Abstract：
The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of β-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for β-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.
摘要：
1型糖尿病(T1DM)的发病机制涉及氧化应激和炎症反应。姜黄素,一种在姜黄中发现的天然多酚化合物，已知具有抗氧化和抗炎特性，化学稳定性差，低生物利用度，和快速的新陈代谢。具有β-二酮结构缺失和增强的稳定性和生物利用度的姜黄素的单羰基类似物(MAC)提出了与使用姜黄素相关的挑战的潜在解决方案。本研究旨在评估两种MAC的效果，C66和B2BrBC，关于氧化应激标志物，抗氧化酶活性，糖尿病相关基因的表达，和信号通路蛋白在T1DM的背景下。链脲佐菌素（STZ）诱导的雄性Wistar大鼠或大鼠胰腺RIN-m细胞用于体内和体外实验，分别。在STZ治疗之前或之后给予C66或B2BrBC。在各种组织中确定了氧化应激标记和抗氧化酶活性。使用RT-qPCR评估糖尿病相关基因的表达，通过Westernblot分析确定胰腺中信号通路蛋白的活性。用C66和B2BrBC处理可显着降低氧化应激标志物，并对抗氧化酶活性产生积极影响。此外，两种化合物均抑制胰腺中的JNK活性，同时增强对β细胞存活以及葡萄糖和氧化还原稳态至关重要的基因的表达。研究结果强调了C66和B2BrBC在改善氧化应激方面的多方面潜力，影响与糖尿病相关的基因表达模式，调节胰腺中的关键信号通路。研究结果表明，这些化合物可以潜在地解决糖尿病相关的病理过程。
