{"title":"Role of Nitric Oxide Modulators in Neuroprotective Effects of Mangiferin in 6-Hydroxydopamine-induced Parkinson's Disease in Rats.","authors":"Prafulla Chandra Tiwari, Manju J Chaudhary, Rishi Pal, Rajendra Nath","doi":"10.1177/09727531231184698","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is typified by inflammation of dopaminergic neurons leading to the release of various inflammatory mediators. These mediators activate the transcription factor NF-κB, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation.</p><p><strong>Purpose: </strong>This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-κB with low-dose nitric oxide (NO) modulators.</p><p><strong>Methods: </strong>A total of eight Wistar rats weighing 200-250 g were used in each group. Stereotactic surgery was performed to induce 6-hydroxydopamine (6-OHDA) lesions. The treatment period extended from day 14 to day 42, during which time behavioral tests were performed to evaluate the effects of mangiferin and its combination with NO modulators. On day 42, the brains of the rats were removed for biochemical and molecular analyzes.</p><p><strong>Results: </strong>Mangiferin significantly improved locomotor activity and decreased inflammatory chemokines levels in rats with 6-OHDA lesions. Mangiferin therapy decreased myeloperoxidase (MPO) levels and reduced oxidative stress. In particular, caspase-3, caspase-9 and COX-2 activities were significantly reduced after the mangiferin treatment. A combination of 45-µg mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA.</p><p><strong>Conclusion: </strong>In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-α and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-µg mangiferin enhanced the anti-inflammatory and anti-Parkinsonian activity of mangiferin. Consequently, the combination therapy of mangiferin and L-NAME is promising for the treatment of PD. However, clinical trials will be required to evaluate the efficacy of this combination therapy in humans.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"186-203"},"PeriodicalIF":16.4000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325687/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/09727531231184698","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/23 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Parkinson's disease (PD) is typified by inflammation of dopaminergic neurons leading to the release of various inflammatory mediators. These mediators activate the transcription factor NF-κB, which in turn activates inducible nitric oxide synthase (iNOS), leading to increased inflammation.
Purpose: This study was intended to study the effect of combination of mangiferin, a specific inhibitor of NF-κB with low-dose nitric oxide (NO) modulators.
Methods: A total of eight Wistar rats weighing 200-250 g were used in each group. Stereotactic surgery was performed to induce 6-hydroxydopamine (6-OHDA) lesions. The treatment period extended from day 14 to day 42, during which time behavioral tests were performed to evaluate the effects of mangiferin and its combination with NO modulators. On day 42, the brains of the rats were removed for biochemical and molecular analyzes.
Results: Mangiferin significantly improved locomotor activity and decreased inflammatory chemokines levels in rats with 6-OHDA lesions. Mangiferin therapy decreased myeloperoxidase (MPO) levels and reduced oxidative stress. In particular, caspase-3, caspase-9 and COX-2 activities were significantly reduced after the mangiferin treatment. A combination of 45-µg mangiferin and 10-mg/kg L-NAME showed the greatest improvement in locomotor, behavioral, biochemical, and molecular parameters impaired by 6-OHDA.
Conclusion: In this study, mangiferin was found to protect rats with 6-OHDA lesions by inhibiting inflammation causing chemokines such as TNF-α and IL-6. Besides, the grouping of iNOS inhibitor L-NAME at a dose of 10 mg/kg with 45-µg mangiferin enhanced the anti-inflammatory and anti-Parkinsonian activity of mangiferin. Consequently, the combination therapy of mangiferin and L-NAME is promising for the treatment of PD. However, clinical trials will be required to evaluate the efficacy of this combination therapy in humans.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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