{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:12:58Z","timestamp":1777417978989,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economic Affairs of Taiwan","award":["102-EC-17-A-20-S1-196"],"award-info":[{"award-number":["102-EC-17-A-20-S1-196"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastrointestinal mucositis is a serious side effect of chemotherapy. Currently, no effective treatment exists for chemotherapy-induced mucositis, prompting the need to develop an anti-mucositis agent for use in clinics. The present study investigated whether azatyrosine-PBHA (AzP), a histone deacetylase inhibitor, has a therapeutic effect on intestinal mucosa. The results indicated that AzP did not affect the proliferation and viability of cancer cells, outcomes that are achieved by suberoylanilide hydroxamic acid (SAHA). However, AzP could decrease production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor-necrosis factor-\u03b1 (TNF-\u03b1). In vivo histopathological assessment showed that AzP reduced cisplatin-induced injury to the jejunum villi and triggered weight loss in the C57BL\/6 mice. Immunohistochemistry (IHC) results demonstrated that mice treated with AzP also recovered from cisplatin-induced injury to the intestinal mucosa. Mechanistic in vitro study using DAVID\/KEGG enrichment analysis of microarray data and confirmation by a Western blot indicated the influence of AzP on the MEK\/ERK and AKT-dependent pathway. In conclusion, the study demonstrated that AzP might regulate the MEK\/ERK MAPK signaling pathway to attenuate MCP-1, TNF-\u03b1, and IL-6 production and provide opportunities for the development of new anti-inflammatory drugs targeting mucositis.<\/jats:p>","DOI":"10.3390\/ijms20020249","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T04:10:16Z","timestamp":1547179816000},"page":"249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of Azatyrosine-Phenylbutyric Hydroxamides, a Histone Deacetylase Inhibitor, on Chemotherapy-Induced Gastrointestinal Mucositis"],"prefix":"10.3390","volume":"20","author":[{"given":"Po-Lin","family":"Liao","sequence":"first","affiliation":[{"name":"Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan"},{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Hsuan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hung","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Kuang","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Hao","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Toxicology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaw-Jou","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Po","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3714-0464","authenticated-orcid":false,"given":"Yu-Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Reyes-Gibby, C.C., Melkonian, S.C., Wang, J., Yu, R.K., Shelburne, S.A., Lu, C., Gunn, G.B., Chambers, M.S., Hanna, E.Y., and Yeung, S.J. 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