Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis
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 p...
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BMC
2025-02-01
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| Series: | Laboratory Animal Research |
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| Online Access: | https://doi.org/10.1186/s42826-025-00237-7 |
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| author | Faisal Albaqami Khawaja Waqas Ahmad Fawad Ali Shah |
| author_facet | Faisal Albaqami Khawaja Waqas Ahmad Fawad Ali Shah |
| author_sort | Faisal Albaqami |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e988c6cb02374c5e9d3520f1fa3dfca9 |
| institution | Kabale University |
| issn | 2233-7660 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Laboratory Animal Research |
| spelling | doaj-art-e988c6cb02374c5e9d3520f1fa3dfca92025-02-09T12:09:16ZengBMCLaboratory Animal Research2233-76602025-02-0141111110.1186/s42826-025-00237-7Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosisFaisal Albaqami0Khawaja Waqas Ahmad1Fawad Ali Shah2Department of Pharmacology and Toxicology, College of Pharmacy Prince Sattam bin Abdulaziz UniversityRiphah Institute of Pharmaceutical Sciences, Riphah International UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy Prince Sattam bin Abdulaziz UniversityAbstract 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.https://doi.org/10.1186/s42826-025-00237-7ParkinsonCarvacrolInflammasomeThalidomideOxidative stressHaloperidol |
| spellingShingle | Faisal Albaqami Khawaja Waqas Ahmad Fawad Ali Shah Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis Laboratory Animal Research Parkinson Carvacrol Inflammasome Thalidomide Oxidative stress Haloperidol |
| title | Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis |
| title_full | Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis |
| title_fullStr | Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis |
| title_full_unstemmed | Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis |
| title_short | Carvacrol attenuated haloperidol-induced Parkinson’s disease via TNF/NFκβ-NLRP3-mediated pyroptosis |
| title_sort | carvacrol attenuated haloperidol induced parkinson s disease via tnf nfκβ nlrp3 mediated pyroptosis |
| topic | Parkinson Carvacrol Inflammasome Thalidomide Oxidative stress Haloperidol |
| url | https://doi.org/10.1186/s42826-025-00237-7 |
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