{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T12:06:00Z","timestamp":1768305960247,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008868","name":"Jiangsu Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["BM2023005"],"award-info":[{"award-number":["BM2023005"]}],"id":[{"id":"10.13039\/501100008868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2010small cell lung cancer (NSCLC) remains the leading cause of cancer\u2010related mortality, with current therapies limited by toxicity and resistance. Fresh\n                    <jats:italic>Panax ginseng C. A. Mey<\/jats:italic>\n                    homogenate extract (FG) retains intact bioactive constituents through nonthermal processing, thereby preserving its native pharmacological integrity. The aim of this study was to systematically investigate the therapeutic effects of FG on nonsmall cell lung cancer and elucidate its mechanism of targeting sphingolipid metabolism. LLC tumor\u2010bearing C57BL\/6J mice were used to evaluate the inhibitory effect of FG on tumors. In\u00a0vitro experiments were conducted using A549 and H1975 cells as models to analyze the effects of FG\u2010containing serum on proliferation and cell cycle through EdU, clone formation, and flow cytometry. The combination of metabolomics (UHPLC Orbitrap MS) and proteomics (DIA\u2010MS) was used to screen differential metabolites and proteins. Western blot and RT\u2010qPCR were used to verify its mechanism, Co\u2010IP was used to detect SPTLC2 ubiquitination levels, and MG132 inhibition experiments were conducted to clarify the ubiquitin proteasome system (UPS) dependence and deepen the mechanism research. FG exerted antitumor activity both in\u00a0vitro and in\u00a0vivo. Notably, SPTLC2 silencing not only phenocopied FG's effects but also diminished FG\u2010mediated tumor suppression, while exogenous sphingosine reversed its therapeutic efficacy in\u00a0vitro. Mechanistically, FG targeted the ubiquitin\u2010proteasome system to degrade SPTLC2, thereby reducing sphingosine secretion, as evidenced by attenuated serum sphingosine levels in SPTLC2\u2010deficient tumors. This study provides evidence that FG inhibits the progression of nonsmall cell lung cancer by targeting the SPTLC2\u2010sphingosine axis, demonstrating its ability to specifically regulate sphingolipid metabolism with low toxicity. These findings support the potential of FG as a promising candidate therapeutic agent for nonsmall cell lung cancer.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70129","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:19:17Z","timestamp":1763684357000},"page":"227-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fresh Ginseng Reduces Sphingosine Secretion Through Ubiquitin Degradation of\n                    <scp>SPTLC2<\/scp>\n                    to Antagonize the Progression of Non\u2010Small Cell Lung Cancer"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-8920","authenticated-orcid":false,"given":"Ruiyang","family":"Jiang","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyang","family":"Shou","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Cui","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangming","family":"Huang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyang","family":"Wan","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Oncology Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunru","family":"Peng","sequence":"additional","affiliation":[{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8806-6077","authenticated-orcid":false,"given":"Zhijun","family":"Fang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Province Academy of Traditional Chinese Medicine  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2018.09.098"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0817-4"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001474"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.09.016"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21338"},{"key":"e_1_2_13_8_1","first-page":"34","article-title":"Research Progress on Modern Clinical Application of Dushen Tang","volume":"34","author":"Chu Saijun D. 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