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

Raghu Ganugula, Meenakshi Arora, Patcharawalai Jaisamut, Ruedeekorn Wiwattanapatapee, Heather G. Jørgensen, Vinod P. Venkatpurwar, Beiyan Zhou, Aline Rodrigues Hoffmann, Rita Basu, Shaodong Guo, Naga Venkata Ravi Kumar Majeti

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Abstract

Background and Purpose: Approaches to prevent selective and progressive loss of insulin-producing beta cells in Type 1 diabetes mellitus (T1DM) will help to manage this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory substance, suppresses diabetes-associated inflammation and cell death. However, very high doses need to be used because of poor oral bioavailability, making it difficult to translate the anti-inflammatory actions to clinical situations. Experimental Approach: We have prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least nine-fold improvement in oral bioavailability. Here, we tested the ability of nCUR to prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic islets and beta cells, in rats. Key Results: Non-fasted rats pretreated with 10 or 50 mg·kg−1 nCUR 6 h prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50 mg·kg−1) results in 12% reduction. This treatment with nCUR was accompanied by decreased islet or beta cell death, as shown by 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. Pre-treatment with nCUR, but not CUR, decreased 8-oxo-2′-deoxyguanosine, a sensitive biomarker of ROS-induced DNA damage, in pancreas. In normal rodents, daily dosing for 28 days, with nCUR (25-100 mg·kg−1) did not cause any deleterious health issues by the carrier. Conclusions and Implications: Together, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving beta cell function, which could prevent T1DM.

Original languageEnglish (US)
Pages (from-to)2074-2084
Number of pages11
JournalBritish Journal of Pharmacology
Volume174
Issue number13
DOIs
StatePublished - Jul 1 2017

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ASJC Scopus subject areas

  • Pharmacology

Cite this

Ganugula, R., Arora, M., Jaisamut, P., Wiwattanapatapee, R., Jørgensen, H. G., Venkatpurwar, V. P., Zhou, B., Rodrigues Hoffmann, A., Basu, R., Guo, S., & Majeti, N. V. R. K. (2017). Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus. British Journal of Pharmacology, 174(13), 2074-2084. https://doi.org/10.1111/bph.13816