Blood-brain barrier breakdown, memory impairment and neurotoxicity caused in mice submitted to orally treatment with thymol

Baldissera, Matheus D.; Souza, Carine F.; Matos, Antônio Francisco Igor Magalhães de; Doleski, Pedro H.; Baldisserotto, Bernardo; Silva, Aleksandro S. Da; Monteiro, Sílvia González

doi:10.1016/j.etap.2018.06.012

Cited by 11 publications

(13 citation statements)

References 49 publications

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“…Although some studies from in vitro cell models and animal experiments indicated thymol supplementation exhibited potent effectiveness for multiple neurological diseases, it still lacks clinical trials for humans. Notably, several studies also found that oral administration of thymol at a higher dose (i.e., 40 mg/kg per day) for 30 days could result in potential neurotoxicity . In addition, it also reported that a higher dose of thymol exposure (i.e., 100 μM) could also induce oxidative stress and apoptotic cell death in zebrafish ( Danio rerio ) embryos .…”

Section: Clinical Applicationmentioning

confidence: 99%

“…A previous study showed that thymol could be detected in liver, kidney, and mucosal tissues in pigs after oral administration . Although data on thymol levels in brain tissues after administration are lacking, numerous studies from different research groups have reported significant neuroprotective effects, mainly reflected in changes in neurobehavioral and pathological damage of brain tissues. ,, Table summarizes the findings of in vitro and animal experiments investigating the neuroprotective effects of thymol and essential oils containing thymol. Overall, thymol supplementation improves various aspects of neurobehavior, including learning and memory deficits, depressive symptoms, neuro-aging, neurotoxicity, Alzheimer’s disease, and Parkinson’s disease.…”

Section: Overview Of Thymol’s Neuroprotective Effectsmentioning

confidence: 99%

“…33 Although data on thymol levels in brain tissues after administration are lacking, numerous studies from different research groups have reported significant neuroprotective effects, mainly reflected in changes in neurobehavioral and pathological damage of brain tissues. 23,24,36…”

Section: Overview Of Thymol's Neuroprotective Effectsmentioning

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: Clinical Applicationmentioning

confidence: 99%

Section: Overview Of Thymol’s Neuroprotective Effectsmentioning

confidence: 99%

See 1 more Smart Citation

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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“…These essential oils contain significant quantities of terpenoids, particularly monoterpenes and sesquiterpenes (Lizarraga‐Valderrama, 2021). Furthermore, studies have reported that monoterpenoids, such as menthol (Liang et al, 2019), geniposide (Li et al, 2019), and thymol (Baldissera et al, 2018), can pass through the BBB.…”

Section: Introductionmentioning

confidence: 99%

Study on the opening effect of eucalyptol on the blood–brain barrier and its brain pharmacokinetics

Dao

Jiang

Chen

et al. 2023

Biomedical Chromatography

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Eucalyptol, a natural epoxide monoterpene, was found in rat brain tissue after oral administration in our previous study, suggesting that the compound may possess the ability to pass the blood–brain barrier (BBB). However, a few studies have demonstrated that eucalyptol does penetrate the BBB. The aims of this study were to determine the opening effect of eucalyptol on the BBB in rats, to establish and validate a method for the determination of eucalyptol in brain tissue, and to reveal its brain pharmacokinetic characteristics. The opening effect of BBB was assessed by dye extravasation and ultrastructural alterations, and the quantitative method of eucalyptol in rat brain tissue was established and confirmed. For pharmacokinetic research, rat brain samples were taken at 0.05, 0.167, 0.5, 1, 2.5, 5, 10, and 15 h after administration. There was a significantly higher extravasation of Evans blue from the brain parenchyma of rats in the medium‐dose eucalyptol group (P < 0.01), which was associated with the BBB's altered ultrastructure. It is suggested that eucalyptol increased the permeability of the BBB. After oral administration, eucalyptol was quickly absorbed by the brain. This study provides valuable information on eucalyptol use to treat illnesses of the central nervous system.

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“…Several studies have currently shown that thymol can lead to the breakdown of adenosine triphosphate (ATP) synthesis, which disrupts the bioenergy balance and damages mitochondrial energy production. It may also cause metabolic disorders of Na + and Ca 2+ in cells to produce excessive oxygen free radicals, leading to cell death [36][37][38]. erefore, application of thymol is considered as an efficient treatment for food preservation and control of microbial growth and infection [16,39,40].…”

Section: Introductionmentioning

confidence: 99%

Thymol Disrupts Cell Homeostasis and Inhibits the Growth of Staphylococcus aureus

Huang

Pan

et al. 2022

Contrast Media & Molecular Imaging

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Staphylococcus aureus (S. aureus) is a typical kind of symbiotic bacteria, which can cause human pneumonia, food poisoning, and other health problems. Nowadays, the corresponding prevention and treatment have been a hot issue of general concern in related research areas. However, the mechanism of action against S. aureus is not well understood. In order to tackle such problem, we used broth microdilution to discuss the antibacterial effect of 5-methyl-2-isopropylphenol and determine inhibitory concentration. In addition, membrane potential and lipid peroxidation levels were also measured under experimental conditions. The experimental results suggested that 300 μg/mL thymol might cause cell membrane damage and decrease of NADPH concentration and increase of NADP+ and lipid peroxidation level. In such condition, thymol has the potential to result in membrane rupture and disruption of cellular homeostasis. Furthermore, we also found that NOX2 is involved in maintaining the balance of NADPH/NADP+ in cells. Finally, our work confirms that NOX2 is a potential downstream target for thymol in the cell. Such target can provide specific guidance and recommendations for its application in antifungal activity. Meanwhile, our study also provides a new inspiration for the molecular mechanism of thymol’s bacteriostatic action.

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Blood-brain barrier breakdown, memory impairment and neurotoxicity caused in mice submitted to orally treatment with thymol

Cited by 11 publications

References 49 publications

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

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

Study on the opening effect of eucalyptol on the blood–brain barrier and its brain pharmacokinetics

Thymol Disrupts Cell Homeostasis and Inhibits the Growth of Staphylococcus aureus

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