In vitro and in silico studies reveal antidiabetic properties of arylbenzofurans from the root bark of Morus mesozygia Stapf.

Diabetes remains an important disease worldwide with about 500 million patients globally. In tropical Africa, Morus mesozygia is traditionally used in the treatment of diabetes. Biological and phytochemical investigation of the root bark extracts of the plant led to the isolation of a new prenylated arylbenzofuran named 7-(3-hydroxy-3-methylbutyl)moracin M (1) and two congeners, moracins P (2) and M (3). When compared to acarbose (IC50 = 486 µM), all the isolated compounds are better inhibitors of α-glucosidase with in vitro IC50 values of 16.9, 16.6, and 40.9 µM, respectively. However, they were not active against α-amylase. The compounds also demonstrated moderate inhibition of dipeptidyl peptidase-4 (DPP4). Based on in silico docking studies, all isolates (1, 2, and 3) exhibit binding affinities of -8.7, -9.5, and -8.5 kcal/mol, respectively against α-glucosidase enzyme (PDB: 3AJ7). They are stabilized within the α-glucosidase active site through hydrogen bonds, pi interactions, and hydrophobic interactions. This study provides scientific support for the traditional use of Morus mesozygia in the treatment of diabetes as well as adding to the repository of α-glucosidase inhibitory agents.

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

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-ß-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 NaV1.8, a key NaV isoform involved in nociception, using automated whole-cell patch-clamp electrophysiology. Aristoteline and hobartine both inhibited Nav1.8 with an IC50 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 NaV channels may contribute to the reported analgesic properties of Aristotelia chilensis used by the Mapuche people.

(-)-Pentylsedinine, a New Alkaloid from the Leaves of Lobelia tupa with Agonist Activity at Nicotinic Acetylcholine Receptor.

Lobelia tupa, also called devil's tobacco, is a native plant from the center-south of Chile which has been used by the native people of Chile as a hallucinogenic and anesthetic plant. A new piperidine alkaloid, called pentylsedinine, which comprises five carbons in the side chain, was isolated from the aerial part of L. tupa, along with lobeline and lobelanidine. The structure was established on the basis of 1D and 2D NMR spectroscopy. While lobeline is a neutral antagonist at α3ß2/α3ß4 nAChR and α7 nAChR, both lobelanidine and pentylsedinine act as partial agonists at nAChR.