Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i>
<i>Plantago australis</i> Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. <i>P. australis</i> was collected in the state of Morelos, México. The hydroalcoholi...
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MDPI AG
2023-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/4/535 |
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| author | Samuel Estrada-Soto Kathia Ornelas-Mendoza Gabriel Navarrete-Vázquez Fabiola Chávez-Silva Julio Cesar Almanza-Pérez Rafael Villalobos-Molina Erandi Ortiz-Barragán Hilda Loza-Rodríguez Julio César Rivera-Leyva Angélica Flores-Flores Irene Perea-Arango Javier-German Rodríguez-Carpena Gabriela Ávila-Villarreal |
| author_facet | Samuel Estrada-Soto Kathia Ornelas-Mendoza Gabriel Navarrete-Vázquez Fabiola Chávez-Silva Julio Cesar Almanza-Pérez Rafael Villalobos-Molina Erandi Ortiz-Barragán Hilda Loza-Rodríguez Julio César Rivera-Leyva Angélica Flores-Flores Irene Perea-Arango Javier-German Rodríguez-Carpena Gabriela Ávila-Villarreal |
| author_sort | Samuel Estrada-Soto |
| collection | DOAJ |
| description | <i>Plantago australis</i> Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. <i>P. australis</i> was collected in the state of Morelos, México. The hydroalcoholic extract (HAE<i>Pa</i>) of <i>P. australis</i> was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAE<i>Pa</i> significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAE<i>Pa</i> induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD<sub>50</sub> of HAE<i>Pa</i> was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAE<i>Pa</i> induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression. |
| first_indexed | 2024-03-11T04:39:17Z |
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| id | doaj.art-5b7e755dc1b34bb5a8b88a2aee2ac576 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T04:39:17Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-5b7e755dc1b34bb5a8b88a2aee2ac5762023-11-17T20:50:18ZengMDPI AGPharmaceuticals1424-82472023-04-0116453510.3390/ph16040535Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i>Samuel Estrada-Soto0Kathia Ornelas-Mendoza1Gabriel Navarrete-Vázquez2Fabiola Chávez-Silva3Julio Cesar Almanza-Pérez4Rafael Villalobos-Molina5Erandi Ortiz-Barragán6Hilda Loza-Rodríguez7Julio César Rivera-Leyva8Angélica Flores-Flores9Irene Perea-Arango10Javier-German Rodríguez-Carpena11Gabriela Ávila-Villarreal12Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MexicoLaboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana—Iztapalapa, Ciudad de Mexico 09340, MexicoLaboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana—Iztapalapa, Ciudad de Mexico 09340, MexicoUnidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, MexicoLaboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana—Iztapalapa, Ciudad de Mexico 09340, MexicoLaboratorio de Microbiología Experimental, División de Tecnología Ambiental, Universidad Tecnológica de Nezahualcoyotl, Nezahualcoyotl 57000, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MexicoDepartamento de Inmunofarmacología, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico 14080, MexicoCentro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, MexicoCentro Nayarita de Innovación y Transferencia de Tecnología “Unidad especializada en I+D+i en Calidad de Alimentos y Productos Naturales”, Universidad Autónoma de Nayarit, Tepic 63000, MexicoCentro Nayarita de Innovación y Transferencia de Tecnología “Unidad especializada en I+D+i en Calidad de Alimentos y Productos Naturales”, Universidad Autónoma de Nayarit, Tepic 63000, Mexico<i>Plantago australis</i> Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. <i>P. australis</i> was collected in the state of Morelos, México. The hydroalcoholic extract (HAE<i>Pa</i>) of <i>P. australis</i> was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAE<i>Pa</i> significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAE<i>Pa</i> induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD<sub>50</sub> of HAE<i>Pa</i> was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAE<i>Pa</i> induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.https://www.mdpi.com/1424-8247/16/4/535α-glucosidases inhibitionantihyperglycemicGLUT-4PPARγoral toxicity assaysursolic acid |
| spellingShingle | Samuel Estrada-Soto Kathia Ornelas-Mendoza Gabriel Navarrete-Vázquez Fabiola Chávez-Silva Julio Cesar Almanza-Pérez Rafael Villalobos-Molina Erandi Ortiz-Barragán Hilda Loza-Rodríguez Julio César Rivera-Leyva Angélica Flores-Flores Irene Perea-Arango Javier-German Rodríguez-Carpena Gabriela Ávila-Villarreal Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> Pharmaceuticals α-glucosidases inhibition antihyperglycemic GLUT-4 PPARγ oral toxicity assays ursolic acid |
| title | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> |
| title_full | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> |
| title_fullStr | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> |
| title_full_unstemmed | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> |
| title_short | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of <i>Plantago australis</i> |
| title_sort | insulin sensitization by pparγ and glut 4 overexpression translocation mediates the antidiabetic effect of i plantago australis i |
| topic | α-glucosidases inhibition antihyperglycemic GLUT-4 PPARγ oral toxicity assays ursolic acid |
| url | https://www.mdpi.com/1424-8247/16/4/535 |
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