Effects of functional electro-stimulation combined with blood flow restriction in affected muscles by spinal cord injury.

Muscle atrophy is a great consequence of spinal cord injuries (SCI) due to immobility. SCI's detrimental effects on large muscle groups may lead to secondary effects such as glucose intolerance, increased risk of metabolic syndrome, and diabetes. Exercising with blood flow restriction (BFR) has been proposed as an effective method to induce hypertrophy using low training loads, with little or no muscle damage. This study investigated acute and chronic effects of low-intensity functional electrical stimulation (FES) combined with BFR on muscles affected by spinal cord injury. The acute effects of one bout of FES with (FES + BFR group) and without BFR (FES group) on muscle thickness (MT) and edema formation were compared. The chronic effects on MT and edema following 8 weeks of twice weekly training with and without BFR were also compared. The FES + BFR group showed MT and edema increases compared to the FES only group (p< 0.05). The FES + BFR showed a chronic MT increase after 4 weeks of training (p <0.05), with no further MT increases from the 4th to the 8th week (p>0.05). Following 3 weeks of detraining, MT decreased to baseline. No MT changes were observed in the FES (p>0.05). The FES + BF stimuli induced MT increases on the paralyzed skeletal muscles of SCI. The acute effects suggest that FES causes a greater metabolite accumulation and edema when combined with BFR. The early increases in MT can be attributed to edema, whereas after the 4th week, it is likely to be related to muscle hypertrophy. Register Clinical Trial Number on ReBeC: RBR-386rm8.

Recent Advances in the Knowledge of Naturally-derived Bioactive Compounds as Modulating Agents of the Renin-angiotensin-aldosterone System: Therapeutic Benefits in Cardiovascular Diseases.

BACKGROUND: One of the biggest challenges to public health worldwide is to reduce the number of events and deaths related to the cardiovascular diseases. Numerous approaches have been applied to reach this goal, and drug treatment intervention has been indispensable along with an effective strategy for reducing both cardiovascular morbidity and mortality. Renin-angiotensin-aldosterone system (RAAS) blockade is currently one of the most important targets of cardiovascular drug therapy. Many studies have proven the valuable properties of naturally-derived bioactive compounds to treat cardiovascular diseases. METHODS: The goal of this review, therefore, is to discuss the recent developments related to medicinal properties about natural compounds as modulating agents of the RAAS, which have made them an attractive alternative to be available to supplement the current therapy options. RESULTS: Data has shown that bioactive compounds isolated from several natural products act either by inhibiting the angiotensin-converting enzyme or directly by modulating the AT1 receptors of angiotensin II, which consequently changes the entire classical axis of this system. CONCLUSION: While there are a few evidence about the positive actions of different classes of secondary metabolites for the treatment of cardiovascular and renal diseases, data is scarce about the clinical assays established to demonstrate their value in humans.

Chemical composition and diuretic, natriuretic and kaliuretic effects of extracts of Mimosa bimucronata (DC.) Kuntze leaves and its majority constituent methyl gallate in rats.

OBJECTIVES: Some species of the genus Mimosa showed promising results in previous investigations, which include diuretic effect; however, no chemical analyses or animal model has been conducted so far to evaluate the biological properties of M. bimucronata. METHODS: Male Wistar rats received the oral treatment with vehicle; hydrochlorothiazide; methanolic extract from M. bimucronata (MEMB), dichloromethane (DCM) and ethyl acetate (EA) fractions or methyl gallate (MG). The cumulative urine volume, electrolytes excretion, pH and osmolality were determined at the end of the experiment. KEY FINDINGS: The chemical studies demonstrated that the phenolic compounds are the majorities in the plant, with the MG being the main substance identified. We showed that MEMB and EA fraction, but not DCM, exhibited diuretic and saluretic effects. Similarly, the MG also revealed diuretic, natriuretic and kaliuretic properties to both normotensive and spontaneously hypertensive rats. Atropine, a muscarinic receptor antagonist, fully prevented MG-induced diuresis and saluresis. In addition, MG did not alter the viability of A7r5 and L929 cell lines and neither stimulated nitric oxide generation. CONCLUSIONS: These findings suggest that M. bimucronata extracts and its majority compound MG present diuretic, natriuretic and kaliuretic properties, which was dependent on the activation of muscarinic acetylcholine receptor.

The Protective Potential of Phyllanthus niruri and Corilagin on Gastric Lesions Induced in Rodents by Different Harmful Agents.

The gastroprotective effect of the methanol extract of Phyllantus niruri and its main constituent, corilagin, were studied in vivo. The extract (50, 125, or 250 mg/kg, p. o.) inhibited ethanol-induced lesions in rats by 43 % (p < 0.001), 69 % (p < 0.001), and 99 % (p < 0.001), respectively. It also inhibited the formation of indomethacin-induced gastric ulcers in rats by 80 % (p < 0.01), 89 % (p < 0.01), and 97 % (p < 0.01). A decrease in lipid hydroperoxide levels (p < 0.01) and in myeloperoxidase activity (p < 0.05) evidenced a reduction of oxidative damage and neutrophil infiltration in gastric tissues from ulcerated mice using ethanol/HCl. Potent in vitro free radical scavenger activity (IC50 = 0.07) using the DPPH assay was observed. In contrast, the extract (250 mg/kg, i. d.) did not show antisecretory activity in pylorus-ligated rats, and also failed to inhibit the H+,K+-ATPase activity in vitro. However, in pylorus-ligated rats, the extract (50, 125, and 250 mg/kg, i. d.) increased adhered mucus content by 22 % (p < 0.05), 28 % (p < 0.01), and 38 % (p < 0.01), respectively. The involvement of prostaglandins, nonprotein endogenous sulfhydryl compounds, α2-receptors, and endogenous nitric oxide in the gastroprotection elicited by the extract was also evaluated. Finally, corilagin reduced the lesion area of ethanol-induced gastric ulcers in mice by 88 % (30 mg/kg, p. o.; p < 0.001). Based on these results, it has been concluded that P. niruri methanol extract possesses gastroprotective activity by different and complementary pathways, which together promote an improvement in gastric cytoprotection. The presence of corilagin may partially explain the effectiveness of the extract against gastric damage.

Gastroresistant microparticles containing sodium alendronate prevent the bone loss in ovariectomized rats.

Sodium alendronate, an antiresorptive drug, primarily used in the treatment of osteoporosis was encapsulated in blended microparticles composed of Eudragit S100 and Methocel K15M. The micropowder obtained by spray-drying technique was characterized in terms of its morphology, particle size, encapsulation efficiency and in vitro drug release. In vivo studies were carried out in order to evaluate the pharmacodynamic effect and the ulcerogenic activity of sodium alendronate-loaded microparticles after oral administration in rats. Drug encapsulation efficiency was close to 80% and particle mean diameter of 13.8 microm. SEM analysis showed spherical collapsed shape particles with smooth surface. At pH 1.2, in vitro experiments showed that <10% of the drug was released from the microparticles. At pH 6.8, the microparticles were able to prolong the sodium alendronate release for 12h. In vivo experiments carried out in ovariectomized rats showed bone mineral density significantly higher for the sodium alendronate-loaded microparticles than for the negative control groups. Furthermore, the microencapsulation of the drug showed a significant reduction in the ulcerative lesion index. In conclusion, the blended microparticles are excellent oral carriers for sodium alendronate since they were able to maintain the drug antiresorptive effect and to reduce the gastrointestinal drug toxicity.

Anti-inflammatory and antinociceptive effects of Baccharis dracunculifolia DC (Asteraceae) in different experimental models.

AIM OF THE STUDY: The aerial parts of Baccharis dracunculifolia D.C., popularly known as "alecrim do campo", are used in folk medicine as anti-inflammatory. The aim of the present study was to evaluate the anti-inflammatory and antinociceptive activities of the crude hydroalcoholic extract obtained from leaves of Baccharis dracunculifolia (BdE), which have not been reported. MATERIALS AND METHODS: BdE was analyzed by HPLC and in vivo evaluated (doses ranging from 50 to 400mg/kg, p.o.) by using the acetic acid-induced abdominal constrictions, paw oedema induced by carrageenan or histamine, overt nociception models using capsaicin, glutamate or phorbol myristate acetate (PMA), formalin-induced nociception and mechanical hypernociception induced by carrageenan or complete Freund adjuvant (CFA). As positive controls it was used paracetamol in both acetic acid and formalin tests; dipyrone in capsaicin, glutamate and PMA-induced nociception; indomethacin in CFA and carrageenan-induced hypernociception models. In addition, the in vitro effects of BdE on COX-2 activity and on the activation of NF-kappaB were also evaluated. RESULTS: BdE (50-400mg/kg, p.o.) significantly diminished the abdominal constrictions induced by acetic acid, glutamate and CFA. Furthermore, BdE also inhibited the nociceptive responses in both phases of formalin-induced nociception. BdE, administered orally, also produced a long-lasting anti-hypernociceptive effect in the acute model of inflammatory pain induced by carrageenan. It was also observed the inhibition of COX-2 activity by BdE. CONCLUSION: In summary, the data reported in this work confirmed the traditional anti-inflammatory indications of Baccharis dracunculifolia leaves and provided biological evidences that Baccharis dracunculifolia, like Brazilian green propolis, possess antinociceptive and anti-inflammatory activities.

Antileishmanial, antimalarial and antimicrobial activities of the extract and isolated compounds from Austroplenckia populnea (Celastraceae).

Austroplenckia populnea (Celastraceae), known as "marmelinho do campo", is used in Brazilian folk medicine as antimicrobial, anti-inflammatory, and antitumoural agent. The aim of the present work was to evaluate the antimicrobial, antileishmanial and antimalarial activities of the crude hydroalcoholic extract of A. populnea (CHE) and some of its isolated compounds. The phytochemical study of the CHE was carried out affording the isolation of methyl populnoate (1), populnoic acid (2), and stigmast-5-en-3-O-beta-(D-glucopyranoside) (3). This is the first time that the presence of compound 3 in A. populnea is reported. The results showed that the CHE presents antifungal and antibacterial activities, especially against Candida glabrata and Candida albicans, for which the CHE showed IC50 values of 0.7 microg mL(-1) and 5.5 microg mL(-1), respectively, while amphotericin B showed an IC50 value of 0.1 microg mL(-1) against both microorganisms. Compounds 1-3 were inactive against all tested microorganisms. In the antileishmanial activity test against Leishmania donovani, the CHE showed an IC50 value of 52 microg mL(-1), while compounds 2 and 3 displayed an IC50 value of 18 microg mL(-1) In the antimalarial assay against Plasmodium falciparum (D6 and W2 clones), it was observed that all evaluated samples were inactive. In order to compare the effect on the parasites with the toxicity to mammalian cells, the cytotoxicity activity of the isolated compounds was evaluated against Vero cells, showing that all evaluated samples exhibited no cytotoxicity at the maximum dose tested.

Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium corymbosum).

Blueberries are among the edible fruits that are recognized best for their potential health benefits. The crude extract from Vaccinium corymbosum was assessed in anti-inflammatory and antinociceptive models. The crude hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg (-1) for all the assays. In the carrageenan test, the crude extract reduced rat paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan, by 42.8 and 46.2%, respectively. With the granulomatous tissue assay dexamethasone displayed significant activity, whereas the blueberry extract was inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%, respectively, were observed for the crude extract, and 61.4% for indometacin. In the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively. Considering that the crude extract of blueberry displayed antinociceptive and anti-inflammatory activity, its consumption may be helpful for the treatment of inflammatory disorders.

Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae).

Many plant crude extracts and their isolated compounds are the most attractive sources of new drugs and show promising results for the treatment of gastric ulcers. Austroplenckia populnea is commonly known as "marmelinho-do campo, mangabeira-brava, mangabarana and vime" and it has been used in folk medicine as anti-dysenteric and anti-rheumatic. Powdered bark wood (3.25 kg) was macerated with aqueous ethanol (96%) and the extract was concentrated under reduced pressure to yield 406 g of crude hydralcoholic extract. The hydralcoholic extract was suspended in aqueous methanol and partitioned with hexane, chloroform and ethyl acetate (EtOAc) in sequence, yielding 8.0 g, 9.5 g and 98.17 g of crude extracts, respectively. Chromatography of the hexane extract over a silica gel column led to the isolation of the triterpene populnoic acid. The oral administration of hydralcoholic, hexane, chloroform and EtOAc extracts (200 mg/kg) decreased the ulcer lesion index (ULI) by 83.15%, 46.87%, 32.2%, 68.12%, respectively. Oral administration of populnoic acid (100 mg/kg) diminished the ULI by 55.29%. All the obtained results were significant in comparison with the negative control, with exception of the chloroform extract.