Hyssopus officinalis exerts hypoglycemic effects on streptozotocin-induced diabetic rats via modulating GSK-3β, C-fos, NF-κB, ABCA1 and ABGA1 gene expression

Objectives: Type 2 diabetes mellitus (DMT2) is contributed to dual interactions between environmental factors and certain genetic factors. This impressed a great need for novel treatment strategy. Nevertheless, Hyssopus officinalis (H. officinalis) as a terrestrial herb is considered to be an important source of natural antioxidants, it could be assessed as an anti-hyperglycemic agent.

Methods: In the current study, HPLC identified the active constitutes of H. officinalis, including total polyphenols, and flavonoids. Type 2 diabetes mellitus was induced in male Wistar albino rats via a single ip dose of streptozotocin (STZ) (35 mg/kg BW). One week post diabetes induction, rats were administrated H. officinalis (500 mg/ kg BW) orally for one month. Molecular analysis was assessed to investigate the efficiency of H. officinalis on modulating ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes, in addition to apoptotic biomarkers, glycogen synthase kinase-3β (GSK-3β) and cellular oncogene-fos (C-fos) genes. Furthermore, inflammatory biomarkers, nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) gene expression were also assessed.

Results: H. officinalis alcoholic extract declared the presence of polyphenols as gallic acid and flavonoids as quercetin in addition to many active constituents. Apigenin-7-glucoside and Chlorgenic acid were the most common constituents in the extract. RT-PCR results declared a significant up-regulation in mRNA gene expression of ABCA1 and ABCG1 upon H. officinalis treatment. Meanwhile, C-fos gene expression recorded a slight down-regulation. Gene expression of apoptotic biomarker GSK-3β demonstrated a significant down regulation as well as inflammatory biomarkers NF-κB and TNF-α.

Conclusion: From the data recorded, it could be concluded that H. officinalis exerts a great hypoglycemic potential via modulating C-fos, GSK-3β, NF-κB, TNF-α, ABCA1 and ABCG1 gene expression and signaling pathways and could be considered as an effective candidate for DMT2 treatment.

Keywords: ABCA1 gene; ABCG1 gene; C-fos & GSK-3β; Hyssopus officinalis; NF-κB; T2DM; TNF-α.