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

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Tan, Swee Ching and Rajendran, Ramkumar and Bhattamisra, Subrat Kumar and Krishnappa, Purushotham and Davamani, Fabian and Chitra, Ebenezer and Ambu, Stephen and Furman, Brian and Candasamy, Mayuren (2023) Effect of madecassoside in reducing oxidative stress and blood glucose in streptozotocin–nicotinamide-induced diabetes in rats. Journal of Pharmacy and Pharmacology, 75 (8). pp. 1034-1045. ISSN 0022-3573 (https://doi.org/10.1093/jpp/rgad063)

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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.

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