Geanne Matos de Andrade

Adenosine A2A receptors control neuroinflammation and consequent hippocampal neuronal dysfunction

J. Neurochem. (2011) 117, 100–111.

Topical anti-inflammatory potential of Physalin E from Physalis angulata on experimental dermatitis in mice

The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis angulata L. was evaluated on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines (TNF-alpha and IFN-gamma), myeloperoxidase (MPO) activity, and histological and immunohistochemical findings were analysed, as indicators of dermal inflammation. Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5 mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and MPO activity. These effects were reversed by mifepristone, a steroid antagonist and confirmed by immunohistochemical and histopathological analysis. The data suggest that physalin E may be a potent and topically effective anti-inflammatory agent useful to treat the acute and chronic skin inflammatory conditions.

Synergistic Effect of the Flavonoid Catechin, Quercetin, or Epigallocatechin Gallate with Fluconazole Induces Apoptosis in Candida tropicalis Resistant to Fluconazole

ABSTRACT Flavonoids are a class of phenolic compounds commonly found in fruits, vegetables, grains, flowers, tea, and wine. They differ in their chemical structures and characteristics. Such compounds show various biological functions and have antioxidant, antimicrobial, anti-inflammatory, and antiapoptotic properties. The aim of this study was to evaluate the in vitro interactions of flavonoids with fluconazole against Candida tropicalis strains resistant to fluconazole, investigating the mechanism of synergism. Three combinations formed by the flavonoids (+)-catechin hydrated, hydrated quercetin, and (−)-epigallocatechin gallate at a fixed concentration with fluconazole were tested. Flavonoids alone had no antifungal activity within the concentration range tested, but when they were used as a cotreatment with fluconazole, there was significant synergistic activity. From this result, we set out to evaluate the possible mechanisms of cell death involved in this synergism. Isolated flavonoids did not induce morphological changes or changes in membrane integrity in the strains tested, but when they were used as a cotreatment with fluconazole, these changes were quite significant. When evaluating mitochondrial damage and the production of reactive oxygen species (ROS) only in the cotreatment, changes were observed. Flavonoids combined with fluconazole were shown to cause a significant increase in the rate of damage and the frequency of DNA damage in the tested strains. The cotreatment also induced an increase in the externalization of phosphatidylserine, an important marker of early apoptosis. It is concluded that flavonoids, when combined with fluconazole, show activity against strains of C. tropicalis resistant to fluconazole, promoting apoptosis by exposure of phosphatidylserine in the plasma membrane and morphological changes, mitochondrial depolarization, intracellular accumulation of ROS, condensation, and DNA fragmentation.

Mangiferin ameliorates 6-hydroxydopamineinduced cytotoxicity and oxidative stress in ketamine model of schizophrenia

BACKGROUND Accumulating evidence indicates that mangiferin (MGF), a natural xanthone, by virtue of its antioxidant and antiinflammatory properties is neuroprotective. Here we sought to verify the cytoprotective role of MGF on cultured rat primary mesencephalic cells exposed to 6-hydroxydopamine (6-OHDA) in vitro, and the MGFs anti-inflammatory potential in mouse model of ketamine-induced schizophrenia in vivo. METHODS 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay was performed tomeasure cell viability inmesencephalic cell cultures exposed to neurotoxin (6-OHDA, 40 μM). Schizophrenia was induced in mice by ketamine (50 mg/kg, ip, twice a day, for 7 days). The treatment effects of MGF (50 mg/kg, po, for 7 days) were verified on locomotor behavioral changes in open-field test, and on the oxidant stress-related increase in lipid-peroxidation (malondialdehyde) and interleukin-6 (IL-6) levels in brain tissues. RESULTS MGF (10-100 μM) produced no per se effect on cell viability as measured by MTT assay, but significantly prevented the 6-OHDA-induced cell death in a concentration-dependent manner. Acridine orange/ethidium bromide (AO/EtBr) staining confirmed the absence of 6-OHDA-induced morphological changes characteristic of apoptosis/necrosis. In open-field test, ketamine-induced impaired locomotor activity and behavioral changes such as grooming and stereotyped but not rearing were effectively ameliorated by MGF pretreatment. Also, ketamine-associated increase in brain tissue levels of IL-6 and MDA were significantly lowered in MGF-pretreated mice. CONCLUSION Mangiferin has a neurocytoprotective role related, at least in part, to an antioxidant and anti-inflammatory mechanism, which could be explored for more effective therapies of schizophrenia and other neurodegenerative diseases.

The impact of antioxidant agents complimentary to periodontal therapy on oxidative stress and periodontal outcomes: A systematic review

There is significant evidence linking chronic periodontitis (CP) and oxidative stress (OS). CP is a multifactorial infecto-inflammatory disease caused by the interaction of microbial agents present in the biofilm associated with host susceptibility and environmental factors. OS is a condition that arises when there is an imbalance between the levels of free radicals (FR) and its antioxidant defences. Antioxidants, defined as substances that are able to delay or prevent the oxidation of a substrate, exist in all bodily tissues and fluids, and their function is to protect against FR. This systematic review assessed the effects of the complimentary use of antioxidant agents to periodontal therapy in terms of oxidative stress/antioxidants. Only randomised, controlled, double-blind or blind studies were included. The majority of the included studies were performed in chronic periodontitis patients. Lycopene, vitamin C, vitamin E, capsules with fruits/vegetables/berry and dietary interventions were the antioxidant approaches employed. Only the studies that used lycopene and vitamin E demonstrated statistically significant improvement when compared to a control group in terms of periodontal parameters. However, oxidative stress outcomes did not follow the same pattern throughout the studies. It may be concluded that the use of some antioxidants has the potential to improve periodontal clinical parameters. The role of antioxidant/oxidative stress parameters needs further investigations.

Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study.

Abstract:  Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double‐blind, placebo‐controlled study on the effects of melatonin in COPD. Thirty‐six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean ± S.D. = 66.6 ± 7.8 yr) were randomized to receive 3 mg melatonin (N = 18) or placebo for 3 months. Oxidative stress was evaluated by 8‐isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL‐8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8‐isoprostane (T0: mean ± S.E.M. = 20.41 ± 2.92 pg/mL; T1: 18.56 ± 2.68 pg/mL; T2: 12.68 ± 2.04 pg/mL; T3: 12.70 ± 2.18 pg/mL; P = 0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P = 0.03) and 3 months (P = 0.01). Dyspnea was improved by melatonin (P = 0.01), despite no significant changes in lung function or exercise capacity. Placebo‐treated patients, but not those who were given melatonin, showed an increase in IL‐8 (P = 0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long‐term management of these patients.

Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke

Medeiros CAM, de Bruin VMS, Andrade GM, Coutinho WM, de Castro‐Silva C, de Bruin PFC. Obstructive sleep apnea and biomarkers of inflammation in ischemic stroke.
Acta Neurol Scand: 2012: 126: 17–22.
© 2011 John Wiley & Sons A/S.

Piperine decreases pilocarpine-induced convulsions by GABAergic mechanisms

Piperine, an alkaloid present in the Piper genus, was shown to have an anticonvulsant activity, evaluated by the pilocarpine-induced model, in mice. Pilocarpine (350mg/kg, i.p.) was administered 30min after piperine (2.5, 5, 10 and 20mg/kg, i.p.) which significantly increased latencies to 1st convulsion and to death, and percentage of survivals. These parameters were also increased in the pilocarpine groups pretreated with atropine plus piperine (10 and 2.5mg/kg, respectively), as related to the pilocarpine group. However, they were not altered in the pilocarpine groups pretreated with memantine (a NMDA-type glutamate receptors blocker, 2mg/kg, p.o.) or nimodipine (a calcium channel blocker, 10mg/kg, p.o.), both associated with piperine (1 or 2.5mg/kg), as compared to the piperine plus pilocarpine group. Moreover, the pilocarpine group pretreated with diazepam (which binds to the GABAA receptor, 0.2 and 0.5mg/kg, i.p.) plus piperine (1 and 2.5mg/kg) significantly increased latency to the 1st convulsion, as related to the pilocarpine group, suggesting that the GABAergic system is involved with the piperine action. Furthermore, the piperine effect was blocked by flumazenil (2mg/kg, i.p.), a benzodiazepine antagonist. Untreated P350 animals showed decreased striatal DA and increased DOPAC and HVA levels that were not affected in the piperine plus pilocarpine groups. Piperine increased striatal levels of GABA, glycine and taurine, and reversed pilocarpine-induced increases in nitrite contents in sera and brain. Hippocampi from the untreated pilocarpine group showed an increased number of TNF-α immunostained cells in all areas, as opposed to the pilocarpine group pretreated with piperine. Taken together, piperine anticonvulsant effects are the result of its anti-inflammatory and antioxidant actions, as well as TNF-α reduction. In addition, piperine effects on inhibitory amino acids and on the GABAergic system may certainly contribute to the drug anticonvulsant activity.

Catechin attenuates behavioral neurotoxicity induced by 6-OHDA in rats

This study was designed to investigate the beneficial effect of catechin in a model of Parkinsons disease. Unilateral, intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats were pretreated with catechin (10 and 30 mg/kg) by intraperitoneal (i.p.) injection 2h before surgery and for 14 days afterwards. After treatments, apomorphine-induced rotations, locomotor activity, working memory and early and late aversive memories were evaluated. The mesencephalon was used to determine the levels of monoamines and measurement of glutathione (GSH). Immunohistochemical staining was also used to evaluate the expression of tyrosine hydroxylase (TH) in mesencephalic and striatal tissues. Catechin administration attenuated the increase in rotational behavior and the decrease in locomotor activity observed in lesioned rats. Although catechin did not rescue the impairment of late aversive memory, it protected the animals against 6-OHDA-induced working memory deficits. Furthermore, catechin treatment restored GSH levels, and significantly increased dopamine and DOPAC content, and TH-immunoreactivity in 6-OHDA-lesioned rats. Catechin protected 6-OHDA-lesioned rats due to its antioxidant action, indicating that it could be useful as an adjunctive therapy for the treatment of Parkinsons disease.

Gastroprotective effect of barbatusin and 3-beta-hydroxy-3-deoxibarbatusin, quinonoid diterpenes isolated from Plectranthus grandis, in ethanol-induced gastric lesions in mice.

ETHNOPHARMACOLOGICAL RELEVANCE Validate the popular use of Plectranthus grandis in gastric disorders through the active components. AIMS Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action. MATERIALS AND METHODS Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances. RESULTS Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments. CONCLUSION The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.