Danielle Gomes Santana

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.

Chemical constituents and potential anti-inflammatory activity of the essential oil from the leaves of Croton argyrophyllus

Many species from Croton genus have been used in traditional medicine and its pharmacological activities demonstrated. Croton argyrophyllus Kunth, Euphorbiaceae, is a shrub that grows in the flora of Northeastern Brazilian. The essential oil of C. argyrophyllus leaves was tested in rodents (10-100 mg/kg, p.o.) in classical models of inflammation (carrageenan-induced paw oedema and peritonitis) and its chemical constituents were determined by GC-MS/FID analysis. Nitric oxide radical-scavenging activity and lipidic peroxidation were determined to evaluate the antioxidant capacity of the essential oil (0.001-100 µg/mL). Forty-two components were identified, among them, bicyclogermacrene (14.60%) and spathulenol (8.27%) were the most abundant ones. C. argyrophyllus essential oil reduced significantly the oedema (30 and 100 mg/kg, p<0.05) and, besides, reduced the carrageenan increase in mieloperoxidase activity (10, 30, and 100 mg/kg, p<0.001). The carrageenan-induced peritonitis was significantly reduced (p<0.001) by the essential oil (10, 30, and 100 mg/kg). The essential oil (100 mg/kg) reduces the total peritoneal lavage NOx- concentration (p<0.01). Nitric oxide radical generated from sodium nitroprusside was found to be inhibited by the essential oil (p<0.001). C. argyrophyllus essential oil was able to prevent Fe2+- or Fe2+ plus H2O2-induced lipid peroxidation (p<0.001). This study suggests that the anti-inflammatory effect of the essential oil of C. argyrophyllus observed in the present study can be related, at least in part, its antioxidant capacity.

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.

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.

Isopropoxy‐Carvacrol, a Derivative Obtained from Carvacrol, Reduces Acute Inflammation and Nociception in Rodents

Monoterpenes, compounds mainly presented in essential oils, have important pharmacological actions. Isopropoxy‐carvacrol (IPC) is a derivative of the monoterpene carvacrol, and its pharmacological properties have not yet been investigated. The aim of this study was to analyse the acute anti‐inflammatory and antinociceptive properties of IPC. Mice (25–30 g) and rats (150–230 g) were pre‐treated (i.p.) with IPC at the doses of 10, 30 or 100 mg/kg or vehicle (Tween 80, 0.5%), 30 min. before injection of the phlogistic agents. Both the first and the second phases of formalin‐induced nociception were significantly reduced by IPC (100 mg/kg). Injection of carrageenan in mice paw reduced the threshold of stimulus intensity, applied with an analgesymeter, necessary to cause paw withdrawal, which was significantly reduced by 100 mg/kg of IPC. The area under curve (0–4 hr) of rat paw oedema induced by injection of carrageenan was also significantly diminished by the administration of IPC (100 mg/kg). Administration of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) markedly increased mice ear oedema and myeloperidase (MPO) activity. Topical co‐administration of IPC (0.3–3 mg/ear) during the induction did not affect TPA‐induced ear oedema, but significantly decreased MPO activity in the ears, when compared with the vehicle. In in vitro experiments, IPC reduced lipoperoxidation induced by different stimuli, showed nitric oxide scavenger activity and did not interfere with murine macrophage viability in concentrations up to 100 μg/mL. These results demonstrate that IPC exerts acute anti‐inflammatory and antinociceptive activities, suggesting that it may represent an alternative in the development of new future therapeutic strategies.

Evaluation of mechanisms involved in the antinociception of the ethanol extract from the inner bark of Caesalpinia pyramidalis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE Caesalpinia pyramidalis Tul. (Fabaceae) is an endemic tree of the Northeast region of Brazil, mainly in the Caatinga region. More commonly, inner bark or flowers are traditionally used to treat many painful and inflammatory processes. A common use of this plant is made by macerating a handful of its stem bark in a liter of wine or sugarcane brandy. It is drunk against stomachache, dysenteries, and diarrheas. MATERIALS AND METHODS The ethanol extract of Caesalpinia pyramidalis inner bark was used in mice via oral route, at the doses of 10, 30, and 100mg/kg, in behavioral models of nociception and investigates some of the mechanisms underlying this effect. RESULTS The ethanol extract (30 and 100mg/kg, P<0.001), given orally, produced dose dependent inhibition of acetic acid-induced visceral pain. The ethanol extract also caused significant and dose-dependent inhibition of capsaicin-(100mg/kg, P<0.001) and glutamate-(10, 30, and 100mg/kg, P<0.01) induced pain. The antinociception caused by the ethanol extract (30mg/kg) in the abdominal constriction test was significantly attenuated (P<0.001) by intraperitoneal treatment of mice with l-arginine (600mg/kg). CONCLUSIONS Collectively, the present results suggest that the ethanol extract of Caesalpinia pyramidalis produced dose-related antinociception in several models of pain through mechanisms that involved both glutamatergic system and/or the l-arginine-nitric oxide pathway, supporting the folkloric usage of the plant to treat various painful processes.

The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400 mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx − were also evaluated. Treatment with EECp (100–400 mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx − induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100 mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400 mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats.

Vaccinium macrocarpon Aiton Extract Ameliorates Inflammation and Hyperalgesia through Oxidative Stress Inhibition in Experimental Acute Pancreatitis

We evaluated the effect of the hydroethanolic extract of fruits of Vaccinium macrocarpon (HEVm) in a model of acute pancreatitis (AP) in mice. AP was induced by two injections of L-arginine and animals were treated with HEVm (50, 100, and 200 mg/kg, p.o.) or vehicle (saline) every 24 h, starting 1 h after the induction of AP. Phytochemical analysis of the extract and measurement of inflammatory and oxidative stress parameters, as well as abdominal hyperalgesia, were performed. Catechin, epicatechin, rutin, and anthocyanins were identified in HEVm. Treatment with HEVm decreased L-arginine-induced abdominal hyperalgesia (from 48 to 72 h). Also, treatment with HEVm decreased L-arginine-induced pancreatic edema, pancreatic and pulmonary neutrophil infiltration, and levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, after 72 h of induction. L-arginine-induced hyperamylasemia and hyperlipasemia were also reduced by the treatment with HEVm in comparison to vehicle-treated group. Moreover, lipoperoxidation, carbonyl radicals, nonprotein sulfhydryl groups, and activity of catalase and superoxide dismutase, but not glutathione peroxidase, were restored by the treatment with HEVm. These results show that treatment with HEVm decreased hyperalgesia and pancreatic/extrapancreatic inflammation and oxidative damage in L-arginine-induced AP, making this extract attractive for future approaches designed to treat this condition.