Polygala sabulosa A.W. Bennett extract mitigates motor and cognitive deficits in a mouse model of acute ischemia.

Stroke is considered one of the leading causes of death worldwide. The treatment is limited; however, the Brazilian flora has a great source of natural products with therapeutic potentials. Studies with the medicinal plant Polygala sabulosa W. Bennett provided evidence for its use as an anti-inflammatory and neuroprotective drug. In the case of ischemic stroke due to lack of oxygen, both acute and chronic inflammatory processes are activated. Thus, we hypothesized that P. sabulosa (HEPs) has the potential to treat the motor and cognitive deficits generated by ischemic stroke. Male mice were subjected to global ischemia for 60 min, followed by reperfusion and orally treated with HEPs (100 mg/kg in saline + 3% tween 20) twice a day (12 h apart) for 48 h starting 3 h after surgery. Motor skills were assessed using grip force and open field tasks. Hippocampi were then collected for mRNA quantification of the cytokines IL-1-ß and TNF-α levels. After 48 h of acute treatment, spatial reference memory was evaluated in a Morris water maze test for another group of animals. We show that HEPs treatment significantly prevented motor weakness induced by ischemia. Brain infarct area was reduced by 22.25% with downregulation of the levels of IL-1ß and TNF-α mRNA. Learning performance and memory ability on Morris water maze task were similar to the sham group. Our data demonstrates the neuroprotective properties of HEPs through its anti-inflammatory activities, which prevent motor and cognitive impairments, suggesting that HEPs may be an effective therapy for ischemic stroke.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin.

Myricitrin exhibits antidepressant-like effects and reduces IL-6 hippocampal levels in the chronic mild stress model.

The flavonoid myricitrin showed an antidepressant-like effect in the tail suspension test and increased hippocampal neurogenesis, as well as demonstrating anti-inflammatory effects. Interestingly, inflammation has been linked to depression, and anti-inflammatory drugs showed promising results as antidepressant-like drugs. Thus, the present study evaluated the effects of myricitrin in the chronic mild stress (CMS) model, a translational and valid animal model of depression, using the mini-experiment design to improve the reproducibility of the findings. The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were the readouts of depressive-like phenotypes induced by CMS. Relative adrenal weight was employed as an index of the hypothalamus-pituitary-adrenal (HPA) axis activation. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels were measured in the hippocampus. Myricitrin (10 mg/kg, intraperitoneally, for 14 days) reversed depressive-like behaviors induced by CMS (increased immobility in the FST, the TST and anhedonia), as well as decreased adrenal hypertrophy and hippocampal levels of IL-6 in stressed mice. Similar results were observed by imipramine (20 mg/kg, intraperitoneally, for 14 days), a serotonin and norepinephrine reuptake inhibitor (positive control). A significant correlation was observed between immobility time in the TST, and hippocampal IL-6 levels. Hippocampal TNF-α levels were not affected by CMS or drug treatment. In conclusion, myricitrin exhibited an antidepressant-like profile in CMS, and this effect may be associated with its anti-inflammatory activity.

Antidepressant-like effect of extract from Polygala paniculata: involvement of the monoaminergic systems.

CONTEXT: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential. OBJECTIVE: The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST). MATERIALS AND METHODS: Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract. RESULTS: The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01-30 mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1 mg/kg, i.p., α2-adrenoceptor antagonist), propranolol (1 mg/kg, i.p., ß-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30 mg/kg). Moreover, ketanserin (5 mg/kg, i.p., preferential 5-HT(2A) receptor antagonist) enhanced the effect of the extract in FST. DISCUSSION AND CONCLUSION: The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT2A receptors), noradrenergic (α2 and ß-receptor) and dopaminergic (D1 and D2 receptors) systems.

Antifungal activity of five species of Polygala.

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.

Proanthocyanidin-rich fraction from Croton celtidifolius Baill confers neuroprotection in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine rat model of Parkinson's disease.

We have recently demonstrated that rodents treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in olfactory, cognitive and motor functions associated with time-dependent disruption of dopaminergic neurotransmission in different brain structures conceivably analogous to those observed during different stages of Parkinson's disease (PD). On the other hand, the proanthocyanidin-rich fraction (PRF) obtained from the bark of Croton celtidifolius Baill (Euphorbiaceae), a tree frequently found in the Atlantic forest in south Brazil, has been described to have several neurobiological activities including antioxidant and anti-inflammatory properties, which may be of interest in the treatment of PD. The present data indicated that the pretreatment with PRF (10 mg/kg, i.p.) during five consecutive days was able to prevent mitochondrial complex-I inhibition in the striatum and olfactory bulb, as well as a decrease of the enzyme tyrosine hydroxylase expression in the olfactory bulb and substantia nigra of rats infused with a single intranasal administration of MPTP (1 mg/nostril). Moreover, pretreatment with PRF was found to attenuate the short-term social memory deficits, depressive-like behavior and reduction of locomotor activity observed at different periods after intranasal MPTP administration in rats. Altogether, the present findings provide strong evidence that PRF from C. celtidifolius may represent a promising therapeutic tool in PD, thus being able to prevent both motor and non-motor early symptoms of PD, together with its neuroprotective potential.

Myricitrin as a substrate and inhibitor of myeloperoxidase: implications for the pharmacological effects of flavonoids.

Flavonoids are increasingly being ingested by the general population as chemotherapeutic and anti-inflammatory agents. They are potentially toxic because of their conversion to free radicals and reactive quinones by peroxidases. Little detailed information is available on how flavonoids interact with myeloperoxidase, which is the predominant peroxidase present at sites of inflammation. This enzyme uses hydrogen peroxide to oxidize chloride to hypochlorous acid, as well as to produce an array of reactive free radicals from organic substrates. We investigated how the flavonoid myricitrin is oxidized by myeloperoxidase and how it affects the activities of this enzyme. Myricitrin was readily oxidized by myeloperoxidase in the presence of hydrogen peroxide. Its main oxidation product was a dimer that underwent further oxidation. In the presence of glutathione, myricitrin was oxidized to a hydroquinone that was conjugated to glutathione. When myeloperoxidase oxidized myricitrin and related flavonoids it became irreversibly inactivated. The number of hydroxyl groups in the B ring of the flavonoids and the presence of a free hydroxyl m-phenol group in the A ring were important for the inhibitory effects. Less enzyme inactivation occurred in the presence of chloride. Neutrophils also oxidized myricitrin to dimers in a reaction that was partially dependent on myeloperoxidase. Myricitrin did not affect the production of hypochlorous acid by neutrophils. We conclude that myricitrin will be oxidized by neutrophils at sites of inflammation to produce reactive free radicals and quinones. It is unlikely to affect hypochlorous acid production by neutrophils.

Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.

Inhibition of H+/K+ ATPase in the gastroprotective effect of Baccharis illinita DC.

Baccharis illinita DC (Compositae) is used in folk medicine to treat gastric disturbances. Preliminary studies with other extracts of B. Illinita showed gastric protection against ethanol-, indometacin- and stress-induced ulcers and the inhibition of gastric secretion. Based on these data, the aim of this study was to verify the pathways involved in the inhibition of gastric secretion. The chloroform extract (CE) of flowers from B. illinita (3, 10, 30 and 100 mg kg(-1) i.p.) tested on rats with pylorus ligature reduced the volume and the total acidity of gastric content by approximately 50% (ED50 = 69 mg kg(-1)). Treatment with CE (100 mg kg(-1) i.p.) reduced the gastric total acidity stimulated by histamine, bethanechol and pentagastrin to 42%, 27% and 57% of that in the stimulated control group, respectively. The CE (10, 30 and 100 microM) inhibited H+/K+ ATPase activity in-vitro, with an IC50 of 37 microM. The isolated flavonoid luteolin (1, 3, 10 and 30 microM) also inhibited H+/K+ ATPase activity by 50%, at a dose of 30 microM. Our results suggest that the reduction in gastric secretion occurs through inhibition of H+/K+ ATPase, which is the final step in acid secretion and therefore one of the most important steps.

Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L.

Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mg kg(-1)) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mg kg(-1) per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mg kg(-1)) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mg kg(-1)) inhibited total acidity by 50%, 60% and 67%, respectively. In-vitro, CE inhibited H+, K+ -ATPase activity with an EC50 of 53 microgmL(-1) and fraction A (30 and 100 microgmL(-1)) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 microgmL(-1)) and fraction B (100 and 250 microgmL(-1)) had free-radical scavenging ability, inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+ -ATPase.

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities.

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2-11 were prepared by classical procedures. Including, five new esters derivatives 7-11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1-11 were confirmed by 1H NMR, 13C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50 = 12.48 µg/mL) and the lowest cytotoxic derivative (CC50 = 161.50 µg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system.

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

Effects of two 6-quinolinyl chalcones on the integrity of plasma membrane of Paracoccidioides brasiliensis.

Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, yet few therapeutic options exist. Our aim was to search for new compounds with high efficacy, low toxicity, shorter treatment time and affordable cost. We studied two synthetic 6-quinolinyl chalcones, 3b and 3e, to determine their effects on VERO cells, antifungal activity, survival curve, interaction with other drugs and phenotypic effects against several isolates of Paracoccidioides spp. In this study, we verified that the compounds were not toxic, exhibited superior in vitro activity compared with that shown by trimethoprim-sulfamethoxazole, and after 5 days of treatment, decreased the fungal cell viability by approximately 70%. Additionally, no interactions were observed between the tested compounds and other drugs. We also found that these compounds induced morphological changes, such as shriveling of cells, fragmentation of the plasma membrane and cytoplasmic disorganization in vitro. The changes observed by microscopy assays corroborate the observation made with propidium iodide, where the number of cells stained with the compounds was higher than that observed after amphotericin B treatment. We observed an increase in the efflux of K+ and a loss of intracellular contents in cells treated with 3b and 3e, confirming their effects on fungal membranes. However, damage to the membrane was not associated with a decrease in membrane ergosterol levels. The experimental evidences showed no direct indications of cellular wall damage caused by these compounds. Thus, these results confirm the antifungal potential of 3b and 3e against Paracoccidioides spp. with possible action on the membrane.

Comparative assessment of kaempferitrin from medicinal extracts of Bauhinia forficata link.

The leaves of the pantropical genus Bauhinia (Fabaceae) are popularly known as cow's-paw or cow's hoof due to their unique characteristic bilobed aspect. The species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk medicine as an antidiabetic. This article deals with the quantitative analysis of kaempferitrin from B. forficata medicinal extract (aqueous and hydro alcoholic) using the LC method, and the comparison of kaempferitrin content in leaves collected from two different regions in the south Brazil. The total flavonoid content assessed by LC was also compared with the classical spectrophotometric determination. Kaempferitrin was found in different amounts, in samples from two geographical areas (Telêmaco Borba/PR and Itajaí/SC), for aqueous (368.68 and 77.91 microg/mL) and hydro alcoholic extracts (1952.59 and 211.61 microg/mL), respectively. The method was subjected to recovery assay, to determine its accuracy. A marked difference in total flavonoid concentration was observed in relation to kaempferitrin content: 2759.95 and 2188.20 microg/mL for the fluidextract and 863.35 and 856.77 microg/mL for the aqueous extract (Telêmaco Borba/PR and Itajaí/SC). The spectrophotometric assay overestimated the total flavonoid content (3620 microg/mL) in relation to the LC assay.

Derivatization does not influence antimicrobial and antifungal activities of applanoxidic acids and sterols from Ganoderma spp.

Applanoxidic acids and sterols, isolated from Ganoderma spp., were acetylated and/or methylated. The antibacterial activity against Escherichia coli and Staphylococcus aureus and the antifungal activity against Candida albicans and Trichophyton mentagrophytes of the derivatives were investigated by a microdilution method, and compared with those of the natural products. Both natural and modified compounds exhibited comparable antibacterial and antifungal activities in a range of 1.0 to > 2.0 mg/ml minimal inhibitory concentration.

Chemical constituents of Eugenia catharinae and their antioxidant activity.

Nine compounds were isolated from the leaves of Eugenia catharinae, namely monomethyl olivetol (1), ß-sitosterol (2), stigmasterol (3), uvaol (4), erythrodiol (5), rotundic acid (6), quercetin (7), catechin (8) and myricitrin (9). The structures of 1-9 were established through analysis of their spectroscopic (1H and 13C NMR) and spectrometric (MS) data. Compounds 1 and 6 are reported the first time in the Eugenia genus. In addition, these data were compared with those reported in the literature. The antioxidant activity of plant samples and compounds was measured using the DPPH radical scavenging assay. Flavonoids 7, 8, 9 and the ethanolic extract showed the best results, with IC50 values of 20.94 µM, 44.20 µM, 30.01 µM and 58.82 µg/mL, respectively.

Antinociceptive effect of hydroalcoholic extract and isoflavone isolated from Polygala molluginifolia in mice: evidence for the involvement of opioid receptors and TRPV1 and TRPA1 channels.

PURPOSE: The plants of the genus Polygala (Polygalaceae) have been used for a long time in folk medicine to treat pain and inflammation. The species Polygala molluginifolia is native to southern Brazil and is popularly known as "cânfora". The presented study analyzes the antinociceptive effect of hydroalcoholic extract from Polygala molluginifolia (HEPm) and an isoflavone (ISO) isolated from the extract, in behavioral models of pain in mice, as well as the mechanism underlying this effect. MATERIALS AND METHODS: The phytochemical analysis of HEPm was performed through a capillary electrophoresis analysis and colorimetric test. The antinociceptive effects of HEPm and ISO (10-1000 mg/kg, i.g.) were evaluated by applying the formalin test; mechanical and thermal hyperalgesia to postoperative pain in mice. The possible involvement of opioid receptors, TRPV1 and TRPA1 channels in the antinociceptive effect of HEPm and ISO were also evaluated. Finally, the nonspecific effects of HEPm and ISO were evaluated by measuring locomotor activity (Open-field Test) and corporal temperature. RESULTS: The 5,3',4'-trihydroxy-6″,6″-dimethylpyrano[2″,3″:7,6] isoflavone (ISO) was identified in HEPm by capillary electrophoresis analysis and selected for the experimental tests. The oral administration of HEPm or of ISO significantly inhibited the neurogenic and inflammatory phases of formalin-induced pain, edema formation and local hyperemia, without causing any change to locomotor activity. Acute and repeated treatment of animals with HEPm reduced mechanical and thermal (heat and cold) hyperalgesia in the postoperative pain. In addition, administering HEPm or ISO markedly reduced nociceptive behavior induced by the peripheral and central injection of TRPV1 and TRPA1 channels activators. Finally, the antinociception provided by the administration of HEPm or ISO was reversed by the preadministration of naloxone. CONCLUSIONS: Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of HEPm and ISO in animal models of acute pain without causing sedation or locomotor dysfunction. This effect appears to be mediated, at least in part, by the activation of opioid receptors and/or by the inhibition of TRPV1 and TRPA1 channels. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant Polygala molluginifolia in the development of phytomedicines with analgesic properties.

Protective effects of Polygala paniculata extract against methylmercury-induced neurotoxicity in mice.

We have examined the possible protective effects of Polygala paniculata extract against methylmercury (MeHg)-induced neurotoxicity in adult mice. MeHg was diluted in drinking water (40 mg L(-1), freely available) and the hydroalcoholic Polygala extract was diluted in a 150 mM NaCl solution and administered by gavage (100 mg kg(-1) b.w., twice a day). After a two-week treatment, MeHg exposure significantly inhibited glutathione peroxidase and increased glutathione reductase activity, while the levels of thiobarbituric acid reactive substances were increased in the cerebral cortex and cerebellum. These alterations were prevented by administration of Polygala extract, except for glutathione reductase activity, which remained elevated in the cerebral cortex. Behavioural interference in the MeHg-exposed animals was evident through a marked deficit in the motor performance in the rotarod task, which was completely recovered to control levels by Polygala extract co-administration. This study has shown, for the first time, the in-vivo protective effects of Polygala extract against MeHg-induced neurotoxicity. In addition, our findings encourage studies concerning the beneficial effects of P. paniculata on neurological conditions related to excitotoxicity and oxidative stress.

Inhalation of Cedrus atlantica essential oil alleviates pain behavior through activation of descending pain modulation pathways in a mouse model of postoperative pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Cedrus atlantica essential oil (CaEO) presents analgesic and anti-inflammatory sedative properties. However, it remains unknown whether CaEO alleviates acute postoperative pain. MATERIALS AND METHODS: Here, we investigated the effect of CaEO on postoperative pain and its mechanisms related to the descending pain control in Swiss males mice induced by a plantar incision surgery (PIS) in the hindpaw. RESULTS: Inhalation of CaEO (5', 30' or 60') markedly reduced mechanical hypersensitivity. This effect was prevented by pre-treatment with naloxone or p-chlorophenylalanine methyl ester (PCPA, 100mg/kg, i.p.)-induced depletion of serotonin. In addition, p-alpha-methyl-para-tyrosin (AMPT, 100mg/kg, i.p.)-induced depletion of norepinephrine, intraperitoneal injection of the α2-adrenergic receptor antagonist yohimbine (0.15 mg/kg, i.p.) or haloperidol (1mg/kg, i.p.) an antagonist of dopaminergic (D1 and D2) receptors prevented the effect of CaEO on hypersensitivity. CONCLUSIONS: These findings suggest that CaEO alleviates postoperative pain by activating the descending pain modulation pathways on the opioidergic, serotonergic, noradrenergic (α2-adrenergic) and dopaminergic (dopamine D1 and D2 receptors) systems.

7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.

CONTEXT: Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant. OBJECTIVE: Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy. MATERIALS AND METHODS: A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1ß and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated. RESULTS: CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1ß and NOS2, and on activation of the NF-κB and p38 MAPK pathways. CONCLUSION: The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.