Combretum lanceolatum extract reverses anxiety and seizure behavior in adult zebrafish through GABAergic neurotransmission: an in vivo and in silico study.

Combretaceae are reported in the literature for presenting neuroprotective and anxiolytic effects in animal models. Combretum lanceolatum Pohl. has few scientific reports on its pharmacological effects. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of the ethanol extract from the leaves of C. lanceolatum Pohl. (EtFoCl) and its possible mechanism of GABAergic action in adult zebrafish. EtFoCl was subjected to determination of the total phenol concentration, identification of phytochemical flavonoids by HPLC and in vitro antioxidant activity test, open field test and 96-hour acute toxicity in zebrafish. Anxiolytic doses were tested for pentylenetetrazole-induced seizures in adult zebrafish. To study the mechanisms of action, molecular docking simulations were performed between the main phytochemicals and the GABAA receptor (anxiolytic activity) and carbonic anhydrase II (anticonvulsant). The non-toxic doses that caused motor impairment were assessed in acute and chronic anxiety using the light and dark test. EtFoCl had altered the animals' locomotion, presenting an effect similar to the anxiolytic and anticonvulsant. These effects were prevented with flumazenil (GABAA antagonist). The phytochemicals homoorientin and quercetin-3-O-galactoside coupling in a region close to that of the inhibitor diazepam (GABAA receptor). Regarding the anticonvulsant mechanism, Homoorientina and Isovitexina were identified as the most favorable for the complex form with the carbonic anhydrase enzyme. C. lanceolatum has pharmacological potential for the treatment of acute and chronic anxiety and seizures, which can be partially explained by an interaction with the GABAA receptor.Communicated by Ramaswamy H. Sarma.

Evaluation of antibacterial and enhancement of antibiotic action by the flavonoid kaempferol 7-O-ß-D-(6″-O-cumaroyl)-glucopyranoside isolated from Croton piauhiensis müll.

There has been a rapid increase in the incidence and prevalence of opportunistic bacterial infections. Inappropriate use of current antibiotics has continuously contributed to the emergence of resistance to conventional antibiotic therapy. Therefore, the search for natural molecules that are able to combat infections is of great public interest, and many of these compounds with antimicrobial properties can be obtained from phytochemical studies of medicinal plants. In this context, this study reports the isolation and characterization of the flavonoid, kaempferol 7-O-ß-D-(6″-O-cumaroyl)-glucopyranoside, from Croton piauhiensis leaves. Additionally, the intrinsic antimicrobial action of the compound and its enhancement against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains were assessed. The minimum inhibitory concentration (MIC) of the compound was determined using broth microdilution assays. To evaluate the modulatory effect of the flavonoid, the MIC of antibiotics amikacin and gentamicin, belonging to the class aminoglycosides was assessed, with and without the compound in sterile microplates. The results of intrinsic antibacterial activity tests revealed that the compound had no antibacterial activity against strains tested at concentrations <1024 µg/mL. The combination of the flavonoid at a concentration of 128 µg/mL with gentamicin presented synergistic effects against S. aureus 10 and E. coli 06, and also reduced the MIC from 16 µg/mL to 4 µg/mL and 8 µg/mL, respectively. Amikacin also showed synergistic effects against S. aureus 10 and E. coli 06. We also observed reduced MIC for both, from 128 µg/mL to 32 µg/mL; however, antagonism for P. aeruginosa increased the MIC from 16 µg/mL to 64 µg/mL. The combination of the flavonoid with the aminoglycosides may be an alternative to potentiate the expected results in treatment against S. aureus and E. coli, since their association leads to a synergistic effect, reducing the MIC of these drugs and decreasing the dose necessary for therapeutic success.

Evaluation of the antimicrobial and antioxidant activity of 7-hydroxy-4', 6-dimethoxy-isoflavone and essential oil from Myroxylon peruiferum L.f.

This study evaluated the antibacterial, antifungal, and antioxidant effect of 7-hydroxy-4',6-dimethoxy-isoflavone and essential oil of Myroxylon peruiferum. The compound was isolated and its structure elucidated by NMR. The chemical composition of essential oil determined by GC-MS analysis. To evaluation of antimicrobial activity, the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) were performed. In addition to analysis of antioxidant activity, DPPH radical scavenging tests, iron chelating assay (FIC), antioxidant reducing power assay (FRAP) and ß-carotene bleaching assay (BCB) were performed. For the essential oil were identified 24 organized compounds having as main constituents; Germacrene D (17.2%), α-pinene (14.8%) and E-caryophyllene (10.8%). The results showed that isoflavone (2000 to 156 µg/mL) and essential oil (5.0 to 1.25%) present antibacterial and antifungal activity against Gram-positive bacteria and filamentous fungi. The isoflavone and the essential oil also presented antioxidant activity in all the tests, mainly on inhibition of the oxidation of ß-carotene test concentrations ranging from 60 to 100%. In conclusion, isoflavone and essential oil from M. peruiferum present an antimicrobial alternative against Gram-positive bacteria, especially of the genus Staphylococcus and dermatophyte fungi of the genus Trichophyton, as well as a natural compound antioxidant.

Structural and Microbiological Characterization of 5-Hydroxy-3,7,4'-Trimethoxyflavone: A Flavonoid Isolated from Vitex gardneriana Schauer Leaves.

INTRODUCTION: Staphylococcus aureus represents the most common etiologic agent of purulent infections, affecting humans and animals. Escherichia coli is one of the principal causes of infectious diseases, mainly diarrheal diseases due to enterotoxin action. There are many reports indicating that these bacteria are multidrug-resistant (MDR) pathogens. OBJECTIVE: In this study, we investigated the antimicrobial and modulatory activities of 5-hydroxy-3,7,4'-trimethoxyflavone (VG.EF.CLII) against E. coli and S. aureus strains. METHODS: 5-Hydroxy-3,7,4'-trimethoxyflavone was isolated from Vitex gardneriana Schauer leaves and structurally characterized using nuclear magnetic resonance. The antibacterial effect of VG.EF.CLII and modulation of antibiotic activity, both determined by minimum inhibitory concentration, were assessed using microtiter plates. RESULTS: VG.EF.CLII showed bacterial growth inhibition at concentrations ≤512 µg/mL, and synergistic effects were observed for the modulation of two distinct antibiotic classes (the fluoroquinolone norfloxacin and the aminoglycoside gentamicin). CONCLUSION: 5-Hydroxy-3,7,4'-trimethoxyflavone isolated from V. gardneriana showed promising antimicrobial activity against MDR bacterial strains S. aureus 358 and E. coli 27 when associated with the antibiotics norfloxacin and gentamicin. Therefore, this natural product can contribute to the control of bacterial resistance.

Identification and modulatory activity assessment of 2-hydroxy-3,4,6-trimethoxyacetophenone isolated from croton anisodontus müll. Arg.(euphorbiaceae).

The n-hexane extract of the stem bark of Croton anisodontus yielded 2-hydroxy-3,4,6-trimethoxyacetophenone, a well-known substance, but isolated from this species for the first time. The antimicrobial and modulatory activities of the compound towards Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, C. krusei and C. tropicalis strains were assessed. Antibiotics such as amikacin, gentamicin and neomycin were used in a sub-inhibitory concentration. Significant activity was observed towards P. aeruginosa and S. aureus 358, with p < 0.001 in association with amikacin. The present results place C anisodontus as an alternative source of 2-hydroxy-3,4,6-trimethoxyacetophenone with antibacterial potential.

Amyrin esters induce cell death by apoptosis in HL-60 leukemia cells.

Four derivatives of an α,ß-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,ß-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3µM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.

Cytotoxic diterpenoids from Croton argyrophylloides.

Two new diterpenes, 1 and 2, together with the known ent-15-oxo-kaur-16-en-18-oic acid (3), were isolated from the bark of Croton argyrophylloides. The structural characterization of 1 and 2 was determined on the basis of spectroscopic data interpretation. The cytotoxicity of each compound was evaluated against HL-60 (leukemia), MDAMB-435 (melanoma), SF-295 (glioblastoma), and HCT-8 (colon carcinoma) human tumor cell lines and against human peripheral blood mononuclear cells. The hemolytic potential in mouse erythrocytes was also tested for 1-3.

Obtenção de derivados da mistura triterpenoídica alfa- e beta-amirina / Obtention of derivatives from the alpha- and beta-amyrin triterpenoid mixture: 13C NMR data

Usando reações clássicas como esterificação e oxidação, uma série de derivados foi obtida a partir da mistura alfa- e beta-amirina, constituintes majoritários da resina de Protium heptaphyllum. Os compostos obtidos foram caracterizados por dados espectroscópicos como: IV, RMN de ¹H e de 13C e comparação com dados da literatura.

Using classic reactions such as esterification and oxidation, a series of derivatives was obtained from the alpha- and beta-amyrin mixture, major compounds of the Protium heptaphyllum resin. The obtained compounds were characterized by spectroscopic data such as: IR, ¹ H and 13C NMR and comparison with literature.