{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:57:43Z","timestamp":1791464263941,"version":"4.3.4"},"reference-count":36,"publisher":"Walter de Gruyter GmbH","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jcim-2026-0053_abs_001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Melanoma is an aggressive skin cancer associated with high mortality. This study evaluated the safety and antitumor efficacy of\n                      <jats:italic>Annona muricata<\/jats:italic>\n                      Linn leaf extract (AME) in a melanoma model in Swiss\n                      <jats:italic>albino<\/jats:italic>\n                      \u00a0mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jcim-2026-0053_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Acute toxicity of AME was assessed in healthy mice. Melanoma was induced by subcutaneous implantation of B16-F10\u202fcells into immunocompetent or cyclophosphamide-immunosuppressed mice. Animals received oral AME (200\u202fmg\/kg), topical AME (20\u202fmg\/mL), or a combination regimen (100\u202fmg\/kg orally + 10\u202fmg\/mL topically). Tumor progression was monitored weekly and histological analysis was performed at study completion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jcim-2026-0053_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The estimated LD\n                      <jats:sub>50<\/jats:sub>\n                      of AME was 2,180.28\u00a0\u00b1\u00a084.76\u202fmg\/kg. B16-F10 tumor growth was detectable from Day 1 in immunodeficient mice and peaked at Week 3. Compared with the untreated group, AME treatment reduced tumor burden and delayed progression, with the combination regimen showing the most pronounced effect (p&lt;0.01). However, histopathological analysis revealed persistent vascular invasion and subcutaneous infiltration, indicating incomplete suppression of tumor invasiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jcim-2026-0053_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AME demonstrated antitumor activity in this melanoma model, particularly with combined oral and topical administration. However, only a limited number of predefined dose levels were evaluated, precluding assessment of dose-response relationships and therapeutic index. These findings should be considered preliminary, and further studies are required to optimize dosing strategies and elucidate underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jcim-2026-0053","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:17:41Z","timestamp":1791461861000},"source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the\n                    <i>in\u00a0vivo<\/i>\n                    acute toxicity and antimelanoma effects of total leaf extract from\n                    <i>Annona muricata<\/i>\n                    Linn"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4213-1998","authenticated-orcid":false,"given":"Huynh Thao Vy","family":"Nguyen","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City , Ho Chi Minh City , Vietnam"},{"name":"Faculty of Pharmacy, Pham Ngoc Thach University of Medicine , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manh Hung","family":"Tran","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoai Nam","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Pham Ngoc Thach University of Medicine , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Han","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Pham Ngoc Thach University of Medicine , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vy Kha","family":"Lam","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Science, VNU-HCMC , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-9315","authenticated-orcid":false,"given":"Hoang Phu","family":"Dang","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Science, VNU-HCMC , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-4482","authenticated-orcid":false,"given":"Ngoc Trinh","family":"Huynh","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City , Ho Chi Minh City , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"2026100812173691232_j_jcim-2026-0053_ref_001","doi-asserted-by":"crossref","unstructured":"Bray, F, Laversanne, M, Sung, H, Ferlay, J, Siegel, RL, Soerjomataram, I, et al.. 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