Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels
<i>Aristotelia chilensis</i> or “maqui” is a tree native to Chile used in the folk medicine of the Mapuche people as an anti-inflammatory agent for the treatment of digestive ailments, fever, and skin lesions. Maqui fruits are black berries which are considered a “superfruit” with notabl...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/21/15504 |
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| author | Rebeca Pérez Claudia Figueredo Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Matthias Heydenreich Andreas Koch Jennifer R. Deuis Irina Vetter Cristian Paz |
| author_facet | Rebeca Pérez Claudia Figueredo Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Matthias Heydenreich Andreas Koch Jennifer R. Deuis Irina Vetter Cristian Paz |
| author_sort | Rebeca Pérez |
| collection | DOAJ |
| description | <i>Aristotelia chilensis</i> or “maqui” is a tree native to Chile used in the folk medicine of the Mapuche people as an anti-inflammatory agent for the treatment of digestive ailments, fever, and skin lesions. Maqui fruits are black berries which are considered a “superfruit” with notable potential health benefits, promoted to be an antioxidant, cardioprotective, and anti-inflammatory. Maqui leaves contain non-iridoid monoterpene indole alkaloids which have previously been shown to act on nicotinic acetylcholine receptors, potassium channels, and calcium channels. Here, we isolated a new alkaloid from maqui leaves, now called makomakinol, together with the known alkaloids aristoteline, hobartine, and 3-formylindole. Moreover, the polyphenols quercetine, ethyl caffeate, and the terpenes, dihydro-β-ionone and terpin hydrate, were also obtained. In light of the reported analgesic and anti-nociceptive properties of <i>A. chilensis</i>, in particular a crude mixture of alkaloids containing aristoteline and hobartinol (PMID 21585384), we therefore evaluated the activity of aristoteline and hobartine on Na<sub>V</sub>1.8, a key Na<sub>V</sub> isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC<sub>50</sub> of 68 ± 3 µM and 54 ± 1 µM, respectively. Hobartine caused a hyperpolarizing shift of the voltage-dependence of the activation, whereas aristoteline did not change the voltage-dependence of the activation or inactivation. The inhibitory activity of these alkaloids on Na<sub>V</sub> channels may contribute to the reported analgesic properties of <i>Aristotelia chilensis</i> used by the Mapuche people. |
| first_indexed | 2024-03-11T11:29:38Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T11:29:38Z |
| publishDate | 2023-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-556faa2c5b3f439f85dacf315e2b4c442023-11-10T15:04:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124211550410.3390/ijms242115504Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> ChannelsRebeca Pérez0Claudia Figueredo1Viviana Burgos2Jaime R. Cabrera-Pardo3Bernd Schmidt4Matthias Heydenreich5Andreas Koch6Jennifer R. Deuis7Irina Vetter8Cristian Paz9Laboratory of Natural Products & Drug Discovery, Center CEBIM, Universidad de La Frontera, Av. Francisco Salazar 01145, Temuco 4780000, ChileLaboratory of Natural Products & Drug Discovery, Center CEBIM, Universidad de La Frontera, Av. Francisco Salazar 01145, Temuco 4780000, ChileDepartamento de Ciencias Biológicas y Químicas, Facultad de Recursos Naturales, Universidad Católica de Temuco, Rudecindo Ortega 02950, Temuco 4780000, ChileLaboratorio de Química Aplicada y Sustentable (LabQAS), Departamento de Química, Facultad de Ciencias, Universidad del Bío-Bío, Concepción 4081112, ChileInstitut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, GermanyInstitut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, GermanyInstitut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, GermanyInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, AustraliaLaboratory of Natural Products & Drug Discovery, Center CEBIM, Universidad de La Frontera, Av. Francisco Salazar 01145, Temuco 4780000, Chile<i>Aristotelia chilensis</i> or “maqui” is a tree native to Chile used in the folk medicine of the Mapuche people as an anti-inflammatory agent for the treatment of digestive ailments, fever, and skin lesions. Maqui fruits are black berries which are considered a “superfruit” with notable potential health benefits, promoted to be an antioxidant, cardioprotective, and anti-inflammatory. Maqui leaves contain non-iridoid monoterpene indole alkaloids which have previously been shown to act on nicotinic acetylcholine receptors, potassium channels, and calcium channels. Here, we isolated a new alkaloid from maqui leaves, now called makomakinol, together with the known alkaloids aristoteline, hobartine, and 3-formylindole. Moreover, the polyphenols quercetine, ethyl caffeate, and the terpenes, dihydro-β-ionone and terpin hydrate, were also obtained. In light of the reported analgesic and anti-nociceptive properties of <i>A. chilensis</i>, in particular a crude mixture of alkaloids containing aristoteline and hobartinol (PMID 21585384), we therefore evaluated the activity of aristoteline and hobartine on Na<sub>V</sub>1.8, a key Na<sub>V</sub> isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC<sub>50</sub> of 68 ± 3 µM and 54 ± 1 µM, respectively. Hobartine caused a hyperpolarizing shift of the voltage-dependence of the activation, whereas aristoteline did not change the voltage-dependence of the activation or inactivation. The inhibitory activity of these alkaloids on Na<sub>V</sub> channels may contribute to the reported analgesic properties of <i>Aristotelia chilensis</i> used by the Mapuche people.https://www.mdpi.com/1422-0067/24/21/15504indole alkaloidsmakomakinolaristotelinehobartine<i>Aristotelia chilensis</i>Na<sub>V</sub>1.8 |
| spellingShingle | Rebeca Pérez Claudia Figueredo Viviana Burgos Jaime R. Cabrera-Pardo Bernd Schmidt Matthias Heydenreich Andreas Koch Jennifer R. Deuis Irina Vetter Cristian Paz Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels International Journal of Molecular Sciences indole alkaloids makomakinol aristoteline hobartine <i>Aristotelia chilensis</i> Na<sub>V</sub>1.8 |
| title | Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels |
| title_full | Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels |
| title_fullStr | Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels |
| title_full_unstemmed | Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels |
| title_short | Natural Compounds Purified from the Leaves of <i>Aristotelia chilensis</i>: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on Na<sub>V</sub> Channels |
| title_sort | natural compounds purified from the leaves of i aristotelia chilensis i makomakinol a new alkaloid and the effect of aristoteline and hobartine on na sub v sub channels |
| topic | indole alkaloids makomakinol aristoteline hobartine <i>Aristotelia chilensis</i> Na<sub>V</sub>1.8 |
| url | https://www.mdpi.com/1422-0067/24/21/15504 |
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