Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of Plantago australis
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. was collected in the state of Morelos, México. The hydroalcoholic extract (HAE ) of was obtained by maceration and concentrated in vac...
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| Published in: | Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 4; p. 535 |
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| Abstract | 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.
was collected in the state of Morelos, México. The hydroalcoholic extract (HAE
) of
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
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
induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD
of HAE
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
induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression. |
|---|---|
| AbstractList | Plantago australis 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. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis 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. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa 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, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression. 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. was collected in the state of Morelos, México. The hydroalcoholic extract (HAE ) of 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 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 induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD of HAE 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 induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression. Plantago australis 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. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAE Pa ) of P. australis 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 Pa 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 Pa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD 50 of HAE Pa 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 Pa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression. |
| Author | Ornelas-Mendoza, Kathia Almanza-Pérez, Julio Cesar Loza-Rodríguez, Hilda Perea-Arango, Irene Chávez-Silva, Fabiola Rivera-Leyva, Julio César Navarrete-Vázquez, Gabriel Rodríguez-Carpena, Javier-German Ávila-Villarreal, Gabriela Estrada-Soto, Samuel Villalobos-Molina, Rafael Ortiz-Barragán, Erandi Flores-Flores, Angélica |
| AuthorAffiliation | 2 Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana—Iztapalapa, Ciudad de Mexico 09340, Mexico 8 Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic 63000, Mexico 1 Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico 4 Laboratorio de Microbiología Experimental, División de Tecnología Ambiental, Universidad Tecnológica de Nezahualcoyotl, Nezahualcoyotl 57000, Mexico 3 Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico 7 Centro 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 5 Departamento de Inmunofarmacología, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico 14080, Mexico 6 Centro de Investigación en Biotecnología, Uni |
| AuthorAffiliation_xml | – name: 4 Laboratorio de Microbiología Experimental, División de Tecnología Ambiental, Universidad Tecnológica de Nezahualcoyotl, Nezahualcoyotl 57000, Mexico – name: 7 Centro 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 – name: 1 Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – name: 3 Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico – name: 2 Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana—Iztapalapa, Ciudad de Mexico 09340, Mexico – name: 6 Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – name: 5 Departamento de Inmunofarmacología, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico 14080, Mexico – name: 8 Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic 63000, Mexico |
| Author_xml | – sequence: 1 givenname: Samuel orcidid: 0000-0003-1860-0744 surname: Estrada-Soto fullname: Estrada-Soto, Samuel organization: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – sequence: 2 givenname: Kathia surname: Ornelas-Mendoza fullname: Ornelas-Mendoza, Kathia organization: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – sequence: 3 givenname: Gabriel orcidid: 0000-0001-5344-4762 surname: Navarrete-Vázquez fullname: Navarrete-Vázquez, Gabriel organization: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – sequence: 4 givenname: Fabiola surname: Chávez-Silva fullname: Chávez-Silva, Fabiola organization: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico – sequence: 5 givenname: Julio Cesar surname: Almanza-Pérez fullname: Almanza-Pérez, Julio Cesar organization: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico – sequence: 6 givenname: Rafael surname: Villalobos-Molina fullname: Villalobos-Molina, Rafael organization: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico – sequence: 7 givenname: Erandi surname: Ortiz-Barragán fullname: Ortiz-Barragán, Erandi organization: Laboratorio de Farmacología, Depto. Ciencias de la Salud, D.C.B.S., Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico 09340, Mexico – sequence: 8 givenname: Hilda surname: Loza-Rodríguez fullname: Loza-Rodríguez, Hilda organization: Laboratorio de Microbiología Experimental, División de Tecnología Ambiental, Universidad Tecnológica de Nezahualcoyotl, Nezahualcoyotl 57000, Mexico – sequence: 9 givenname: Julio César orcidid: 0000-0002-5521-1791 surname: Rivera-Leyva fullname: Rivera-Leyva, Julio César organization: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – sequence: 10 givenname: Angélica orcidid: 0000-0002-3431-3879 surname: Flores-Flores fullname: Flores-Flores, Angélica organization: Departamento de Inmunofarmacología, Instituto Nacional de Enfermedades Respiratorias, Ciudad de Mexico 14080, Mexico – sequence: 11 givenname: Irene surname: Perea-Arango fullname: Perea-Arango, Irene organization: Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico – sequence: 12 givenname: Javier-German orcidid: 0000-0001-6380-504X surname: Rodríguez-Carpena fullname: Rodríguez-Carpena, Javier-German organization: Centro 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 – sequence: 13 givenname: Gabriela orcidid: 0000-0001-5241-5732 surname: Ávila-Villarreal fullname: Ávila-Villarreal, Gabriela organization: Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de Nayarit, Tepic 63000, Mexico |
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| Keywords | α-glucosidases inhibition antihyperglycemic GLUT-4 caffeic acid PPARγ oral toxicity assays ursolic acid |
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| Snippet | Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of... Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for... Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for... |
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| Title | Insulin Sensitization by PPARγ and GLUT-4 Overexpression/Translocation Mediates the Antidiabetic Effect of Plantago australis |
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