Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.
Folk medicine suggests that pomegranate (peels, seeds and leaves) has anti-inflammatory properties; however, the precise mechanisms by which this plant affects the inflammatory process remain unclear. Herein, we analyzed the anti-inflammatory properties of a hydroalcoholic extract prepared from pomegranate leaves using a rat model of lipopolysaccharide-induced acute peritonitis. Male Wistar rats were treated with either the hydroalcoholic extract, sodium diclofenac, or saline, and 1?h later received an intraperitoneal injection of lipopolysaccharides. Saline-injected animals (i.?p.) were used as controls. Animals were culled 4?h after peritonitis induction, and peritoneal lavage and peripheral blood samples were collected. Serum and peritoneal lavage levels of TNF-? as well as TNF-? mRNA expression in peritoneal lavage leukocytes were quantified. Total and differential leukocyte populations were analyzed in peritoneal lavage samples. Lipopolysaccharide-induced increases of both TNF-? mRNA and protein levels were diminished by treatment with either pomegranate leaf hydroalcoholic extract (57?% and 48?% mean reduction, respectively) or sodium diclofenac (41?% and 33?% reduction, respectively). Additionally, the numbers of peritoneal leukocytes, especially neutrophils, were markedly reduced in hydroalcoholic extract-treated rats with acute peritonitis. These results demonstrate that pomegranate leaf extract may be used as an anti-inflammatory drug which suppresses the levels of TNF-? in acute inflammation.
This study aimed to evaluate the safety of the hydroalcoholic extract (HE) of Syzygium cumini (L.) Skeels, Myrtaceae, leaves in rodents. Acute toxicity was evaluated through the determination of a LD50 in mice and rats (up to 14 days). In mice, the oral administration (p.o.) of the HE (0.1 at 6 g/kg) did not cause any death. When administered by intraperitoneal route (i.p.) the HE (0.1 at 1 g/kg) caused death of the animals (LD50 of 0.489 g/kg). In rats, the HE (0.5, 1 and 2 g/kg, p.o.) did not cause any death, while by i.p., only the 2 g/kg dose was lethal to 67% of the animals. To evaluate chronic toxicity, groups of rats daily received the HE (0.05, 0.1 and 0.25 g/kg) through p.o., during 30, 90 or 180 days and the effects on behavior, body weight, feed consumed were measured. Histology, hematology and biochemical parameters were measured at the end of the treatment. After a 30-day treatment, the HE caused changes in some biochemical parameters. Histological examination of the liver, kidneys, lungs, heart, stomach, intestine and pancreas showed normal architecture suggesting no morphological disturbances. These data may mean that the HE of S. cumini does not exert acute or chronic toxic effects by oral administration.
This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E
max) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.
Anabolic androgen steroids (AASs) are drugs synthesized from testosterone. Their anabolic action is mainly due to increased synthesis and reduced degradation of muscle proteins. The purpose of this study was to investigate the effects of swimming training associated to nandrolonedecanoate treatment on the blood pressure, the myocardial dimensions, vascular reactivity. Forty Wistar male rats, aged 60 days, were divided into 4 groups (n = 10): sedentary (SN), sedentary treated (ST), trained (TN) and trained treated (TT). TN and TT animals performed a swimming training during 12 weeks and ST and TT animals received weekly nandrolonedecanoate (15mg/kg). The heart and testicles were removed and weighted. The left ventricular diameter (LVD) and left ventricular wall thickness (LVWT) had been measured with an electronic pachymeter. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was weekly measured, while the mesenteric arteries vascular reactivity was studied for its response to noradrenaline. There were no alterations in the heart weight, but the LVD increased (p < 0.05) in TN rats, while the LVWT increased (p < 0.05) in ST and TT rats, both in relation to SN. Testicle weight decreased (p < 0.05) in the ST and TT animals in relation to SN. There was no alteration in blood pressure, neither in vascular reactivity. It was concluded that swimming training increased the left ventricular diameter, while nandrolonedecanoate treatment increased mainly the left ventricular wall thickness, suggesting concentric hypertrophy.
Abstract:The antispasmodic activity of Jatropha gossypiifolia L., Euphorbiaceae, aerial parts was investigated in rodents using the mouse intestinal transit model and acetylcholine (ACh, to 10 -4 M) and calcium (CaCl 2 , 10 -4 to 10 -1 M)-induced contractions of isolated rat jejunum. Similar to atropine (1 mg/kg), oral doses of ethanolic extract (EE) of J. gossypiifolia (500, 1000 and 2000 mg/kg) produced a decrease in intestinal transit (37.6 to 57.1%) when compared with control. The ACh-induced contraction in the jejunum was inhibited by EE (0.5, 1.0 and 2.0 mg/ mL), chloroformic (CF) and aqueous fractions (0.1 and 0.5 mg/mL) and methanolic subfraction (0.05 and 0.25 mg/mL), suggesting an antimuscarinic mechanism. CaCl 2 -induced responses in jejunum were also attenuated in the presence of CF (0.05 and 0.1 mg/mL) implying a direct interference of CF with the influx of calcium ions in the cells. Only the organic fraction of the extract had a calcium-antagonist effect, whereas both chloroformic and aqueous fractions had anticholinergic effect. These results suggest that the antispasmodic effect of J. gossypiifolia may be due a combination of anticholinergic and calcium antagonist mechanisms.
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