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Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain targ...

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Autores principales: Casertano, Marcello, Genovese, Massimo, Santi, Alice, Pranzini, Erica, Balestri, Francesco, Piazza, Lucia, Del Corso, Antonella, Avunduk, Sibel, Imperatore, Concetta, Menna, Marialuisa, Paoli, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964544/
https://www.ncbi.nlm.nih.gov/pubmed/36839851
http://dx.doi.org/10.3390/pharmaceutics15020528
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author Casertano, Marcello
Genovese, Massimo
Santi, Alice
Pranzini, Erica
Balestri, Francesco
Piazza, Lucia
Del Corso, Antonella
Avunduk, Sibel
Imperatore, Concetta
Menna, Marialuisa
Paoli, Paolo
author_facet Casertano, Marcello
Genovese, Massimo
Santi, Alice
Pranzini, Erica
Balestri, Francesco
Piazza, Lucia
Del Corso, Antonella
Avunduk, Sibel
Imperatore, Concetta
Menna, Marialuisa
Paoli, Paolo
author_sort Casertano, Marcello
collection PubMed
description Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain target glycemia levels. The use of multitarget drugs instead of mono- or multidrug therapies has been emerging as a main strategy to treat multifactorial diseases, including T2DM. Therefore, modern drug discovery in its early stages aims to identify potential modulators for multiple targets; for this purpose, exploration of the chemical space of natural products represents a powerful tool. Our study demonstrates that avarone, a sesquiterpene quinone obtained from the sponge Dysidea avara, is capable of inhibiting in vitro PTP1B, the main negative regulator of the insulin receptor, while it improves insulin sensitivity, and mitochondria activity in C2C12 cells. We observe that when avarone is administered alone, it acts as an insulin-mimetic agent. In addition, we show that avarone acts as a tight binding inhibitor of aldose reductase (AKR1B1), the enzyme involved in the development of diabetic complications. Overall, avarone could be proposed as a novel natural hit to be developed as a multitarget drug for diabetes and its pathological complications.
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spelling pubmed-99645442023-02-26 Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara Casertano, Marcello Genovese, Massimo Santi, Alice Pranzini, Erica Balestri, Francesco Piazza, Lucia Del Corso, Antonella Avunduk, Sibel Imperatore, Concetta Menna, Marialuisa Paoli, Paolo Pharmaceutics Article Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain target glycemia levels. The use of multitarget drugs instead of mono- or multidrug therapies has been emerging as a main strategy to treat multifactorial diseases, including T2DM. Therefore, modern drug discovery in its early stages aims to identify potential modulators for multiple targets; for this purpose, exploration of the chemical space of natural products represents a powerful tool. Our study demonstrates that avarone, a sesquiterpene quinone obtained from the sponge Dysidea avara, is capable of inhibiting in vitro PTP1B, the main negative regulator of the insulin receptor, while it improves insulin sensitivity, and mitochondria activity in C2C12 cells. We observe that when avarone is administered alone, it acts as an insulin-mimetic agent. In addition, we show that avarone acts as a tight binding inhibitor of aldose reductase (AKR1B1), the enzyme involved in the development of diabetic complications. Overall, avarone could be proposed as a novel natural hit to be developed as a multitarget drug for diabetes and its pathological complications. MDPI 2023-02-04 /pmc/articles/PMC9964544/ /pubmed/36839851 http://dx.doi.org/10.3390/pharmaceutics15020528 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Casertano, Marcello
Genovese, Massimo
Santi, Alice
Pranzini, Erica
Balestri, Francesco
Piazza, Lucia
Del Corso, Antonella
Avunduk, Sibel
Imperatore, Concetta
Menna, Marialuisa
Paoli, Paolo
Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title_full Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title_fullStr Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title_full_unstemmed Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title_short Evidence of Insulin-Sensitizing and Mimetic Activity of the Sesquiterpene Quinone Avarone, a Protein Tyrosine Phosphatase 1B and Aldose Reductase Dual Targeting Agent from the Marine Sponge Dysidea avara
title_sort evidence of insulin-sensitizing and mimetic activity of the sesquiterpene quinone avarone, a protein tyrosine phosphatase 1b and aldose reductase dual targeting agent from the marine sponge dysidea avara
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964544/
https://www.ncbi.nlm.nih.gov/pubmed/36839851
http://dx.doi.org/10.3390/pharmaceutics15020528
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