Evaluation of Antidiabetic Activity of Rosmarinus officinalis var. prostratus Growing in Syria in Alloxan Diabetic Rats

Page: [187 - 193] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: The genus of Rosmarinus officinalis (Rosemary) is found in many parts of the world. Traditionally, Rosemary has been used in traditional medicine due to its therapeutic virtues and its ability to treat some diseases. Rosmarinus officinalis var. prostratus grows in the Al Kalamoon region of Syria but only a limited amount of scientific research on the medicinal uses of this plant has been done. This study focused on the medicinally active substances found in ethanolic extract of the leaves and flowers of this plant and their antidiabetic effect in alloxan-induced diabetic rats. First, an acute toxicity study was carried out to detect the optimal dose of the Rosmarinus officinalis var. prostratus extract. Then, the effect of the optimal dose of 300mg/kg was measured over 36 days.

Methods: During the study, diabetic rats were treated with different doses of extract (100, 200, 300, 400, 500, and 600 mg/kg). The percentage of Fasting Blood Glucose (FBG) was measured immediately after administration of the extract and at 2h, 4h and 8h after administration. The dose of 300mg/kg was then used in the second part of the study, which involved four groups of rats: a healthy group, a diabetic group without treatment (the control group), a diabetic group treated with 300mg/kg of the extract, and a diabetic group treated by metformin (50mg/kg). The treatment continued for 36 days.

Results: The results showed that the extract was rich with flavonoids, phenols and tannins. Levels of FBG and DPP-4 were significantly lower in the extract-treated group in comparison with the control group; however, the level of insulin was significantly elevated in the extract-treated group compared to the control group. This effect may be caused by two factors. First, the antioxidant effects of flavonoids that protect pancreatic beta cells from damage caused by alloxan, supports regeneration of pancreatic beta cells, and therefore insulin production. Second, the inhibition of DPP- 4 activity, which in turn leads to increased secretion of insulin.

Conclusion: The ethanolic extract of Rosmarinus officinalis var. prostratus has an antidiabetic effect.

Keywords: Rosmarinus officinalis var. prostratus, anti-diabetic, insulin, DPP-4, hypocholesterolemia, hyperglycaemia.

Graphical Abstract

[1]
Hassani, F.V.; Shirani, K.; Hosseinzadeh, H. Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: A review. Naunyn Schmiedebergs Arch. Pharmacol., 2016, 389(9), 931-949.
[http://dx.doi.org/10.1007/s00210-016-1256-0] [PMID: 27178264]
[2]
Cui, L.; Kim, M.O.; Seo, J.H.; Kim, I.S.; Kim, N.Y.; Lee, S.H.; Park, J.; Kim, J.; Lee, H.S. Abietane diterpenoids of Rosmarinus officinalis and their diacylglycerol acyltransferase-inhibitory activity.
[3]
Pérez-Fons, L.; Garzón, M.T.; Micol, V. Relationship between the antioxidant capacity and effect of rosemary (Rosmarinus officinalis L.) polyphenols on membrane phospholipid order. J. Agric. Food Chem., 2010, 58(1), 161-171.
[http://dx.doi.org/10.1021/jf9026487] [PMID: 19924866]
[4]
Naimi, M.; Vlavcheski, F.; Shamshoum, H.; Tsiani, E. Rosemary extract as a potential anti-hyperglycemic agent: Current evidence and future perspectives. Nutrients, 2017, 9(9), 968.
[5]
Martynyuk, L.; Martynyuk, L.; Ruzhitska, O.; Martynyuk, O. Effect of the herbal combination Canephron N on diabetic nephropathy in patients with diabetes mellitus: Results of a comparative cohort study. J. Altern. Complement. Med., 2014, 20(6), 472-478.
[http://dx.doi.org/10.1089/acm.2013.0400] [PMID: 24738695]
[6]
Hamidpour, R.; Hamidpour, S.; Elias, G. Rosmarinus Officinalis (Rosemary): A novel therapeutic agent for antioxidant, antimicrobial, anticancer, antidiabetic, antidepressant, neuroprotective, anti-inflammatory, and anti-obesity treatment. Biomed J. Sci . Tech. Res., 2017, 1(4), 1-6.
[http://dx.doi.org/10.26717/BJSTR.2017.01.000371]
[7]
Sedighi, R.; Zhao, Y.; Yerke, A.; Sang, S. Preventive and protective properties of Rosemary (Rosmarinus officinalis L.) in obesity and diabetes mellitus of metabolic disorders: A brief review. Curr. Opin. Food Sci., 2015, 2, 58-70.
[http://dx.doi.org/10.1016/j.cofs.2015.02.002]
[8]
Ullevig, S.L.; Zhao, Q.; Zamora, D.; Asmis, R. Ursolic acid protects diabetic mice against monocyte dysfunction and accelerated atherosclerosis. Atherosclerosis, 2011, 219(2), 409-416.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.06.013] [PMID: 21752377]
[9]
Kwon, Y.I.; Vattem, D.A.; Shetty, K. Evaluation of clonal herbs of Lamiaceae species for management of diabetes and hypertension. Asia Pac. J. Clin. Nutr., 2006, 15(1), 107-118.
[PMID: 16500886]
[10]
Afonso, M.S. Phenolic compounds from Rosemary (Rosmarinus officinalis L.) attenuate oxidative stress and reduce blood cholesterol concentrations in dietinduced hypercholesterolemic rats. Nutr. Metab., 2013, 10(1), 1-19.
[11]
Zheng, Q.; Li, W.; Lv, Z.; Fan, J. Study on Extraction Method of Rosemary antioxidant. In IOP Conference Series: Earth and Environmental Science, vol. 300, no. 5, p. 052013. IOP Publishing, 2019.
[12]
Rahila, M.P.; Nath, B.S.; Naik, N.L.; Pushpadass, H.A.; Magdaline, M.; Franklin, M.E.E. Rosemary (Rosmarinus officinalis Linn.) extract: A source of natural antioxidants for imparting autoxidative and thermal stability to ghee. Food Processing and Preservation, 2018, 42(2).
[13]
Colica, C.; Di Renzo, L.; Aiello, V.; De Lorenzo, A.; Abenavoli, L. Rosmarinic acid as potential anti-inflammatory agent. Rev. Recent Clin. Trials, 2018, 13(4), 240-242.
[http://dx.doi.org/10.2174/157488711304180911095818] [PMID: 30328397]
[14]
Benedec, D.; Hanganu, D.; Oniga, I.; Tiperciuc, B.; Olah, N.K.; Raita, O.; Bischin, C.; Silaghi-Dumitrescu, R.; Vlase, L. Assessment of rosmarinic acid content in six Lamiaceae species extracts and their antioxidant and antimicrobial potential. Pak. J. Pharm. Sci., 2015, 28(6)(Suppl.), 2297-2303.
[PMID: 26687747]
[15]
Bellumori, M.; Innocenti, M.P.; Binello, A.; Boffa, L.; Mulinacci, N.; Cravotto, G. Selective recovery of rosmarinic and carnosic acids from Rosemary leaves under ultrasound- and microwave-assisted extraction procedures. C. R. Chim., 2016, 19(6), 699-706.
[http://dx.doi.org/10.1016/j.crci.2015.12.013]
[16]
Borrás-Linares, I.; Stojanović, Z.; Quirantes-Piné, R.; Arráez-Román, D.; Švarc-Gajić, J.; Fernández-Gutiérrez, A.; Segura-Carretero, A. Rosmarinus officinalis leaves as a natural source of bioactive compounds. Int. J. Mol. Sci., 2014, 15(11), 20585-20606.
[http://dx.doi.org/10.3390/ijms151120585] [PMID: 25391044]
[17]
Mena, P.; Cirlini, M.; Tassotti, M.; Herrlinger, K.A.; Dall’Asta, C.; Del, R.D. Phytochemical profiling of flavonoids, phenolic acids, terpenoids, and volatile fraction of a rosemary (Rosmarinus officinalis L.) extract. Molecules, 2016, 21(11), 1576.
[18]
Fernández-Ochoa, A.; Borrás-Linares, I.; Barrajón-Catalán, E.; González-Álvarez, I.; Arráez-Román, D.; Micolc, V. Phenolic compounds in Rosemary as potential source of bioactive compounds against colorectal cancer: In situ absorption and metabolism study. J. Funct. Foods, 2017, 33, 202-210.
[http://dx.doi.org/10.1016/j.jff.2017.03.046]
[19]
Al-Baoqai, N. Al- mahbashi, H.; Al-Adhal, A. Antidiabetic and antihyperlipidemic activity of dracaena cinnabari balf resin ethanolic extract of soqatra island in experimental animals. Univ. J. Pharm. Res., 2018, 3(5), 1-11.
[20]
Joseph, B.S.; Kumbhare, P.H.; Kale, M.C. Preliminary phytochemical screening of selected Medicinal Plants. Int. Res. Journal of Science & Engineering, 2013, 2(1), 55-62.
[21]
Joshna, K.; Gopal, V.; Kavitha, B. Phytochemical screening, physicochemical properties and total phenolic content of bitter honey samples. Int. Res. J. Pharm, 2019, 10(2), 121-125.
[http://dx.doi.org/10.7897/2230-8407.100255]
[22]
Banu, K.S.; Cathrine, L. General Techniques involved in the phytochemical analysis. Int J Adv Res Computer Sci, 2015, 2, 25-32.
[23]
Gul, R.; Jan, S.U.; Faridullah, S.; Sherani, S.; Jahan, N. Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from ephedra intermedia indigenous to Balochistan. ScientificWorldJournal, 2017, 2017, 5873648.
[http://dx.doi.org/10.1155/2017/5873648] [PMID: 28386582]
[24]
Herrero, M.; Plaza, M.; Cifuentes, A.; Ibáñez, E. Green processes for the extraction of bioactives from Rosemary: Chemical and functional characterization via ultra-performance liquid chromatography-tandem mass spectrometry and in-vitro assays. J. Chromatogr. A, 2010, 1217(16), 2512-2520.
[http://dx.doi.org/10.1016/j.chroma.2009.11.032] [PMID: 19945706]
[25]
Kontogianni, V.G.; Tomic, G.; Nikolic, I.; Nerantzaki, A.A.; Sayyad, N.; Stosic-Grujicic, S.; Stojanovic, I.; Gerothanassis, I.P.; Tzakos, A.G. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. Food Chem., 2013, 136(1), 120-129.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.091] [PMID: 23017402]
[26]
Aumeeruddy-Elalfi, Z.; Gurib-Fakim, A.; Mahomoodally, F. Antimicrobial, antibiotic potentiating activity and phytochemical profile of essential oils from exotic and endemic medicinal plants of Mauritius. Ind. Crops Prod., 2015, 71, 197-204.
[http://dx.doi.org/10.1016/j.indcrop.2015.03.058]
[27]
Aumeeruddy-Elalfi, Z.; Gurib-Fakim, A.; Mahomoodally, M F. Chemical composition, antimicrobial an dantibiotic potentiating activity of essential oils from 10 tropical medicinal plants from Mauritius. J. Herb. Med., 2016, 6(2), 88-95.
[http://dx.doi.org/10.1016/j.hermed.2016.02.002]
[28]
Jacob, B; Narendhirakannan, R.T. Role of medicinal plants in the management of diabetes mellitus: A review. 3 Biotech, 2019, 9(1), PP.4.
[29]
Labban, L.; Mustafa, E.U.; Ibrahim, Y.M. The effects of rosemary (Rosmarinus officinalis) leaves powder on glucose level, lipid profile and lipid perodoxation. Int. J. Clin. Med., 2014, 5, 297-304.
[http://dx.doi.org/10.4236/ijcm.2014.56044]
[30]
McCue, P.P.; Shetty, K. Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro. Asia Pac. J. Clin. Nutr., 2004, 13(1), 101-106.
[PMID: 15003922]
[31]
Vanithadevi, B.; Anuradha, C.V. Effect of rosmarinic acid on insulin sensitivity, glyoxalase system and oxidative events in liver of fructose-fed mice. Int. J. Diabetes Metab., 2008, 16, 35-44.
[32]
Alnahdi, H.S. Effect of Rosmarinus officinalis extract on some dates. Saudi Med. J., 2012, 23(5), 536-538.
[33]
Bakirel, T.; Bakirel, U.; Keleş, O.U.; Ulgen, S.G.; Yardibi, H. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits. J. Ethnopharmacol., 2008, 116(1), 64-73.
[http://dx.doi.org/10.1016/j.jep.2007.10.039] [PMID: 18063331]
[34]
Sepici-Dincel, A.; Açikgöz, S.; Çevik, C.; Sengelen, M.; Yeşilada, E. Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits. J. Ethnopharmacol., 2007, 110(3), 498-503.
[http://dx.doi.org/10.1016/j.jep.2006.10.015] [PMID: 17101252]
[35]
Shukri, R.; Mohamed, S.; Noordin, M.M. Cloves protect the heart, liver and lens of diabetic rats. Food Chem., 2010, 122(4), 1116-1121.
[http://dx.doi.org/10.1016/j.foodchem.2010.03.094]
[36]
Yabe, D.; Eto, T.; Shiramoto, M.; Irie, S.; Murotani, K.; Seino, Y.; Kuwata, H.; Kurose, T.; Seino, S.; Ahrén, B.; Seino, Y. Effects of DPP-4 inhibitor linagliptin and GLP-1 receptor agonist liraglutide on physiological response to hypoglycaemia in Japanese subjects with type 2 diabetes: A randomized, open-label, 2-arm parallel comparative, exploratory trial. Diabetes Obes. Metab., 2017, 19(3), 442-447.
[http://dx.doi.org/10.1111/dom.12817] [PMID: 27800649]
[37]
Seino, Y.; Fukushima, M.; Yabe, D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J. Diabetes Investig., 2010, 1(1-2), 8-23.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00022.x] [PMID: 24843404]
[38]
Salim, B.; Hocine, A.; Said, G. First study on anti-diabetic effect of rosemary and salvia by using molecular docking. Int. J. Pharm. Res., 2017, 19(4), 1-12.
[http://dx.doi.org/10.9734/JPRI/2017/37061]