Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model

Abstract

Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.