Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis
2025
Faisal Albaqami | Khawaja Waqas Ahmad | Fawad Ali Shah
Abstract Background Parkinson’s disease is a debilitating and the second most common neurodegenerative disorder with a high prevalence. Parkinson’s disease has a multifaceted etiology characterized by an altered redox state and an excessive inflammatory response. In this study, we investigated the potential neuroprotective properties of carvacrol in a haloperidol-induced Parkinson’s model. In female Sprague-Dawley rats, the animal Parkinson model was induced by intraperitoneally administering 1 mg / kg of haloperidol once daily for fifteen days. Carvacrol was administered at a dose of 25 and 50 mg / kg once daily for fifteen days before haloperidol administration. In order to further illustrate the vital role of the tumor necrosis factor (TNF-α) pathway, we administered 50 mg / kg of the TNF-α inhibitor thalidomide once daily for 15 days. Results Our results showed that haloperidol-induced motor deficits, changed endogenous antioxidant enzymes, along with higher levels of inflammasome (NLRP3) and other inflammatory mediators. Moreover, increased levels of lipid peroxidase (LPO) indicated a significant rise in oxidative stress due to haloperidol. Moreover, carvacrol reduced these effects by preventing pyroptosis mediated by the inflammasome (NLRP3) and TNF-α. The administration of thalidomide mitigated oxidative stress and suppresses inflammatory pathways through the augmentation of the intrinsic antioxidant system. Further, co-treatment of carvacrol with thalidomide synergized the neuroprotective effect of carvacrol as demonstrated by various immunoassays and histology analyses. Conclusions Taken together, our findings suggest that carvacrol mitigated haloperidol-induced Parkinson-like symptoms, partially through the downregulation of TNF-α and NLRP3.
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