Abstract
Both thymoquinone (TQ) and thymol (T) have been proved to possess a positive impact on human health. In this research, we aimed to investigate the effect of these compounds separately and together on the Attention-deficit/hyperactivity disorder (ADHD)-like behavior induced by monosodium glutamate (MSG) in rats. Forty male, Spargue Dawley rat pups (postnatal day 21), were randomly allocated into five groups: Normal saline (NS), MSG, MSG+TQ, MSG+T, and MSG+TQ+T. MSG (0.4 mg/kg/day), TQ (10 mg/kg/day) and T (30 mg/kg/day) were orally administered for 8 weeks. The behavioral tests proved that rats treated with TQ and/or T showed improved locomotor, attention and cognitive functions compared to the MSG group with more pronounced effect displayed with their combination. All treated groups showed improvement in MSG-induced aberrations in brain levels of GSH, IL-1β, TNF-α, GFAP, glutamate, calcium, dopamine, norepinephrine, Wnt3a, β-Catenin and BDNF. TQ and/or T treatment also enhanced the mRNA expression of Nrf2, HO-1 and Bcl2 while reducing the protein expression of TLR4, NFκB, NLRP3, caspase 1, Bax, AIF and GSK3β as compared to the MSG group. However, the combined therapy showed more significant effects in all measured parameters. All of these findings were further confirmed by the histopathological examinations. Current results concluded that the combined therapy of TQ and T had higher protective effects than their individual supplementations against MSG-induced ADHD-like behavior in rats.
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•The repeated neonatal monosodium glutamate exposure induces ADHD-like behavior in rats.•Oxidative stress and neuroinflammation are implicated in monosodium glutamate-induced excitotoxicity.•Thymoquinone and thymol effectively alleviate monosodium glutamate-induced neurotoxicity.•Thymoqinone has superior protective effect over Thymol in all tested biomarkers for protecting against ADHD except for GSK-3β.•Thymoquinone and thymol targets Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/β-Catenin signaling pathways in their protective effect.•Combination therapy gives better effect than each individual drug.