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 (25­30 g) and rats (150­230 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 (0­4 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 (0.3­3 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 lg/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.

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.

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.

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.

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.