 30116475]
[42]
Zhang, D.; Li, M. Puerarin prevents cataract development and progression in diabetic rats through Nrf2/HO- 1 signaling. Mol. Med. Rep., 2019, 20(2), 1017-1024.
[http://dx.doi.org/10.3892/mmr.2019.10320] [PMID: 31173182]
[43]
Strycharz, J.; Rygielska, Z.; Swiderska, E.; Drzewoski, J.; Szemraj, J.; Szmigiero, L.; Sliwinska, A. SIRT1 as a therapeutic target in diabetic complications. Curr. Med. Chem., 2018, 25(9), 1002-1035.
[http://dx.doi.org/10.2174/0929867324666171107103114] [PMID: 29110598]
[44]
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]
[45]
Imran, A.; Butt, M.S.; Arshad, M.S.; Arshad, M.U.; Saeed, F.; Sohaib, M.; Munir, R. Exploring the potential of black tea based flavonoids against hyperlipidemia related disorders. Lipids Health Dis., 2018, 17(1), 57.
[http://dx.doi.org/10.1186/s12944-018-0688-6] [PMID: 29592809]
[46]
Krishnaraju, A.V.; Rao, T.V.; Sundararaju, D.; Vanisree, M.; Tsay, H.S.; Subbaraju, G.V. Assessment of bioactivity of Indian medicinal plants using brine shrimp (Artemia salina) lethality assay. Int. J. Appl. Sci. Eng, 2005, 3(2), 125-134.
[47]
Kharchoufa, L.; Bouhrim, M.; Bencheikh, N.; El Assri, S.; Amirou, A.; Yamani, A.; Choukri, M.; Mekhfi, H.; Elachouri, M. Acute and subacute toxicity studies of the aqueous extract from Haloxylon scoparium pomel (Hammada scoparia (Pomel)) by oral administration in rodents. BioMed Res. Int., 2020, 2020, 1-11.
[http://dx.doi.org/10.1155/2020/4020647] [PMID: 33123573]

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