Research Article Oleander Stem and Root Standardized Extracts Mitigate Acute Hyperglycaemia by Limiting Systemic Oxidative Stress Response in Diabetic Mice Priyankar Dey , 1,2 Manas Ranjan Saha, 3 Sumedha Roy Choudhuri, 4 Indrani Sarkar, 3 Biswajit Halder, 5 Mousumi Poddar-Sarkar, 4 Arnab Sen , 3 and Tapas Kumar Chaudhuri 1,6 1 Cellular Immunology Laboratory, Department of Zoology, University of North Bengal, Siliguri, West Bengal 734013, India 2 Human Nutrition Program, Department of Human Sciences, e Ohio State University, Columbus, Ohio 43210, USA 3 Molecular Cytogenetics Laboratory, Department of Botany, University of North Bengal, Siliguri, West Bengal 734013, India 4 Chemical Signal and Lipidomics Laboratory, Department of Botany, University of Calcutta, Kolkata, West Bengal 700019, India 5 Department of Pathology, North Bengal Medical College, West Bengal 734011, India 6 Visiting Professor, Department of Zoology, Bodoland University, Kokrajhar, Assam 734011, India Correspondence should be addressed to Tapas Kumar Chaudhuri; dr_tkc_nbu@rediffmail.com Received 17 August 2018; Revised 17 October 2018; Accepted 24 October 2018; Published 8 January 2019 Guest Editor: Ghulam Hussain Copyright©2019PriyankarDeyetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. e extracts of different parts of Nerium oleander L. are used as antidiabetic remedy in the traditional medicinal systems of different parts of the world. Despite these uses in ethnomedicinal system, the antihyperglycemic potentials of oleander stem (NOSE) and root (NORE) extracts have not been pharmacologically evaluated. erefore, we aimed at evaluating the antidiabetic ethnomedicinal claims of NOSE and NORE, primarily focusing on glucose homeostasis and associated metabolic implications. Alloxan-treated mice with hyperglycaemia (blood glucose >200 mg/dL) were treated with oleander 70% hydromethanolic extracts (200 mg/kg) for 20 consecutive days, and the results were compared with positive control glibenclamide. Blood glucose level was 52–65% lowered (P < 0.001) in oleander treated groups, which was otherwise 4.62 times higher in diabetic mice, compared to control. Insulin resistance was lowered 51–36% irrespective of any significant (P > 0.05) changes in insulin sensitivity throughout the treatments. Improved serum insulin remained associated with lowered glucose level (r P � −0.847 and −0.772; P < 0.01). Markers of hyperglycaemia-related hepatic glycogen, glycated haemoglobin (HbA1c), hyperlipidaemia, hepatic injury, and diabetic nephropathy were normalized as well. Improvement of systemic intrinsic antioxidant enzymes (catalase and peroxidase) were correlated (r P � −0.952 to −0.773; P < 0.01) with lower lipid peroxidation by-product malondialdehyde (MDA) in the circulation. Principal component analysis coupled with hierarchical cluster analysis represented shift in metabolic homeostasis in diabetic mice, which was further normalized by oleander and glibenclamide treatment. Additionally, molecular docking studies of the phenolic acids measured by HPLC with intracellular cytoprotective transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) revealed strong molecular interactions. e results collectively support the ethnomedicine antidiabetic claims of oleander stem and root and suggest that the oleander mediated elevation of systemic antioxidant status is likely responsible for the improved glycaemic control. 1. Introduction Diabetes mellitus (DM) is a systemic disorder, primarily characterized by loss of glucose homeostasis, impaired in- sulin signalling, carbohydrate, and lipid metabolism, ultimately resulting in progressive systemic complications such as hyperlipidemia, hyperglycaemia, nephropathy, he- patic injury, vascular dysfunction, etc. e global prevalence of diabetes has quadrupled in the last 30years [1]. It is expected to deteriorate based on estimate that 642 million Hindawi Advances in Pharmacological Sciences Volume 2019, Article ID 7865359, 12 pages https://doi.org/10.1155/2019/7865359