Honey polyphenolic fraction inhibits cyclooxygenase-2 expression via upregulation of microRNA-26a-5p expression in pancreatic islets

Objectives Honey total polyphenolic fraction (HTPF) is reported to have anti-disease potential, however the role of HTPF in the regulation of microRNAs (miRNAs) has never been investigated. This study was undertaken to investigate the potential of HTPF against inflammation via regulation of miRNAs in pancreatic islets of Langerhans. Methods Pancreatic islets were isolated from C57BL/6 mice and HTPF was purified from honey. Bioinformatics algorithms were used to determine miRNA target genes. Expression of miRNA and mRNA was determined using their specific taqman assays. Pairing between miRNA and 3(') untranslated region (3(')UTR) of mRNA was confirmed using luciferase reporter clone containing the 3(')UTR of mRNA sequences and results were verified by transfection of mouse pancreatic beta-cell line Min6 with miRNA inhibitors. Results The data showed that mmu-miR-26a-5p is a direct regulator of cyclooxygenase-2 (COX-2) expression and HTPF inhibits COX-2 expression or prostaglandin E-2 (PGE(2)) production via up-regulating mmu-miR-26a-5p expression. Transfection of islets with anti-miR-26a-5p significantly enhanced COX-2 expression and PGE(2) production (p < .01), while HTPF treatment significantly inhibited anti-miR-26a-5p transfection-induced COX-2 expression or PGE(2) production (p < .05). These findings were further verified in pancreatic beta-cells Min6. Moreover, the data also determined that HTPF also inhibits glucose-induced nuclear transcription factor (NF)-kappa B activity. Conclusion HTPF suppresses glucose-induced PGE(2) production and activation of NF-kappa B via negative regulation of COX-2 and mmu-miR26a-5p. These novel pharmacological actions of HTPF on glucose-stimulated pancreatic islets provide new suggestions that HTPF or HTPF-derived compounds inhibit glucose induced inflammation in pancreas by up-regulating the expression of microRNAs.