Targeting Hypoglycemic Natural Products from the Cloud Forest Plants Using Chemotaxonomic Computer-Assisted Selection

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Publicado en:International Journal of Molecular Sciences vol. 25, no. 20 (2024), p. 10881
Autor principal: Mayo-Montor, Cecilia I
Otros Autores: Vidal-Limon, Abraham, Loyola-Vargas, Víctor Manuel, Carmona-Hernández, Oscar, José Martín Barreda-Castillo, Monribot-Villanueva, Juan L, Guerrero-Analco, José A
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024 7 |a 10.3390/ijms252010881  |2 doi 
035 |a 3120650260 
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100 1 |a Mayo-Montor, Cecilia I  |u Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C., Xalapa 91073, Mexico; <email>cecilia.mayo@posgrado.ecologia.edu.mx</email> (C.I.M.-M.); <email>abraham.vidal@inecol.mx</email> (A.V.-L.); <email>jose.barreda@posgrado.ecologia.edu.mx</email> (J.M.B.-C.) 
245 1 |a Targeting Hypoglycemic Natural Products from the Cloud Forest Plants Using Chemotaxonomic Computer-Assisted Selection 
260 |b MDPI AG  |c 2024 
513 |a Journal Article 
520 3 |a The cloud forest (CF), a hugely biodiverse ecosystem, is a hotspot of unexplored plants with potential for discovering pharmacologically active compounds. Without sufficient ethnopharmacological information, developing strategies for rationally selecting plants for experimental studies is crucial. With this goal, a CF metabolites library was created, and a ligand-based virtual screening was conducted to identify molecules with potential hypoglycemic activity. From the most promising botanical families, plants were collected, methanolic extracts were prepared, and hypoglycemic activity was evaluated through in vitro enzyme inhibition assays on α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Metabolomic analyses were performed to identify the dominant metabolites in the species with the best inhibitory activity profile, and their affinity for the molecular targets was evaluated using ensemble molecular docking. This strategy led to the identification of twelve plants (in four botanical families) with hypoglycemic activity. Sida rhombifolia (Malvaceae) stood out for its DPP-IV selective inhibition versus S. glabra. A comparison of chemical profiles led to the annotation of twenty-seven metabolites over-accumulated in S. rhombifolia compared to S. glabra, among which acanthoside D and cis-tiliroside were noteworthy for their potential selective inhibition due to their specific intermolecular interactions with relevant amino acids of DPP-IV. The workflow used in this study presents a novel targeting strategy for identifying novel bioactive natural sources, which can complement the conventional selection criteria used in Natural Product Chemistry. 
651 4 |a Mexico 
653 |a Glucagon 
653 |a Hyperglycemia 
653 |a Metabolism 
653 |a Flowers & plants 
653 |a Libraries 
653 |a Natural products 
653 |a Enzymes 
653 |a Metabolites 
653 |a Carbohydrates 
700 1 |a Vidal-Limon, Abraham  |u Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C., Xalapa 91073, Mexico; <email>cecilia.mayo@posgrado.ecologia.edu.mx</email> (C.I.M.-M.); <email>abraham.vidal@inecol.mx</email> (A.V.-L.); <email>jose.barreda@posgrado.ecologia.edu.mx</email> (J.M.B.-C.) 
700 1 |a Loyola-Vargas, Víctor Manuel  |u Unidad de Biología Integrativa, Centro de Investigación Científica de Yucatán, Mérida 97205, Mexico; <email>vmloyola@cicy.mx</email> 
700 1 |a Carmona-Hernández, Oscar  |u Facultad de Biología, Universidad Veracruzana, Xalapa 91090, Mexico; <email>ocarmona@uv.mx</email> 
700 1 |a José Martín Barreda-Castillo  |u Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C., Xalapa 91073, Mexico; <email>cecilia.mayo@posgrado.ecologia.edu.mx</email> (C.I.M.-M.); <email>abraham.vidal@inecol.mx</email> (A.V.-L.); <email>jose.barreda@posgrado.ecologia.edu.mx</email> (J.M.B.-C.) 
700 1 |a Monribot-Villanueva, Juan L  |u Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C., Xalapa 91073, Mexico; <email>cecilia.mayo@posgrado.ecologia.edu.mx</email> (C.I.M.-M.); <email>abraham.vidal@inecol.mx</email> (A.V.-L.); <email>jose.barreda@posgrado.ecologia.edu.mx</email> (J.M.B.-C.) 
700 1 |a Guerrero-Analco, José A  |u Red de Estudios Moleculares Avanzados, Instituto de Ecología A.C., Xalapa 91073, Mexico; <email>cecilia.mayo@posgrado.ecologia.edu.mx</email> (C.I.M.-M.); <email>abraham.vidal@inecol.mx</email> (A.V.-L.); <email>jose.barreda@posgrado.ecologia.edu.mx</email> (J.M.B.-C.) 
773 0 |t International Journal of Molecular Sciences  |g vol. 25, no. 20 (2024), p. 10881 
786 0 |d ProQuest  |t Health & Medical Collection 
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