{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:55:24Z","timestamp":1779890124322,"version":"3.53.1"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004861","name":"Mackay Memorial Hospital","doi-asserted-by":"publisher","award":["MMH-111-78 and 120"],"award-info":[{"award-number":["MMH-111-78 and 120"]}],"id":[{"id":"10.13039\/501100004861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathic pain (NPP) remains therapeutically challenging, with oxidative\/nitrosative stress and neuroinflammation\u2014amplified by nitric oxide (NO)\u2014as key drivers. This study investigated geraniin (GRN), a naturally occurring hydrolyzable ellagitannin widely distributed in various plant species, including Phyllanthus spp. and Nephelium lappaceum (rambutan), in a rat model of sciatic nerve chronic constriction injury (CCI), focusing on NO-pathway involvement. Male Wistar rats (n = 8\/group) received intraperitoneal GRN (3, 10, 30, or 100 mg\/kg) or vehicle (1% DMSO in saline) daily for 21 days. Behavioral (thermal hyperalgesia, mechanical allodynia, sciatic functional index), electrophysiological (nerve conduction velocity), and biochemical markers\u2014oxidative\/nitrosative stress (nitrite, MDA), antioxidant defenses (GSH, SOD, CAT), inflammation (TNF-\u03b1, IL-1\u03b2, IL-6, MPO), and apoptosis (caspase-3)\u2014were quantified. L-arginine or L-NAME was co-administered to probe NO signaling. GRN at 30 and 100 mg\/kg produced significant antinociceptive and neuroprotective effects; 30 mg\/kg was selected for detailed analysis. By day 21, GRN improved pain thresholds and nerve conduction, enhanced antioxidant capacity, suppressed inflammatory mediators, and reduced caspase-3 activity. L-arginine reversed, whereas L-NAME potentiated these effects, confirming NO-dependent modulation. Collectively, GRN mitigates CCI-induced NPP via coordinated antioxidant, anti-inflammatory, and anti-apoptotic actions, supporting its potential as a multi-target candidate for pharmacokinetic and translational development.<\/jats:p>","DOI":"10.3390\/ijms27010507","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:35:47Z","timestamp":1767620147000},"page":"507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Geraniin Mitigates Neuropathic Pain Through Antioxidant, Anti-Inflammatory, and Nitric Oxide Modulation in a Rat Model of Chronic Constriction Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Chih-Chuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Hsien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, En Chu Kon Hospital, New Taipei City 23702, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-6584","authenticated-orcid":false,"given":"Chih-Hsiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine, China Medical University Hospital, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chi","family":"Chang","sequence":"additional","affiliation":[{"name":"National Applied Research Laboratories, Institute of Taiwan Instrument Research, Hsinchu 300092, Taiwan"},{"name":"Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 10608, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chia","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan"},{"name":"Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neurol.2018.09.016","article-title":"Neuropathic pain: Definition, assessment and epidemiology","volume":"175","author":"Bouhassira","year":"2019","journal-title":"Rev. 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