Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic ß-cells for effective management of type 1 diabetes mellitus

Ganugula, R. et al. (2017) Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic ß-cells for effective management of type 1 diabetes mellitus. British Journal of Pharmacology, 174(13), pp. 2074-2084. (doi: 10.1111/bph.13816) (PMID:28409821)

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Abstract

Background and Purpose: Approaches to prevent selective and progressive loss of insulin-producing ß-cells in Type 1 diabetes mellitus (T1DM) will help conquer this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory, suppresses diabetes associated inflammation and cell death. However, very high doses have been tested owing to poor oral bioavailability, making it difficult to translate to the clinic. Experimental approach: We recently prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least 9-fold improvement in oral bioavailability. In the current study, we tested nCUR's ability to prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic islet/ß-cells. Key Results: Nonfasted rats pretreated with 10 or 50 mg/kg nCUR 6 hours prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50 mg/kg) results in 12% reduction. This is owing to nCUR's ability to prevent islet/β-cell death evident from TUNEL assay, and H&E staining. Both CUR and nCUR significantly decreased levels of inflammatory cytokines in pancreatic tissue homogenates that correlated well with minimal histiocytic infiltration. The nCUR, rather than CUR pre-treatment prevented 8-oxo-2'-deoxyguanosine (8-oxo-dG), a sensitive biomarker of reactive oxygen species (ROS)-induced DNA damage in pancreas. Our data in normal rodents indicates that 28 days daily dosing with nCUR (25 to 100 mg/kg) did not cause any deleterious health issues by the carrier. Conclusions & Implications: Together, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving the ß-cell function, possibly preventing T1DM.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jorgensen, Dr Heather
Authors: Ganugula, R., Arora, M., Jaisamut, P., Wiwattanapatapee, R., Jørgensen, H. G., Venkatpurwar, V. P., Zhou, B., Rodrigues Hoffmann, A., Basu, R., Guo, S., and Ravi Kumar, M. N. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Pharmacology
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:13 April 2017
Copyright Holders:Copyright © 2017 Wiley
First Published:First published in British Journal of Pharmacology 174(13):2074-2084
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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