{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:48:58Z","timestamp":1792082938459,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dalian Science and Technology Talent Innovation and Entrepreneurship Program","award":["2022RG09"],"award-info":[{"award-number":["2022RG09"]}]},{"name":"Dalian Science and Technology Talent Innovation and Entrepreneurship Program","award":["2022JJ12SN050"],"award-info":[{"award-number":["2022JJ12SN050"]}]},{"name":"Science and Technology Innovation Team project of Liaoning Provincial Department of Education","award":["LJ222410161077"],"award-info":[{"award-number":["LJ222410161077"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP\u2019s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and \u03b17nAChR-Janus kinase 2 (JAK2)\/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in \u03b17nAChR knockout mice. Mechanistically, SVHRSP activated JAK2\/STAT3 signaling through \u03b17nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via \u03b17nAChR-dependent JAK2\/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders.<\/jats:p>","DOI":"10.3390\/antiox14111296","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"1296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Scorpion Venom Heat-Resistant Synthetic Peptide Alleviates DSS-Induced Colitis via \u03b17nAChR-Mediated Modulation of the JAK2\/STAT3 Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Kang","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology and Microecology (Pathogen Biology Laboratory), School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangbo","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology and Microecology (Pathogen Biology Laboratory), School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology and Microecology (Pathogen Biology Laboratory), School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology and Microecology (Pathogen Biology Laboratory), School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Cui","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jau-Shyong","family":"Hong","sequence":"additional","affiliation":[{"name":"Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"},{"name":"Department of Biochemistry, School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology and Microecology (Pathogen Biology Laboratory), School of Basic Medical Science, Dalian Medical University, Dalian 116044, China"},{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1136\/gut.2008.163667","article-title":"Crohn\u2019s Disease: Th1, Th17 or Both? 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