Abstract
Background: Diabetes mellitus is associated with high blood glucose levels due to insulin shortcoming (insulinopenia) or defective insulin action. The objective of the study was to investigate the antidiabetic and antioxidant effects of Foeniculum vulgare in streptozotocin-induced diabetic rat.
Methods: The effects of the leaves aqueous extract (LAE) of Foeniculum vulgare (F. vulgare) at a dose of 10 mg/kg on blood glucose levels were evaluated in normal and streptozotocin (STZ)- induced diabetic rats. Histopathological changes were also evaluated in liver in STZ-induced rats.
Results: Single oral administration of F. vulgare LAE reduced blood glucose levels 6 h after administration in STZ diabetic rats (p<0.0001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after the fifteenth day of treatment. During this test, both groups did not show any significant change in their body weight. Moreover, this aqueous extract improved oral glucose tolerance in diabetic rats and revealed a positive effect on liver histology. On the other hand, the extract used in this experiment showed an inhibitory concentration (IC50) of 50% of free radicals with a concentration of 43±1.19 µg/ml. While the synthetic antioxidant (BHT) had an IC50 equal to 22.67±2.17µg /ml.
Conclusion: This study demonstrates the antihyperglycemic, hypoglycemic and antioxidant effects of the leaves of F. vulgare in normal and diabetic rats.
Keywords: Glucose tolerance, histopathological changes, streptozotocin, Foeniculum vulgare, insulin, chronic pathology.
Graphical Abstract
[1]
Ajebli, M.; Eddouks, M. Buxus sempervirens L improves streptozotocin-induced diabetes mellitus in rats. Cardiovasc. Hematol. Disord. Drug Targets, 2017, 17(2), 142-152.
[http://dx.doi.org/10.2174/1871529X17666170918140817] [PMID: 28925906]
[http://dx.doi.org/10.2174/1871529X17666170918140817] [PMID: 28925906]
[2]
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]
[http://dx.doi.org/10.1016/j.biopha.2016.12.111] [PMID: 28061406]
[3]
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]
[http://dx.doi.org/10.2337/diacare.12.8.553] [PMID: 2673695]
[4]
Faudale, M.; Viladomat, F.; Bastida, J.; Poli, F.; Codina, C. Antioxidant activity and phenolic composition of wild, edible, and medicinal fennel from different Mediterranean countries. J. Agric. Food Chem., 2008, 56(6), 1912-1920.
[http://dx.doi.org/10.1021/jf073083c] [PMID: 18303817]
[http://dx.doi.org/10.1021/jf073083c] [PMID: 18303817]
[5]
Hilmi, Y.; Abushama, M.F.; Abdalgadir, H.; Khalid, A.; Khalid, H. A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of selected traditional Sudanese plants with anti-diabetic potential. BMC Complement. Altern. Med., 2014, 14, 149.
[http://dx.doi.org/10.1186/1472-6882-14-149] [PMID: 24885334]
[http://dx.doi.org/10.1186/1472-6882-14-149] [PMID: 24885334]
[6]
Abed, K.F. Antimicrobial activity of essential oils of some medicinal plantsfrom Saudi Arabia. Saudi J. Biol. Sci., 2007, 14, 53-60.
[7]
Mohsenzadeh, M. Evaluation of antibacterial activity of selected Iranian essential oils against Staphylococcus aureus and Escherichia coli in nutrient broth medium. Pak. J. Biol. Sci., 2007, 10(20), 3693-3697.
[http://dx.doi.org/10.3923/pjbs.2007.3693.3697] [PMID: 19093484]
[http://dx.doi.org/10.3923/pjbs.2007.3693.3697] [PMID: 19093484]
[8]
Abou El-Soud, N.; El-Laithy, N.; El-Saeed, G.; Wahby, M.S.; Khalil, M.; Morsy, F.; Shaffie, N. Antidiabetic activities of FoeniculumvulgareMill. Essential oil instreptozotocin-induced diabetic rats. Maced. J. Med. Sci., 2011, 4, 139-146.
[9]
Ozbek, H.; Uğraş, S.; Dülger, H.; Bayram, I.; Tuncer, I.; Oztürk, G.; Oztürk, A. Hepatoprotective effect of Foeniculum vulgare essential oil. Fitoterapia, 2003, 74(3), 317-319.
[http://dx.doi.org/10.1016/S0367-326X(03)00028-5] [PMID: 12727504]
[http://dx.doi.org/10.1016/S0367-326X(03)00028-5] [PMID: 12727504]
[10]
Dongare, V.; Kulkarni, C.; Kondawar, M.; Magdum, C.; Haldavnekar, V.; Arvindekar, A. Inhibition of aldose reductase and anti-cataract action of trans-anethole isolated from Foeniculum vulgare Mill. fruits. Food Chem., 2012, 132(1), 385-390.
[http://dx.doi.org/10.1016/j.foodchem.2011.11.005] [PMID: 26434305]
[http://dx.doi.org/10.1016/j.foodchem.2011.11.005] [PMID: 26434305]
[11]
Anitha, T.; Balakumar, C.; Ilango, K.B.; Benedict Jose, C.; Vetrivel, D. Antidiabetic activity of the aqueous extracts of Foeniculumvulgare on streptozotocin-induced diabetic rats. Intern. J. Adv Pharm. Biol. Chem., 2014, 3, 487-494.
[12]
Barros, L.; Heleno, S.A.; Carvalho, A.M.; Ferreira, I.C. Systematic evaluation of the antioxidant potential of different parts of Foeniculumvulgare Mill. from Portugal. Food Chem. Toxicol., 2009, 47(10), 2458-2464.
[http://dx.doi.org/10.1016/j.fct.2009.07.003] [PMID: 19596397]
[http://dx.doi.org/10.1016/j.fct.2009.07.003] [PMID: 19596397]
[13]
Hebi, M.; Eddouks, M. Leaf Aqueous Extract of Argania spiniosa Exhibits Antihyperglycemic Effect in Diabetic Rats. Cardiovasc. Hematol. Agents Med. Chem., 2019, 17(1), 64-71.
[14]
Farid, O.; Hebi, M.; Ajebli, M.; Hidani, A.E.L.; Eddouks, M. Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats. J. Basic Clin. Physiol. Pharmacol., 2017, 28(3), 275-282.
[http://dx.doi.org/10.1515/jbcpp-2016-0030] [PMID: 28121617]
[http://dx.doi.org/10.1515/jbcpp-2016-0030] [PMID: 28121617]
[15]
Bouhlali, E.D.T.; Alem, C.; Zegzouti, Y.F. Antioxidant and antihemolytic activities of phenolic constituents of six moroccan date fruit (Phoenix dactylifera L.) syrups. Biotechnol. Ind. J., 2015, 12(1), 45-52. b
[16]
Day, C. Traditional plant treatments for diabetes mellitus: pharmaceutical foods. Br. J. Nutr., 1998, 80(1), 5-6.
[http://dx.doi.org/10.1017/S0007114598001718] [PMID: 9797638]
[http://dx.doi.org/10.1017/S0007114598001718] [PMID: 9797638]
[17]
Day, C. Traditional plant treatments for diabetes mellitus. Acta Chim Therap, 2000, 26, 131-150.
[18]
Swanston-Flatt, S.K.; Day, C.; Bailey, C.J.; Flatt, P.R. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia, 1990, 33(8), 462-464. a
[http://dx.doi.org/10.1007/BF00405106] [PMID: 2210118]
[http://dx.doi.org/10.1007/BF00405106] [PMID: 2210118]
[19]
Swanston–Flatt, S.K.; Day, C.; Flatt, P.R.; Bailey, C.J. Evaluation
of the antihyperglycaemic properties of traditional plant treatments
for diabetes in streptozotocin-diabetic and db/db mice; Frontiers in
diabetes research. Lessons from animal diabetes III: London,
Smith-Gordon, 1990. pp. Sha fir, E 286-293. b
[20]
Giugliano, D.; Ceriello, A.; Paolisso, G. Oxidative stress and diabetic vascular complications. Diabetes Care, 1996, 19(3), 257-267.
[http://dx.doi.org/10.2337/diacare.19.3.257] [PMID: 8742574]
[http://dx.doi.org/10.2337/diacare.19.3.257] [PMID: 8742574]
[21]
Oberley, L.W. Free radicals and diabetes. Free Radic. Biol. Med., 1988, 5(2), 113-124.
[http://dx.doi.org/10.1016/0891-5849(88)90036-6] [PMID: 3075947]
[http://dx.doi.org/10.1016/0891-5849(88)90036-6] [PMID: 3075947]
[22]
Lipinski, B. Pathophysiology of oxidative stress in diabetes mellitus. J. Diabetes Complications, 2001, 15(4), 203-210.
[http://dx.doi.org/10.1016/S1056-8727(01)00143-X] [PMID: 11457673]
[http://dx.doi.org/10.1016/S1056-8727(01)00143-X] [PMID: 11457673]
[23]
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]
[http://dx.doi.org/10.1016/j.jep.2016.12.017] [PMID: 28003130]
[24]
Torres, I.C.; Suarez, J.C. A preliminary study of hypoglycemic activity of Lythrum salicaria. J. Nat. Prod., 1980, 43(5), 559-563.
[http://dx.doi.org/10.1021/np50011a004] [PMID: 7007584]
[http://dx.doi.org/10.1021/np50011a004] [PMID: 7007584]
[25]
Gupta, M.P.; Solis, N.G.; Avella, M.E.; Sanchez, C. Hypoglycemic activity of Neurolaena lobata (L.) R. BR. J. Ethnopharmacol., 1984, 10(3), 323-327.
[http://dx.doi.org/10.1016/0378-8741(84)90020-5] [PMID: 6748709]
[http://dx.doi.org/10.1016/0378-8741(84)90020-5] [PMID: 6748709]
[26]
Karawya, M.S.; Abdel Wahab, S.M.; El-Olemy, M.M.; Farrag, N.M. Diphenylamine, an antihyperglycemic agent from onion and tea. J. Nat. Prod., 1984, 47(5), 775-780.
[http://dx.doi.org/10.1021/np50035a003] [PMID: 6512531]
[http://dx.doi.org/10.1021/np50035a003] [PMID: 6512531]
[27]
Farjou, I.B.; Al-Ani, M.; Guirgues, S.Y. Lowering of blood glucose in diabetics rabbits by Artemisia extract. J. Fac. Med. Baghdad, 1987, 92, 137-141.
[28]
Jouad, H.; Eddouks, M.; Lacaille-Dubois, M.A.; Lyoussi, B. Hypoglycaemic effect of spergularia purpurea in normal and streptozotocin-induced diabetic rats. J. Ethnopharmacol., 2000, 71(1-2), 169-177.
[http://dx.doi.org/10.1016/S0378-8741(99)00199-3] [PMID: 10904160]
[http://dx.doi.org/10.1016/S0378-8741(99)00199-3] [PMID: 10904160]
[29]
Chitra, V.; Leelamma, S. Coriandrum sativum-mechanism of hypoglycemic action. Food Chem., 1999, 67, 229-231.
[http://dx.doi.org/10.1016/S0308-8146(99)00113-2]
[http://dx.doi.org/10.1016/S0308-8146(99)00113-2]
[30]
Gelfand, R.A.; DeFronzo, R.A. Hypoglycemic counterregulation in normal and diabetic man. Ann. Clin. Res., 1984, 16(2), 84-93.
[PMID: 6380391]
[PMID: 6380391]
[31]
Cryer, P.E.; Gerich, J.E. Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. N. Engl. J. Med., 1985, 313(4), 232-241.
[http://dx.doi.org/10.1056/NEJM198507253130405] [PMID: 2861565]
[http://dx.doi.org/10.1056/NEJM198507253130405] [PMID: 2861565]
[32]
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]
[PMID: 15927932]
[33]
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.
[34]
Dawei, G.; Qinwang, Li. Antioxidant phenyl propanoid esters of triterpenes from dioclealasiophylla. Biol, 2004, 42, 36-38.
[35]
Shih, C.C.; Lin, C.H.; Lin, W.L.; Wu, J.B. Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. J. Ethnopharmacol., 2009, 123(1), 82-90.
[http://dx.doi.org/10.1016/j.jep.2009.02.039] [PMID: 19429344]
[http://dx.doi.org/10.1016/j.jep.2009.02.039] [PMID: 19429344]
[36]
Benhaddou, A.; Martineau, L.; Vuong, T.; Meddah, B.; Madiraju, P.; Settaf, A.; Haddad, P. The In Vivo Pathway and Increased Muscle Glut 4 Content. Evid. Based Complement. Alternat. Med., 2011, 9, 10-1155.
[37]
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]
[http://dx.doi.org/10.1248/cpb.46.113] [PMID: 9468642]
[38]
Jang, Y.Y.; Song, J.H.; Shin, Y.K.; Han, E.S.; Lee, C.S. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats. Pharmacol. Res., 2000, 42(4), 361-371.
[http://dx.doi.org/10.1006/phrs.2000.0705] [PMID: 10987997]
[http://dx.doi.org/10.1006/phrs.2000.0705] [PMID: 10987997]
[39]
Sarkhail, P.; Rahmanipour, S.; Fadyevatan, S.; Mohammadirad, A.; Dehghan, G.; Amin, G.; Shafiee, A.; Abdollahi, M. Antidiabetic effect of Phlomis anisodonta: Effects on hepatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Pharmacol. Res., 2007, 56(3), 261-266.
[http://dx.doi.org/10.1016/j.phrs.2007.07.003] [PMID: 17714953]
[http://dx.doi.org/10.1016/j.phrs.2007.07.003] [PMID: 17714953]
[40]
Tjälve, H. Streptozotocin: distribution, metabolism and mechanisms of action. Ups. J. Med. Sci., 1983, 39, 145-147.
[41]
Chen, Y.T.; Zheng, R.L.; Jia, Z.J.; Ju, Y. Flavonoids as superoxide scavengers and antioxidants. Free Radic. Biol. Med., 1990, 9(1), 19-21.
[http://dx.doi.org/10.1016/0891-5849(90)90045-K] [PMID: 2170243]
[http://dx.doi.org/10.1016/0891-5849(90)90045-K] [PMID: 2170243]
[42]
Kröncke, K.D.; Fehsel, K.; Sommer, A.; Rodriguez, M.L.; Kolb-Bachofen, V. Nitric oxide generation during cellular metabolization of the diabetogenic N-methyl-N-nitroso-urea streptozotozin contributes to islet cell DNA damage. Biol. Chem. Hoppe Seyler, 1995, 376(3), 179-185.
[http://dx.doi.org/10.1515/bchm3.1995.376.3.179] [PMID: 7542008]
[http://dx.doi.org/10.1515/bchm3.1995.376.3.179] [PMID: 7542008]
[43]
Zhou, K.; Yu, L. Effects of extraction solvent on wheat bran antioxidant activity estimation. Lebensm. Wiss. Technol., 2004, 37(7), 717-721.
[http://dx.doi.org/10.1016/j.lwt.2004.02.008]
[http://dx.doi.org/10.1016/j.lwt.2004.02.008]
[44]
Poulios, E.; Giaginis, C.; Vasios, G.K. Current state of the art on the antioxidant activity of sage (Salvia spp.) and its bioactive components. Planta Med., 2020, 23
[http://dx.doi.org/10.1055/a-1087-8276]
[http://dx.doi.org/10.1055/a-1087-8276]
[45]
Ceriello, A. Postprandial hyperglycemia and diabetes complications is it time to treat? Diabetes, 2005, 54(1), 1-7.
[46]
Choi, E.M.; Hwang, J.K. Antiinflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare. Fitoterapia, 2004, 75(6), 557-565.
[http://dx.doi.org/10.1016/j.fitote.2004.05.005] [PMID: 15351109]
[http://dx.doi.org/10.1016/j.fitote.2004.05.005] [PMID: 15351109]
[47]
Kataoka, H.; Horiyama, S.; Yamaki, M.; Oku, H.; Ishiguro, K.; Katagi, T.; Takayama, M.; Semma, M.; Ito, Y. Anti-inflammatory and anti-allergic activities of hydroxylamine and related compounds. Biol. Pharm. Bull., 2002, 25(11), 1436-1441.
[http://dx.doi.org/10.1248/bpb.25.1436] [PMID: 12419955]
[http://dx.doi.org/10.1248/bpb.25.1436] [PMID: 12419955]
[48]
Albert-Puleo, M. Fennel and anise as estrogenic agents. J. Ethnopharmacol., 1980, 2(4), 337-344.
[http://dx.doi.org/10.1016/S0378-8741(80)81015-4] [PMID: 6999244]
[http://dx.doi.org/10.1016/S0378-8741(80)81015-4] [PMID: 6999244]
Article Metrics
4