Ethyl Acetate Fraction of Harpagophytum procumbens Prevents Oxidative Stress In Vitro and Amphetamine-Induced Alterations in Mice Behavior.

Microglial activation has been associated to the physiopathology of neurodegenerative diseases, such as schizophrenia, and can occur during inflammation and oxidative stress. Pharmacological treatment is associated with severe side effects, and studies for use of plant extracts may offer alternatives with lower toxicity. Harpagophytum procumbens (HP) is a plant known for its anti-inflammatory properties. In the present study, we characterized the ethyl acetate fraction of HP (EAF HP) by ESI-ToF-MS and investigated the effects EAF HP in a lipopolysaccharide (LPS) induced inflammation model on microglial cells (BV-2 lineage). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DCFH-DA (2',7'-dichlorofluorescein diacetate) and cell cycle flow cytometer analysis were performed. In vivo was investigated the amphetamine-induced psychosis model through behavioral (locomotor and exploratory activities, stereotypies and working memory) and biochemical (DCFH-DA oxidation and protein thiols) parameters in cortex and striatum of mice. EAF HP reduced activation and proliferation of microglial cells in 48 h (300 µg/mL) and in 72 h after treatments (50-500 µg/mL). Reactive oxygen species levels were lower at the concentration of 100 µg/mL EAF HP. We detected a modulatory effect on the cell cycle, with reduction of cells in S and G2/M phases. In mice, the pre-treatment with EAF HP, for 7 days, protected against positive and cognitive symptoms, as well as stereotypies induced by amphetamine. No oxidative stress was observed in this amphetamine-induced model of psychosis. Such findings suggest that EAF HP can modulate the dopaminergic neurotransmission and be a promising adjuvant in the treatment of locomotor alterations, cognitive deficits, and neuropsychiatric disorders.

Investigating the Effect of Inosine on Brain Purinergic Receptors and Neurotrophic and Neuroinflammatory Parameters in an Experimental Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.

Iron localization in the guinea pig choroid plexus: A light and transmission electron microscopy study.

The role of the choroid plexus (CP) in iron (Fe) homeostasis has been suggested as the main mechanism of Fe uptake and storage in the mammalian central nervous system. Thus, the CP of the lateral and fourth ventricles was studied in guinea pigs with light and electron microscopy using methods including Perls' Prussian blue and Gomori acid phosphatase staining, immunoreactivity for ferritin and transferrin, as well as energy dispersive spectrometry microanalysis. The present study reveals the presence of endogenous Fe in CP epithelial cells. Under light microscopy, Prussian blue staining revealed dark blue precipitates (i.e., Fe3+) with a preferentially perinuclear localization. The Fe was also positive for such granules with similar cellular localization. Ultrastructural analysis demonstrated the presence of dense bodies and siderosomes with molecular ferritin. The spectra obtained by the microanalysis demonstrated emissions for Fe, both in dense bodies and siderosomes. This study suggests that guinea pig CP epithelial cells accumulate Fe in the form of ferritin, possibly in cytoplasmic organelles such as lysosomes.

Antinociceptive and antidepressant-like effects of the crude extract of Vitex megapotamica in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex megapotamica (Spreng) Moldenke has been used in South American folk medicine to treat inflammatory diseases. However, the effects of V. megapotamica on animal models of nociception and depression have not been evaluated. AIM OF THE STUDY: This study investigated whether the crude leaf extract of V. megapotamica exhibits antinociceptive and antidepressant-like effects in a Freund's adjuvant-induced chronic inflammation and depression model. MATERIALS AND METHODS: Chronic inflammation was induced in rats by the intraplantar administration of complete Freund's adjuvant (CFA; 100µl). The effect of oral crude extract of V. megapotamica (VmE; 3-30mg/kg, p.o.) on nociception (thermal hyperalgesia, mechanical allodynia and arthritis score), inflammation (edema, myeloperoxidase activity), immobility (forced swimming test), locomotor activity (open field), gastrointestinal transit, hyperalgesia and naloxone-precipitated morphine withdrawal syndrome was evaluated. Naloxone (0.4mg/kg, i.p.) was used to investigate the involvement of opioid system in the currently described effects of VmE. RESULTS: Crude extract caused antinociceptive/antidepressant-like effects in the CFA-induced chronic inflammation model, which was prevented by naloxone. The VmE extract (10mg/kg, p.o.) did not alter the locomotor activity, gastrointestinal function and inflammatory parameters and did not cause hyperalgesia. CONCLUSION: V. megapotamica induces opioid-dependent antinociception and antidepressant-like effect, without anti-inflammatory activity. The results support the use of VmE as analgesic and antidepressant.

Estudo morfoanatômico das folhas de Cuphea glutinosa Cham. & Schltdl., Lythraceae / Morpho-anatomical study of the leaves of Cuphea glutinosa Cham. et Schltdl. (Lythraceae)

Adeterminação de características macro e microscópicas das folhas de Cuphea glutinosa Cham. & Schltdl., Lythraceae, foi o objetivo deste trabalho. Esta planta é utilizada tradicionalmente como medicinal. As características macroscópicas das folhas como a forma, a textura e a consistência, bem como o ápice e a base da lâmina foliar são relevantes na determinação da autenticidade de insumos farmacêuticos desta espécie. Microscopicamente a presença de formações epicuticulares, cristais de oxalato de cálcio na forma de drusas, tricomas tectores e glandulares, estômatos do tipo diacítico, células mucilaginosas e floema interxilemático são características úteis no controle botânico de qualidade desta planta como insumo farmacêutico, quando analisados em conjunto.

The determination of macroscopic and microscopic characteristics of Cuphea glutinosa Cham. & Schltdl., Lythraceae, leaves were the aim of this work. This plant is traditionally used as medicinal. The macroscopic characteristics of the leaves as the shape, texture and consistency as well as the apex and the base of the leaf are relevant to determinate pharmaceutical insumes autenticity of this plant. In the leaves microscopy there are epicuticular formations, crystals of calcium oxalate in the form of druses, and glandular trichomes, xerophytytic stoma of the diacytic type, mucilaginous cells, and interxilematic phloem are important characteristics in the botanical quality control of this plant as pharmaceutical insume.

Morfonatomia do caule de Cuphea glutinosa Cham. & Schltdl. (Lythraceae) / Morpho-anatomy of the stem of Cuphea glutinosa Cham & Schltdl. (Lythraceae)

Foram determinados parâmetros morfo-anatômicos do caule de Cuphea glutinosa cham. & Schltdl, planta reconhecida tradicionalmente como medicinal, objetivando sua autenticidade como insumo farmacêutico. As características macroscópicas do caule são insuficientes para a determinação da autenticidade dos insumos farmacêuticos desta planta, havendo necessidade de verificar a presença de sementes não aladas e de vesículas infraestaminais nas flores. Microscopicamente a presença de formações epicuticulares, cristais de oxalato de cálcio na forma de drusas, tricomas tectores e glandulares, estômatos xerofíticos, células mucilaginosas e floema interxilemático, são características significativas no controle botânico de qualidade desta espécie para a indústria farmacêutica, quando analisadas em conjunto.

Morpho-anatomical parameters of Cuphea glutinosa cham. & Schltdl, stem were determined aiming its authenticity as a pharmaceutical drug. This plant is traditionally known as medicinal. The macroscopic characteristics of the stem are insuficient to determine the autenticity of this plant pharmaceutics input, it requires checking out the presence of not winged seeds and vesicles placed under the stamens of the flowers. Microscopically, the presence of epicuticular formations, crystals of calcium oxalato in druses form, glandular and non-glandular thricomes, xerophytic stomatas, mucilages cells and interxilematic phloem are meaningful characteristics in the botanical quality control of this plant for the pharmaceutical industry, when analyzed together.