Raghu Ganugula1, Meenakshi Arora1, Patcharawalai Jaisamut1,2, Ruedeekorn Wiwattanapatapee3, Heather G Jørgensen4, Vinod P Venkatpurwar5, Beiyan Zhou6, Aline Rodrigues Hoffmann7, Rita Basu8, Shaodong Guo9, Naga Venkata Ravi Kumar Majeti1. 1. Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, USA. 2. Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat-Yai, Songkhla, Thailand. 3. Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, Thailand. 4. Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 5. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. 6. Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA. 7. Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, USA. 8. The Integrated Carbohydrate Physiology and Translation Laboratory, Mayo Clinic, Rochester, MN, USA. 9. Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA.
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.
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.
Authors: Michael J Curtis; Richard A Bond; Domenico Spina; Amrita Ahluwalia; Stephen P A Alexander; Mark A Giembycz; Annette Gilchrist; Daniel Hoyer; Paul A Insel; Angelo A Izzo; Andrew J Lawrence; David J MacEwan; Lawrence D F Moon; Sue Wonnacott; Arthur H Weston; John C McGrath Journal: Br J Pharmacol Date: 2015-07 Impact factor: 8.739
Authors: Angelo A Izzo; Mauro Teixeira; Steve P H Alexander; Giuseppe Cirino; James R Docherty; Christopher H George; Paul A Insel; Yong Ji; David A Kendall; Reynold A Panattieri; Christopher G Sobey; S Clare Stanford; Barbara Stefanska; Gary Stephens; Amrita Ahluwalia Journal: Br J Pharmacol Date: 2020-04-16 Impact factor: 8.739