{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:41:41Z","timestamp":1789076501883,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":256,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HF21C0100"],"award-info":[{"award-number":["HF21C0100"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Lumbar spinal stenosis (LSS) is a common degenerative spinal condition in older individuals that causes impaired walking and other disabilities due to severe lower back and leg pain. Ligamentum flavum hypertrophy is a major LSS cause that may result from oxidative stress caused by degenerative cascades, including imbalanced iron homeostasis that leads to excessive reactive oxygen species production. We investigated the effects of <jats:italic>Harpagophytum procumbens<\/jats:italic> (HP) on iron\u2010induced oxidative stress associated with LSS pathophysiology. Primary spinal cord neuron cultures were incubated in FeSO<jats:sub>4<\/jats:sub>\u2010containing medium, followed by addition of 50, 100, or 200\u2009<jats:italic>\u03bc<\/jats:italic>g\/mL HP. Cell viability was assessed by CCK\u20108 and live\/dead cell assays and by propidium iodide\u2010live imaging. In an <jats:italic>in vivo<\/jats:italic> rat model of LSS, HP were administered at 100, 200, and 400\u2009mg\/kg, and disease progression was monitored for up to 3 weeks. We investigated the <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> effects of HP on iron\u2010induced neurotoxicity by immunochemistry, real\u2010time PCR, and flow cytometry. HP exerted neuroprotective effects and enhanced neurite outgrowths of iron\u2010injured rat primary spinal cord neurons <jats:italic>in vitro<\/jats:italic>. HP treatment significantly reduced necrotic cell death and improved cells\u2019 antioxidative capacity via the NRF2 signaling pathway in iron\u2010treated neurons. At 1 week after HP administration in LSS rats, the inflammatory response and oxidative stress markers were substantially reduced through regulation of excess iron accumulation. Iron that accumulated in the spinal cord underneath the implanted silicone was also regulated by HP administration via NRF2 signaling pathway activation. HP\u2010treated LSS rats showed gradually reduced mechanical allodynia and amelioration of impaired behavior for 3 weeks. We demonstrated that HP administration can maintain iron homeostasis within neurons via activation of NRF2 signaling and can consequently facilitate functional recovery by regulating iron\u2010induced oxidative stress. This fundamentally new strategy holds promise for LSS treatment.<\/jats:p>","DOI":"10.1155\/2022\/3472443","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T22:35:05Z","timestamp":1663194905000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<i>Harpagophytum procumbens<\/i> Inhibits Iron Overload\u2010Induced Oxidative Stress through Activation of <i>Nrf2<\/i> Signaling in a Rat Model of Lumbar Spinal Stenosis"],"prefix":"10.1155","volume":"2022","author":[{"given":"Jin Young","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunseong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junseon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jin","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Jae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-6723","authenticated-orcid":false,"given":"In-Hyuk","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2009.11.001"},{"key":"e_1_2_10_2_2","article-title":"Management of lumbar spinal stenosis","volume":"352","author":"Lurie J.","year":"2016","journal-title":"BMJ"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/BMR-160688"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181bfca15"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S158513"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100982"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0244-7"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-007-0048-7"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.104105"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01162"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3164734"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3649-08.2008"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.08.015"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.09.036"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.027"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000485089"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6235641"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2095-2_10"},{"key":"e_1_2_10_19_2","first-page":"1895","article-title":"The role of iron homeostasis and iron-mediated ROS in cancer","volume":"11","author":"Ying J. 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