Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus
Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus
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DOI：
10.1111/bph.13816
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发表时间：
2017-07-01
影响因子：
7.3
通讯作者：
Majeti, Naga Venkata Ravi Kumar
中科院分区：
文献类型：
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作者：
Ganugula, Raghu;Arora, Meenakshi;Majeti, Naga Venkata Ravi Kumar
背景和目的预防1型糖尿病（T1 DM）中产生胰岛素的β细胞的选择性和进行性丧失的方法将有助于控制这种流行的毁灭性疾病。姜黄素（CUR），一种天然的抗炎物质，抑制糖尿病相关的炎症和细胞死亡。然而，非常高的剂量需要使用，因为口服生物利用度差，使其难以翻译的抗炎作用，以临床situation.Experimental ApproachWe已经制备了可生物降解的纳米系统封装姜黄素（nCUR），导致在口服生物利用度的至少9倍的改善。在这里，我们测试了nCUR的能力，以防止链脲佐菌素（STZ）诱导的炎症和细胞凋亡的胰岛和β细胞，在rats.Key ResultsNon-fasted大鼠预处理10或50 mgkg（-1）nCUR 6小时前STZ的挑战有高达37%的葡萄糖水平下降，而平原CUR（50 mgkg（-1））的结果在12%的下降。用nCUR的这种处理伴随着胰岛或β细胞死亡的减少，如TUNEL测定和H&E染色所示。CUR和nCUR均显着降低胰腺组织匀浆中炎症细胞因子的水平，这与最小的组织细胞浸润密切相关。用nCUR预处理，而不是CUR，减少胰腺中ROS诱导的DNA损伤的敏感生物标志物8-氧代-2-脱氧鸟苷。在正常啮齿类动物中，每日给药nCUR（25- 100 mgkg（-1））28天不会引起携带者的任何有害健康问题。结论和启示总之，这些数据表明nCUR的潜在可转化剂量在改善β细胞功能方面是安全有效的，这可以预防T1 DM。
Background and PurposeApproaches 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 ApproachWe 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 ResultsNon-fasted rats pretreated with 10 or 50mgkg(-1) nCUR 6h prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50mgkg(-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 28days, with nCUR (25-100mgkg(-1)) did not cause any deleterious health issues by the carrier.Conclusions and ImplicationsTogether, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving beta cell function, which could prevent T1DM.