Methanolic Extract of Sambucus ebulus Ameliorates Clinical Symptoms in Experimental Type 1 Diabetes through Anti-Inflammatory and Immunomodulatory Actions

Abstract

Objective: Sambucus ebulus (SE), a famous traditional Iranian medicine, is grown in the north of Iran. As a traditional medicine with anti-inflammatory effects, SE has been utilized against inflammatory joint diseases, insect bites, infectious wounds, edema, and eczema. Type1 diabetes, is an autoimmune disease, characterized by the destruction of pancreatic beta cells by the immune system. For the first time, we investigated the effect of methanolic extract of SE on CD4+, CD8+ and regulatory T cells in experimental type 1 diabetes (T1D). Materials and Methods: In this experimental study, fifty-six C57BL\6 mice in 8 groups (G1-G8), were enrolled. Diabetes was induced by a multiple low-dose streptozotocin (MLDS) protocol and mice were daily treated with SE extract at 200 and 400 mg/kg doses, for 35 days. Fasting blood glucose was weekly measured by a glucometer. Islets insulin content was analyzed by immunohistochemistry. Percentage of CD4+, CD8+ and regulatory T cells and cytokines production levels were evaluated by flow cytometer and ELISA, respectively. Results: The clinical symptoms of diabetes were significantly alleviated in G2 group mice which received 400 mg/kg SE extract. Immunohistochemistry analysis showed that the insulin content of islets increased in G2 group mice. Immunophenotyping analysis indicated that the percentage of CD4+ and CD8+ T cells in G2 group mice was significantly decreased. SE extract significantly increased the percentage of regulatory T cells. The extract in G2 and G4 groups mice significantly decreased IFN-γ and IL-17levels. The extract significantly increased IL-10 in G2 group mice. Conclusion: The protective effect of SE extract in MLDS-induced diabetes could be partly due to a decrease of CD4+ and CD8+ T cells and an increase of Treg cells resulting in an inflammation reduction in the pancreatic islets.

Keywords

• cd4+ t cell
• cd8+ t cell
• regulatory t cell
• sambucu sebulus
• type 1 diabetes