Natural Compounds Purified from the Leaves of Aristotelia chilensis: Makomakinol, a New Alkaloid and the Effect of Aristoteline and Hobartine on NaV Channels

Perez, Rebeca; Figueredo, Claudia; Burgos, Viviana; Cabrera-Pardo, Jaime R.; Schmidt, Bernd; Heydenreich, Matthias; Koch, Andreas; Deuis, Jennifer R.; Vetter, Irina; Paz, Cristian


Aristotelia chilensis 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-beta-ionone and terpin hydrate, were also obtained. In light of the reported analgesic and anti-nociceptive properties of A. chilensis, in particular a crude mixture of alkaloids containing aristoteline and hobartinol (PMID 21585384), we therefore evaluated the activity of aristoteline and hobartine on Na(V)1.8, a key Na-V isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC50 of 68 +/- 3 mu M and 54 +/- 1 mu M, 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-V channels may contribute to the reported analgesic properties of Aristotelia chilensis used by the Mapuche people.

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Título según WOS: ID WOS:001103271900001 Not found in local WOS DB
Volumen: 24
Número: 21
Editorial: MDPI
Fecha de publicación: 2023


Notas: ISI