Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach...
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doaj-ee35bab8b84a470b869a31ad9bbb93f32021-03-07T00:02:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222664266410.3390/ijms22052664Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering PotentialGiuseppe Mannino0Piera Iovino1Antonino Lauria2Tullio Genova3Alberto Asteggiano4Monica Notarbartolo5Alessandra Porcu6Graziella Serio7Giorgia Chinigò8Andrea Occhipinti9Andrea Capuzzo10Claudio Medana11Luca Munaron12Carla Gentile13Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyBiosfered S.R.L., 10148 Turin, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyDepartment of Life Sciences and Systems Biology, University of Turin, 10123 Turin, ItalyBiosfered S.R.L., 10148 Turin, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyAbel Nutraceuticals S.R.L., 10148 Turin, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyDepartment of Life Sciences and Systems Biology, University of Turin, 10123 Turin, ItalyAbel Nutraceuticals S.R.L., 10148 Turin, ItalyAbel Nutraceuticals S.R.L., 10148 Turin, ItalyDepartment of Molecular Biotechnology and Health Sciences, University of Torino, 10125 Torino, ItalyDepartment of Life Sciences and Systems Biology, University of Turin, 10123 Turin, ItalyDepartment of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128 Palermo, ItalyHypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of <i>Protium heptaphyllum</i> gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS<sup>2</sup> and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (<i>HMGCR</i>, <i>PCSK9</i>, <i>LDLR</i>, <i>FXR</i>, <i>IDOL</i>, and <i>PPAR</i>). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds.https://www.mdpi.com/1422-0067/22/5/2664hypercholesterolemiagene expressionHMGCRPCSK9PPARαenzymatic activity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giuseppe Mannino Piera Iovino Antonino Lauria Tullio Genova Alberto Asteggiano Monica Notarbartolo Alessandra Porcu Graziella Serio Giorgia Chinigò Andrea Occhipinti Andrea Capuzzo Claudio Medana Luca Munaron Carla Gentile |
spellingShingle |
Giuseppe Mannino Piera Iovino Antonino Lauria Tullio Genova Alberto Asteggiano Monica Notarbartolo Alessandra Porcu Graziella Serio Giorgia Chinigò Andrea Occhipinti Andrea Capuzzo Claudio Medana Luca Munaron Carla Gentile Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential International Journal of Molecular Sciences hypercholesterolemia gene expression HMGCR PCSK9 PPARα enzymatic activity |
author_facet |
Giuseppe Mannino Piera Iovino Antonino Lauria Tullio Genova Alberto Asteggiano Monica Notarbartolo Alessandra Porcu Graziella Serio Giorgia Chinigò Andrea Occhipinti Andrea Capuzzo Claudio Medana Luca Munaron Carla Gentile |
author_sort |
Giuseppe Mannino |
title |
Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential |
title_short |
Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential |
title_full |
Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential |
title_fullStr |
Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential |
title_full_unstemmed |
Bioactive Triterpenes of <i>Protium heptaphyllum</i> Gum Resin Extract Display Cholesterol-Lowering Potential |
title_sort |
bioactive triterpenes of <i>protium heptaphyllum</i> gum resin extract display cholesterol-lowering potential |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
Hypercholesterolemia is one of the major causes of cardiovascular disease, the risk of which is further increased if other forms of dyslipidemia occur. Current therapeutic strategies include changes in lifestyle coupled with drug administration. Statins represent the most common therapeutic approach, but they may be insufficient due to the onset of resistance mechanisms and side effects. Consequently, patients with mild hypercholesterolemia prefer the use of food supplements since these are perceived to be safer. Here, we investigate the phytochemical profile and cholesterol-lowering potential of <i>Protium heptaphyllum</i> gum resin extract (PHE). Chemical characterization via HPLC-APCI-HRMS<sup>2</sup> and GC-FID/MS identified 13 compounds mainly belonging to ursane, oleanane, and tirucallane groups. Studies on human hepatocytes have revealed how PHE is able to reduce cholesterol production and regulate the expression of proteins involved in its metabolism. (<i>HMGCR</i>, <i>PCSK9</i>, <i>LDLR</i>, <i>FXR</i>, <i>IDOL</i>, and <i>PPAR</i>). Moreover, measuring the inhibitory activity of PHE against HMGR, moderate inhibition was recorded. Finally, molecular docking studies identified acidic tetra- and pentacyclic triterpenoids as the main compounds responsible for this action. In conclusion, our study demonstrates how PHE may be a useful alternative to contrast hypercholesterolemia, highlighting its potential as a sustainable multitarget natural extract for the nutraceutical industry that is rapidly gaining acceptance as a source of health-promoting compounds. |
topic |
hypercholesterolemia gene expression HMGCR PCSK9 PPARα enzymatic activity |
url |
https://www.mdpi.com/1422-0067/22/5/2664 |
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