Molecular mechanism of the anti-diabetic activity of an identified oligosaccharide from Rosa canina

Gholamreza Bahrami , Seyed Shahram Miraghaee , Bahar Mohammadi, Mohammad Taher Bahrami, Gholamreza Taheripak, Samira Keshavarzi, Atefeh Babaei, Soraya Sajadimajd, Razieh Hatami

Abstract


Background and purpose: Because of the high prevalence, diabetes is considered a global health threat. Hence, the need for effective, cheap, and comfortable therapies are highly felt. In previous study,                        a novel oligosaccharide with strong anti-diabetic activity in the crude extract of Rosa canina fruits,                      from the rosacea family, was identified. The present study was designed to ensure its efficacy using in vivo and in vitro studies.

Experimental approach: Crude extract and its purified oligosaccharide were prepared from corresponding herb. Adult male Wistar rats were randomly divided into four groups of 10 each, as follows: group 1,            healthy control rats given only sterile normal saline; group 2, diabetic control rats received sterile normal saline; group 3, diabetic rats treated with crude extract of Rosa canina (40% w/v) by oral gavage for 8 weeks; group 4, diabetic rats treated with purified oligosaccharide of Rosa canina (2 mg/kg) by oral gavage for                 8 weeks. After treatment, body weight, fasting blood glucose, serum insulin levels and islet beta-cell repair and proliferation were investigated. The possible cytoprotective action of oligosaccharide was evaluated                in vitro. The effect of oligosaccharide on apoptosis and insulin secretion in cell culture media were examined. Real-time PCR was used to determine the expression level of some glucose metabolism-related regulator genes.

Findings / Results: In the animal model of diabetes, the insulin levels were increased significantly due to             the regeneration of beta-cells in the islands of langerhans by the purified oligosaccharide. In vitro cell apoptosis examination showed that high concentration of oligosaccharide increased cell death, while                    at low concentration protected cells from streptozotocin-induced apoptosis. Molecular study showed that                   the expression of Ins1 and Pdx1 insulin production genes were increased, leading to increased expression of insulin-dependent genes such as Gck and Ptp1b. On the other hand, the expression of the Slc2a2 gene,     which is related to the glucose transporter 2, was significantly reduced due to insulin concentrations.

Conclusion and implications: The purified oligosaccharide from Rosa canina was a reliable anti-diabetic agent, which acted by increasing insulin production in beta-cells of the islands of Langerhans.


Keywords


Apoptosis; Cell viability; Diabetes; Insulin; Rosa canina.

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References


Davidson MB. Correction to the 2010 report on the diagnosis and classification of diabetes. Diabetes Care. 2010;33(4):e57.

Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-281.

Das M, Sarma BP, Khan AK, Mosihuzzaman M, Nahar N, Ali L, Bhoumik A, Rokeya B. The antidiabetic and antilipidemic activity of aqueous extract of Urtica dioica L. on type2 diabetic model rats. J Biosci. 2009;17:1-6.

Khazaei M, Pazhouhi M, Khazaei S. Evaluation of hydro-alcoholic extract of Trifolium Pratens L. for its anti-cancer potential on U87MG cell line. Cell J. 2018;20(3):412-421.

Chang HY, Wallis M, Tiralongo E. Use of complementary and alternative medicine among people living with diabetes: literature review. J Adv Nurs. 2007;58(4):307-319.

Ahangarpour A, Heidari H, Salehizade Junghani M, Absari R, Khoogar M, Ghaedi E. Effects of hydroalcoholic extract of Rhus coriaria seed on glucose and insulin related biomarkers, lipid profile, and hepatic enzymes in nicotinamide-streptozotocin-induced type II diabetic male mice. Res Pharm Sci. 2017;12(5): 416-424

Pate DK, Prasad SK, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012;2(4):320-330.

Dabaghian HF, Abdollahifard M, Khalighi Sigarudi F, Taghavi Shirazi M, Shojaee A, Sabet Z, et al. Effects of Rosa canina L. fruit on glycemia and lipid profile in type 2 diabetic patients: a randomized, double-blind, placebo-controlled clinical trial. J Med Plant. 2015;14(55):95-104.

Orhan N, Aslan M, Hosbas S, Deliorman OD. Antidiabetic effect and antioxidant potential of Rosa canina fruits. Pharmacogn Mag. 2009;5(20): 309-316.

Ilchizadeh K, Eidi M, Ghahramani R, Sasaninejad Z, Ahmarinezhad Z. Antidiabetic effect of Rosa Canina L. fruit in alloxan induced diabetic male rats. Qom Univ Med Sci J. 2015;9(5):23-34.

Taghizadeh M, Rashidi AA, Taherian AA, Vakili Z, Sajad Sajadian M, Ghardashi M. Antidiabetic and antihyperlipidemic effects of ethanol extract of Rosa canina L. Fruit on diabetic rats: An experimental study with histopathological evaluations. J Evid Based Complementary Altern Med. 2016;21(4):NP25-NP30.

Fattahi A, Niyazi F, Shahbazi B, Farzaei MH, Bahrami G. Antidiabetic mechanisms of Rosa canina fruits: an in vitro evaluation. J Evid Based Complementary Altern Med. 2017;22(1): 127-133.

Bahrami Gh. Herbal extract composition for the treatment of diabetes and a method of extracting the same. 2016. Google Patents. No. US20140256673A1.

Khazaei M, Pazhouhi M. Temozolomide-mediated apoptotic death is improved by thymoquinone in U87MG cell line. Cancer Invest. 2017;35(4): 225-236.

Khazaei M, Pazhouhi M. Protective effect of hydroalcoholic extracts of Trifolium pratense L. on pancreatic β cell line (RIN-5F) against cytotoxicty of streptozotocin. Res Pharm Sci. 2018;13(4):324-331.

Pazhouhi M, Sariri R, Khazaei MR, Moradi MT, Khazaei M. Synergistic effect of temozolomide and thymoquinone on human glioblastoma multiforme cell line (U87MG). J Can Res Ther 2018;14:1023-1028.

De Paula AC, Sousa RV, Figueiredo-Ribeiro RC, Buckeridge MS. Hypoglycemic activity of polysaccharide fractions containing beta-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae. Braz J Med Biol Res. 2005;38(6):885-893.

Shukla A, Bigoniya P, Srivastava B. Hypoglycemic activity of Lepidium sativum Linn seed total alkaloid on alloxan induced diabetic rats. Res J Med Plant. 2012;6:587-596.

Manikandan R, Vijaya Anand A, Sampathkumar P, Manoharan N. Protective effect of Psidium guajava leaf ethanolic extract against streptozotocin-induced diabetes and lipidosis in rats. Indian J Anim Res. 2018;52:1190-1194.

Bhatia A, Mishra T. Hypoglycemic activity of Ziziphus mauritiana aqueous ethanol seed extract in alloxan-induced diabetic mice. Pharm Biol. 2010;48:604-610.

Müller A, Schott-Ohly P, Dohle C, Gleichmann H. Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin. Immunobiology. 2002;205(1):35-50.

Sun N, Yang G, Zhao H, Savelkoul HF, An L. Multidose streptozotocin induction of diabetes in BALB/c mice induces a dominant oxidative macrophage and a conversion of TH1 to TH2 phenotypes during disease progression. Mediators Inflamm. 2005;2005(4):202-209.

Zhou J, Zhou S, Tang J, Zhang K, Guang L, Huang Y, et al. Protective effect of berberine on beta-cells in streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol. 2009;606(1-3):262-268.

Javdan N, Estakhr J. Neuropharmacological and antidiarrhoeal activity of ethanolic extract of Salvia hypoleuca in rat. Pharmacologyonline. 2011;2: 905-910.

Numata T, Araya J, Fujii S, Hara H, Takasaka N, Kojima J, et al. Insulin-dependent phosphatidylinositol 3-kinase/Akt and ERK signaling pathways inhibit TLR3-mediated human bronchial epithelial cell apoptosis. J Immunol. 2011;187(1):510-519.

Garg A, Aggarwal BB. Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia. 2002;16(6):1053-1068.

Gao R, Ustinov J, Korsgren O, Otonkoski T. In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells. Diabetologia. 2005;48(11):2296-2304.

Cerf ME. Transcription factors regulating β-cell function. Eur J Endocrinol. 2006;155(5):671-679.

Aziz MT, El-Asmar MF, Rezq AM, Wassef MA, Fouad H, Roshdy NK, et al. Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro. Chin Med. 2014;9(1):3-14.

Hansmannel F, Mordier S, Iynedjian PB. Insulin induction of glucokinase and fatty acid synthase in hepatocytes: analysis of the roles of sterol-regulatory-element-binding protein-1c and liver X receptor. Biochem J. 2006;399(2):275-283.

Leibowitz G, Oprescu AI, Uçkaya G, Gross DJ, Cerasi E, Kaiser N. Insulin does not mediate glucose stimulation of proinsulin biosynthesis. Diabetes. 2003;52(4):998-1003.

Evans-Molina C, Garmey JC, Ketchum R, Brayman KL, Deng S, Mirmira RG. Glucose regulation of insulin gene transcription and pre-mRNA processing in human islets. Diabetes. 2007;56(3):827-35.

Butler PC, Meier JJ, Butler AE, Bhushan A. The replication of β cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab. 2007;3(11):758-768.

Elghazi L, Weiss AJ, Barker DJ, Callaghan J, Staloch L, Sandgren EP, et al. Regulation of pancreas plasticity and malignant transformation by Akt signaling. Gastroenterology, 2009;136(3):1091-1103.

Galic S, Hauser C, Kahn BB, Haj FG, Neel BG, Tonks NK, Tiganis T. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol. 2005;25(2):819-829.

McCulloch LJ, van de Bunt M, Braun M, Frayn KN, Clark A, Gloyn AL. GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta-cells: implications for understanding genetic association signals at this locus. Mol Genet Metab. 2011;104(4):648-653.


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