Cannabinoid and Opioid Receptor Affinity and Modulation of Cancer-Related Signaling Pathways of Machaeriols and Machaeridiols from Machaerium Pers.

Machaeriols and machaeridiols are unique hexahydrodibenzopyran-type aralkyl phytocannabinoids isolated from Machaerium Pers. Earlier studies of machaeriol A (1) and B (2) did not show any affinity for cannabinoid receptor 1 (CB1 or CNR1), although they are structural analogs of psychoactive hexahydrocannabinol. This study comprehensively reports on the affinities of isolated Machaerium Pers. compounds, namely machaeriol A-D (1-4) and machaeridiol A-C (5-7), against cannabinoid (CB1 and CB2) and opioid (κ, δ and µ) receptors. Among the isolated compounds, machaeriol D (4) and machaeridiol A-C (5-7) showed some selective binding affinity for the CB2 receptor, using a radioligand binding assay, with Ki values of >1.3, >1.77, >2.18 and >1.1 µM, respectively. On the other hand, none of the compounds showed any binding to the CB1 receptor. Due to recent reports on the anticancer potential of the endocannabinoid system, compounds 1-7 were tested against a battery of luciferase reporter gene vectors that assess the activity of many cancer-related signaling pathways, including Stat3, Smad2/3, AP-1, NF-κB, E2F, Myc, Ets, Notch, FoxO, Wnt, Hedgehog and pTK in HeLa and T98G glioblastoma cells. Complete dose-response curves have been determined for each compound in both of these cell lines, which revealed that machaeridiol 6 displayed activities (IC50 in µM in HeLa and T98G cells) towards Stat3 (4.7, 1.4), Smad2/3 (1.2, 3.0), AP-1 (5.9, 4.2), NF-κB (0.5, 4.0), E2F (5.7, 0.7), Myc (5.3, 2.0), ETS (inactive, 5.9), Notch (5.3, 4.6), Wnt (4.2, inactive) and Hedgehog (inactive, 5.0). Furthermore, a combination study between machaeriol C (3) and machaeridiol B (6) displayed additive effects for E2F, ETS, Wnt and Hedgehog pathways, where these compounds individually were either minimally active or inactive. None of the compounds inhibited luciferase expression driven by the minimal thymidine kinase promoter (pTK), indicating the lack of general cytotoxicity for luciferase enzyme inhibition at the 50 µM concentration in both of these cell lines. The significance of the inhibition of these signaling pathways via machaeridiol 5-7 and their cross-talk potential has been discussed.

Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens.

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6-9) and machaeridiols A-C (10-12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, -1708, -1717, -33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6-8 and 10-12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC's, compared to 12, against MRSA 1708 and -1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5-8 µg/mL for two strains of Acinetobacter baumannii, 2-16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.

Machaerium acutifolium compounds with larvicidal activity against Aedes aegypti.

BACKGROUND: Plant extracts and isolated compounds are known for their insecticidal activity. The Aedes aegypti mosquito has a significant medical impact as it transmits a number of arboviruses and is able to develop resistance to the commercially available insecticides. This study investigates larvicidal compounds isolated from Machaerium acutifolium, designated by the Brazilian Forest Service as a sustainable species. RESULTS: A M. acutifolium trunk ethyl acetate extract was fractionated using chromatographic methods with full structural elucidation by mass spectrometry (MS), nuclear magnetic resonance and specific rotation analyses revealing: one new 3-arylcoumarin derivative 1; two flavonoids 2 and 3; a trans-stilbene 4, and an unprecedented natural indene 5. The larvicidal activity against Ae. aegypti after 24 h exposure was: crude extract (median lethal dose, LC50 205 mg L-1 ), fraction C (LC50 27 mg L-1 ) and 5 (LC50 24 mg L-1 ). CONCLUSION: A M. acutifolium extract showed larvicidal activity, which increased with prolonged exposure, demonstrating LC50 75 mg L-1 after 72 h. Although the flavonoids 2 and 3 and trans-stilbene 4 were deemed inactive according to the adopted mortality limit, additional tests revealed their ability to cause 65% Ae. aegypti larvae mortality, suggesting they could contribute to the larvicidal activity. Compound 5, identified by liquid chromatography-MS, was over eight-fold more toxic to larvae than the crude extract after 24 h. Therefore, 5 constitutes a structural model for new prototypes to control Ae. aegypti. These data reinforce the potential of natural products as a source of commercial alternatives for vector control strategies, respecting both sustainability and eco-friendly principles. © 2020 Society of Chemical Industry.

Four new gelechioid species to honor Costa Rica's conservation of wild biodiversity (Lepidoptera).

We described four new gelechioid species from Costa Rica: Philtronoma cbdora Metz, new species; Tinaegeria carlosalvaradoi Metz, new species; Tinaegeria romanmacayai Metz, new species (Depressariidae: Tinaegeriinae revised status); and Percnarcha claudiadoblesae Metz, new species (Gelechiidae: Gelechiinae). We provide these honorifics to recognize commitment and devotion to conservation of biodiversity. The new species are all highly diagnostic among other species of Gelechioidea, and species of Tinaegeria and Percnarcha demonstrate striking mimesis for presumed wasp and beetle models. The family-group name Tinaegeriidae Hampson, 1893 is clarified, including the previously overlooked priority of the family-group name synonyms, and is placed as a valid subfamily in Depressariidae comprised of the genera Filinota Busck, 1911, Nematochares Meyrick, 1931, Philtronoma Meyrick, 1914, Profilinota Clarke, 1973, and Tinaegeria Walker, 1856.

Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action.

:Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, ß-amyrin, allantoin, apigenin-7-methoxy-6-C-ß-D-glucopyranoside, and apigenin-6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.

The genus Machaerium (Fabaceae): taxonomy, phytochemistry, traditional uses and biological activities.

Machaerium, in the family Fabaceae, predominantly is a genus of a Neotropical distribution of trees, shrubs, and lianas occurring from southern Mexico to Brazil and northern Argentina and as far as South America. Several Machaerium species are widely used in traditional medicine and are considered to have multiple medicinal properties. This review aims to provide up-to-date and comprehensive information on the taxonomy, phytochemistry, traditional uses and biological activities of plants in the genus Machaerium.

Contributions of organic matter and nutrients via leaf litter in an urban tropical dry forest fragment / Contribuciones de materia orgánica y nutrientes a través de la hojarasca en un fragmento de bosque seco tropical urbano

Abstract The litterfall and decomposition represent the main transfer of organic matter and nutrients from the vegetation to the soil surface and determine positive trajectories in the process of rehabilitating and restoring degraded ecosystems. The aim of this study was to evaluate the contributions of organic materials and nutrients through the characterization of fine litter in an urban dry forest fragment. Litter production was monitored for one year by collecting 29 traps (0.5 m2). To evaluate leaf nutrient resorption, green leaves were collected from 5-10 individuals that represented the dominant tree species. Litter-bags (20 x 20 cm, 2 mm pore) were used for six months to evaluate the decomposition of leaf litter. Annual fine litter production was found to be 8 574 kg ha-1, with the Cordia alba species contributing the most leaf litter (1 134 kg ha-1) and nutrients (N: 6.16; P: 0.21; Ca: 4.72; Mg: 0.47; K: 1.27 kg ha-1). Decomposition rates (k constant) followed the decreasing order: C. alba (k: 4.6) > Machaerium milleflorum (k: 3.5). M. milleflorum and Albizia niopoides presented a pattern of rapid N and P release in the first 30 days, with more than 80 % and 60 % released from M. milleflorum and C. alba, respectively, by the end of the experiment. The litterfall monitoring carried out in this urban dry forest fragment revealed some important aspects of the functioning of an ecosystem as seriously threatened as the tropical dry forest. Rev. Biol. Trop. 66(2): 571-585. Epub 2018 June 01.

Resumen La caída de hojarasca y su descomposición representan la principal transferencia de materia orgánica y nutrientes desde la vegetación a la superficie del suelo y determinan trayectorias positivas en el proceso de rehabilitación y restauración de ecosistemas degradados. El objetivo de este estudio fue evaluar los aportes de materiales orgánicos y nutrientes a través de la caracterización de la hojarasca fina en un fragmento de bosque seco urbano. La producción de hojarasca fina se monitoreó durante un año mediante 29 trampas (0.5 m2). Para evaluar la reabsorción de nutrientes foliares, se recogieron hojas verdes de 5-10 individuos que representaban las especies arbóreas dominantes. Bolsas de descomposición (20 x 20 cm, 2 mm de poro) fueron usadas durante seis meses para evaluar la descomposición de la hojarasca foliar. La producción de hojarasca fina anual fue de 8 574 kg ha-1. La especie Cordia alba presentó los mayores aportes de hojarasca foliar (1 134 kg ha-1) y nutrientes (N: 6.16; P: 0.21; Ca: 4.72; Mg: 0.47; K: 1.27 kg ha -1). Las tasas de descomposición (constante k) siguieron el orden decreciente: C. alba (k: 4.6)> Machaerium milleflorum (k: 3.5). M. milleflorum y Albizia niopoides presentaron un patrón de liberación rápido de N y P en los primeros 30 días, con más del 80 % y 60 % de M. milleflorum y C. alba, respectivamente, al final del experimento. El monitoreo de la caída de hojarasca llevado a acabo en este fragmento de bosque seco urbano reveló algunos aspectos importantes del funcionamiento de un ecosistema tan seriamente amenazado como es el bosque seco tropical.