Effect of madecassoside in reducing oxidative stress and blood glucose in streptozotocin–nicotinamide-induced diabetes in rats

Author:

Tan Swee Ching1,Rajendran Ramkumar23,Bhattamisra Subrat Kumar34,Krishnappa Purushotham5,Davamani Fabian6,Chitra Ebenezer6,Ambu Stephen1,Furman Brian7,Candasamy Mayuren38ORCID

Affiliation:

1. School of Postgraduate Studies, International Medical University , Kuala Lumpur , Malaysia

2. Faculty of Medicine, University of Adelaide , Adelaide , Australia

3. Department of Life Sciences, School of Pharmacy, International Medical University , Kuala Lumpur , Malaysia

4. GITAM School of Pharmacy, GITAM (Deemed to be University) , Visakhapatnam , India

5. Department of Pathology, School of Medicine, International Medical University , Kuala Lumpur , Malaysia

6. Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, International Medical University , Kuala Lumpur , Malaysia

7. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow , UK

8. Centre for Bioactive Molecules & Drug Discovery, Institute for Research, Development and Innovation, International Medical University , Kuala Lumpur , Malaysia

Abstract

Abstract Objectives Madecassoside (MAD) is a triterpenoid constituent of Centella asiatica (L.) Urb., an ethnomedical tropical plant, extracts of which were shown to reduce blood glucose in experimental diabetes. This study examines MAD for its anti-hyperglycaemic effects and tests the hypothesis that it reduces the blood glucose in experimentally induced diabetic rats by protecting the β-cells. Methods Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken. Key findings MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats. Conclusions The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function.

Funder

Ministry of Higher Education, Malaysia

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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