{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:17Z","timestamp":1782279977755,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Spinal cord injury (SCI) is a profoundly disabling condition affecting the central nervous system. Neuronal apoptosis constitutes a critical pathological event leading to neurological dysfunctions, which is further exacerbated by oxidative stress following SCI. Esculentoside A (EsA), a bioactive saponin isolated from Phytolaca esculenta, exhibits neuroprotective potential in our preliminary studies. However, whether EsA attenuates oxidative stress and neuronal apoptosis in SCI remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The current study aimed to investigate the protective potential of EsA against oxidative stress and neuronal apoptosis following SCI, and to elucidate the associated molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SCI was modeled in rats via contusion using the PSI-IH 0400 Striker impactor, and rats were treated intraperitoneally with 10 mg\/kg EsA once daily. The Basso, Beattie, and Bresnahan (BBB) scale, grid walk analysis, and footprint test were adopted to evaluate motor function dynamically. Histopathological alterations in spinal cord tissue were examined by Hematoxylin-eosin (HE), Luxol Fast Blue (LFB), and Nissl staining. Oxidative stress markers, including hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) and malondialdehyde (MDA), along with antioxidant enzymes glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), were quantified in spinal cord homogenates using commercial assay kits. Western blot, immunofluorescence staining, and molecular docking were employed to investigate the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EsA significantly improved motor function and reduced histopathological damage in SCI rats. This neuroprotective effect was accompanied by a significant improvement in oxidative stress biomarkers and neuronal apoptosis in the injured spinal cord, coinciding with activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)\/heme oxygenase-1 (HO-1) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, EsA exerts a neuroprotective effect against SCI by modulating oxidative stress and neuronal apoptosis partially through activation of the Nrf2\/HO-1 pathway, indicating its promise as a therapeutic agent for SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1861879","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:46:58Z","timestamp":1782276418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Esculentoside A mitigates oxidative stress and neuronal apoptosis in spinal cord injury by modulating the Nrf2\/HO-1 pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Guoqing","family":"Zhu","sequence":"first","affiliation":[{"name":"Laboratory Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengge","family":"Sun","sequence":"additional","affiliation":[{"name":"Laboratory Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Yan","sequence":"additional","affiliation":[{"name":"Laboratory Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.bbi.2025.01.014","article-title":"Brain inflammation and cognitive decline induced by spinal cord injury can be reversed by spinal cord cell 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