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

Research output: Contribution to journalArticle

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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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Curcumin
Insulin-Secreting Cells
Streptozocin
Type 1 Diabetes Mellitus
Apoptosis
Inflammation
Islets of Langerhans
Biological Availability
Cell Death
Anti-Inflammatory Agents
In Situ Nick-End Labeling
DNA Damage
Pancreas
Rodentia
Biomarkers

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ganugula, R., Arora, M., Jaisamut, P., Wiwattanapatapee, R., Jørgensen, H. G., Venkatpurwar, V. P., ... 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

Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus. / Ganugula, Raghu; Arora, Meenakshi; Jaisamut, Patcharawalai; Wiwattanapatapee, Ruedeekorn; Jørgensen, Heather G.; Venkatpurwar, Vinod P.; Zhou, Beiyan; Rodrigues Hoffmann, Aline; Basu, Rita; Guo, Shaodong; Majeti, Naga Venkata Ravi Kumar.

In: British Journal of Pharmacology, Vol. 174, No. 13, 01.07.2017, p. 2074-2084.

Research output: Contribution to journalArticle

Ganugula, R, Arora, M, Jaisamut, P, Wiwattanapatapee, R, Jørgensen, HG, Venkatpurwar, VP, Zhou, B, Rodrigues Hoffmann, A, Basu, R, Guo, S & Majeti, NVRK 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, vol. 174, no. 13, pp. 2074-2084. https://doi.org/10.1111/bph.13816
Ganugula, Raghu ; Arora, Meenakshi ; Jaisamut, Patcharawalai ; Wiwattanapatapee, Ruedeekorn ; Jørgensen, Heather G. ; Venkatpurwar, Vinod P. ; Zhou, Beiyan ; Rodrigues Hoffmann, Aline ; Basu, Rita ; Guo, Shaodong ; Majeti, Naga Venkata Ravi Kumar. / Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus. In: British Journal of Pharmacology. 2017 ; Vol. 174, No. 13. pp. 2074-2084.
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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.",
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AU - Arora, Meenakshi

AU - Jaisamut, Patcharawalai

AU - Wiwattanapatapee, Ruedeekorn

AU - Jørgensen, Heather G.

AU - Venkatpurwar, Vinod P.

AU - Zhou, Beiyan

AU - Rodrigues Hoffmann, Aline

AU - Basu, Rita

AU - Guo, Shaodong

AU - Majeti, Naga Venkata Ravi Kumar

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AB - 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.

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