{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:33Z","timestamp":1760060793519,"version":"build-2065373602"},"reference-count":85,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"]}]},{"name":"Tri-Service General Hospital","award":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"]}]},{"name":"Taipei Medical University Hospital","award":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"],"award-info":[{"award-number":["NSTC 113-2320-B-038-066 and NTSC 114-2314-B-A49-025","TSGH C01-113030","114TMUH-C01-4 and 114TMU-TMUH-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Lepidium meyenii Walpers (LMW), a high-altitude plant, is known to stimulate hormone release, counteract neurodegeneration, and protect against oxidative stress. Saliva is vital for oral health, and reduced production leads to xerostomia, often caused by aging, radiation, or Sj\u00f6gren\u2019s syndrome. Key pathological features include mesenchymal fibrosis and acinar atrophy, largely regulated by the TGF-\u03b21 pathway. Current treatments are limited, with many patients relying on artificial saliva. Developing therapies to restore salivary function could offer significant benefits. Methods: In this study, we assessed the protective effects of LMW extract (LMWE) in irradiated C57BL\/6J mice and TGF-\u03b21-treated rat parotid acinar cells (Par-C10) using histological, molecular, bioenergetic, and 3D organoid analyses to evaluate salivary gland regeneration and lineage-specific differentiation. Results: LMWE significantly restored gland weight, shortened secretion lag time, and increased amylase activity in irradiated mice. Histological and molecular analyses showed reduced acinar atrophy and fibrosis, preservation of epithelial polarity, and upregulation of Mist1, AQP5, and amylase. In vitro, LMWE protected Par-C10 cells from TGF-\u03b21-induced senescence, preserved mitochondrial membrane potential, and improved epithelial barrier function. In 3D organoid cultures of Par-C10 cells embedded in matrix, (1E,4Z)-1-(2,4-dihydroxyphenyl)-5-(3,4-dihydroxyphenyl) penta-1,4-dien-3-one (DHPPD) and (Z)-N-phenyldodec-2-enamide (E4Z-PD)-selectively enhanced acinar and ductal lineage differentiation, respectively. Conclusions: These results suggest that LMWE promotes salivary gland regeneration through antioxidative and lineage-specific mechanisms and may represent a safe and effective therapeutic strategy for xerostomia.<\/jats:p>","DOI":"10.3390\/nu17193033","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:48:37Z","timestamp":1758635317000},"page":"3033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lepidium meyenii Walpers Promotes the Regeneration of Salivary Gland and Prevents Xerostomia After Irradiation Injury"],"prefix":"10.3390","volume":"17","author":[{"given":"Yi-Ting","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei City 11490, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Chuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"},{"name":"School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien City 97004, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Jen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Life Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Ming","family":"Shih","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Sung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, Tri-Service General Hospital, National Defense Medical University, Taipei City 11490, Taiwan"},{"name":"Department and Graduate Institute of Pharmacology, National Defense Medical University, Taipei City 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze-Hao","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology, National Yang Ming Chiao Tung University (Yangming Campus), Taipei City 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2004-4874","authenticated-orcid":false,"given":"Ching-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Oral Biology, National Yang Ming Chiao Tung University (Yangming Campus), Taipei City 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science, College of Medicine, University of Arizona, Phoenix, AZ 85721, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-2899","authenticated-orcid":false,"given":"Feng-Yen","family":"Lin","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"},{"name":"Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei City 11031, Taiwan"},{"name":"Departments of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 11031, Taiwan"},{"name":"Institute of Oral Biology, National Yang Ming Chiao Tung University (Yangming Campus), Taipei City 112304, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10266-008-0099-7","article-title":"Diagnosis and treatment of xerostomia (dry mouth)","volume":"97","author":"Napenas","year":"2009","journal-title":"Odontology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/joor.12664","article-title":"Salivary secretion in health and disease","volume":"45","author":"Pedersen","year":"2018","journal-title":"J. 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