TY - JOUR
T1 - Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus
AU - Ganugula, Raghu
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
N1 - Publisher Copyright:
© 2017 The British Pharmacological Society
PY - 2017
Y1 - 2017
N2 - 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.
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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U2 - 10.1111/bph.13816
DO - 10.1111/bph.13816
M3 - Article
C2 - 28409821
AN - SCOPUS:85019683522
SN - 0007-1188
VL - 174
SP - 2074
EP - 2084
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 13
ER -