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To explore the effects on the central nervous system (CNS) and the acute toxicity (LD50) of the polar extracts and fractions obtained from the A. macroprophyllata seeds, their potential as a possible source of anxiolytic drugs was evaluated. After determining LD50, one or two doses were selected to evaluate the neuronal activity using electrocorticographic (ECoG) recordings, and the anxiolytic-like behavior in mice treated with the crude extracts or some of their fractions was assessed in the experimental models of anxiety, such as the open-field, hole-board, and plus-maze tests. Phytochemical analysis was carried out to identify the most abundant constituents, whose possible mechanism of action was also evaluated by in silico analysis. Results showed CNS depressant activity associated with an anxiolytic-like behavior, in which cherimolacyclopeptide D and squamins C and D were identified. According to a docking analysis, the inhibitory receptors GABAA and 5-HT1A of serotonin are possible mechanisms of action involved in the anxiolytic-like effects of these cyclopeptides, which, in conclusion, might be potential molecules for anxiety therapy.<\/jats:p>","DOI":"10.3390\/molecules31142517","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"2517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioassay-Guided Fractionation of Annona macroprophyllata Seeds to Evaluate Their Anxiolytic and Toxicological Effects"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1041-4090","authenticated-orcid":false,"given":"Ulises","family":"Murrieta-Dionicio","sequence":"first","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda de Productos Naturales, Direcci\u00f3n de Investigaciones Biom\u00e9dicas en Salud Mental, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calz. M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"},{"name":"Laboratorio de Productos Naturales, \u00c1rea de Qu\u00edmica, Departamento de Preparatoria Agr\u00edcola, Universidad Aut\u00f3noma Chapingo, Km 38.5 Carretera M\u00e9xico-Texcoco, Chapingo 56230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mart\u00ednez-Vargas","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofisiolog\u00eda del Control y la Regulaci\u00f3n, Direcci\u00f3n de Investigaciones Biom\u00e9dicas en Salud Mental, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calz. M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4399-1508","authenticated-orcid":false,"given":"Mar\u00eda Eva","family":"Gonz\u00e1lez-Trujano","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda de Productos Naturales, Direcci\u00f3n de Investigaciones Biom\u00e9dicas en Salud Mental, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calz. M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1968-8813","authenticated-orcid":false,"given":"Gabriel Fernando","family":"Moreno-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofarmacolog\u00eda de Productos Naturales, Direcci\u00f3n de Investigaciones Biom\u00e9dicas en Salud Mental, Instituto Nacional de Psiquiatr\u00eda Ram\u00f3n de la Fuente Mu\u00f1iz, Calz. M\u00e9xico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de M\u00e9xico 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-4675","authenticated-orcid":false,"given":"Hugo Fernando","family":"Narv\u00e1ez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Hospital de Especialidades Dr. Belisario Dom\u00ednguez, Av. Tl\u00e1huac 4866, San Lorenzo Tezonco, Iztapalapa, Ciudad de M\u00e9xico 09930, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Reyes","sequence":"additional","affiliation":[{"name":"Facultad de Qu\u00edmica, Departamento de Qu\u00edmica Org\u00e1nica, Universidad Nacional Aut\u00f3noma M\u00e9xico, Circuito Escolar S\/N, Ciudad Universitaria, Coyoac\u00e1n, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-2885","authenticated-orcid":false,"given":"Holber","family":"Zuleta-Prada","sequence":"additional","affiliation":[{"name":"Laboratorio de Productos Naturales, \u00c1rea de Qu\u00edmica, Departamento de Preparatoria Agr\u00edcola, Universidad Aut\u00f3noma Chapingo, Km 38.5 Carretera M\u00e9xico-Texcoco, Chapingo 56230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8672-0567","authenticated-orcid":false,"given":"Federico del","family":"R\u00edo-Portilla","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma M\u00e9xico, Circuito Escolar S\/N, Ciudad Universitaria, Coyoac\u00e1n, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-2646","authenticated-orcid":false,"given":"Benito","family":"Reyes-Trejo","sequence":"additional","affiliation":[{"name":"Laboratorio de Productos Naturales, \u00c1rea de Qu\u00edmica, Departamento de Preparatoria Agr\u00edcola, Universidad Aut\u00f3noma Chapingo, Km 38.5 Carretera M\u00e9xico-Texcoco, Chapingo 56230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"ref_1","first-page":"80","article-title":"Manual of tropical and Sub-tropical fruits","volume":"12","author":"Popenoe","year":"1921","journal-title":"Agric. 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