Institute for Biological Research "Siniša Stanković" National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
Section of Organic Chemistry & Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece.
Life Sci. 2022 Jan 1;288:120184. doi: 10.1016/j.lfs.2021.120184. Epub 2021 Nov 25.
Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D).
T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days.
PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b and CD11c myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c, CD8, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group.
These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.
迷迭香酸（RA）是一种存在于唇形科植物中的多酚。RA 的苯乙基酯（PERA）是一种新型 RA 衍生物，已在 1 型糖尿病（T1D）动物模型中进行了体内开发和评估。
通过腹腔内连续 5 天注射多次低剂量链脲佐菌素（STZ）在雄性 C57BL/6 小鼠中诱导 T1D。从第一次 STZ 注射开始，腹腔内给予 PERA（2.5mg/kg bw），持续 20 天。
接受 PERA 治疗的小鼠 T1D 发生率较低（从疾病诱导开始监测长达 38 天），荧光组织化学分析显示其胰岛表达更多的胰岛素。PERA 治疗在 T1D 发病早期（T1D 诱导后第 9 天）显著下调了胰岛免疫细胞浸润中 CD11b 和 CD11c 髓样细胞的比例，而在第 15 天，PERA 显著降低了 CD11c、CD8、Th1 和 Th17 细胞的比例。同时，发现接受 PERA 治疗的小鼠胰腺浸润细胞产生的活性氧明显少于对照组。
这些发现表明 PERA 可有效预防小鼠 T1D 的发生。有趣的是，PERA 通过对先天和适应性免疫反应进行时间特异性干扰，减轻了胰岛中的炎症过程，因此具有作为新型 T1D 治疗药物进行进一步临床评估的巨大潜力。
