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

Abu-Elfotuh, Karema; Abdel-Sattar, Somaia A.; Abbas, Ashwaq Najemaldeen; Mahran, Yasmen F.; Alshanwani, Aliah R.; Hamdan, Ahmed M.; Atwa, Ahmed M.; Reda, Enji; Ahmed, Yasmin Moustafa; Zaghlool, Sameh S.; El-Din, Mahmoud Nour

doi:10.1016/j.biopha.2022.113799

Cited by 26 publications

(21 citation statements)

References 115 publications

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“…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.…”

Section: •−mentioning

confidence: 99%

“…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.…”

Section: Suppression Of Neuroinflammatory Reactionsmentioning

confidence: 99%

“…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.…”

Section: Suppression Of Neuroinflammatory Reactionsmentioning

confidence: 99%

“…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.…”

Section: Modulation Of Neurotransmittersmentioning

confidence: 99%

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

Peng,

Zhang,

Sharma

et al. 2024

J. Agric. Food Chem.

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Neurodegenerative diseases pose a growing global health challenge, with limited effective therapeutic options. Mitochondrial dysfunction, oxidative stress, neuroinflammation, apoptosis, and autophagy are common underlying mechanisms in these diseases. Thymol is a phenolic monoterpene compound that has gained attention for its diverse biological properties, including antioxidant, anti-inflammatory, and immunomodulatory activities. Thymol supplementation could provide potential neuroprotection and improve cognitive deficits, depressant-like effects, learning, and memory impairments in rodents. Mechanistic investigations reveal that the neuroprotective effects of thymol involve the improvement of oxidative stress, mitochondrial dysfunction, and inflammatory response. Several signaling pathways, including mitochondrial apoptotic, NF-κB, AKT, Nrf2, and CREB/BDNF pathways are also involved. In this review, the neuroprotective effects of thymol, the potential molecular mechanisms, safety, applications, and current challenges toward development as a neuroprotective agent were summarized and discussed. We hope that this review provides valuable insights for the further development of this promising natural product as a promising neuroprotective agent.

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Section: •−mentioning

confidence: 99%

Section: Suppression Of Neuroinflammatory Reactionsmentioning

confidence: 99%

Section: Suppression Of Neuroinflammatory Reactionsmentioning

confidence: 99%

Section: Modulation Of Neurotransmittersmentioning

confidence: 99%

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

Peng,

Zhang,

Sharma

et al. 2024

J. Agric. Food Chem.

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“…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 …”

Section: Introductionmentioning

confidence: 99%

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

Xing,

Zhang,

You

et al. 2023

ACS Chem. Neurosci.

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Paclitaxel-induced peripheral neuropathy (PIPN) is one of the common adverse effects during the paclitaxel (PTX) treatment of cancer. In this study, we investigated the neuroprotective effects and mechanisms of thymoquinone (TQ) in the PIPN model. Through pain behavioral assays and histological assessment, we demonstrated that TQ significantly alleviated the nociceptive behavior, modulated the pathological changes in peripheral nerves, and decreased the expression of inflammatory factors TNF-α, IL-1β, and IL-6 induced by PIPN in mice. In addition, TQ significantly reversed the reduced viability and inflammatory response of primary DRG neurons caused by PTX. Moreover, the gene expression of related pathways was detected by Western blot, qPCR, and immunofluorescence, and the results showed that TQ exerts neuroprotective effects by regulating TLR4/MyD88 and its downstream NF-κB and MAPKs inflammatory pathways in vivo and in vitro. The treatment with TLR4 antagonist TAK-242 further indicated the important role of the TLR4/MyD88 signaling pathway in PIPN. Furthermore, molecular docking and a cellular thermal shift assay were used to confirm the interaction of TQ with TLR4. In summary, our study shows that TQ can inhibit inflammatory responses against PIPN by regulating TLR4 and MyD88 and its downstream inflammatory pathways.

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Preclinical Evaluation of Protective Effects of Terpenoids Against Nanomaterial‐Induced Toxicity: A Meta‐Analysis

Sun,

Zhou,

Xie

et al. 2024

J of Applied Toxicology

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Terpenoids, the largest class of natural products, have been demonstrated to confer antioxidant, anti‐inflammatory, anti‐apoptotic, and antitumor activities. However, whether terpenoids benefit populations exposed to nanomaterials through these mechanisms remains unclear. This meta‐analysis was to evaluate the effects of terpenoids in preclinical models with nanomaterial exposure. Electronic database searching identified 39 studies. The meta‐analysis by Stata 15.0 showed that terpenoid supplementation significantly improved cell viability and altered oxidative stress (decreased ROS, NO, MDA, and TOC and increased SOD, CAT, GPx, GSH, GSH‐Px, and TAC)–, inflammation (decreased IL‐6, IL‐1β, TNF‐α, NF‐κB, monocytes, and increased IL‐10)–, apoptosis (reduced Bax, caspase‐3, caspase‐9, P53, and elevated Bcl‐2)–, genotoxic (reduced tail length, % tail DNA, tail moment, DNA fragmentation, chromosomal aberration, and MNPCEs)–, liver function (reduced ALT, AST, and ALP)–, renal function (reduced creatinine, urea, and uric acid)–, reproductive function (increased sperm count, testosterone, Johnsen's score, and number of progeny)–, lipid profile (lower cholesterol, TG, LDL, and higher HDL)–, and carcinogenesis (downregulated AFP and CEA)–related biomarkers induced by nanomaterials. Subgroup analysis indicated that monoterpenoids and tetraterpenoids were particularly effective. Collectively, terpenoids may be a promising candidate for prevention of toxicities caused by nanomaterials.

show abstract

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

Cited by 26 publications

References 115 publications

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

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

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

Preclinical Evaluation of Protective Effects of Terpenoids Against Nanomaterial‐Induced Toxicity: A Meta‐Analysis

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