The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/β-Catenin signaling pathways in rat model

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects

“…24 Thymol's antioxidant capacity is partly attributed to its ability to regulate the Nrf2 and protein kinase B (AKT) signaling pathways. 29,50,51 Nrf2 is a critical transcription factor that governs the regulation of over 200 genes, including those encoding SOD, CAT, and GPX, to resist oxidative stress. 29,52 In another study, it found that Monarda didyma L. essential oil and thymol supplementation in mice could both significantly upregulate the expressions of Nrf2, and its downstream HO-1, SOD2, and NAD (P)H: quinone oxidoreductase 1(NQO1) proteins, protecting against aging-induced learning and memory impairments and brain oxidative stress damage.…”

“…2,27 In line with these findings, Abu-Elfotuh et al found that oral thymol supplementation at the dose of 30 mg/kg/day for 56 days significantly inhibited the expressions of TLR4, NF-κB, and NLRP3 mRNAs, then reduced nuclear pyknosis and degeneration in the cerebral cortex and hippocampus regions in the brain tissues, finally improving monosodium glutamate exposure-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats. 71 Caspase-1 and caspase-8 could lyse gasdermin D (GSDMD) to cause cell pyroptosis, which is required for the secretion and release of IL-1β. 72 Necroptosis is another death that depends on receptorinteracting protein kinase 1 (RIPK1) and RIPK3, and it promotes the formation of NLRP3 inflammasome and the release of IL-1β.…”

“…Additionally, thymol has been associated with reduced expression of glial fibrillary acidic protein (GFAP), an indicator of neuroinflammation. 23,71,75 The expression of GFAP could be regulated by NF-κB at the transcriptional level. 76 This further demonstrated the inhibition of NF-κB plays a central role for thymol against neuroinflammation.…”

“…92 Thymol and essential oils containing thymol have been shown to improve neurobehavioral changes, including locomotor, attention, learning, and cognitive functions in animal models. 22,24,50,69 Thymol's regulation of neurotransmitters, including DA, NE, 5-HT, GABA, and Ach, contributes to its neuroprotective effects.…”

Thymoquinone Alleviates Paclitaxel-Induced Peripheral Neuropathy through Regulation of the TLR4-MyD88 Inflammatory Pathway

“…TQ has great anti-inflammatory and antioxidant activities and is frequently utilized in studies on antidiabetic, anticancer, cardioprotective, and neuroprotective studies. The anti-inflammatory activity of TQ has been reported to be based on its ability to effectively inhibit the activation of TLR4 and its downstream inflammatory pathways. , There is evidence that TQ has a protective effect on the sciatic nerve and DRG in peripheral nerve injury , and can reduce peripheral neuropathy caused by diabetes. , In addition, there is preliminary in vitro evidence that TQ can prevent cisplatin-mediated neurotoxicity in primary DRG neurons, but the mechanism of action is unclear …”