Enilton A. Camargo

Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis

ETHNOPHARMACOLOGICAL RELEVANCE Caesalpinia pyramidalis Tul. (Fabaceae) is a plant found in the Northeast of Brazil that is popularly used to treat inflammation. Acute pancreatitis (AP) is an inflammatory disease for which abdominal pain is a relevant symptom. As there is no specific therapy for AP, we investigated the effect of the ethanol extract from the inner bark of C. pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in rats. MATERIAL AND METHODS AP was induced in male Wistar rats (200-250 g, n=6-8) through laparotomy and subsequent CBDO. Animals were euthanized after 6 (G6h) or 24 h (G24h) of induction. In the G6h protocol, animals were pretreated with EECp (100-400 mg/kg, p.o.) or vehicle (Tween 80; 0.2%) 1h before CBDO or sham surgery. For the G24h protocol, rats were pretreated with EECp (400mg/kg, 1h before CBDO or 1 h before and 12 h after CBDO) or vehicle. The following parameters were measured: inflammatory/oxidative (myeloperoxidase activity and malondialdehyde formation in the pancreas and lung, leukocyte counts in the blood and serum nitrate/nitrite), enzymatic (serum amylase and lipase levels) and nociceptive (abdominal hyperalgesia). RESULTS Induction of AP by CBDO significantly increased all the parameters evaluated in both G6h and G24h protocols when compared with the respective sham group. In the G6h protocol, the EECp pretreatment (400 mg/kg) significantly reduced all these parameters, besides completely inhibiting abdominal hyperalgesia. The same profile of reduction was observed from two administrations of EECp in the G24h protocol, while one single dose of EECp was able to significantly reduce pancreatic MDA, serum lipase levels, leukocyte counts in the blood and abdominal hyperalgesia without affecting the other parameters in the G24h protocol. Furthermore, rutin was found in the EECp. CONCLUSIONS Our results demonstrated that EECp decreases inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of interest in future approaches to treat this condition.

Inhibition of inducible nitric oxide synthase-derived nitric oxide as a therapeutical target for acute pancreatitis induced by secretory phospholipase A2

Nitric oxide is a key signalling molecule in the pathogenesis of inflammation, but its role in acute pancreatitis and related abdominal pain induced by secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus (Cdt) venom has not been investigated.

Antinociceptive and anti-inflammatory effects of Caesalpinia pyramidalis in rodents

Caesalpinia pyramidalis Tul., Fabaceae, is a plant with an anti-inflammatory activity that is used in folk medicine. To evaluate the mechanism of action of this plant, studies were performed on its antinociceptive and anti-inflammatory properties using an ethanol extract (EE) made from the inner bark. Oral treatment of mice with the EE (100, 200, and 400 mg/kg) decreased their acetic acid-induced abdominal writhes (p<0.001) and their formalin-induced paw licking in both the first and second phases (p<0.001). This treatment increased the reaction time of mice on the hot-plate test (400 mg/kg, p<0.05); however, it did not alter their performance on the Rotarod performance test. The carrageenan-induced paw edema in the rats and the leukocyte migration into the peritoneal cavity of the mice were also reduced by the EE given at a dose of 400 mg/kg (p<0.05). In addition, the EE (100-400 mg/kg, v.o.) did not alter the arterial pressure of non-anesthetized rats. In conclusion, the EE of C. pyramidalis shows antinociceptive and anti-inflammatory activities in rodents, supporting the usage of this plant to treat various inflammatory diseases for which it has traditionally been used.

Anti-inflammatory properties of rose oxide

Rose-oxide is a fragrance found in roses and rose oil. There are no reports about the pharmacological activity of this molecule. The present study was undertaken to evaluate whether rose-oxide (RO) has anti-inflammatory properties and to investigate possible mechanisms involved with its effects. The anti-inflammatory activity of RO was first suggested by the formalin test in mice, an inflammatory pain model, because intraperitoneal (i.p.) administration of RO (50 and 100mg/kg) inhibited only the late phase of this test. To further investigate the anti-inflammatory properties of RO, the complete Freunds adjuvant (CFA)- and carrageenan-induced paw inflammation models were used. Pre-treatment with RO (50 and 100mg/kg) significantly reduced paw edema at 4, 6 and 24h after the CFA injection. In addition, RO (100mg/kg) reduced the IL-1β, but not TNF-α, local production induced by CFA. Administration of RO (25-100mg/kg) decreased the paw edema induced by carrageenan in rats, which was more evident at 3 and 4h after induction. In addition, neutrophil migration to the hind paw was measured by MPO assay after the carrageenan injection. The MPO activity was significantly inhibited by RO at 25-100mg/kg, 4h after stimulus. In another experimental set, administration of RO (25-100mg/kg) significantly reduced the leukocyte migration in the carrageenan-induced peritonitis model in mice. The results described here are the first report of pharmacological properties of RO and strongly suggest that RO possesses anti-inflammatory activity related to its ability to inhibit the IL-1β production and the leukocyte migration.

Modelo de obesidade induzida por dieta hiperlipídica e associada à resistência à ação da insulina e intolerância à glicose

OBJECTIVE Validate a model of high-fat diet-induced obesity, of low cost, easy reproducibility, that could express characteristics observed in human, and would enable subsequent therapy proposals. MATERIALS AND METHODS Sixteen Swiss mice received a standard diet (DP) or high-fat diet (DH) for 10 weeks. RESULTS Although the DP group had greater water (p < 0.01) and feed (p < 0.001) consumption, the DH group had greater body weight (p < 0.5) and adipose tissue gain (p < 0.001), favoring higher adiposity index (p < 0.001), glucose (p < 0.01), and area under the curve in the insulin (p < 0.001) and glucose (p < 0.01) tolerance tests. CONCLUSION A high-fat diet-induced obesity model has been validated, which was also associated with insulin resistance and glucose intolerance after a period of 10 weeks.

Vascular Kinin B1 and B2 Receptors Determine Endothelial Dysfunction through Neuronal Nitric Oxide Synthase

B1- and B2-kinin receptors are G protein-coupled receptors that play an important role in the vascular function. Therefore, the present study was designed to evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced vascular relaxation, focusing on the protein-protein interaction involving kinin receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS). Vascular reactivity, nitric oxide (NO·) and reactive oxygen species (ROS) generation, co-immunoprecipitation were assessed in thoracic aorta from male wild-type (WT), B1- (B1R−/−), B2- (B2R−/−) knockout mice. Some vascular reactivity experiments were also performed in a double kinin receptors knockout mice (B1B2R−/−). For pharmacological studies, selective B1- and B2-kinin receptors antagonists, NOS inhibitors and superoxide dismutase (SOD) mimetic were used. First, we show that B1- and B2-kinin receptors form heteromers with nNOS and eNOS in thoracic aorta. To investigate the functionality of these protein-protein interactions, we took advantage of pharmacological tools and knockout mice. Importantly, our results show that kinin receptors regulate ACh-induced relaxation via nNOS signaling in thoracic aorta with no changes in NO· donor-induced relaxation. Interestingly, B1B2R−/− presented similar level of vascular dysfunction as found in B1R−/− or B2R−/− mice. In accordance, aortic rings from B1R−/− or B2R−/− mice exhibit decreased NO· bioavailability and increased superoxide generation compared to WT mice, suggesting the involvement of excessive ROS generation in the endothelial dysfunction of B1R−/− and B2R−/− mice. Alongside, we show that impaired endothelial vasorelaxation induced by ACh in B1R−/− or B2R−/− mice was rescued by the SOD mimetic compound. Taken together, our findings show that B1- and B2-kinin receptors regulate the endothelium-dependent vasodilation of ACh through nNOS activity and indicate that molecular disturbance of short-range interaction between B1- and B2-kinin receptors with nNOS might be involved in the oxidative pathogenesis of endothelial dysfunction.

A systematic review of medicinal plants used for weight loss in Brazil: Is there potential for obesity treatment?

ETHNOPHARMACOLOGICAL RELEVANCE Obesity is a pandemic disease and its prevalence is still increasing. Moreover, it has important costs to public health. In Brazil, many plants are used for weight loss by overweight or obese people, but there is a lack of scientific basis for this practice. Many ethnobotanical studies aiming to characterize this usage have been published, but they are still limited by the region considered and the diversity of the popular knowledge. AIM OF THE STUDY The present study was undertaken to systematically review the ethnobotanical surveys regarding the species utilized to reduce body weight in overweight or obese people in Brazil. METHODS Ethnobotanical surveys related to this usage and performed in Brazilian regions were systematically found in MEDLINE, LILACS and Scopus. RESULTS Thirty-three studies were included in this review. Fifty species were popularly utilized to lose weight. The most cited species were Baccharis trimera (Less.) DC, Annona muricata L. and Hancornia speciosa Gomes. Camellia sinensis (L.) Kuntze and Hibiscus sabdariffa L. were also cited and are supported by either animal or human investigations that indicate some beneficial activity against obesity. However, for the majority of species cited in the included studies, there is no scientific basis that assures the biological effects of this usage. Many studies have demonstrated important effects of these plants on glycemia, serum lipid levels or body weight control in non-obese conditions, which is not sufficient to recommend the use of these plants to reduce body weight in overweight or obese people. CONCLUSIONS Although many plants are popularly used to reduce weight in overweight or obese people in Brazil, there is little scientific evidence corroborating its usage. Based on the ethnobotanical data presented, this review indicates the plants that should be considered for scientifically controlled studies devoted to investigating their effects on obesity.

Citronellal, a monoterpene present in Java citronella oil, attenuates mechanical nociception response in mice

Abstract Context: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae). Objective: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO–cGMP–ATP-sensitive K+ channel pathway. Materials and methods: We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 μl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E2 (PGE2; 100 ng/paw) or dopamine (DA; 30 μg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). Results: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE2 test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE2 test. Discussion and conclusion: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP--ATP-sensitive K+ channel pathway.

Anti-inflammatory activity of hydroxydihydrocarvone.

Hydroxydihydrocarvone (HC) is a synthetic intermediate obtained by hydration of the natural compound (R)-(-)-carvone. The aim of the present study was to investigate the possible anti-inflammatory activity of orally administered HC. Toxicity, motor coordination, tail immersion test, as well as carrageenan-induced paw edema and myeloperoxidase (MPO) activity or peritonitis were all evaluated in rodents. HC was force-fed to the animals 1 h before the stimulus. The lethal dose 50% (LD50) of orally administered HC was 1259 mg/kg. No changes in motor coordination were recorded in HC-treated mice in the rotarod test. The time of response to the thermoceptive stimulus in the tail immersion test was longer in HC-treated animals (50, 100, and 200 mg/kg) than in the vehicle-treated group. HC also significantly decreased the area under curve of carrageenan-induced rat paw edema at 100 and 200 mg/kg and MPO activity at 200 mg/kg. Carrageenan-induced neutrophil recruitment to the peritoneal cavity was significantly reduced by HC at doses of 100 or 200 mg/kg, but not 50 mg/kg. These findings demonstrate that orally administered HC exerts antinociceptive and anti-inflammatory activities in rats and mice.

Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice

Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P < .05) and fasting blood glucose (192.8 ± 14.2 vs. 132.3 ± 6.4 mg/dL, P < .05) and inhibit weight gain (39 ± 5.7%) and fat storage in liver (72.60 ± 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extracts effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice.