Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada.
Molecules. 2023 Nov 16;28(22):7619. doi: 10.3390/molecules28227619.
Inflammation is a natural immune response to injury, infection, or tissue damage. It plays a crucial role in maintaining overall health and promoting healing. However, when inflammation becomes chronic and uncontrolled, it can contribute to the development of various inflammatory conditions, including type 2 diabetes. In type 2 diabetes, pancreatic β-cells have to overwork and the continuous impact of a high glucose, high lipid (HG-HL) diet contributes to their loss and dedifferentiation. This study aimed to investigate the anti-inflammatory effects of eugenol and its impact on the loss and dedifferentiation of β-cells. THP-1 macrophages were pretreated with eugenol for one hour and then exposed to lipopolysaccharide (LPS) for three hours to induce inflammation. Additionally, the second phase of NLRP3 inflammasome activation was induced by incubating the LPS-stimulated cells with adenosine triphosphate (ATP) for 30 min. The results showed that eugenol reduced the expression of proinflammatory genes, such as , and , potentially by inhibiting the activation of transcription factors NF-κB and TYK2. Eugenol also demonstrated inhibitory effects on the levels of NLRP3 mRNA and protein and Pannexin-1 (PANX-1) activation, eventually impacting the assembly of the NLRP3 inflammasome and the production of mature IL-1β. Additionally, eugenol reduced the elevated levels of adenosine deaminase acting on RNA 1 (ADAR1) transcript, suggesting its role in post-transcriptional mechanisms that regulate inflammatory responses. Furthermore, eugenol effectively decreased the loss of β-cells in response to HG-HL, likely by mitigating apoptosis. It also showed promise in suppressing HG-HL-induced β-cell dedifferentiation by restoring β-cell-specific biomarkers. Further research on eugenol and its mechanisms of action could lead to the development of therapeutic interventions for inflammatory disorders and the preservation of β-cell function in the context of type 2 diabetes.
炎症是机体对损伤、感染或组织损伤的天然免疫反应。它在维持整体健康和促进愈合方面起着至关重要的作用。然而，当炎症变成慢性和不受控制时，它可能会导致各种炎症性疾病的发展，包括 2 型糖尿病。在 2 型糖尿病中，胰岛β细胞需要过度工作，高糖高脂（HG-HL）饮食的持续影响导致其损失和去分化。本研究旨在探讨丁香酚的抗炎作用及其对β细胞损失和去分化的影响。THP-1 巨噬细胞用丁香酚预处理 1 小时，然后用脂多糖（LPS）孵育 3 小时诱导炎症。此外，通过用三磷酸腺苷（ATP）孵育 LPS 刺激的细胞 30 分钟来诱导 NLRP3 炎性小体激活的第二阶段。结果表明，丁香酚通过抑制转录因子 NF-κB 和 TYK2 的激活，降低了促炎基因如、和的表达。丁香酚还对 NLRP3 mRNA 和蛋白水平以及 Pannexin-1（PANX-1）的激活具有抑制作用，最终影响 NLRP3 炎性小体的组装和成熟 IL-1β的产生。此外，丁香酚降低了腺苷脱氨酶作用于 RNA 1（ADAR1）转录物的升高水平，表明其在调节炎症反应的转录后机制中发挥作用。此外，丁香酚有效减少了 HG-HL 引起的β细胞丢失，可能通过减轻细胞凋亡来实现。它还显示出通过恢复β细胞特异性生物标志物抑制 HG-HL 诱导的β细胞去分化的潜力。对丁香酚及其作用机制的进一步研究可能会导致开发治疗炎症性疾病的干预措施，并在 2 型糖尿病的背景下保护β细胞功能。
