Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice

• Published in: Life sciences (1973) 2022-01, Vol.288, p.120184-120184, Article 120184
• Main Authors: Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Gajić, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas G., Stojanović, Ivana
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Animal models; Animals; Autoimmunity; CD11b antigen; CD11c antigen; CD8 antigen; Cinnamates - chemistry; Cinnamates - pharmacology; Depsides - chemistry; Depsides - pharmacology; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - prevention & control; Esters - chemistry; Fluorescence; Helper cells; Histochemical analysis; Immune response; Immune system; In vivo methods and tests; Inflammation; Insulin; Islets of Langerhans - drug effects; Islets of Langerhans - immunology; Islets of Langerhans - pathology; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; Myeloid cells; Pancreas; Pathogenesis; Phenylethyl Alcohol - chemistry; Reactive oxygen species; Rosmarinic Acid; Streptozocin; Streptozotocin; Type 1 diabetes
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120184

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. [Display omitted]