Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II
ilustraciones, diagramas
- Autores:
-
Valderrama Parra, Ivonne Helena
- Tipo de recurso:
- Doctoral thesis
- Fecha de publicación:
- 2023
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/85315
- Palabra clave:
- 610 - Medicina y salud::615 - Farmacología y terapéutica
diabetes mellitus/veterinaria
diabetes mellitus/farmacoterapia
antioxidantes/síntesis química
Diabetes Mellitus/veterinary
Diabetes Mellitus/drug therapy
Antioxidants/chemical synthesis
Physalis peruviana
Flavonoide
Rutina
Síndrome metabólico
Antioxidante
Perfil lipídico
Polifenoles
Hiperglicemia
Physalis peruviana
Flavonoid
Lipid profile
Rutin
Metabolic syndrome
Anioxidant
Polyphenols
Hyperglycemia
- Rights
- openAccess
- License
- Atribución-NoComercial 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| dc.title.translated.eng.fl_str_mv |
Study of the activity of an extract of Physalis peruviana calyxes on oxidative stress in rodents with type II diabetes mellitus |
| title |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| spellingShingle |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II 610 - Medicina y salud::615 - Farmacología y terapéutica diabetes mellitus/veterinaria diabetes mellitus/farmacoterapia antioxidantes/síntesis química Diabetes Mellitus/veterinary Diabetes Mellitus/drug therapy Antioxidants/chemical synthesis Physalis peruviana Flavonoide Rutina Síndrome metabólico Antioxidante Perfil lipídico Polifenoles Hiperglicemia Physalis peruviana Flavonoid Lipid profile Rutin Metabolic syndrome Anioxidant Polyphenols Hyperglycemia |
| title_short |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| title_full |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| title_fullStr |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| title_full_unstemmed |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| title_sort |
Estudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II |
| dc.creator.fl_str_mv |
Valderrama Parra, Ivonne Helena |
| dc.contributor.advisor.spa.fl_str_mv |
Ospina Giraldo, Luis Fernando Modesti Costa, Geison |
| dc.contributor.author.spa.fl_str_mv |
Valderrama Parra, Ivonne Helena |
| dc.contributor.researchgroup.spa.fl_str_mv |
Principios Bioactivos en Plantas Medicinales |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud::615 - Farmacología y terapéutica |
| topic |
610 - Medicina y salud::615 - Farmacología y terapéutica diabetes mellitus/veterinaria diabetes mellitus/farmacoterapia antioxidantes/síntesis química Diabetes Mellitus/veterinary Diabetes Mellitus/drug therapy Antioxidants/chemical synthesis Physalis peruviana Flavonoide Rutina Síndrome metabólico Antioxidante Perfil lipídico Polifenoles Hiperglicemia Physalis peruviana Flavonoid Lipid profile Rutin Metabolic syndrome Anioxidant Polyphenols Hyperglycemia |
| dc.subject.decs.spa.fl_str_mv |
diabetes mellitus/veterinaria diabetes mellitus/farmacoterapia antioxidantes/síntesis química |
| dc.subject.decs.eng.fl_str_mv |
Diabetes Mellitus/veterinary Diabetes Mellitus/drug therapy Antioxidants/chemical synthesis |
| dc.subject.proposal.spa.fl_str_mv |
Physalis peruviana Flavonoide Rutina Síndrome metabólico Antioxidante Perfil lipídico Polifenoles Hiperglicemia |
| dc.subject.proposal.eng.fl_str_mv |
Physalis peruviana Flavonoid Lipid profile Rutin Metabolic syndrome Anioxidant Polyphenols Hyperglycemia |
| description |
ilustraciones, diagramas |
| publishDate |
2023 |
| dc.date.issued.none.fl_str_mv |
2023 |
| dc.date.accessioned.none.fl_str_mv |
2024-01-16T00:39:47Z |
| dc.date.available.none.fl_str_mv |
2024-01-16T00:39:47Z |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Doctorado |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_db06 |
| dc.type.content.spa.fl_str_mv |
Text |
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http://purl.org/redcol/resource_type/TD |
| format |
http://purl.org/coar/resource_type/c_db06 |
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acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/85315 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
| dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/85315 https://repositorio.unal.edu.co/ |
| identifier_str_mv |
Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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spa |
| language |
spa |
| dc.relation.indexed.spa.fl_str_mv |
Bireme |
| dc.relation.references.spa.fl_str_mv |
Abdelhameed, R.F.A., Ibrahim, A.K., Elfaky, M.A., Habib, E.S., Mahamed, M.I., Mehanna, E.T., Darwish, K.M., Khodeer, D.M., Ahmed, S.A., Elhady, S.S., 2021. Antioxidant and anti-inflammatory activity of cynanchum acutum l. Isolated flavonoids using experimentally induced type 2 diabetes mellitus: Biological and in silico investigation for nf-κb pathway/mir-146a expression modulation. Antioxidants. https://doi.org/10.3390/antiox10111713 Abu-Amsha, R., Croft, K.D., Puddey, I.B., Proudfoot, J.M., Beilin, L.J., 1996. Phenolic content of various beverAGEs determines the extent of inhibition of human serum and low density lipoprotein oxidation in vitro: Identification and mechanism of action of some cinnamic acid derivatives from red wine. Clinical Science. 91, 449–458. https://doi.org/10.1042/cs0910449 Adjimani, J.P., Asare, P., 2015. Antioxidant and free radical scavenging activity of iron chelators. Toxicology Reports. 2, 721–728. https://doi.org/10.1016/j.toxrep.2015.04.005 Al-Romaiyan, A., Liu, B., Asare-Anane, H., Maity, C.R., Chatterjee, S.K., Koley, N., Biswas, T., Chatterji, A.K., Huang, G.C., Amiel, S.A., Persaud, S.J., Jones, P.M., 2010. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytotherapy Research. 24, 1370–1376. https://doi.org/10.1002/ptr.3125 Alam, S., Sarker, M., Sultana, T., Chowdhury, M., Rashid, M., Chaity, N., Zhao, C., Xiao, J., Hafez, E., Khan, S., Mohamed, I., 2022. Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development. Frontiers in Endocrinology. 13. https://doi.org/10.3389/fendo.2022.800714 Albu, E., Lupaşcu, D., Filip, C., Jaba, I.M., Zamosteanu, N., 2013. The influence of a new rutin derivative on homocysteine, cholesterol and total antioxidative status in experimental diabetes in rat. Farmacia. 61, 1167–1177. American Diabetes Association, 2019. ¿Tiene riesgo de padecer de diabetes tipo 2? ¿Qué sigue? 2019. Ang, S., Eckling, K., Arcone, M., Akuda, Y., Sao, R. 2011. Synergistic , additive , and antagonistic effects of food mixtures on total antioxidant capacities. Journal of Agriculture Food Chemistry. 59, 960–968. https://doi.org/10.1021/jf1040977 Antia, B.S., Okokon, J.E., Okon, P.A., 2005. Hypoglycemic activity of aqueous leaf extract of Persea americana Mill. Indian Journal of Pharmacology. 37, 325–326. https://doi.org/10.4103/0253-7613.16858 Aragón, D.M., Echeverry, S.M., Valderrama, I.H., Costa, G.M., Ospina, L.F., 2018. Development and optimization of microparticles containing a hypoglycemic fraction of calyces from Physalis peruviana. Journal of Applied Pharmaceutical Science. 8, 10–18. https://doi.org/10.7324/JAPS.2018.8502 Aragón Novoa, D.M., Ospina Giraldo, L.F., Ramos Rodríguez, F.A., Castellanos Hernández, L., Costa Modesti, G., Barreto Silva, F.R.M., 2021. Passiflora ligularis Juss. (granadilla): estudios quimicos y farmacológicos de una es planta con potencial terapéutico. Universidad Nacional de Colombia, Bogotá,Colombia. https://doi.org/https://doi.org/10.36385/FCBOG-12-0 Arias Díaz, J., Balibrea, J., 2007. Modelos animales de intolerancia a la glucosa y diabetes tipo 2. Revista Nutrición Hospitalaria. 22, 160–168. Aristizábal, A.M. (Corporación U.L., 2013. Uchuva (Physalis peruviana L): estudio de su potencial aplicación en el desarrollo de alimentos con características funcionales. Tesis Maest. 1–43. Arumugam, G., Manjula, P., Paari, N., 2013. A review: Anti diabetic medicinal plants used for diabetes mellitus. Journal of Acute Disease. 2, 196–200. https://doi.org/10.1016/S2221- 6189(13)60126-2 Asano, N., Kato, A., Matsui, K., Watson, A.A., Nash, R.J., Molyneux, R.J., Hackett, L., Topping, J., Winchester, B., 1997. The effects of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases. Glycobiology 7. 1085–1088. https://doi.org/10.1093/glycob/7.8.1085 Assadi, S., Shafiee, S.M., Erfani, M., Akmali, M., 2021. Antioxidative and antidiabetic effects of Capparis spinosa fruit extract on high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats. Biomedicine & Pharmacotheraphy. 138, 111391. https://doi.org/10.1016/j.biopha.2021.111391 Bernal, C.A., Castellanos, L., Aragón, D.M., Martínez-Matamoros, D., Jiménez, C., Baena, Y., Ramos, F.A., 2018. Peruvioses A to F, sucrose esters from the exudate of Physalis peruviana fruit as α-amylase inhibitors. Carbohydrate research. 461, 4–10. https://doi.org/10.1016/j.carres.2018.03.003 Bernal, M., Correa, Q., 1998. Especies vegetales promisorias de los países del convenio Andrés Bello. Editora Guadalupe Ltda, Bogotá,Colombia. Black, P.H., 2003. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behavior, and Immunity. 17, 350–364. https://doi.org/10.1016/S0889- 1591(03)00048-5 Boden, G., Homko, C., Barrero, C.A., Stein, T.P., 2017. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Science Translational medicine. 7, 304. https://doi.org/10.1126/scitranslmed.aac4765. Boudreau, A., Poulev, A., Ribnicky, D.M., Raskin, I., Rathinasabapathy, T., Richard, A.J., Stephens, J.M., 2019. Distinct fractions of an Artemisia scoparia extract contain compounds with novel adipogenic bioactivity. Frontiers in Nutrition. 6, 1–13. https://doi.org/10.3389/fnut.2019.00018 Bradmus, J.A. Adedosu, T.O., Fatoki, J.O., Adegbite V.A., Adaramoye O.A., Odunola, O., 2011. Lipid Peroxidation Inhibition and Antiradical Activities of Some Leaf Fractions of Mangifera Indica. Acta Pol Pharm. 68, 23–29. Brand-Williams, W., Cuvelier, M.E., Berset, C., 1995. Use of a free radical method to evaluate antioxidant activity. LWT - Food Science and Technology. 28, 25–30. https://doi.org/10.1016/S0023-6438(95)80008-5 Cameron, A.R., Morrison, V.L., Levin, D., Mohan, M., Forteath, C., Beall, C., McNeilly, A.D., Balfour, D.J.K., Savinko, T., Wong, A.K.F., Viollet, B., Sakamoto, K., Fagerholm, S.C., Foretz, M., Lang, C.C., Rena, G., 2016. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circulation Research. 119, 652–665. https://doi.org/10.1161/CIRCRESAHA.116.308445 Cardona, M.I., 2014. Aporte a la estandarización de un extracto de cálices de Physalis peruviana. Tesis de maestría. Universidad Nacional de Colombia. Cardona, M.I., Toro, R.M., Costa, G.M., Ospina, L.F., Castellanos, L., Ramos, F.A., Aragón, D.M., 2017. Influence of extraction process on antioxidant activity and rutin content in Physalis peruviana calyces extract. Journal Applied Pharmaceutical Science. 7, 164–168. https://doi.org/10.7324/JAPS.2017.70623 Carvalho, E.N. de, Carvalho, N.A. de, Ferreira, L.M., 2003. Experimental model of induction of diabetes mellitus in rats. Acta Cirurgica Brasilera. 18, 60–64. https://doi.org/10.1590/s0102-86502003001100009 Cazarolli, L., Zanatta, L., Alberton, E., Bonorino Figueiredo, M.S., Folador, P., Damazio, R., Pizzolatti, M., Barreto Silva, F.R., 2008. Flavonoids: Prospective Drug Candidates. Mini Reviews in Medicinal Chemistry. 8, 1429–1440. https://doi.org/10.2174/138955708786369564 Chasquibol, N., Yacono, J., 2015. Composicion fitoquimica del aceite de las semillas del fruto del “Aguaymanto”, Physalis peruviana L. Revista de la Sociedad Química del Perú. 81, 311–318. Cooper, M.A., Ryals, J.M., Wu, P.Y., Wright, K.D., Walter, K.R., Wright, D.E., 2017. Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation. Journal of the Peripheral Nervous System. 22, 39–46. https://doi.org/10.1111/jns.12199. Costa, G.M., 2013. Estudo Químico de Espécies Brasileiras e Colombianas de Passiflora. Tesis de Doctorado. Universidad Federal de Santa Catarina. Cryer, P.E., 2016. Hypoglycemia in Type 2 Diabetes. Type 2 Diabetes melluitus: An evidence based Approach to Practical Management. Second Ed. 28, 227–236. https://doi.org/10.3109/9780849379581-19 Darwish, A.G., Mahmoud, H.I., Refaat, I., 2020. Antioxidative and Antidiabetic Effect of Goldenberries juice and pomace on Experimental Rats Induced with streptozotocin In vitro. Journal of Food Dairy Science. 11, 277–283. https://doi.org/10.21608/jfds.2020.118371 De La O-Quezada, G.A., Damaris, ;, Ojeda-Barrios, L., Ofelia, ¶ ;, Hernández-Rodríguez, A., Sánchez-Chávez, E., Jaime Martínez-Tellez, ;, 2011. Biomasa, Prolina Y Parámetros Nitrogenados En Plántulas De Nogal Bajo Estrés Hídrico Y Fertilización Nitrogenada. Revista Chapingo. Serie Horticultura. 17, 13–18. De Paiva, L.B., Goldbeck, R., dos Santos, W.D., Squina, F.M., 2013. Ferulic acid and derivatives: Molecules with potential application in the pharmaceutical field. Brazilian Journal of Pharmeutical Science. 49, 395–411. https://doi.org/10.1590/S1984- 82502013000300002 Derbré, S., Gatto, J., Pelleray, A., 2010. Automating a 96-well microtiter plate assay for identification of AGEs inhibitors or inducers : Application to the screening of a small natural. Analytical & Bioanalytical Chemistry. 398, 1747–1758. https://doi.org/10.1007/s00216-010-4065-1 Devkar, S.T., Muthal, A.P., Patil, P. V., Mukherjee-Kandhare, A.A., Kandhare, A.D., Jagtap, S.D., Bodhankar, S.L., Hegde, M. V., 2021. Evaluation of the physicochemical stability and biological activity of withanolide rich fraction from Withania somnifera root by hplc and cyclic voltammetry: A simple, reliable, and cost-effective approach. Latin American Journal of Pharmacy. 40, 946–956. Dinan, L.N., Sarker, S.D., Šik, V., 1997. 28-Hydroxywithanolide E. from Physalis peruviana. Phytochemistry 44, 509–512. https://doi.org/10.1016/S0031-9422(96)00553-5 Diagnosis and Classification of Diabetes Mellitus, 2014. Diabetes Care. 37. Domínguez Moré, G.P., Cardona, M.I., Sepúlveda, P.M., Echeverry, S.M., Oliveira Simões, C.M., Aragón, D.M., 2021. Matrix effects of the hydroethanolic extract of calyces of Physalis peruviana l. On rutin pharmacokinetics in wistar rats using population modeling. Pharmaceutics. 13,(4), 535. https://doi.org/10.3390/pharmaceutics13040535 Dos Santos, M., Prestes, A.S., de Macedo, G.T., Ecker, A., Barcelos, RP., Boligon, A.A & Barbosa, N.V. 2018. Syzygium cumini leaf extract inhibits LDL oxidation, but does not protect the liproprotein from glycation. Journal of Ethnopharmacology. 210, 69–79. https://doi.org/10.1016/j.jep.2017.08.033 Dos Santos, J.M., Alves Junior, V.V., Boleti, A.P. de A., Lima, E.S., Carollo, C.A., dos Santos, E.L., Rabelo, L.A., Alfredo, T.M., Melo da Cunha, J. da S., de Picoli Souza, K., 2018. Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea. PLoS One. 13 (6). https://doi.org/10.1371/journal.pone.0197071 Endale, M & Endalo M. 2015. Recent trends in rapid dereplication of natural product extracts: an update. Journal of Coastal Life Medicine. 3 (3), 178-182 https://doi.org/10.12980/jclm.3.201514j66 Ezzat, S.M., Abdallah, H.M.I., Yassen, N.N., Radwan, R.A., Mostafa, E.S., Salama, M.M., Salem, M.A., 2021. Phenolics from Physalis peruviana fruits ameliorate streptozotocin induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression. Biomedicine & Pharmacotherapy. 142. https://doi.org/10.1016/j.biopha.2021.111948 Fischer, G., Almanza-Merchán, P.J., Miranda, D., 2014. Importancia y cultivo de la uchuva (Physalis peruviana L.). Revista Brasileira de Fruticultura. 36, 01–15. https://doi.org/10.1590/0100-2945-441/13 Flórez, V., Fischer, G., 2000. Producción, poscosecha y exportación de la uchuva (Physalis peruviana l.). Editorial Universidad Nacional de Colombia. https://doi.org/: 958-8051-74-6 Folch, J., Lees, M., Sloane, G.H., 1957. A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biological Chemistry. 226, 497–509. https://doi.org/10.1016/s0021-9258(18)64849-5 Fontana, D., Cazarolli, L.H., Lavado, C., Mengatto, V., Figueiredo,., Guedes, A., Pizzolatti, M., Silva, F., 2011. Effects of flavonoids on α-glucosidase activity: Potential targets for glucose homeostasis. Nutrition . 27, 1161–1167. https://doi.org/10.1016/j.nut.2011.01.008 Franco, L.A., Ocampo, Y.C., Gómez, H.A., De La Puerta, R., Espartero, J.L., Ospina, L.F., 2014. Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity. Planta Médica. 80, 1605–1614. https://doi.org/10.1055/s-0034-1383192 Franco LA, Matiz GE, Calle J, Pinzón R, O.L., 2007. Actividad antinflamatoria de extractos y fracciones obtenidas de cálices de Physalis peruviana L. Biomédica. 27, 110–5. Fuangchan, A., Sonthisombat, P., Seubnukarn, T., Chanouan, R., Chotchaisuwat, P., Sirigulsatien, V., Ingkaninan, K., Plianbangchang, P., Haines, S.T., 2011. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. Journal of Ethnopharmacoly. 134, 422–428. https://doi.org/10.1016/j.jep.2010.12.045 Furman, B.L., 2015. Streptozotocin-Induced Diabetic Models in Mice and Rats. Current Protocols in Pharmacology. 70, 5.47.1-5.47.20. https://doi.org/10.1002/0471141755.ph0547s70 Gastell, P., De Alejo, J. 2000. Métodos para medir el daño oxidativo. Revista Cubana de Medicina Militar. 29, 192–198. Giacco, F., Brownlee, M., 2010. Oxidative stress and diabetic complications. Circulation Research. 107, 1058–1070. https://doi.org/10.1161/circresaha.110.223545 Gironés-Vilaplana, A., Baenas, N., Villaño, D., Speisky, H., García-Viguera, C., Moreno, D.A., 2014. Evaluation of Latin-American fruits rich in phytochemicals with biological effects. Journal of Functional Foods. 7, 599–608. https://doi.org/10.1016/j.jff.2013.12.025 Goss, M J, Nunes, M.L., Machado, I.D., Merlin, L., Macedo, N.B., Silva, A.M., Bresolin, TM., Santin, J.R., 2018. Peel flour of Passiflora edulis Var. Flavicarpa supplementation prevents the insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats. Biomedicine & Pharmacotherapy. 102, 848–854. https://doi.org/10.1016/j.biopha.2018.03.137 Guo, M., Perez, C., Wei, Y., Rapoza, E., Su, G., Bou-abdallah, F., Chasteen, N.D., 2007. Iron-binding properties of plant phenolics and cranberry ’ s bio-effects. Dalton Transactions. 43, 4951–4961. https://doi.org/10.1039/b705136k Huang, X.L., He, Y., Ji, L.L., Wang, K.Y., Wang, Y.L., Chen, D.F., Geng, Y., OuYang, P., Lai, W.M., 2017. Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats. Oncotarget. 8, 101545–101559. https://doi.org/10.18632/oncotarget.21074 Hussain, S.A.R., 2007. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. Journal of Medicinal Food. 10, 543–547. https://doi.org/10.1089/jmf.2006.089 Ibrahim, M.A., Habila, J.D., Koorbanally, N.A., Islam, M.S., 2016. Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats. Journal of Ethnopharmacoly. 183, 103-111. https://doi.org/10.1016/j.jep.2016.02.018 Imran, A., Butt, M.S., Arshad, M.S., Arshad, M.U., Saeed, F., Sohaib, M., Munir, R., 2018. Exploring the potential of black tea based flavonoids against hyperlipidemia related disorders. Lipids in Health and Disease. 17, 1–16. https://doi.org/10.1186/s12944-018-0688-6 Ishibashi, Y., Matsui, T., Nakamura, N., Sotokawauchi, A., Higashimoto, Y., Yamagishi, S.I., 2017. Methylglyoxal-derived hydroimidazolone-1 evokes inflammatory reactions in endothelial cells via an interaction with receptor for advanced glycation end products. Diabetes and Vascular Disease Research. 14, 450–453. https://doi.org/10.1177/1479164117715855 Janssen, B., De Celle, T., Debets, J., Brouns, A., Callahan, M., Smith, T., 2004. Effects of anesthetics on systemic hemodynamics in mice. American Journal of Physiology-Heart and Circulatory Physiology. 287, 1618–1625. https://doi.org/10.1152/ajpheart.01192.2003 Je, H.D., Shin, C.Y., Park, S.Y., Yim, S.H., Kum, C., Huh, I.H., Kim, J.H., Sohn, U.D., 2002. Combination of vitamin C and rutin on neuropathy and lung damage of diabetes mellitus rats. Archives of Pharmacal Research. 25, 184–190. https://doi.org/10.1007/BF02976561 Ji, S., Zhu, C., Gao, S., Shao, X., Chen, X., Zhang, H., Tang, D., 2021. Morus alba leaves ethanol extract protects pancreatic islet cells against dysfunction and death by inducing autophagy in type 2 diabetes. Phytomedicine. 83, 153478. https://doi.org/10.1016/j.phymed.2021.153478 Jiang, P., Burczynski, F., Campbell, C., Pierce, G., Austria, J.A., Briggs, C.J., 2007. Rutin and flavonoid contents in three buckwheat species Fagopyrum esculentum, F. tataricum, and F. homotropicum and their protective effects against lipid peroxidation. Food Research International. 40, 356–364. https://doi.org/10.1016/j.foodres.2006.10.009 Joo, T., Sowndhararajan, K., Hong, S., Lee, J., Park, S.Y., Kim, S., Jhoo, J.W., 2014. Inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells by stem bark of Ulmus pumila L. Saudi Journal of Biological Science. 21, 427–435. https://doi.org/10.1016/j.sjbs.2014.04.003 Jurado, B., Aparcana, I.M., Villarreal, L.S., Ramos, E., Hurtado, P.E., Acosta, K.M. Calixto, M.R. 2016. Evaluación del contenido de polifenoles totales y la capacidad antioxidante de los extractos etanólicos de los frutos de Aguaymanto (Physalis peruviana L.) de diferentes lugares del Perú. Revista de la Sociedad Química del Perú. 82, 272–279. https://doi.org/10.37761/rsqp.v82i3.58 Kamalakkannan, N., Prince, P.S.M., 2006. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic & Clinical Pharmacology & Toxicology. 98, 97–103. https://doi.org/10.1111/j.1742-7843.2006.pto_241. Kappel, V.D., Cazarolli, L.H., Pereira, D.F., Postal, B.G., Madoglio, F.A., Buss, Z. da S., Reginatto, F.H., Silva, F.R.M.B., 2013. Beneficial effects of banana leaves (Musa x paradisiaca) on glucose homeostasis: Multiple sites of action. Brazilian Journal of Pharmacognosy. 23, 706–715. https://doi.org/10.1590/S0102-695X2013005000062 Kappel, V.D., Frederico, M.J.S., Postal, B.G., Mendes, C.P., Cazarolli, L.H., Silva, F.R.M.B., 2013. The role of calcium in intracellular pathways of rutin in rat pancreatic islets: Potential insulin secretagogue effect. European Journal of Pharmacology. 702, 264–268. https://doi.org/10.1016/j.ejphar.2013.01.055 Kasali, F.M., Kadima, J.N., Mpiana, P.T., Ngbolua-Koto-te-Nyiwa, Tshibangu, D.S.-T., 2013. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig. Asian Pacific Journal of Tropical Biomedicine. 3, 841–846. https://doi.org/doi.org/10.1016/S2221-1691(13)60166-5 Kasali, F.M., Tusiimire, J., Kadima, J.N., Tolo, C.U., Weisheit, A., Agaba, A.G., 2021. Ethnotherapeutic Uses and Phytochemical Composition of Physalis peruviana L.: An Overview. The Scientific World Journal. https://doi.org/10.1155/2021/5212348 Kasali, F.M., Tuyiringire, N., Peter, E.L., Ahovegbe, L.Y., Ali, M.S., Tusiimire, J., Ogwang, P.E., Kadima, N.J., Agaba, A.G., 2022. Chemical constituents and evidence-based pharmacological properties of Physalis peruviana L .: An overview. Jounal of Herbmed Pharmacology. 1, 35–47. https://doi.org/10.34172/jhp.2022.04 Kennedy, M.L., María, E., Diarte, G., Monserrat, C., Escurra, C., Campuzano, M.Á., Farmacología, D. De, Ciencias, F. De, Campus, Q., 2010. Evaluación preliminar de la toxicidad, el efecto sobre el comportamiento y la actividad analgésica de Aloysia virgata var. platiphylla en ratones. Kurien, B.T., Hensley, K., Bachmann, M., Scofield, R.H., 2006. Oxidatively modified autoantigens in autoimmune diseases. Free Radical Biology and Medicine. 41, 549–556. https://doi.org/10.1016/j.freeradbiomed.2006.05.020 Laguerre, M., Lecomte, J., Villeneuve, P., 2007. Evaluation of the ability of antioxidants to counteract lipid oxidation: Existing methods, new trends and challenges. Progress in Lipid Research. 46 (5), 224-282. https://doi.org/10.1016/j.plipres.2007.05.002 Lan, Y.H., Chang, F.R., Pan, M.J., Wu, C.C., Wu, S.J., Chen, S.L., Wang, S.S., Wu, M.J., Wu, Y.C., 2009. New cytotoxic withanolides from Physalis peruviana. Food Chemistry. 116, 462–469. https://doi.org/10.1016/j.foodchem.2009.02.061 Lee, K.H., Cha, M., Lee, B.H., 2020. Neuroprotective effect of antioxidants in the brain. International Journal of Molecular Science. 21 (19), 7152. https://doi.org/10.3390/ijms21197152 Lenzen, S., 2008. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 51, 216–226. https://doi.org/10.1007/s00125-007-0886-7 Lenzen, S., Drinkgern, J., Tiedge, M., 1996. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radical Biology and Medicine. 20 (3), 463–466. https://doi.org/10.1016/0891-5849(96)02051-5 Levin-Arama, M., Abraham, L., Waner, T., Harmelin, A., Steinberg, D.M., Lahav, T., Harlev, M., 2016. Subcutaneous compared with intraperitoneal ketamine-xylazine for anesthesia of mice. Journal of the American Association for Laboratory Animal Science. 55, 794–800. Levitan, I., Volkov, S., Subbaiah, P. V., 2010. Oxidized LDL: Diversity, patterns of recognition, and pathophysiology. Antioxidants & Redox Signaling. 13 (1), 39-75. https://doi.org/10.1089/ars.2009.2733 Li, J.M., Wang, C., Hu, Q.H., Kong, L.D., 2008. Fructose induced leptin dysfunction and improvement by quercetin and rutin in rats. Chinese Journal of Natural Medicines. 6 (6), 466–473. https://doi.org/10.3724/SP.J.1009.2008.00466 Li, T., Chen, S., Feng, T., Dong, J., Li, Y., Li, H., 2016. Rutin protects against aging-related metabolic dysfunction. Food &Nutrition. 7, (2). 1147–1154. https://doi.org/10.1039/c5fo01036e Lim, J.S., Mietus-Snyder, M., Valente, A., Schwarz, J.M., Lustig, R.H., 2010. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nature Reviews Gastroenterology & Hepatology. 7, 251–264. https://doi.org/10.1038/nrgastro.2010.41 Lisset, M., Regal, L., Hermes, L., Otero, G., Alina, Z., Otero, G., Omar, J., 2013. Etiopatogenia de la microangiopatía diabética . Consideraciones bioquímicas y moleculares. Revista Finlay. 3, 2–12. Liu, Z., Hu, M., 2007. Natural polyphenol disposition via coupled metabolic pathways. Expert Opinion on Drug Metabolism & Toxicology. 3 (3), 389–406. https://doi.org/10.1517/17425255.3.3.389 Lock O, Perez E, Villar M, Flores D, Rojas R, 2016. Bioactive Compounds from Plants Used in Peruvian Traditional Medicine. Natural Product Communications. 11, 1–29. Lockwood, G.B., 2005. Fundamentals of pharmacognosy and phytotherapy, Phytochemistry. https://doi.org/10.1016/j.phytochem.2005.04.008 Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275. https://doi.org/10.1016/s0021-9258(19)52451-6 Lu, Q., Zhou, Y., Hao, M., Li, C., Wang, J., Shu, F., Du, L., Zhu, X., Zhang, Q., Yin, X., 2018. The mTOR promotes oxidative stress-induced apoptosis of mesangial cells in diabetic nephropathy. Molecular and Cellular Endocrinology. 473, 31–43. https://doi.org/10.1016/j.mce.2017.12.012 Lue, B.M., Nielsen, N.S., Jacobsen, C., Hellgren, L., Guo, Z., Xu, X., 2010. Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays. Food Chemistry. 123 (2), 221–230. https://doi.org/10.1016/j.foodchem.2010.04.009 Lv, Y., Zhao, P., Pang, K., Ma, Y., Huang, H., Zhou, T., Yang, X., 2021. Antidiabetic effect of a flavonoid-rich extract from Sophora alopecuroides L. in HFD- and STZ- induced diabetic mice through PKC/GLUT4 pathway and regulating PPARα and PPARγ expression. Journal of Ethnopharmacology. 268, 113654. https://doi.org/10.1016/j.jep.2020.113654 Mahecha, J.N., 2017. Aporte a la caracterización fitoquímica de un extracto hidroalcohólico de cálices de Physalis peruviana recolectados en el municipio de Granada-Cundinamarca Contribution to the phytochemical characterization of an hydroalcoholic extract. Tesis. Universidad Nacional de Colombia. Mahrous, R.S., Fathy, H.M., El-Khair, R.M.A., Omar, A.A., 2019. Chemical constituents of egyptian Withania somnifera leaves and fruits and their anticholinesterase activity. Journal of the Mexican Chemical Society. 63, 208–217. https://doi.org/10.29356/jmcs.v63i4.944 Mansour, H.B., Yatouji, S., Mbarek, S., Houas, I., Delai, A., Dridi, D., 2011. Correlation between antibutyrylcholinesterasic and antioxidant activities of three aqueous extracts from Tunisian Rhus pentaphyllum. Annals of Clinical Microbiology and Antimicrobials. 10 (1), 1-9. https://doi.org/10.1186/1476-0711-10-32 Mansuroǧlu, B., Derman, S., Yaba, A., Kizilbey, K., 2015. Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats. International Journal of Biological Macromolecules. 72, 79–87. https://doi.org/10.1016/j.ijbiomac.2014.07.039 Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., Turner, R.C., 1985. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28, 412–419. https://doi.org/10.1007/BF00280883 Mattson, M.P., 2008. Hormesis defined. Ageing Research Reviewes. 7 (1), 1–7. https://doi.org/10.1016/j.arr.2007.08.007 McColl, A.J., Kong, C., Nimmo, L., Collins, J., Elkeles, R.S., Richmond, W., 1997. 132 Total antioxidant status, protein glycation, lipid hydroperoiides in non insulin dependent diabetes mellitus. Biochemical Society Transactions. 25. https://doi.org/10.1042/bst025s660 Medina, S., Collado-González, J., Ferreres, F., Londoño-Londoño, J., Jiménez-Cartagena, C., Guy, A., Durand, T., Galano, J.M., Gil-Izquierdo, Á., 2019. Potential of Physalis peruviana calyces as a low-cost valuable resource of phytoprostanes and phenolic compounds. Journal of the Science of Food and Agriculture. 99 (5), 2194–2204. https://doi.org/10.1002/jsfa.9413 Ministerio de Salud y Proteccion social, 2022. En el Día Mundial de la Diabetes: MinSalud promueve prácticas de vida saludable. Boletín prensa No. 543 2022. https://www.minsalud.gov.co Miranda, C.A., Schönholzer, T.E., Klöppel, E., Sinzato, Y.K., Volpato, G.T., Damasceno, D.C., Campos, K.E., 2019. Repercussions of low fructose-drinking water in male rats. Anais da Academia Brasileira de Ciencias. 91, 1–10. https://doi.org/10.1590/0001-3765201920170705 Monzón, G., Meneses, C., Forero, A.M., Rodríguez, J., Aragón, M., Jiménez, C., Ramos, F.A., Castellanos, L., 2021. Identification of α-Amylase and α-Glucosidase Inhibitors and Ligularoside A, a New Triterpenoid Saponin from Passiflora ligularis Juss (Sweet Granadilla) Leaves, by a Nuclear Magnetic Resonance-Based Metabolomic Study. Journal of Agricultural and Food Chemistry. 69 (9), 2919–2931. https://doi.org/10.1021/acs.jafc.0c07850 Mora, Á.C., Aragón, D.M., Ospina, L.F., 2010. Effects of Physalis peruviana fruit extract on stress oxidative parameters in streptozotocin-diabetic rats. Latin American Journal of Pharmacy. 29, 1132–1136. Muñoz, Ó.A., Torres, G.A., Núñez, J.A., De la Rosa, L.A., Rodrigo, J., Aya, J.F., Álvarez, E. 2017. Nuevo Acercamiento a La Interacción Del Reactivo De Folin-Ciocalteu Con Azúcares Durante La Cuantificación De Polifenoles Totales. Tip. 20 (2), 23–28. https://doi.org/10.1016/j.recqb.2017.04.003 Murillo, E., Tique, M., Ospina, F., Lombo, O., 2006. Evaluación preliminar de la actividad hipoglicemiante en ratones diabéticos por aloxano y capacidad antioxidante in vitro de extractos de Bauhinia kalbreyeri Harms. Revista Colombiana de Ciencias Químico Farmacéuticas. 35, 64–80. Nayak, B.N., Kaur, G., Buttar, H.S., 2016. TNF-α modulation by natural bioactive molecules in mouse RAW 264.7 macrophage cells. Journal of Complementary and Integrative Medicine. 13 (1), 1–7. https://doi.org/10.1515/jcim-2015-0024 Nowotny, K., Jung, T., Höhn, A., Weber, D., Grune, T., 2015. Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus. Biomolecules. 194–222. https://doi.org/10.3390/biom5010194 Oboh, G., Ademosun, A.O., Ayeni, P.O., Omojokun, O.S., Bello, F., 2015. Comparative effect of quercetin and rutin on α-amylase, α-glucosidase, and some pro-oxidant-induced lipid peroxidation in rat pancreas. Comparative Clinical Pathology. 24, 1103–1110. https://doi.org/10.1007/s00580-014-2040-5 Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 95 (2), 351–358. https://doi.org/10.1016/0003-2697(79)90738-3 Ohkawa, H., Ohishi, N., Yagi, K., Ajith, T.A., 2010. Ameliorating reactive oxygen species-induced in vitro lipid peroxidation in brain, liver, mitochondria and DNA damage by Zingiber officinale Roscoe. Indian Journal of Clinical Biochemistry. 25, 351–358. https://doi.org/10.1016/0003-2697(79)90738-3 Olabiyi, A.A., Alli Smith, Y.R., Babatola, L.J., Akinyemi, A.J., Oboh, G., 2016. Inhibitory effect of aqueous extract of different parts of Gossypium herbaceum on key enzymes linked with type 2 diabetes and oxidative stress in rat pancreas in vitro. Beni-Suef University Journal of Basic and Applied Science. 5 (2), 180–186. https://doi.org/10.1016/j.bjbas.2016.05.003 OPS, 2022. Diabetes. Citado el 14 febrero de 2022. Disponible en: https://www.paho.org/es/temas/diabetes Pai Kotebagilu, N., Reddy Palvai, V., Urooj, A., 2014. Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates. International Journal of Medicinal Chemistry. 2014, 1–7. https://doi.org/10.1155/2014/861084 Panunti, B., Jawa, A.A., Fonseca, V.A., 2004. Mechanisms and therapeutic targets in type 2 diabetes mellitus. Drug Discovery Today: Disease Mechanisms. 1 (2), 151–157. https://doi.org/10.1016/j.ddmec.2004.09.011 Parthasarathy, S., Carew, T.E., Khoo, J.C., Witztum, J.L., Barnett, J., Fong, L.G., Stocker, R., Rapp, J.H., Kim, K.Y., Feingold, K.R., Kohlschiitter, A., Beisiegel, U., Stanley, K.K., Stocker, R., Nordestgaard, B.G., Nielsen, L.B., Wootton, R., Lewis, B., Gaziano, J.M., Hiibner, C., Finckh, B., Kohlschtitter, A., Beisiegel, U., 1999. Measurement of oxidizability of blood plasma. Methods in Enzymology. 299, 35–49. Patel, S., Santani, D., 2009. Role of NF-κB in the pathogenesis of diabetes and its associated complications. Pharmacological Reports. 61 (4), 595–603. https://doi.org/10.1016/S1734-1140(09)70111-2 Perera, H., 2016. Antidiabetic Effects of Pterocarpus marsupium (Gammalu). European Journal of Medicinal Plants. 13 (4), 1–14. https://doi.org/10.9734/ejmp/2016/23930 Poovitha, S., Siva Sai, M., Parani, M., 2017. Protein extract from the fruit pulp of Momordica dioica shows anti-diabetic, anti-lipidemic and antioxidant activity in diabetic rats. Journal of Functional Foods. 33, 181–187. https://doi.org/10.1016/j.jff.2017.03.042 Puente, L., Pinto, M.C., Castro, E., Cortés, M., 2011. Physalis peruviana L, the multiple properties of a highly functional fruit: A review. Food Research International. 44 (7), 1733-1740. Qu, H.Q., Li, Q., Rentfro, A.R., Fisher-Hoch, S.P., McCormick, J.B., 2011. The definition of insulin resistance using HOMA-IR for americans of mexican descent using machine learning. PLoS One 6. 6 (6), e21041. https://doi.org/10.1371/journal.pone.0021041 Ramadan, M.F., 2012. Physalis peruviana pomace suppresses high-cholesterol diet-induced hypercholesterolemia in rats. Grasas y aceites. 63 (4), 411–422. Ramadan, M.F., 2011. Bioactive phytochemicals, nutritional value, and functional properties of cape gooseberry (Physalis peruviana): An overview. Food Research International. 44 (7), 1830–1836. https://doi.org/10.1016/j.foodres.2010.12.042 Ramadan, M.F., Moersel, J.T., 2007. Impact of enzymatic treatment on chemical composition, physicochemical properties and radical scavenging activity of goldenberry (Physalis peruviana L.) juice. Journal of Science, Food & Agriculture. 87 (3), 452–460. https://doi.org/10.1002/jsfa.2728 Ramadan, M.F., Morsel, J.T., 2003. Oil goldenberry (Physalis peruviana L.). Journal of Agriculture and Food Chemistry. 51 (4), 969–974. https://doi.org/10.1021/jf020778z Ramchoun, M., Sellam, K., Harnafi, H., Alem, C., Benlyas, M., El Rhaffari, L., Amrani, S., 2015. Biological investigations of antioxydant and antimicrobial properties of Thymus satureioides collected in Tafilalet region, south-east of Morocco. International Journal of Pharmacy. 5 (2), 339–346. Ramos, V.W., Batista, L.O., Albuquerque, K.T., 2017. Effects of fructose consumption on food intake and biochemical and body parameters in Wistar rats. Revista Portuguesa de Cardiología. 36 (12), 937–941. Reddy, S., Akhila, M., Subrahmanyam, C.V.S., Trimurtulu, G., Raghavendra, N.M., 2015. Isolation, in vitro antidiabetic, antioxidant activity and molecular docking studies of pentacyclic triterpenoids from Syzygium alternifolium (wt.) Walp bark. Journal of Pharmacy and Biologycal Sciences. 10 (6), 2319–7676. https://doi.org/10.9790/3008-1062148154 Rey, D.P., Ospina, L.F., Aragón, D.M., 2015. Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases. Revista Colombiana de Ciencias Químico Farmacéuticas. 44, 72–89. https://doi.org/10.15446/rcciquifa.v44n1.54281 Rey Padilla, D.P., 2015. Evaluación del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales. Tesis de maestría. Universidad Nacional de Colombia. Rodrigo, R., Libuy, M., 2014. Modulation of Plant Endogenous Antioxidant Systems by Polyphenols. Polyphenols in Plants. 65-85. https://doi.org/10.1016/B978-0-12-397934-6.00005-X Rodríguez, L., 2012. Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World Journal of Diabetes. 3 (1), 7. https://doi.org/10.4239/wjd.v3.i1.7 Rodríguez, C.P., Torres, M.C.., Aguilar, C.A., Medina, O.N., 2017. Mecanismos inmunológicos involucrados en la obesidad. Investigación Clinica. 58 (2), 175–196. Sahin, G., Telli, M., Ünlü, E.S., Pehlivan Karakaş, F., 2020. Effects of moderate high temperature and uv-b on accumulation of withanolides and relative expression of the squalene synthase gene in Physalis peruviana. Turkish Journal of Biology. 44, 295–303. https://doi.org/10.3906/biy-2002-69 Sánchez N., J.C., López Z., D.F., Pinzón D., Ó.A., Sepúlveda A., J.C., 2010. Adipocinas y síndrome metabólico: múltiples facetas de un proceso fisiopatológico complejo. Revista Colombiana de Cardiología. 17, 167–176. https://doi.org/10.1016/s0120-5633(10)70236-9 Sang-Ngern, M., Youn, U.J., Park, E.J., Kondratyuk, T.P., Simmons, C.J., Wall, M.M., Ruf, M., Lorch, S.E., Leong, E., Pezzuto, J.M., Chang, L.C., 2016. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorganic & Medicinal Chemistry Letters. 26 (12), 2755–2759. https://doi.org/10.1016/j.bmcl.2016.04.077 Séro, L., Sanguinet, L., Blanchard, P., Dang, B.T., Morel, S., Richomme, P., Séraphin, D., Derbré, S., 2013. Tuning a 96-well microtiter plate fluorescence-based assay to identify AGE inhibitors in crude plant extracts. Molecules .18, 14320–14339. https://doi.org/10.3390/molecules181114320 Shanmugasundaram, E.R., Rajeswari, G., Baskaran, K., Kumar, B.R., Shanmugasundaram, K.R., Ahmath, B.K., 1990. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. Journal of Ethnopharmacology. 30, 281–294. https://doi.org/10.1016/0378-8741(90)90107-5 Sharma, R., Dave, V., Sharma, S., Jain, P., Yadav, S., 2013. Experimental Models on Diabetes : A Comprehensive Review. International Journal of Advances in Pharmaceutical Sciences. 4, (1) 1–8. Shen, Y., Zhang, H., Cheng, L., Wang, L., Qian, H., Qi, X., 2016. In vitro and in vivo antioxidant activity of polyphenols extracted from black highland barley. Food Chemistry. 194, 1003–1012. https://doi.org/10.1016/j.foodchem.2015.08.083 Shi, W., Liu, L., Li, J., Qu, L., Pang, X., Yu, H., Zhang, Y., Wang, T., 2017. Bioactive flavonoids from Flos Sophorae. Journal of Natural Medicine. 71, 513–522. https://doi.org/10.1007/s11418-017-1084-7 Singleton, V. L., Orthofer, R., & Lamuela-Raventós, R.M., 1999. Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent. Methods in Enzymology. 299, 152–178. https://doi.org/10.1016/s0076-6879(99)99017-1 Smith, C., Mitchinson, M.J., Aruoma, O.I., Halliwell, B., 1992. Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions. Biochemical Journal. 286, 901–905. https://doi.org/10.1042/bj2860901 Soczyńska-Kordala, M., Bakowska, A., Oszmiański, J., Gabrielska, J., 2001. Metal ion-flavonoid associations in bilayer phospholipid membranes. Cellular and Molecular Biology Letters. 6, 277–281. Soler, A., 2009. Estudio de la capacidad antioxidante y la biodisponibilidad de los compuestos fenólicos del aceite de oliva. Primeras etapas en el desarrollo de un aceite de oliva funcional. Tesis de doctorado. Universitat de Lleida. Spruss, A., Kanuri, G., Wagnerberger, S., Haub, S., Bischoff, S.C., Bergheim, I., 2009. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology. 50 (4), 1094–1104. https://doi.org/10.1002/hep.23122 Stanley, J., 1995. Síndrome: un concepto en evolución. Acimed. 3, 30–38. Stumvoll, M., Goldstein, B.J., Haeften, T.W. Van, 2005. Pathogenesis of type 2 diabetes.pdf. Lancet 365, 1333–1346. Tanaka, S., Aida, K., Nishida, Y., Kobayashi, T., 2013. Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes. Endocrine Journal. 60 (7), 837–845. https://doi.org/10.1507/endocrj.EJ13-0222 Tang, Y., Gao, C., Xing, M., Li, Y., Zhu, L., Wang, D., Yang, X., Liu, L., Yao, P., 2012. Quercetin prevents ethanol-induced dyslipidemia and mitochondrial oxidative damage. Food and Chemical Toxicology. 50, 1194–1200. https://doi.org/10.1016/j.fct.2012.02.008 Tankova, T., Chakarova, N., Atanassova, I., Dakovska, L., 2011. Evaluation of the Finnish Diabetes Risk Score as a screening tool for impaired fasting glucose, impaired glucose tolerance and undetected diabetes. Diabetes Research and Clinical Practice. 92 (1), 46–52. https://doi.org/10.1016/j.diabres.2010.12.020 Tariq, S., Imran, M., Mushtaq, Z., Asghar, N., 2016. Phytopreventive antihypercholesterolmic and antilipidemic perspectives of zedoary (Curcuma Zedoaria Roscoe.) herbal tea. Lipids in Health Disease. https://doi.org/10.1186/s12944-016-0210-y Toro, R., Aragón, M Ospina, LF. 2013. Hepatoprotective effect of calyces extract of Physalis peruviana on hepatotoxicity induced by CCl4 in Wistar rats. Vitae 20, 125–132. https://doi.org/10.17533/udea.vitae.12560 Toro, R., Arangon, M., 2014. Propuesta de un marcador analítico como herramienta en la microencapsulación de un extracto con actividad antioxidante de cálices de Physalis peruviana. Tesis de maestria. Universidad Nacional de Colombia. Toro, R.M., Aragón, D.M., Ospina, L.F., Ramos, F.A., Castellanos, L., 2014. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana. Natural Products Communications. 9, 1573–1575. https://doi.org/10.1177/1934578x1400901111 Unnikrishnan, M.K., Veerapur, V., Nayak, Y., Mudgal, P.P., Mathew, G., 2013. Antidiabetic, Antihyperlipidemic and Antioxidant Effects of the Flavonoids. Polyphenols in Human Health and Disease. 143-161. https://doi.org/10.1016/B978-0-12-398456-2.00013-X Vessal, M., Hemmati, M., Vasei, M., 2003. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comparative Biochemistry and Physiology part C: Toxicology and Pharmacology. 135, 357–364. https://doi.org/10.1016/S1532-0456(03)00140-6 Wang, J., Mazza, G., 2002. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-γ-activated RAW 264.7 macrophAGEs. Journal of Agricultural and Food Chemistry. 50 (4), 850–857. https://doi.org/10.1021/jf010976a Wang, Y., Alkhalidy, H., Liu, D., 2021. The emerging role of polyphenols in the management of type 2 diabetes. Molecules 26, 1–25. https://doi.org/10.3390/molecules26030703 Wiernsperger, N.F., 2003. Oxidative stress as a therapeutic target in diabetes: Revisiting the controversy. Diabetes & Metabolism. 29, 579–585. https://doi.org/10.1016/S1262-3636(07)70072-1 Wu, C.H., Yen, G.C., 2005. Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts. Journal of Agriculture and Food Chemistry. 53, 3167–3173. https://doi.org/10.1021/jf048550u Wu, S.-J., NG, L.-T., Huang, Y.-M., Lin, D.-L., Wang, S.-S., Huang, S.-N., Lin, C.-C., 2005. Antioxidant activities of Physalis peruviana. Biological and Pharmaceutical Bulletin. 28 (6), 963–966. https://doi.org/10.1248/bpb.28.963 Wu, S.J., Ng, L.T., Lin, D.L., Huang, S.N., Wang, S.S., Lin, C.C., 2004. Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway. Cancer Letters. 215, 199–208. https://doi.org/10.1016/j.canlet.2004.05.001 Yaribeygi, H., Sathyapalan, T., Atkin, S.L., Sahebkar, A., 2020. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. Oxididative Medicine and Cellular. Longevity. 2020. https://doi.org/10.1155/2020/8609213 Zhang, M., Lv, X.Y., Li, J., Xu, Z.G., Chen, L., 2008. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Journal of Diabetes Research. https://doi.org/10.1155/2008/704045 Zhang, X., Zhou, Y., Cheong, M.S., Khan, H., Ruan, C.C., Fu, M., Xiao, J., Cheang, W.S., 2022. Citri Reticulatae Pericarpium extract and flavonoids reduce inflammation in RAW 264.7 macrophages by inactivation of MAPK and NF-κB pathways. Food Frontiers. 3 (4), 785–795. https://doi.org/10.1002/fft2.169 |
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Atribución-NoComercial 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Ospina Giraldo, Luis Fernandobfb3464e494e8bac88c6cb72a6754547Modesti Costa, Geisona1bdfe0b89eeb5d3c67ebafaa8d5f426Valderrama Parra, Ivonne Helena1b90a7db479112d4797dbee20a3500c4600Principios Bioactivos en Plantas Medicinales2024-01-16T00:39:47Z2024-01-16T00:39:47Z2023https://repositorio.unal.edu.co/handle/unal/85315Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasEstudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo II Se ha demostrado que el estrés oxidativo juega un papel importante en el desarrollo de complicaciones diabéticas, siendo esta enfermedad un trastorno metabólico caracterizado principalmente por obesidad, hiperglucemia, perfil lipídico alterado, estrés oxidativo y compromiso vascular. Physalis peruviana es una planta utilizada en la medicina tradicional colombiana por sus conocidas actividades como regulador de la glucosa. Este estudio tuvo como objetivo evaluar la actividad antidiabética de un extracto estandarizado de P. peruviana y sus fracciones (en Acetato de Etilo, Butanol y Acuosa). Después de diferentes ensayos de detección, se seleccionó la FBuOH (fracción butanólica) por sus efectos promisorios la para pasar a la siguiente etapa del estudio en ensayos crónicos in vivo en dos biomodelos; uno fue un modelo de diabetes inducida por una dieta High Fat Diet/Streptozotocin (HFD/STZ) en ratones CD-1 y el segundo fue el modelo de síndrome metabólico inducido por la administración de fructosa en agua de bebida, en ratones CD- 1. La FBuOH resultó útil para regular la glucosa en sangre, así como el índice de resistencia a la insulina. Además, el perfil lipídico mostró una mejora en comparación con el grupo no tratado y la dosis de 100 mg/kg demostrando mayor protección contra el estrés oxidativo (niveles de catalasa, superóxido dismutasa y malondialdehído). El análisis histopatológico en varios tejidos evidenció preservación de la estructura pancreática, hepática y renal en la mayoría de los animales tratados. La fracción butanólica de Physalis peruviana a 100 mg/kg mostró resultados beneficiosos en cuanto disminuir la hiperglucemia, hiperlipidemia, el estado de estrés oxidativo y el inflamatorio. En experimentos in vivo la fracción butanólica moduló la expresión de citoquinas proinflamatorias IL-6 e TNF- α en hígado de animales con síndrome metabólico, así como en el modelo de células RAW 264.7, demostrando además en este modelo celular protección frente a la formación de nitritos. La fracción butanólica mejoró el estatus diabético por disminución del estrés oxidativo y las complicaciones adyacentes, por lo que podría considerarse beneficioso como coadyuvante en la terapia de la diabetes mellitus. (Texto tomado de la fuente).Study of the activity of an extract of Physalis peruviana calyxes on oxidative stress in rodents with type II diabetes mellitus It has been shown that oxidative stress plays an important role in the development of diabetic complications, being this disease, a metabolic disorder characterized mainly by obesity, hyperglycemia, altered lipid profile, oxidative stress, and vascular compromise. Physalis peruviana is a plant used in traditional Colombian medicine for its known activities as glucose regulation. This study aimed to evaluate the antidiabetic activity of a standardized extract from P. peruviana and its fraction (FAcEt, FBuOH, and H2O). After different detection tests, and checking the promising effects from the fractions, FBuOH (the butanolic fraction) was selected for its promising effects, to continue to the next stage of the study in chronic in vivo in two biomodels; one is a model of diabetes induced by a High Fat Diet/Streptozotocin (HFD/STZ) diet in CD-1 mice and the second was the model of metabolic syndrome induced by the administration of fructose in drinking water, in CD-1 mice. The FBuOH is exhibited to regulate the blood glucose and insulin resistance index. Also, the lipid profile exhibited improvement compared to the non-treated group, and the dose of 100 mg/kg demonstrated major protection against oxidative stress (catalase, superoxide dismutase, and malondialdehyde levels). Histopathological in several tissues evidenced structure preservation of most of the animals treated. The butanol fraction from Physalis peruviana at 100 mg/kg improved hyperglycemia, hyperlipidemia, oxidative stress, and inflammatory outcome. In in vivo experiments, the butanolic fraction modulated the expression of proinflammatory cytokines IL-6 and TNF-α in the liver of animals with metabolic syndrome, as well as in the RAW 264.7 cell model, also demonstrating in this cell model protection against the formation of nitrites. The butanolic fraction improved diabetic status by reducing oxidative stress and related complications, so it could be considered beneficial as an adjuvant in diabetes mellitus therapy. Keywords: Flavonoid, rutin, polyphenols, antioxidant, lipid profile, hyperglycemia, metabolic syndrome, Physalis peruviana.DoctoradoDoctor en Ciencias Farmacéuticasxviii, 126 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en Ciencias FarmacéuticasFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::615 - Farmacología y terapéuticadiabetes mellitus/veterinariadiabetes mellitus/farmacoterapiaantioxidantes/síntesis químicaDiabetes Mellitus/veterinaryDiabetes Mellitus/drug therapyAntioxidants/chemical synthesisPhysalis peruvianaFlavonoideRutinaSíndrome metabólicoAntioxidantePerfil lipídicoPolifenolesHiperglicemiaPhysalis peruvianaFlavonoidLipid profileRutinMetabolic syndromeAnioxidantPolyphenolsHyperglycemiaEstudio de la actividad de un extracto de cálices de Physalis peruviana sobre estrés oxidativo en roedores con diabetes mellitus tipo IIStudy of the activity of an extract of Physalis peruviana calyxes on oxidative stress in rodents with type II diabetes mellitusTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDBiremeAbdelhameed, R.F.A., Ibrahim, A.K., Elfaky, M.A., Habib, E.S., Mahamed, M.I., Mehanna, E.T., Darwish, K.M., Khodeer, D.M., Ahmed, S.A., Elhady, S.S., 2021. Antioxidant and anti-inflammatory activity of cynanchum acutum l. Isolated flavonoids using experimentally induced type 2 diabetes mellitus: Biological and in silico investigation for nf-κb pathway/mir-146a expression modulation. Antioxidants. https://doi.org/10.3390/antiox10111713Abu-Amsha, R., Croft, K.D., Puddey, I.B., Proudfoot, J.M., Beilin, L.J., 1996. Phenolic content of various beverAGEs determines the extent of inhibition of human serum and low density lipoprotein oxidation in vitro: Identification and mechanism of action of some cinnamic acid derivatives from red wine. Clinical Science. 91, 449–458. https://doi.org/10.1042/cs0910449Adjimani, J.P., Asare, P., 2015. Antioxidant and free radical scavenging activity of iron chelators. Toxicology Reports. 2, 721–728. https://doi.org/10.1016/j.toxrep.2015.04.005Al-Romaiyan, A., Liu, B., Asare-Anane, H., Maity, C.R., Chatterjee, S.K., Koley, N., Biswas, T., Chatterji, A.K., Huang, G.C., Amiel, S.A., Persaud, S.J., Jones, P.M., 2010. A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro. Phytotherapy Research. 24, 1370–1376. https://doi.org/10.1002/ptr.3125Alam, S., Sarker, M., Sultana, T., Chowdhury, M., Rashid, M., Chaity, N., Zhao, C., Xiao, J., Hafez, E., Khan, S., Mohamed, I., 2022. Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development. Frontiers in Endocrinology. 13. https://doi.org/10.3389/fendo.2022.800714Albu, E., Lupaşcu, D., Filip, C., Jaba, I.M., Zamosteanu, N., 2013. The influence of a new rutin derivative on homocysteine, cholesterol and total antioxidative status in experimental diabetes in rat. Farmacia. 61, 1167–1177.American Diabetes Association, 2019. ¿Tiene riesgo de padecer de diabetes tipo 2? ¿Qué sigue? 2019.Ang, S., Eckling, K., Arcone, M., Akuda, Y., Sao, R. 2011. Synergistic , additive , and antagonistic effects of food mixtures on total antioxidant capacities. Journal of Agriculture Food Chemistry. 59, 960–968. https://doi.org/10.1021/jf1040977Antia, B.S., Okokon, J.E., Okon, P.A., 2005. Hypoglycemic activity of aqueous leaf extract of Persea americana Mill. Indian Journal of Pharmacology. 37, 325–326. https://doi.org/10.4103/0253-7613.16858Aragón, D.M., Echeverry, S.M., Valderrama, I.H., Costa, G.M., Ospina, L.F., 2018. Development and optimization of microparticles containing a hypoglycemic fraction of calyces from Physalis peruviana. Journal of Applied Pharmaceutical Science. 8, 10–18. https://doi.org/10.7324/JAPS.2018.8502Aragón Novoa, D.M., Ospina Giraldo, L.F., Ramos Rodríguez, F.A., Castellanos Hernández, L., Costa Modesti, G., Barreto Silva, F.R.M., 2021. Passiflora ligularis Juss. (granadilla): estudios quimicos y farmacológicos de una es planta con potencial terapéutico. Universidad Nacional de Colombia, Bogotá,Colombia. https://doi.org/https://doi.org/10.36385/FCBOG-12-0Arias Díaz, J., Balibrea, J., 2007. Modelos animales de intolerancia a la glucosa y diabetes tipo 2. Revista Nutrición Hospitalaria. 22, 160–168.Aristizábal, A.M. (Corporación U.L., 2013. Uchuva (Physalis peruviana L): estudio de su potencial aplicación en el desarrollo de alimentos con características funcionales. Tesis Maest. 1–43.Arumugam, G., Manjula, P., Paari, N., 2013. A review: Anti diabetic medicinal plants used for diabetes mellitus. Journal of Acute Disease. 2, 196–200. https://doi.org/10.1016/S2221- 6189(13)60126-2Asano, N., Kato, A., Matsui, K., Watson, A.A., Nash, R.J., Molyneux, R.J., Hackett, L., Topping, J., Winchester, B., 1997. The effects of calystegines isolated from edible fruits and vegetables on mammalian liver glycosidases. Glycobiology 7. 1085–1088. https://doi.org/10.1093/glycob/7.8.1085Assadi, S., Shafiee, S.M., Erfani, M., Akmali, M., 2021. Antioxidative and antidiabetic effects of Capparis spinosa fruit extract on high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats. Biomedicine & Pharmacotheraphy. 138, 111391. https://doi.org/10.1016/j.biopha.2021.111391Bernal, C.A., Castellanos, L., Aragón, D.M., Martínez-Matamoros, D., Jiménez, C., Baena, Y., Ramos, F.A., 2018. Peruvioses A to F, sucrose esters from the exudate of Physalis peruviana fruit as α-amylase inhibitors. Carbohydrate research. 461, 4–10. https://doi.org/10.1016/j.carres.2018.03.003Bernal, M., Correa, Q., 1998. Especies vegetales promisorias de los países del convenio Andrés Bello. Editora Guadalupe Ltda, Bogotá,Colombia.Black, P.H., 2003. The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behavior, and Immunity. 17, 350–364. https://doi.org/10.1016/S0889- 1591(03)00048-5Boden, G., Homko, C., Barrero, C.A., Stein, T.P., 2017. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Science Translational medicine. 7, 304. https://doi.org/10.1126/scitranslmed.aac4765.Boudreau, A., Poulev, A., Ribnicky, D.M., Raskin, I., Rathinasabapathy, T., Richard, A.J., Stephens, J.M., 2019. Distinct fractions of an Artemisia scoparia extract contain compounds with novel adipogenic bioactivity. Frontiers in Nutrition. 6, 1–13. https://doi.org/10.3389/fnut.2019.00018Bradmus, J.A. Adedosu, T.O., Fatoki, J.O., Adegbite V.A., Adaramoye O.A., Odunola, O., 2011. Lipid Peroxidation Inhibition and Antiradical Activities of Some Leaf Fractions of Mangifera Indica. Acta Pol Pharm. 68, 23–29.Brand-Williams, W., Cuvelier, M.E., Berset, C., 1995. Use of a free radical method to evaluate antioxidant activity. LWT - Food Science and Technology. 28, 25–30. https://doi.org/10.1016/S0023-6438(95)80008-5Cameron, A.R., Morrison, V.L., Levin, D., Mohan, M., Forteath, C., Beall, C., McNeilly, A.D., Balfour, D.J.K., Savinko, T., Wong, A.K.F., Viollet, B., Sakamoto, K., Fagerholm, S.C., Foretz, M., Lang, C.C., Rena, G., 2016. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circulation Research. 119, 652–665. https://doi.org/10.1161/CIRCRESAHA.116.308445Cardona, M.I., 2014. Aporte a la estandarización de un extracto de cálices de Physalis peruviana. Tesis de maestría. Universidad Nacional de Colombia.Cardona, M.I., Toro, R.M., Costa, G.M., Ospina, L.F., Castellanos, L., Ramos, F.A., Aragón, D.M., 2017. Influence of extraction process on antioxidant activity and rutin content in Physalis peruviana calyces extract. Journal Applied Pharmaceutical Science. 7, 164–168. https://doi.org/10.7324/JAPS.2017.70623Carvalho, E.N. de, Carvalho, N.A. de, Ferreira, L.M., 2003. Experimental model of induction of diabetes mellitus in rats. Acta Cirurgica Brasilera. 18, 60–64. https://doi.org/10.1590/s0102-86502003001100009Cazarolli, L., Zanatta, L., Alberton, E., Bonorino Figueiredo, M.S., Folador, P., Damazio, R., Pizzolatti, M., Barreto Silva, F.R., 2008. Flavonoids: Prospective Drug Candidates. Mini Reviews in Medicinal Chemistry. 8, 1429–1440. https://doi.org/10.2174/138955708786369564Chasquibol, N., Yacono, J., 2015. Composicion fitoquimica del aceite de las semillas del fruto del “Aguaymanto”, Physalis peruviana L. Revista de la Sociedad Química del Perú. 81, 311–318.Cooper, M.A., Ryals, J.M., Wu, P.Y., Wright, K.D., Walter, K.R., Wright, D.E., 2017. Modulation of diet-induced mechanical allodynia by metabolic parameters and inflammation. Journal of the Peripheral Nervous System. 22, 39–46. https://doi.org/10.1111/jns.12199.Costa, G.M., 2013. Estudo Químico de Espécies Brasileiras e Colombianas de Passiflora. Tesis de Doctorado. Universidad Federal de Santa Catarina.Cryer, P.E., 2016. Hypoglycemia in Type 2 Diabetes. Type 2 Diabetes melluitus: An evidence based Approach to Practical Management. Second Ed. 28, 227–236. https://doi.org/10.3109/9780849379581-19Darwish, A.G., Mahmoud, H.I., Refaat, I., 2020. Antioxidative and Antidiabetic Effect of Goldenberries juice and pomace on Experimental Rats Induced with streptozotocin In vitro. Journal of Food Dairy Science. 11, 277–283. https://doi.org/10.21608/jfds.2020.118371De La O-Quezada, G.A., Damaris, ;, Ojeda-Barrios, L., Ofelia, ¶ ;, Hernández-Rodríguez, A., Sánchez-Chávez, E., Jaime Martínez-Tellez, ;, 2011. Biomasa, Prolina Y Parámetros Nitrogenados En Plántulas De Nogal Bajo Estrés Hídrico Y Fertilización Nitrogenada. Revista Chapingo. Serie Horticultura. 17, 13–18.De Paiva, L.B., Goldbeck, R., dos Santos, W.D., Squina, F.M., 2013. Ferulic acid and derivatives: Molecules with potential application in the pharmaceutical field. Brazilian Journal of Pharmeutical Science. 49, 395–411. https://doi.org/10.1590/S1984- 82502013000300002Derbré, S., Gatto, J., Pelleray, A., 2010. Automating a 96-well microtiter plate assay for identification of AGEs inhibitors or inducers : Application to the screening of a small natural. Analytical & Bioanalytical Chemistry. 398, 1747–1758. https://doi.org/10.1007/s00216-010-4065-1Devkar, S.T., Muthal, A.P., Patil, P. V., Mukherjee-Kandhare, A.A., Kandhare, A.D., Jagtap, S.D., Bodhankar, S.L., Hegde, M. V., 2021. Evaluation of the physicochemical stability and biological activity of withanolide rich fraction from Withania somnifera root by hplc and cyclic voltammetry: A simple, reliable, and cost-effective approach. Latin American Journal of Pharmacy. 40, 946–956.Dinan, L.N., Sarker, S.D., Šik, V., 1997. 28-Hydroxywithanolide E. from Physalis peruviana. Phytochemistry 44, 509–512. https://doi.org/10.1016/S0031-9422(96)00553-5Diagnosis and Classification of Diabetes Mellitus, 2014. Diabetes Care. 37.Domínguez Moré, G.P., Cardona, M.I., Sepúlveda, P.M., Echeverry, S.M., Oliveira Simões, C.M., Aragón, D.M., 2021. Matrix effects of the hydroethanolic extract of calyces of Physalis peruviana l. On rutin pharmacokinetics in wistar rats using population modeling. Pharmaceutics. 13,(4), 535. https://doi.org/10.3390/pharmaceutics13040535Dos Santos, M., Prestes, A.S., de Macedo, G.T., Ecker, A., Barcelos, RP., Boligon, A.A & Barbosa, N.V. 2018. Syzygium cumini leaf extract inhibits LDL oxidation, but does not protect the liproprotein from glycation. Journal of Ethnopharmacology. 210, 69–79. https://doi.org/10.1016/j.jep.2017.08.033Dos Santos, J.M., Alves Junior, V.V., Boleti, A.P. de A., Lima, E.S., Carollo, C.A., dos Santos, E.L., Rabelo, L.A., Alfredo, T.M., Melo da Cunha, J. da S., de Picoli Souza, K., 2018. Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea. PLoS One. 13 (6). https://doi.org/10.1371/journal.pone.0197071Endale, M & Endalo M. 2015. Recent trends in rapid dereplication of natural product extracts: an update. Journal of Coastal Life Medicine. 3 (3), 178-182 https://doi.org/10.12980/jclm.3.201514j66Ezzat, S.M., Abdallah, H.M.I., Yassen, N.N., Radwan, R.A., Mostafa, E.S., Salama, M.M., Salem, M.A., 2021. Phenolics from Physalis peruviana fruits ameliorate streptozotocin induced diabetes and diabetic nephropathy in rats via induction of autophagy and apoptosis regression. Biomedicine & Pharmacotherapy. 142. https://doi.org/10.1016/j.biopha.2021.111948Fischer, G., Almanza-Merchán, P.J., Miranda, D., 2014. Importancia y cultivo de la uchuva (Physalis peruviana L.). Revista Brasileira de Fruticultura. 36, 01–15. https://doi.org/10.1590/0100-2945-441/13Flórez, V., Fischer, G., 2000. Producción, poscosecha y exportación de la uchuva (Physalis peruviana l.). Editorial Universidad Nacional de Colombia. https://doi.org/: 958-8051-74-6Folch, J., Lees, M., Sloane, G.H., 1957. A simple method for the isolation and purification of total lipides from animal tissues. Journal of Biological Chemistry. 226, 497–509. https://doi.org/10.1016/s0021-9258(18)64849-5Fontana, D., Cazarolli, L.H., Lavado, C., Mengatto, V., Figueiredo,., Guedes, A., Pizzolatti, M., Silva, F., 2011. Effects of flavonoids on α-glucosidase activity: Potential targets for glucose homeostasis. Nutrition . 27, 1161–1167. https://doi.org/10.1016/j.nut.2011.01.008Franco, L.A., Ocampo, Y.C., Gómez, H.A., De La Puerta, R., Espartero, J.L., Ospina, L.F., 2014. Sucrose esters from Physalis peruviana calyces with anti-inflammatory activity. Planta Médica. 80, 1605–1614. https://doi.org/10.1055/s-0034-1383192Franco LA, Matiz GE, Calle J, Pinzón R, O.L., 2007. Actividad antinflamatoria de extractos y fracciones obtenidas de cálices de Physalis peruviana L. Biomédica. 27, 110–5.Fuangchan, A., Sonthisombat, P., Seubnukarn, T., Chanouan, R., Chotchaisuwat, P., Sirigulsatien, V., Ingkaninan, K., Plianbangchang, P., Haines, S.T., 2011. Hypoglycemic effect of bitter melon compared with metformin in newly diagnosed type 2 diabetes patients. Journal of Ethnopharmacoly. 134, 422–428. https://doi.org/10.1016/j.jep.2010.12.045Furman, B.L., 2015. Streptozotocin-Induced Diabetic Models in Mice and Rats. Current Protocols in Pharmacology. 70, 5.47.1-5.47.20. https://doi.org/10.1002/0471141755.ph0547s70Gastell, P., De Alejo, J. 2000. Métodos para medir el daño oxidativo. Revista Cubana de Medicina Militar. 29, 192–198.Giacco, F., Brownlee, M., 2010. Oxidative stress and diabetic complications. Circulation Research. 107, 1058–1070. https://doi.org/10.1161/circresaha.110.223545Gironés-Vilaplana, A., Baenas, N., Villaño, D., Speisky, H., García-Viguera, C., Moreno, D.A., 2014. Evaluation of Latin-American fruits rich in phytochemicals with biological effects. Journal of Functional Foods. 7, 599–608. https://doi.org/10.1016/j.jff.2013.12.025Goss, M J, Nunes, M.L., Machado, I.D., Merlin, L., Macedo, N.B., Silva, A.M., Bresolin, TM., Santin, J.R., 2018. Peel flour of Passiflora edulis Var. Flavicarpa supplementation prevents the insulin resistance and hepatic steatosis induced by low-fructose-diet in young rats. Biomedicine & Pharmacotherapy. 102, 848–854. https://doi.org/10.1016/j.biopha.2018.03.137Guo, M., Perez, C., Wei, Y., Rapoza, E., Su, G., Bou-abdallah, F., Chasteen, N.D., 2007. Iron-binding properties of plant phenolics and cranberry ’ s bio-effects. Dalton Transactions. 43, 4951–4961. https://doi.org/10.1039/b705136kHuang, X.L., He, Y., Ji, L.L., Wang, K.Y., Wang, Y.L., Chen, D.F., Geng, Y., OuYang, P., Lai, W.M., 2017. Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats. Oncotarget. 8, 101545–101559. https://doi.org/10.18632/oncotarget.21074Hussain, S.A.R., 2007. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. Journal of Medicinal Food. 10, 543–547. https://doi.org/10.1089/jmf.2006.089Ibrahim, M.A., Habila, J.D., Koorbanally, N.A., Islam, M.S., 2016. Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats. Journal of Ethnopharmacoly. 183, 103-111. https://doi.org/10.1016/j.jep.2016.02.018Imran, A., Butt, M.S., Arshad, M.S., Arshad, M.U., Saeed, F., Sohaib, M., Munir, R., 2018. Exploring the potential of black tea based flavonoids against hyperlipidemia related disorders. Lipids in Health and Disease. 17, 1–16. https://doi.org/10.1186/s12944-018-0688-6Ishibashi, Y., Matsui, T., Nakamura, N., Sotokawauchi, A., Higashimoto, Y., Yamagishi, S.I., 2017. Methylglyoxal-derived hydroimidazolone-1 evokes inflammatory reactions in endothelial cells via an interaction with receptor for advanced glycation end products. Diabetes and Vascular Disease Research. 14, 450–453. https://doi.org/10.1177/1479164117715855Janssen, B., De Celle, T., Debets, J., Brouns, A., Callahan, M., Smith, T., 2004. Effects of anesthetics on systemic hemodynamics in mice. American Journal of Physiology-Heart and Circulatory Physiology. 287, 1618–1625. https://doi.org/10.1152/ajpheart.01192.2003Je, H.D., Shin, C.Y., Park, S.Y., Yim, S.H., Kum, C., Huh, I.H., Kim, J.H., Sohn, U.D., 2002. Combination of vitamin C and rutin on neuropathy and lung damage of diabetes mellitus rats. Archives of Pharmacal Research. 25, 184–190. https://doi.org/10.1007/BF02976561Ji, S., Zhu, C., Gao, S., Shao, X., Chen, X., Zhang, H., Tang, D., 2021. Morus alba leaves ethanol extract protects pancreatic islet cells against dysfunction and death by inducing autophagy in type 2 diabetes. Phytomedicine. 83, 153478. https://doi.org/10.1016/j.phymed.2021.153478Jiang, P., Burczynski, F., Campbell, C., Pierce, G., Austria, J.A., Briggs, C.J., 2007. Rutin and flavonoid contents in three buckwheat species Fagopyrum esculentum, F. tataricum, and F. homotropicum and their protective effects against lipid peroxidation. Food Research International. 40, 356–364. https://doi.org/10.1016/j.foodres.2006.10.009Joo, T., Sowndhararajan, K., Hong, S., Lee, J., Park, S.Y., Kim, S., Jhoo, J.W., 2014. Inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells by stem bark of Ulmus pumila L. Saudi Journal of Biological Science. 21, 427–435. https://doi.org/10.1016/j.sjbs.2014.04.003Jurado, B., Aparcana, I.M., Villarreal, L.S., Ramos, E., Hurtado, P.E., Acosta, K.M. Calixto, M.R. 2016. Evaluación del contenido de polifenoles totales y la capacidad antioxidante de los extractos etanólicos de los frutos de Aguaymanto (Physalis peruviana L.) de diferentes lugares del Perú. Revista de la Sociedad Química del Perú. 82, 272–279. https://doi.org/10.37761/rsqp.v82i3.58Kamalakkannan, N., Prince, P.S.M., 2006. Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats. Basic & Clinical Pharmacology & Toxicology. 98, 97–103. https://doi.org/10.1111/j.1742-7843.2006.pto_241.Kappel, V.D., Cazarolli, L.H., Pereira, D.F., Postal, B.G., Madoglio, F.A., Buss, Z. da S., Reginatto, F.H., Silva, F.R.M.B., 2013. Beneficial effects of banana leaves (Musa x paradisiaca) on glucose homeostasis: Multiple sites of action. Brazilian Journal of Pharmacognosy. 23, 706–715. https://doi.org/10.1590/S0102-695X2013005000062Kappel, V.D., Frederico, M.J.S., Postal, B.G., Mendes, C.P., Cazarolli, L.H., Silva, F.R.M.B., 2013. The role of calcium in intracellular pathways of rutin in rat pancreatic islets: Potential insulin secretagogue effect. European Journal of Pharmacology. 702, 264–268. https://doi.org/10.1016/j.ejphar.2013.01.055Kasali, F.M., Kadima, J.N., Mpiana, P.T., Ngbolua-Koto-te-Nyiwa, Tshibangu, D.S.-T., 2013. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig. Asian Pacific Journal of Tropical Biomedicine. 3, 841–846. https://doi.org/doi.org/10.1016/S2221-1691(13)60166-5Kasali, F.M., Tusiimire, J., Kadima, J.N., Tolo, C.U., Weisheit, A., Agaba, A.G., 2021. Ethnotherapeutic Uses and Phytochemical Composition of Physalis peruviana L.: An Overview. The Scientific World Journal. https://doi.org/10.1155/2021/5212348Kasali, F.M., Tuyiringire, N., Peter, E.L., Ahovegbe, L.Y., Ali, M.S., Tusiimire, J., Ogwang, P.E., Kadima, N.J., Agaba, A.G., 2022. Chemical constituents and evidence-based pharmacological properties of Physalis peruviana L .: An overview. Jounal of Herbmed Pharmacology. 1, 35–47. https://doi.org/10.34172/jhp.2022.04Kennedy, M.L., María, E., Diarte, G., Monserrat, C., Escurra, C., Campuzano, M.Á., Farmacología, D. De, Ciencias, F. De, Campus, Q., 2010. Evaluación preliminar de la toxicidad, el efecto sobre el comportamiento y la actividad analgésica de Aloysia virgata var. platiphylla en ratones.Kurien, B.T., Hensley, K., Bachmann, M., Scofield, R.H., 2006. Oxidatively modified autoantigens in autoimmune diseases. Free Radical Biology and Medicine. 41, 549–556. https://doi.org/10.1016/j.freeradbiomed.2006.05.020Laguerre, M., Lecomte, J., Villeneuve, P., 2007. Evaluation of the ability of antioxidants to counteract lipid oxidation: Existing methods, new trends and challenges. Progress in Lipid Research. 46 (5), 224-282. https://doi.org/10.1016/j.plipres.2007.05.002Lan, Y.H., Chang, F.R., Pan, M.J., Wu, C.C., Wu, S.J., Chen, S.L., Wang, S.S., Wu, M.J., Wu, Y.C., 2009. New cytotoxic withanolides from Physalis peruviana. Food Chemistry. 116, 462–469. https://doi.org/10.1016/j.foodchem.2009.02.061Lee, K.H., Cha, M., Lee, B.H., 2020. Neuroprotective effect of antioxidants in the brain. International Journal of Molecular Science. 21 (19), 7152. https://doi.org/10.3390/ijms21197152Lenzen, S., 2008. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 51, 216–226. https://doi.org/10.1007/s00125-007-0886-7Lenzen, S., Drinkgern, J., Tiedge, M., 1996. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radical Biology and Medicine. 20 (3), 463–466. https://doi.org/10.1016/0891-5849(96)02051-5Levin-Arama, M., Abraham, L., Waner, T., Harmelin, A., Steinberg, D.M., Lahav, T., Harlev, M., 2016. Subcutaneous compared with intraperitoneal ketamine-xylazine for anesthesia of mice. Journal of the American Association for Laboratory Animal Science. 55, 794–800.Levitan, I., Volkov, S., Subbaiah, P. V., 2010. Oxidized LDL: Diversity, patterns of recognition, and pathophysiology. Antioxidants & Redox Signaling. 13 (1), 39-75. https://doi.org/10.1089/ars.2009.2733Li, J.M., Wang, C., Hu, Q.H., Kong, L.D., 2008. Fructose induced leptin dysfunction and improvement by quercetin and rutin in rats. Chinese Journal of Natural Medicines. 6 (6), 466–473. https://doi.org/10.3724/SP.J.1009.2008.00466Li, T., Chen, S., Feng, T., Dong, J., Li, Y., Li, H., 2016. Rutin protects against aging-related metabolic dysfunction. Food &Nutrition. 7, (2). 1147–1154. https://doi.org/10.1039/c5fo01036eLim, J.S., Mietus-Snyder, M., Valente, A., Schwarz, J.M., Lustig, R.H., 2010. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nature Reviews Gastroenterology & Hepatology. 7, 251–264. https://doi.org/10.1038/nrgastro.2010.41Lisset, M., Regal, L., Hermes, L., Otero, G., Alina, Z., Otero, G., Omar, J., 2013. Etiopatogenia de la microangiopatía diabética . Consideraciones bioquímicas y moleculares. Revista Finlay. 3, 2–12.Liu, Z., Hu, M., 2007. Natural polyphenol disposition via coupled metabolic pathways. Expert Opinion on Drug Metabolism & Toxicology. 3 (3), 389–406. https://doi.org/10.1517/17425255.3.3.389Lock O, Perez E, Villar M, Flores D, Rojas R, 2016. Bioactive Compounds from Plants Used in Peruvian Traditional Medicine. Natural Product Communications. 11, 1–29.Lockwood, G.B., 2005. Fundamentals of pharmacognosy and phytotherapy, Phytochemistry. https://doi.org/10.1016/j.phytochem.2005.04.008Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275. https://doi.org/10.1016/s0021-9258(19)52451-6Lu, Q., Zhou, Y., Hao, M., Li, C., Wang, J., Shu, F., Du, L., Zhu, X., Zhang, Q., Yin, X., 2018. The mTOR promotes oxidative stress-induced apoptosis of mesangial cells in diabetic nephropathy. Molecular and Cellular Endocrinology. 473, 31–43. https://doi.org/10.1016/j.mce.2017.12.012Lue, B.M., Nielsen, N.S., Jacobsen, C., Hellgren, L., Guo, Z., Xu, X., 2010. Antioxidant properties of modified rutin esters by DPPH, reducing power, iron chelation and human low density lipoprotein assays. Food Chemistry. 123 (2), 221–230. https://doi.org/10.1016/j.foodchem.2010.04.009Lv, Y., Zhao, P., Pang, K., Ma, Y., Huang, H., Zhou, T., Yang, X., 2021. Antidiabetic effect of a flavonoid-rich extract from Sophora alopecuroides L. in HFD- and STZ- induced diabetic mice through PKC/GLUT4 pathway and regulating PPARα and PPARγ expression. Journal of Ethnopharmacology. 268, 113654. https://doi.org/10.1016/j.jep.2020.113654Mahecha, J.N., 2017. Aporte a la caracterización fitoquímica de un extracto hidroalcohólico de cálices de Physalis peruviana recolectados en el municipio de Granada-Cundinamarca Contribution to the phytochemical characterization of an hydroalcoholic extract. Tesis. Universidad Nacional de Colombia.Mahrous, R.S., Fathy, H.M., El-Khair, R.M.A., Omar, A.A., 2019. Chemical constituents of egyptian Withania somnifera leaves and fruits and their anticholinesterase activity. Journal of the Mexican Chemical Society. 63, 208–217. https://doi.org/10.29356/jmcs.v63i4.944Mansour, H.B., Yatouji, S., Mbarek, S., Houas, I., Delai, A., Dridi, D., 2011. Correlation between antibutyrylcholinesterasic and antioxidant activities of three aqueous extracts from Tunisian Rhus pentaphyllum. Annals of Clinical Microbiology and Antimicrobials. 10 (1), 1-9. https://doi.org/10.1186/1476-0711-10-32Mansuroǧlu, B., Derman, S., Yaba, A., Kizilbey, K., 2015. Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats. International Journal of Biological Macromolecules. 72, 79–87. https://doi.org/10.1016/j.ijbiomac.2014.07.039Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., Turner, R.C., 1985. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28, 412–419. https://doi.org/10.1007/BF00280883Mattson, M.P., 2008. Hormesis defined. Ageing Research Reviewes. 7 (1), 1–7. https://doi.org/10.1016/j.arr.2007.08.007McColl, A.J., Kong, C., Nimmo, L., Collins, J., Elkeles, R.S., Richmond, W., 1997. 132 Total antioxidant status, protein glycation, lipid hydroperoiides in non insulin dependent diabetes mellitus. Biochemical Society Transactions. 25. https://doi.org/10.1042/bst025s660Medina, S., Collado-González, J., Ferreres, F., Londoño-Londoño, J., Jiménez-Cartagena, C., Guy, A., Durand, T., Galano, J.M., Gil-Izquierdo, Á., 2019. Potential of Physalis peruviana calyces as a low-cost valuable resource of phytoprostanes and phenolic compounds. Journal of the Science of Food and Agriculture. 99 (5), 2194–2204. https://doi.org/10.1002/jsfa.9413Ministerio de Salud y Proteccion social, 2022. En el Día Mundial de la Diabetes: MinSalud promueve prácticas de vida saludable. Boletín prensa No. 543 2022. https://www.minsalud.gov.coMiranda, C.A., Schönholzer, T.E., Klöppel, E., Sinzato, Y.K., Volpato, G.T., Damasceno, D.C., Campos, K.E., 2019. Repercussions of low fructose-drinking water in male rats. Anais da Academia Brasileira de Ciencias. 91, 1–10. https://doi.org/10.1590/0001-3765201920170705Monzón, G., Meneses, C., Forero, A.M., Rodríguez, J., Aragón, M., Jiménez, C., Ramos, F.A., Castellanos, L., 2021. Identification of α-Amylase and α-Glucosidase Inhibitors and Ligularoside A, a New Triterpenoid Saponin from Passiflora ligularis Juss (Sweet Granadilla) Leaves, by a Nuclear Magnetic Resonance-Based Metabolomic Study. Journal of Agricultural and Food Chemistry. 69 (9), 2919–2931. https://doi.org/10.1021/acs.jafc.0c07850Mora, Á.C., Aragón, D.M., Ospina, L.F., 2010. Effects of Physalis peruviana fruit extract on stress oxidative parameters in streptozotocin-diabetic rats. Latin American Journal of Pharmacy. 29, 1132–1136.Muñoz, Ó.A., Torres, G.A., Núñez, J.A., De la Rosa, L.A., Rodrigo, J., Aya, J.F., Álvarez, E. 2017. Nuevo Acercamiento a La Interacción Del Reactivo De Folin-Ciocalteu Con Azúcares Durante La Cuantificación De Polifenoles Totales. Tip. 20 (2), 23–28. https://doi.org/10.1016/j.recqb.2017.04.003Murillo, E., Tique, M., Ospina, F., Lombo, O., 2006. Evaluación preliminar de la actividad hipoglicemiante en ratones diabéticos por aloxano y capacidad antioxidante in vitro de extractos de Bauhinia kalbreyeri Harms. Revista Colombiana de Ciencias Químico Farmacéuticas. 35, 64–80.Nayak, B.N., Kaur, G., Buttar, H.S., 2016. TNF-α modulation by natural bioactive molecules in mouse RAW 264.7 macrophage cells. Journal of Complementary and Integrative Medicine. 13 (1), 1–7. https://doi.org/10.1515/jcim-2015-0024Nowotny, K., Jung, T., Höhn, A., Weber, D., Grune, T., 2015. Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus. Biomolecules. 194–222. https://doi.org/10.3390/biom5010194Oboh, G., Ademosun, A.O., Ayeni, P.O., Omojokun, O.S., Bello, F., 2015. Comparative effect of quercetin and rutin on α-amylase, α-glucosidase, and some pro-oxidant-induced lipid peroxidation in rat pancreas. Comparative Clinical Pathology. 24, 1103–1110. https://doi.org/10.1007/s00580-014-2040-5Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 95 (2), 351–358. https://doi.org/10.1016/0003-2697(79)90738-3Ohkawa, H., Ohishi, N., Yagi, K., Ajith, T.A., 2010. Ameliorating reactive oxygen species-induced in vitro lipid peroxidation in brain, liver, mitochondria and DNA damage by Zingiber officinale Roscoe. Indian Journal of Clinical Biochemistry. 25, 351–358. https://doi.org/10.1016/0003-2697(79)90738-3Olabiyi, A.A., Alli Smith, Y.R., Babatola, L.J., Akinyemi, A.J., Oboh, G., 2016. Inhibitory effect of aqueous extract of different parts of Gossypium herbaceum on key enzymes linked with type 2 diabetes and oxidative stress in rat pancreas in vitro. Beni-Suef University Journal of Basic and Applied Science. 5 (2), 180–186. https://doi.org/10.1016/j.bjbas.2016.05.003OPS, 2022. Diabetes. Citado el 14 febrero de 2022. Disponible en: https://www.paho.org/es/temas/diabetesPai Kotebagilu, N., Reddy Palvai, V., Urooj, A., 2014. Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates. International Journal of Medicinal Chemistry. 2014, 1–7. https://doi.org/10.1155/2014/861084Panunti, B., Jawa, A.A., Fonseca, V.A., 2004. Mechanisms and therapeutic targets in type 2 diabetes mellitus. Drug Discovery Today: Disease Mechanisms. 1 (2), 151–157. https://doi.org/10.1016/j.ddmec.2004.09.011Parthasarathy, S., Carew, T.E., Khoo, J.C., Witztum, J.L., Barnett, J., Fong, L.G., Stocker, R., Rapp, J.H., Kim, K.Y., Feingold, K.R., Kohlschiitter, A., Beisiegel, U., Stanley, K.K., Stocker, R., Nordestgaard, B.G., Nielsen, L.B., Wootton, R., Lewis, B., Gaziano, J.M., Hiibner, C., Finckh, B., Kohlschtitter, A., Beisiegel, U., 1999. Measurement of oxidizability of blood plasma. Methods in Enzymology. 299, 35–49.Patel, S., Santani, D., 2009. Role of NF-κB in the pathogenesis of diabetes and its associated complications. Pharmacological Reports. 61 (4), 595–603. https://doi.org/10.1016/S1734-1140(09)70111-2Perera, H., 2016. Antidiabetic Effects of Pterocarpus marsupium (Gammalu). European Journal of Medicinal Plants. 13 (4), 1–14. https://doi.org/10.9734/ejmp/2016/23930Poovitha, S., Siva Sai, M., Parani, M., 2017. Protein extract from the fruit pulp of Momordica dioica shows anti-diabetic, anti-lipidemic and antioxidant activity in diabetic rats. Journal of Functional Foods. 33, 181–187. https://doi.org/10.1016/j.jff.2017.03.042Puente, L., Pinto, M.C., Castro, E., Cortés, M., 2011. Physalis peruviana L, the multiple properties of a highly functional fruit: A review. Food Research International. 44 (7), 1733-1740.Qu, H.Q., Li, Q., Rentfro, A.R., Fisher-Hoch, S.P., McCormick, J.B., 2011. The definition of insulin resistance using HOMA-IR for americans of mexican descent using machine learning. PLoS One 6. 6 (6), e21041. https://doi.org/10.1371/journal.pone.0021041Ramadan, M.F., 2012. Physalis peruviana pomace suppresses high-cholesterol diet-induced hypercholesterolemia in rats. Grasas y aceites. 63 (4), 411–422.Ramadan, M.F., 2011. Bioactive phytochemicals, nutritional value, and functional properties of cape gooseberry (Physalis peruviana): An overview. Food Research International. 44 (7), 1830–1836. https://doi.org/10.1016/j.foodres.2010.12.042Ramadan, M.F., Moersel, J.T., 2007. Impact of enzymatic treatment on chemical composition, physicochemical properties and radical scavenging activity of goldenberry (Physalis peruviana L.) juice. Journal of Science, Food & Agriculture. 87 (3), 452–460. https://doi.org/10.1002/jsfa.2728Ramadan, M.F., Morsel, J.T., 2003. Oil goldenberry (Physalis peruviana L.). Journal of Agriculture and Food Chemistry. 51 (4), 969–974. https://doi.org/10.1021/jf020778zRamchoun, M., Sellam, K., Harnafi, H., Alem, C., Benlyas, M., El Rhaffari, L., Amrani, S., 2015. Biological investigations of antioxydant and antimicrobial properties of Thymus satureioides collected in Tafilalet region, south-east of Morocco. International Journal of Pharmacy. 5 (2), 339–346.Ramos, V.W., Batista, L.O., Albuquerque, K.T., 2017. Effects of fructose consumption on food intake and biochemical and body parameters in Wistar rats. Revista Portuguesa de Cardiología. 36 (12), 937–941.Reddy, S., Akhila, M., Subrahmanyam, C.V.S., Trimurtulu, G., Raghavendra, N.M., 2015. Isolation, in vitro antidiabetic, antioxidant activity and molecular docking studies of pentacyclic triterpenoids from Syzygium alternifolium (wt.) Walp bark. Journal of Pharmacy and Biologycal Sciences. 10 (6), 2319–7676. https://doi.org/10.9790/3008-1062148154Rey, D.P., Ospina, L.F., Aragón, D.M., 2015. Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases. Revista Colombiana de Ciencias Químico Farmacéuticas. 44, 72–89. https://doi.org/10.15446/rcciquifa.v44n1.54281Rey Padilla, D.P., 2015. Evaluación del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales. Tesis de maestría. Universidad Nacional de Colombia.Rodrigo, R., Libuy, M., 2014. Modulation of Plant Endogenous Antioxidant Systems by Polyphenols. Polyphenols in Plants. 65-85. https://doi.org/10.1016/B978-0-12-397934-6.00005-XRodríguez, L., 2012. Pathophysiological role and therapeutic implications of inflammation in diabetic nephropathy. World Journal of Diabetes. 3 (1), 7. https://doi.org/10.4239/wjd.v3.i1.7Rodríguez, C.P., Torres, M.C.., Aguilar, C.A., Medina, O.N., 2017. Mecanismos inmunológicos involucrados en la obesidad. Investigación Clinica. 58 (2), 175–196.Sahin, G., Telli, M., Ünlü, E.S., Pehlivan Karakaş, F., 2020. Effects of moderate high temperature and uv-b on accumulation of withanolides and relative expression of the squalene synthase gene in Physalis peruviana. Turkish Journal of Biology. 44, 295–303. https://doi.org/10.3906/biy-2002-69Sánchez N., J.C., López Z., D.F., Pinzón D., Ó.A., Sepúlveda A., J.C., 2010. Adipocinas y síndrome metabólico: múltiples facetas de un proceso fisiopatológico complejo. Revista Colombiana de Cardiología. 17, 167–176. https://doi.org/10.1016/s0120-5633(10)70236-9Sang-Ngern, M., Youn, U.J., Park, E.J., Kondratyuk, T.P., Simmons, C.J., Wall, M.M., Ruf, M., Lorch, S.E., Leong, E., Pezzuto, J.M., Chang, L.C., 2016. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity. Bioorganic & Medicinal Chemistry Letters. 26 (12), 2755–2759. https://doi.org/10.1016/j.bmcl.2016.04.077Séro, L., Sanguinet, L., Blanchard, P., Dang, B.T., Morel, S., Richomme, P., Séraphin, D., Derbré, S., 2013. Tuning a 96-well microtiter plate fluorescence-based assay to identify AGE inhibitors in crude plant extracts. Molecules .18, 14320–14339. https://doi.org/10.3390/molecules181114320Shanmugasundaram, E.R., Rajeswari, G., Baskaran, K., Kumar, B.R., Shanmugasundaram, K.R., Ahmath, B.K., 1990. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. Journal of Ethnopharmacology. 30, 281–294. https://doi.org/10.1016/0378-8741(90)90107-5Sharma, R., Dave, V., Sharma, S., Jain, P., Yadav, S., 2013. Experimental Models on Diabetes : A Comprehensive Review. International Journal of Advances in Pharmaceutical Sciences. 4, (1) 1–8.Shen, Y., Zhang, H., Cheng, L., Wang, L., Qian, H., Qi, X., 2016. In vitro and in vivo antioxidant activity of polyphenols extracted from black highland barley. Food Chemistry. 194, 1003–1012. https://doi.org/10.1016/j.foodchem.2015.08.083Shi, W., Liu, L., Li, J., Qu, L., Pang, X., Yu, H., Zhang, Y., Wang, T., 2017. Bioactive flavonoids from Flos Sophorae. Journal of Natural Medicine. 71, 513–522. https://doi.org/10.1007/s11418-017-1084-7Singleton, V. L., Orthofer, R., & Lamuela-Raventós, R.M., 1999. Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent. Methods in Enzymology. 299, 152–178. https://doi.org/10.1016/s0076-6879(99)99017-1Smith, C., Mitchinson, M.J., Aruoma, O.I., Halliwell, B., 1992. Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions. Biochemical Journal. 286, 901–905. https://doi.org/10.1042/bj2860901Soczyńska-Kordala, M., Bakowska, A., Oszmiański, J., Gabrielska, J., 2001. Metal ion-flavonoid associations in bilayer phospholipid membranes. Cellular and Molecular Biology Letters. 6, 277–281.Soler, A., 2009. Estudio de la capacidad antioxidante y la biodisponibilidad de los compuestos fenólicos del aceite de oliva. Primeras etapas en el desarrollo de un aceite de oliva funcional. Tesis de doctorado. Universitat de Lleida.Spruss, A., Kanuri, G., Wagnerberger, S., Haub, S., Bischoff, S.C., Bergheim, I., 2009. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology. 50 (4), 1094–1104. https://doi.org/10.1002/hep.23122Stanley, J., 1995. Síndrome: un concepto en evolución. Acimed. 3, 30–38.Stumvoll, M., Goldstein, B.J., Haeften, T.W. Van, 2005. Pathogenesis of type 2 diabetes.pdf. Lancet 365, 1333–1346.Tanaka, S., Aida, K., Nishida, Y., Kobayashi, T., 2013. Pathophysiological mechanisms involving aggressive islet cell destruction in fulminant type 1 diabetes. Endocrine Journal. 60 (7), 837–845. https://doi.org/10.1507/endocrj.EJ13-0222Tang, Y., Gao, C., Xing, M., Li, Y., Zhu, L., Wang, D., Yang, X., Liu, L., Yao, P., 2012. Quercetin prevents ethanol-induced dyslipidemia and mitochondrial oxidative damage. Food and Chemical Toxicology. 50, 1194–1200. https://doi.org/10.1016/j.fct.2012.02.008Tankova, T., Chakarova, N., Atanassova, I., Dakovska, L., 2011. Evaluation of the Finnish Diabetes Risk Score as a screening tool for impaired fasting glucose, impaired glucose tolerance and undetected diabetes. Diabetes Research and Clinical Practice. 92 (1), 46–52. https://doi.org/10.1016/j.diabres.2010.12.020Tariq, S., Imran, M., Mushtaq, Z., Asghar, N., 2016. Phytopreventive antihypercholesterolmic and antilipidemic perspectives of zedoary (Curcuma Zedoaria Roscoe.) herbal tea. Lipids in Health Disease. https://doi.org/10.1186/s12944-016-0210-yToro, R., Aragón, M Ospina, LF. 2013. Hepatoprotective effect of calyces extract of Physalis peruviana on hepatotoxicity induced by CCl4 in Wistar rats. Vitae 20, 125–132. https://doi.org/10.17533/udea.vitae.12560Toro, R., Arangon, M., 2014. Propuesta de un marcador analítico como herramienta en la microencapsulación de un extracto con actividad antioxidante de cálices de Physalis peruviana. Tesis de maestria. Universidad Nacional de Colombia.Toro, R.M., Aragón, D.M., Ospina, L.F., Ramos, F.A., Castellanos, L., 2014. Phytochemical analysis, antioxidant and anti-inflammatory activity of calyces from Physalis peruviana. Natural Products Communications. 9, 1573–1575. https://doi.org/10.1177/1934578x1400901111Unnikrishnan, M.K., Veerapur, V., Nayak, Y., Mudgal, P.P., Mathew, G., 2013. Antidiabetic, Antihyperlipidemic and Antioxidant Effects of the Flavonoids. Polyphenols in Human Health and Disease. 143-161. https://doi.org/10.1016/B978-0-12-398456-2.00013-XVessal, M., Hemmati, M., Vasei, M., 2003. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comparative Biochemistry and Physiology part C: Toxicology and Pharmacology. 135, 357–364. https://doi.org/10.1016/S1532-0456(03)00140-6Wang, J., Mazza, G., 2002. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-γ-activated RAW 264.7 macrophAGEs. Journal of Agricultural and Food Chemistry. 50 (4), 850–857. https://doi.org/10.1021/jf010976aWang, Y., Alkhalidy, H., Liu, D., 2021. The emerging role of polyphenols in the management of type 2 diabetes. Molecules 26, 1–25. https://doi.org/10.3390/molecules26030703Wiernsperger, N.F., 2003. Oxidative stress as a therapeutic target in diabetes: Revisiting the controversy. Diabetes & Metabolism. 29, 579–585. https://doi.org/10.1016/S1262-3636(07)70072-1Wu, C.H., Yen, G.C., 2005. Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts. Journal of Agriculture and Food Chemistry. 53, 3167–3173. https://doi.org/10.1021/jf048550uWu, S.-J., NG, L.-T., Huang, Y.-M., Lin, D.-L., Wang, S.-S., Huang, S.-N., Lin, C.-C., 2005. Antioxidant activities of Physalis peruviana. Biological and Pharmaceutical Bulletin. 28 (6), 963–966. https://doi.org/10.1248/bpb.28.963Wu, S.J., Ng, L.T., Lin, D.L., Huang, S.N., Wang, S.S., Lin, C.C., 2004. Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway. Cancer Letters. 215, 199–208. https://doi.org/10.1016/j.canlet.2004.05.001Yaribeygi, H., Sathyapalan, T., Atkin, S.L., Sahebkar, A., 2020. Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus. Oxididative Medicine and Cellular. Longevity. 2020. https://doi.org/10.1155/2020/8609213Zhang, M., Lv, X.Y., Li, J., Xu, Z.G., Chen, L., 2008. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Journal of Diabetes Research. https://doi.org/10.1155/2008/704045Zhang, X., Zhou, Y., Cheong, M.S., Khan, H., Ruan, C.C., Fu, M., Xiao, J., Cheang, W.S., 2022. Citri Reticulatae Pericarpium extract and flavonoids reduce inflammation in RAW 264.7 macrophages by inactivation of MAPK and NF-κB pathways. Food Frontiers. 3 (4), 785–795. https://doi.org/10.1002/fft2.169Público generalORIGINAL52931406.2023.pdf52931406.2023.pdfTesis de Doctorado en Ciencias Farmacéuticasapplication/pdf2145728https://repositorio.unal.edu.co/bitstream/unal/85315/2/52931406.2023.pdf939fce50d77dae7016bc33220f0914bbMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85315/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51THUMBNAIL52931406.2023.pdf.jpg52931406.2023.pdf.jpgGenerated Thumbnailimage/jpeg4490https://repositorio.unal.edu.co/bitstream/unal/85315/3/52931406.2023.pdf.jpgf91d56b7b10d02c1579ba98faa0846c8MD53unal/85315oai:repositorio.unal.edu.co:unal/853152024-01-15 23:04:10.817Repositorio Institucional Universidad Nacional de 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