Plants of the genus Polygala have been shown to possess protective effects against neuronal death and cognitive impairments in neurodegenerative disorders related to excitotoxicity. Moreover, previous reports from our group have shown the neuroprotective effects of the plant Polygala paniculata against methylmercury (MeHg)-induced neurotoxicity. In this work, we have examined the potential protective effects of three compounds (7-prenyloxy-6-methoxycoumarin, quercetin, and 1,5-dihidroxi-2,3-dimethoxy xanthone) from Polygala species against MeHg- and mercuric chloride (HgCl2)-induced disruption of mitochondrial function under in vitro conditions using mitochondrial-enriched fractions from mouse brain. MeHg and HgCl2 (10-100 microM) significantly decreased mitochondrial viability; this phenomenon was positively correlated to mercurial-induced glutathione oxidation. Among the isolated compounds, only quercetin (100-300 microM) prevented mercurial-induced disruption of mitochondrial viability. Moreover, quercetin, which did not display any chelating effect on MeHg or HgCl2, prevented mercurial-induced glutathione oxidation. The present results suggest that the protective effects of quercetin against mercurial-induced mitochondrial dysfunction is related to the removal of oxidant species generated in the presence of either MeHg or HgCl2. Reinforcing this hypothesis, MeHg and HgCl2 increased the production of hydrogen peroxide in the brain mitochondria, as well as the levels of malondialdehyde. These oxidative phenomena were prevented by co-incubation with quercetin or catalase. These results are the first to show the involvement of hydrogen peroxide as a crucial molecule related to the toxic effects of both organic and inorganic mercurials in brain mitochondria. In addition, the study is the first to show the protective effect of quercetin against mercurial-induced toxicity, pointing to its capability to counteract mercurial-dependent hydrogen peroxide generation as a potential molecular mechanism of protection. Taken together, these data render quercetin a promising molecule for pharmacological studies with respects to mercurials' poisoning.
The relationship between depression and monoaminergic systems has been hypothesized for many years. In this study, we have investigated the possible antidepressant-like effect of scopoletin, a coumarin from Polygala sabulosa in the tail suspension test and forced swimming test. Moreover, the ability of scopoletin to reverse the depression-like behavior in the forced swimming test induced by immobility stress in mice was evaluated. Scopoletin reduced the immobility time in the tail suspension test (10-100mg/kg, p.o.), but not in the forced swimming test. Fluoxetine (positive control) decreased the immobility time in the forced swimming and tail suspension tests (20mg/kg, p.o. and 10mg/kg. p.o., respectively). Immobility stress caused an increase in the immobility time in the forced swimming test (depression-like behavior), which was reversed by scopoletin (1-100mg/kg, p.o.) and fluoxetine (10mg/kg, p.o.). Scopoletin produced no psychostimulant effect in the open-field test. The pretreatment of mice with ketanserin (5mg/kg, i.p., a preferential 5-HT(2A) receptor antagonist), prazosin (1mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), haloperidol (0.2mg/kg, i.p., a dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist) or sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist), but not WAY100635 (0.1mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) prevented the antidepressant-like effect of scopoletin (10mg/kg, p.o.) in the tail suspension test. The results indicate that its antidepressant-like effect is dependent on the serotonergic (5-HT(2A) receptors), noradrenergic (alpha(1)- and alpha(2)-adrenoceptors) and dopaminergic (dopamine D(1) and D(2) receptors) systems.
Crude extracts and fractions of five species of Polygala - P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa - were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC) assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 µg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 µg/mL and 250 µg/mL, respectively) and C. gattii (both with MICs of 250 µg/mL). Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 µg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain
Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.
RESUMO:Os extratos obtidos pela maceração em CHCl 3 /MeOH (2:1) de 8 amostras de espécies medicinais e 11 amostras comerciais de chás foram analisados por cromatografi a em camada delgada (CCD). Glicolipídios foram detectados em todas as amostras, porém com diferenças qualiquantitativas. Para as plantas medicinais, a maior concentração de glicolipídios foi detectada em Lippia alba e Cymbopogon citratus, enquanto em amostras comerciais, o melhor perfi l glicolipídico foi encontrado nos extratos de C. citratus e Baccharis trimera.Unitermos: Glicolipídios, plantas medicinais, cromatografi a em camada delgada.ABSTRACT: "Screening of glycolipids in medicinal plants". The extracts obtained by maceration in CHCl 3 /MeOH (2:1) of 8 medicinal plants and 11 commercial samples (tea bags) were analysed by thin-layer chromatography. Glycolipids were detected in all the samples, with qualitative and quantitative differences. For the medicinal plants, the highest concentrations were detected in Lippia alba and Cymbopogon citratus. For the commercial samples, the best glycolipidic profi les were found in C. citratus and Baccharis trimera extracts.
This study investigated the role of the glutamatergic system on the antinociception caused by Polygala sabulosa hydroalcoholic extract (HE). The systems mediated by substance P, capsaicin, interleukin-1 β (IL-1 β ) and tumour necrosis factor-α (TNF-α ) were also investigated. P. sabulosa HE given orally produced a significant inhibition of glutamateinduced paw licking ) mg/kg and inhibition of 79 ± 6% at 1000 mg/kg]. The plant derivatives α -spinasterol, scopoletin and styryl-2-pyrones (compound 1 and 3) (10 mg/kg, intraperitoneally) inhibited 80 ± 7%, 46 ± 11%, 45 ± 11% and 35 ± 13% the nociceptive response caused by glutamate, respectively. Furthermore, P. sabulosa HE (500 mg/kg, orally) caused marked inhibition of nociceptive response induced by intrathecal injection of glutamate, N-methyl-d -aspartic acid, α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, TNF-α and IL-1 β , with inhibitions of 44 ± 7%, 55 ± 4%, 38 ± 10%, 61 ± 7%, 76 ± 9% and 100%, respectively. In contrast, P. sabulosa HE (500 mg/kg, orally) did not affect the biting response induced by the metabotropic glutamatergic receptor agonist (±)-1-aminocyclopentanetrans -1,3-dicarboxylic acid, substance P and capsaicin. The locomotor activity was altered only in mice treated with a very high dose (1000 mg/kg) of P. sabulosa HE. Our results showed that the antinociceptive effects of P. sabulosa HE are associated with an inhibition of glutamatergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. The plant derivatives α -spinasterol, scopoletin and styryl-2-pyrones play an important role on the antinociceptive effects of P. sabulosa HE.The plants of genus Polygala are widely distributed in Santa Catarina state, Brazil, and have been employed to treat disorders of the bowel and kidney, as a topical anaesthetic and expectorant [1]. Scientific studies in isolated cells and in animals have confirmed the biological activities of the plants from genus Polygala [2-10]. The chemical constituents of Polygala , coumarins, steroids, saponins, lignans, flavonoids and xanthones confer to these plants valuable pharmacological properties [7][8][9][10][11][12][13].Recently, we have demonstrated that Polygala sabulosa hydroalcoholic extract (HE) A. W. Bennett (Polygalaceae) produced antinociceptive action against the acetic acidinduced visceral nociception. The presence of styryl-2-pyrones, coumarin (scopoletin) and steroid ( α -spinasterol) gives to the plant a potent antinociceptive effect [9]. However, the model of nociception previously employed did not allow to clearly identify the mechanism of the antinociceptive action of the plant extract. Indeed, the acetic acid-induced visceral nociception involves a chain of inflammatory mediators that are released into the abdominal cavity and in the central nervous system [14][15][16].In this concern, the aim of this study was to identify the mechanism by which P. sabulosa HE exerts its antinociceptive effect. For this purpose, the effects of the P. sabulosa HE we...
The present data support a partial BDZ-bs mediation of the anxiolytic-like and anticonvulsant effects of EA of P. sabulosa and its main isolated constituents, DST and STY.
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