Aims: There is a close link between oxidative stress, inflammation, and type 2 diabetes mellitus (T2DM). Gentisic acid (GA) is a di-phenolic compound and an active metabolite of aspirin that possesses antioxidant and anti-inflammatory properties, but its potential anti-diabetic effects have not been evaluated so far. Therefore, this study aimed to evaluate GA's potential antidiabetic effects through the Nuclear Factor Erythroid 2-Related Factor (Nrf2) and Nuclear Factor Kappa Beta (NF-кB) signaling pathways.
Material and methods: In this study, T2DM induced by a single intraperitoneal injection of STZ (65 mg/kg B.W) after 15 min nicotinamide (120 mg/kg B.W) injection. After seven days of injections, fasting blood glucose (FBS) was measured. Seven days after FBS monitoring treatments started. Grouping and treatments were as follows: 1) Normal control group; NC, 2) Diabetic control group; DC, 3) Metformin group; MT (150 mg/kg B.W, daily), 4) Test group; GA (100 mg/kg B.W, daily). Treatments continued for 14 consecutive days.
Key findings: Diabetic mice treatment with GA significantly decreased FBS, improved plasma lipid profiles and pancreatic antioxidant status. GA modulated Nrf2 pathway by upregulation of Nrf2 protein, NAD(P)H: quinone oxidoreductase 1 (Nqo1), and p21, and downregulation of miR-200a, Kelch-like ECH-associated protein 1 (Keap1), and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2). Also, GA attenuated inflammation by upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and interleukin-10 (IL-10) and downregulation of miR-125b, NF-кB, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß).
Significance: GA attenuates T2DM, possibly by improving antioxidant status through the Nrf2 pathway and attenuation of inflammation.
Keywords: Gentisic acid; Inflammation; NF-кB; Nrf2 pathway; Oxidative stress; Type 2 diabetes mellitus.
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