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Botanical extracts are viable and sustainable alternatives to synthetic drugs, being essential in drug discovery for various diseases. Senna septemtrionalis (Viv.) H.S. Irwin &amp; Barneby is a medical plant traditionally used to treat inflammation. However, its antioxidant and anti-inflammatory properties and the molecular pathways activated in microglial cells require further investigation. Therefore, this study examines the antioxidant and anti-inflammatory properties of Senna septemtrionalis (Viv.) H.S. Irwin &amp; Barneby methanol extracts (SMEs) in lipopolysaccharide (LPS)-stimulated mouse microglial cells. SMEs significantly inhibit LPS-induced nitric oxide (NO) and proinflammatory cytokine production, which are mediated through the dephosphorylation of mitogen-activated protein kinases and inhibition of nuclear factor kappa B (NF-\u03baB) translocation into the nucleus. Additionally, SME treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1, reducing oxidative stress, indicated by a decrease in reactive oxygen species and restoration of the total glutathione content in LPS-stimulated BV2 cells. The inhibitory effects of SMEs on inflammatory mediator production and NF-\u03baB nuclear translocation were significantly reversed by Sn-protoporphyrin, a specific HO-1 inhibitor. These findings demonstrate that SME protects microglial cells by activating the Nrf2\/HO-1 pathway and inhibiting NF-\u03baB translocation.<\/jats:p>","DOI":"10.3390\/ijms26051932","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:47:17Z","timestamp":1740379637000},"page":"1932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antioxidant and Anti-Inflammatory Activities of Methanol Extract of Senna septemtrionalis (Viv.) H.S. Irwin &amp; Barneby Through Nrf2\/HO-1-Mediated Inhibition of NF-\u03baB Signaling in LPS-Stimulated Mouse Microglial Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Jae Sung","family":"Lim","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangying","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Young","family":"Lee","sequence":"additional","affiliation":[{"name":"R&D Center, CUOME BIO Co., Ltd., Sandan-gil, Hwasun-eup, Hwasun-gun 58141, Jeollanam-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1939-0187","authenticated-orcid":false,"given":"Guijae","family":"Yoo","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5363-4870","authenticated-orcid":false,"given":"Sang Mi","family":"Eum","sequence":"additional","affiliation":[{"name":"International Biological Material Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-ro, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3227-579X","authenticated-orcid":false,"given":"Young-Chang","family":"Cho","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7393-5040","authenticated-orcid":false,"given":"Somy","family":"Yoon","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-2714","authenticated-orcid":false,"given":"Su-Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si 56212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia Function in the Central Nervous System During Health and Neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. 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