The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia
There is evidence that in schizophrenia, imbalances in inflammatory and oxidative processes occur during pregnancy and in the early postnatal period, generating interest in the potential therapeutic efficacy of anti-inflammatory and antioxidant compounds. Mangiferin is a polyphenolic compound abunda...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.886514/full |
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| author | Jose Antonio Garcia-Partida Jose Antonio Garcia-Partida Sonia Torres-Sanchez Sonia Torres-Sanchez Sonia Torres-Sanchez Karina MacDowell Karina MacDowell Maria Teresa Fernández-Ponce Lourdes Casas Casimiro Mantell María Luisa Soto-Montenegro María Luisa Soto-Montenegro María Luisa Soto-Montenegro Diego Romero-Miguel Diego Romero-Miguel Nicolás Lamanna-Rama Nicolás Lamanna-Rama Juan Carlos Leza Juan Carlos Leza Manuel Desco Manuel Desco Manuel Desco Manuel Desco Esther Berrocoso Esther Berrocoso Esther Berrocoso |
| author_facet | Jose Antonio Garcia-Partida Jose Antonio Garcia-Partida Sonia Torres-Sanchez Sonia Torres-Sanchez Sonia Torres-Sanchez Karina MacDowell Karina MacDowell Maria Teresa Fernández-Ponce Lourdes Casas Casimiro Mantell María Luisa Soto-Montenegro María Luisa Soto-Montenegro María Luisa Soto-Montenegro Diego Romero-Miguel Diego Romero-Miguel Nicolás Lamanna-Rama Nicolás Lamanna-Rama Juan Carlos Leza Juan Carlos Leza Manuel Desco Manuel Desco Manuel Desco Manuel Desco Esther Berrocoso Esther Berrocoso Esther Berrocoso |
| author_sort | Jose Antonio Garcia-Partida |
| collection | DOAJ |
| description | There is evidence that in schizophrenia, imbalances in inflammatory and oxidative processes occur during pregnancy and in the early postnatal period, generating interest in the potential therapeutic efficacy of anti-inflammatory and antioxidant compounds. Mangiferin is a polyphenolic compound abundant in the leaves of Mangifera indica L. that has robust antioxidant and anti-inflammatory properties, making it a potential candidate for preventive or co-adjuvant therapy in schizophrenia. Hence, this study set-out to evaluate the effect of mango leaf extract (MLE) in a model of schizophrenia based on maternal immune activation, in which Poly I:C (4 mg/kg) is administered intravenously to pregnant rats. Young adult (postnatal day 60–70) or adolescent (postnatal day 35–49) male offspring received MLE (50 mg/kg of mangiferin) daily, and the effects of MLE in adolescence were compared to those of risperidone, assessing behavior, brain magnetic resonance imaging (MRI), and oxidative/inflammatory and antioxidant mediators in the adult offspring. MLE treatment in adulthood reversed the deficit in prepulse inhibition (PPI) but it failed to attenuate the sensitivity to amphetamine and the deficit in novel object recognition (NOR) induced. By contrast, adolescent MLE treatment prevented the sensorimotor gating deficit in the PPI test, producing an effect similar to that of risperidone. This MLE treatment also produced a reduction in grooming behavior, but it had no effect on anxiety or novel object recognition memory. MRI studies revealed that adolescent MLE administration partially counteracted the cortical shrinkage, and cerebellum and ventricle enlargement. In addition, MLE administration in adolescence reduced iNOS mediated inflammatory activation and it promoted the expression of biomarkers of compensatory antioxidant activity in the prefrontal cortex and hippocampus, as witnessed through the reduction of Keap1 and the accumulation of NRF2 and HO1. Together, these findings suggest that MLE might be an alternative therapeutic or preventive add-on strategy to improve the clinical expression of schizophrenia in adulthood, while also modifying the time course of this disease at earlier stages in populations at high-risk. |
| first_indexed | 2024-12-10T09:08:52Z |
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| id | doaj.art-8f198daeb60b4b85a4b301ee2c60b614 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-10T09:08:52Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-8f198daeb60b4b85a4b301ee2c60b6142022-12-22T01:55:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.886514886514The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophreniaJose Antonio Garcia-Partida0Jose Antonio Garcia-Partida1Sonia Torres-Sanchez2Sonia Torres-Sanchez3Sonia Torres-Sanchez4Karina MacDowell5Karina MacDowell6Maria Teresa Fernández-Ponce7Lourdes Casas8Casimiro Mantell9María Luisa Soto-Montenegro10María Luisa Soto-Montenegro11María Luisa Soto-Montenegro12Diego Romero-Miguel13Diego Romero-Miguel14Nicolás Lamanna-Rama15Nicolás Lamanna-Rama16Juan Carlos Leza17Juan Carlos Leza18Manuel Desco19Manuel Desco20Manuel Desco21Manuel Desco22Esther Berrocoso23Esther Berrocoso24Esther Berrocoso25Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, University of Cádiz, Cádiz, SpainInstituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, SpainInstituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Psychobiology Area, Department of Psychology, University of Cádiz, Cádiz, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Health Research Institute Hospital 12 de Octubre (imas12), Institute of Research in Neurochemistry IUIN-UCM, Madrid, SpainDepartment of Chemical Engineering and Food Technology, Science Faculty, University of Cádiz, Cádiz, SpainDepartment of Chemical Engineering and Food Technology, Science Faculty, University of Cádiz, Cádiz, SpainDepartment of Chemical Engineering and Food Technology, Science Faculty, University of Cádiz, Cádiz, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainHigh Performance Research Group in Physiopathology and Pharmacology of the Digestive System (NeuGut), Universidad Rey Juan Carlos, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainDepartamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainDepartamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Health Research Institute Hospital 12 de Octubre (imas12), Institute of Research in Neurochemistry IUIN-UCM, Madrid, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainInstituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainDepartamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain0Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, SpainInstituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, SpainNeuropsychopharmacology and Psychobiology Research Group, Psychobiology Area, Department of Psychology, University of Cádiz, Cádiz, SpainCiber of Mental Health (CIBERSAM), ISCIII, Madrid, SpainThere is evidence that in schizophrenia, imbalances in inflammatory and oxidative processes occur during pregnancy and in the early postnatal period, generating interest in the potential therapeutic efficacy of anti-inflammatory and antioxidant compounds. Mangiferin is a polyphenolic compound abundant in the leaves of Mangifera indica L. that has robust antioxidant and anti-inflammatory properties, making it a potential candidate for preventive or co-adjuvant therapy in schizophrenia. Hence, this study set-out to evaluate the effect of mango leaf extract (MLE) in a model of schizophrenia based on maternal immune activation, in which Poly I:C (4 mg/kg) is administered intravenously to pregnant rats. Young adult (postnatal day 60–70) or adolescent (postnatal day 35–49) male offspring received MLE (50 mg/kg of mangiferin) daily, and the effects of MLE in adolescence were compared to those of risperidone, assessing behavior, brain magnetic resonance imaging (MRI), and oxidative/inflammatory and antioxidant mediators in the adult offspring. MLE treatment in adulthood reversed the deficit in prepulse inhibition (PPI) but it failed to attenuate the sensitivity to amphetamine and the deficit in novel object recognition (NOR) induced. By contrast, adolescent MLE treatment prevented the sensorimotor gating deficit in the PPI test, producing an effect similar to that of risperidone. This MLE treatment also produced a reduction in grooming behavior, but it had no effect on anxiety or novel object recognition memory. MRI studies revealed that adolescent MLE administration partially counteracted the cortical shrinkage, and cerebellum and ventricle enlargement. In addition, MLE administration in adolescence reduced iNOS mediated inflammatory activation and it promoted the expression of biomarkers of compensatory antioxidant activity in the prefrontal cortex and hippocampus, as witnessed through the reduction of Keap1 and the accumulation of NRF2 and HO1. Together, these findings suggest that MLE might be an alternative therapeutic or preventive add-on strategy to improve the clinical expression of schizophrenia in adulthood, while also modifying the time course of this disease at earlier stages in populations at high-risk.https://www.frontiersin.org/articles/10.3389/fphar.2022.886514/fullmangiferinschizophreniaPoly I:Coxidative/nitrosative stressneuroinflammationmagnetic resonace imaging (MRI) |
| spellingShingle | Jose Antonio Garcia-Partida Jose Antonio Garcia-Partida Sonia Torres-Sanchez Sonia Torres-Sanchez Sonia Torres-Sanchez Karina MacDowell Karina MacDowell Maria Teresa Fernández-Ponce Lourdes Casas Casimiro Mantell María Luisa Soto-Montenegro María Luisa Soto-Montenegro María Luisa Soto-Montenegro Diego Romero-Miguel Diego Romero-Miguel Nicolás Lamanna-Rama Nicolás Lamanna-Rama Juan Carlos Leza Juan Carlos Leza Manuel Desco Manuel Desco Manuel Desco Manuel Desco Esther Berrocoso Esther Berrocoso Esther Berrocoso The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia Frontiers in Pharmacology mangiferin schizophrenia Poly I:C oxidative/nitrosative stress neuroinflammation magnetic resonace imaging (MRI) |
| title | The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| title_full | The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| title_fullStr | The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| title_full_unstemmed | The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| title_short | The effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| title_sort | effects of mango leaf extract during adolescence and adulthood in a rat model of schizophrenia |
| topic | mangiferin schizophrenia Poly I:C oxidative/nitrosative stress neuroinflammation magnetic resonace imaging (MRI) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.886514/full |
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