{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:39:20Z","timestamp":1790203160465,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002641","name":"Konkuk University","doi-asserted-by":"publisher","award":["2020"],"award-info":[{"award-number":["2020"]}],"id":[{"id":"10.13039\/501100002641","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson\u2019s disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinflammatory effects of HMA (0.1, 1.0, and 10 \u03bcM) were mediated by phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (I\u03baB\u03b1) in LPS-stimulated BV-2 cells. In vivo evaluations revealed that intraperitoneal administration of potent neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg\/kg, four times a 1 day) in mice resulted in activation of microglia in the brain in association with severe behavioral deficits as assessed using a pole test. However, prevention of microglial activation and attenuation of Parkinson\u2019s disease (PD)-like behavioral changes was obtained by oral administration of HMA (30 mg\/kg) for 14 days. Considering the overall results, our study showed that HMA exhibited strong anti-neuroinflammatory effects at lower concentrations than its parent compound. Further work is warranted in other animal and genetic models of PD for evaluating the efficacy of HMA to develop a potential therapeutic agent in the treatment of microglia-mediated neuroinflammatory disorders, including PD.<\/jats:p>","DOI":"10.3390\/ijms21218195","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T09:04:46Z","timestamp":1604307886000},"page":"8195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["2-Hydroxy-4-Methylbenzoic Anhydride Inhibits Neuroinflammation in Cellular and Experimental Animal Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"Soo-Yeol","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Konkuk University, Chungju 380-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-8433","authenticated-orcid":false,"given":"In-Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Konkuk University, Chungju 380-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushruta","family":"Koppula","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Konkuk University, Chungju 380-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8390-7713","authenticated-orcid":false,"given":"Byung-Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Konkuk University, Chungju 380-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hwa","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-1524","authenticated-orcid":false,"given":"Dong-Kug","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Konkuk University, Chungju 380-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.neuroscience.2008.07.031","article-title":"Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: Underlying mechanisms","volume":"158","author":"Perry","year":"2009","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00401-010-0722-x","article-title":"Contribution of systemic inflammation to chronic neurodegeneration","volume":"120","author":"Perry","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/imm.12922","article-title":"Inflammation in CNS neurodegenerative diseases","volume":"154","author":"Stephenson","year":"2018","journal-title":"Immunology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/imm.12134","article-title":"Innate and adaptive immune responses in neurodegeneration and repair","volume":"141","author":"Amor","year":"2014","journal-title":"Immunology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the immune response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. 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