{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:40:05Z","timestamp":1784554805026,"version":"3.55.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2023-KH139287"],"award-info":[{"award-number":["RS-2023-KH139287"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastric ulcers affect approximately 10% of the global population, while current acid-suppressive therapies have notable limitations including impaired digestion and long-term safety concerns. Naeso-san (NSS), a traditional botanical formulation, has shown promising gastroprotective effects, yet its precise molecular mechanisms remain incompletely understood. This study investigated the molecular pathways underlying its gastroprotective effects versus conventional therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the gastroprotective effects of NSS (75, 300, 1200\u00a0mg\/kg) in 7-week-old male ICR mice using a hydrochloric acid\/ethanol (HCl\/EtOH)-induced gastric injury model, with ranitidine (40\u00a0mg\/kg) as positive control. Macroscopic damage scores were assessed, and molecular mechanisms including pro-inflammatory cytokines and mitogen-activated protein kinase (MAPK), protein kinase B (AKT), and nuclear factor-\u03baB (NF-\u03baB) signaling pathways were analyzed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies using TNF-\u03b1-stimulated human gastric adenocarcinoma cell line (MKN45) gastric epithelial cells assessed inflammatory gene expression and cell viability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NSS demonstrated dose-dependent gastroprotection with superior efficacy compared to ranitidine. While ranitidine effectively reduced macroscopic damage and TNF-\u03b1 mRNA expression, it showed no significant effects on IL-1\u03b2 expression or JNK, p38, AKT, and NF-\u03baB signaling pathways. In contrast, NSS significantly suppressed pro-inflammatory cytokines and comprehensively inhibited multiple molecular pathways including MAPK, AKT, and NF-\u03baB activation across all doses.\n                      <jats:italic>In vitro<\/jats:italic>\n                      studies confirmed dose-dependent suppression of TNF-\u03b1-induced inflammatory gene expression (IL-6, IL-8, IL-1\u03b2, COX-2) without cytotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NSS exhibits gastroprotective effects through multi-target anti-inflammatory mechanisms. These mechanistic advantages over conventional acid-suppressive therapies suggest NSS as a promising candidate for preclinical and translational studies evaluating its clinical applicability in inflammatory gastric conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1672854","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:15:19Z","timestamp":1768205719000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Naeso-san, a traditional herbal formula, attenuates HCl\/ethanol-induced gastric injury via MAPK and NF-\u03baB pathway modulation in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Suji","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Gyoung","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minji","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungmin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsik","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Hye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hoon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyangsook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Pyo","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Huh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Sook","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1497668","DOI":"10.3389\/fphar.2024.1497668","article-title":"Plant and marine-derived natural products: sustainable pathways for future drug discovery and therapeutic development","volume":"15","author":"Ahmad","year":"2024","journal-title":"Front. 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