Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms.

Evaluation of the antiedematogenic and anti-inflammatory properties of Ximenia americana L. (Olacaceae) bark extract in experimental models of inflammation.

Edema is one of the obvious indicators of inflammation and a crucial factor to take into account when assessing a substance's capacity to reduce inflammation. We aimed to evaluate the antiedematogenic and anti-inflammatory profile of the hydroethanolic barks extract of Ximenia americana (HEXA). The possible antiedematogenic and anti-inflammatory effect of EHXA (50, 100 mg/kg and 250 mg/kg v.o) was evaluated using the paw edema induced by carrageenan, zymosan, dextran, CFA and by different agents inflammatory (serotonin, histamine, arachidonic acid and PGE2), and pleurisy model induced by carrageenan and its action on IL-1ß and TNF-α levels was also evaluated. HEXA demonstrated a significant antiedematogenic effect at concentrations of 50, 100 and 250 mg/kg on paw edema induced by carrageenan, zymosan and dextran. However, the concentration of 50 mg/kg as standard, demonstrating the effect in the subchronic model, induced CFA with inhibition of 59.06 %. In models of histamine-induced paw edema, HEXA showed inhibition of - 30 min: 40.49 %, 60 min: 44.70 % and 90 min: 48.98 %; serotonin inhibition - 30 min: 57.09 %, 60 min: 66.04 % and 90 min: 61.79 %; arachidonic acid inhibition - 15 min: 36.54 %, 30 min: 51.10 %, 45 min: 50.32 % and 60 min: 76.17 %; and PGE2 inhibition - 15 min: 67.78 %, 30 min: 62.30 %, 45 min: 54.25 % and 60 min: 47.92 %. HEXA significantly reduced (p < 0.01) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1ß levels in pleural lavage (p < 0.0001). The results showed that HEXA has the potential to have an antiedematogenic impact in both acute and chronic inflammation processes, with a putative mode of action including the suppression or regulation of inflammatory mediators.

GC-MS Chemical Characterization and In Vitro Evaluation of Antioxidant and Toxic Effects Using Drosophila melanogaster Model of the Essential Oil of Lantana montevidensis (Spreng) Briq.

Background and objectives: Natural products such as essential oils with antioxidant potential can reduce the level of oxidative stress and prevent the oxidation of biomolecules. In the present study, we investigated the antioxidant potential of Lantana montevidensis leaf essential oil (EOLM) in chemical and biological models using Drosophila melanogaster. Materials and methods: in addition, the chemical components of the oil were identified and quantified by gas chromatography coupled to mass spectrometry (GC-MS), and the percentage compositions were obtained from electronic integration measurements using flame ionization detection (FID). Results: our results demonstrated that EOLM is rich in terpenes with Germacrene-D (31.27%) and ß-caryophyllene (28.15%) as the major components. EOLM (0.12-0.48 g/mL) was ineffective in scavenging DPPH radical, and chelating Fe(II), but showed reducing activity at 0.24 g/mL and 0.48 g/mL. In in vivo studies, exposure of D. melanogaster to EOLM (0.12-0.48 g/mL) for 5 h resulted in 10% mortality; no change in oxidative stress parameters such as total thiol, non-protein thiol, and malondialdehyde contents, in comparison to control (p > 0.05). Conclusions: taken together, our results indicate EOLM may not be toxic at the concentrations tested, and thus may not be suitable for the development of new botanical insecticides, such as fumigants or spray-type control agents against Drosophila melanogaster.

Anti-inflammatory and anti-edematogenic action of the Croton campestris A. St.-Hil (Euphorbiaceae) essential oil and the compound ß-caryophyllene in in vivo models.

BACKGROUND: Inflammation makes up a set of vascularized tissue reactions acting in the defense of the body against harmful stimuli. Natural products are a lower cost alternative with better benefit, often used in popular medicine in the treatment of inflammatory processes. Several species from the genus Croton have scientifically proven anti-inflammatory action. PURPOSE: This study aims to analyze the chemical composition of the Croton campestris A. St.-Hil essential oil (EOCC), derived from fresh leaves, as well as to evaluate the anti-inflammatory potential and the possible mechanisms of action of the EOCC and its constituent ß-caryophyllene. METHODS: The assays were performed in in vivo models of acute and chronic inflammation. Initially, the chemical composition of the EOCC was determined and its oral toxicity was evaluated, followed by the evaluation of its topical antiedematogenic effect through acute and chronic ear edema induced by Croton oil. For the systemic verification of an anti-inflammatory action, the abdominal contortions, formalin test, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, as well as a peritonitis test, vascular permeability and granuloma assays were performed. RESULTS: The evaluation of the essential oil chemical composition revealed the presence of ß-caryophyllene (15.91%), 1,8-cineol (16.98%) and germacrene-D (14.51%) as its main constituents. The EOCC had no relevant clinical toxicity on oral administration, with an LD50 of more than 5000 mg/kg. The tested substances showed anti-inflammatory action in the abdominal contortions, paw edema induced by carrageenan, dextran, histamine and arachidonic acid models, the formalin test, peritonitis test and vascular permeability; however, ß-caryophyllene had no significant effect on the granuloma assay. This suggests as a hypothesis that both substances tested showed significant influence on the arachidonic acid and histamine pathway reducing edema in these models. CONCLUSION: The tested substances have a clinically safe profile, additionally the EOCC and ß-caryophyllene presented relevant anti-inflammatory activity. This study supports the hypothesis that ß-caryophyllene, in association with other constituents present in the EOCC such as 1,8-cineole, contributed to the anti-inflammatory effect observed, in addition to suggesting that one of the mechanisms of action probably involves the inhibition of cytokines with the involvement of the arachidonic acid and histamine pathways.

Phytochemical profile and mechanisms involved in the anti-nociception caused by the hydroethanolic extract obtained from Tocoyena formosa (Cham. & Schltdl.) K. Schum (Jenipapo-bravo) leaves in mice.

Tocoyena formosa, a small ornamental tree growing in the dry regions of central Brazil, is commonly known as 'genipapo do bravo'. This is a medicinal plant traditionally used as an analgesic for rheumatic pain, lower back pain and myalgia, however its use is carried out without scientific evidence, which thus justifies the development of studies to investigate and prove its therapeutic potential. Therefore, the objective of this study was to evaluate the phytochemical profile of Tocoyena formosa (Cham. & Schlecht.) K. Schum (TFLHE) and the mechanisms involved in its anti-nociceptive effect. The TFLHE revealed the presence of gallic acid, catechin, chlorogenic acid, caffeic acid, ellagic acid, rutin, quercetin and luteolin. The TFLHE at doses of 200 and 400mg/kg significantly decreased acetic acid-induced abdominal contortions, the reaction time for the formalin test in both phases and increased the paw withdrawal time in the hot plate thermal stimulus test. The 200mg/kg dose also significantly inhibited the plantar mechanical hyperalgesia intensity induced by formalin within 24h. TREATMENT: with the TFLHE did not cause significant changes in motor performance and coordination in the Rota Rod test. The investigation on the possible mechanism of antinociceptive action of TFLHE indicates the involvement of opioid, glutamatergic, nitric oxide/cGMP and vanilloid systems. It is concluded that the TFLHE has an antinociceptive effect promoted by the aforementioned mechanisms.

Anti-edematogenic and anti-inflammatory activity of the essential oil from Croton rhamnifolioides leaves and its major constituent 1,8-cineole (eucalyptol).

The species Croton rhamnifolioides, belonging to the Croton genus, is known in ethnomedicine as "quebra faca" and is used in the treatment of stomach pain, vomiting and fever. This study aims to evaluate the anti-edematogenic and anti-inflammatory effect of Croton rhamnifolioides leaf essential oil (OEFC) and its major constituent: 1,8-cineole (eucalyptol). The essential oil was extracted from fresh leaves through a hydrodistillation system. The chemical analysis was determined by gas chromatography-mass spectrometry (GC-MS). The acute anti-inflammatory activity was determined from the models of: ear edema by the single application of croton oil, paw edema induced by: carrageenan, dextran, histamine and arachidonic acid, while vascular permeability was determined by Evans blue extravasation and chronic anti-inflammatory activity by granuloma induction using the implantation of cotton pellets. The GC-MS results identified and quantified 11 constituents, with the major component being 1,8-cineole (41.33%). The OEFC (20mg/mL) and 1,8-cineole (8.26mg/mL) significantly reduced the edema induced by croton oil by 42.1 and 34.9%, respectively. The OEFC (25, 50, 100 and 200mg/kg) and 1,8-cineole (10.33, 20.66, 41.33 and 82.66mg/kg) statistically reduced paw edema induced by carrageenan, dextran as well as vascular permeability (protein extravasation). The OEFC (25mg/kg) and 1,8-cineole (10.33mg/kg) demonstrated efficacy in reducing edema induced by histamine and arachidonic acid and granuloma. In conclusion, the OEFC and 1,8-cineole have anti-inflammatory activity in the acute and chronic phase, suggesting therapeutic potential as a source for the development of new anti-inflammatory agents.

Gastroprotective effect and mechanism of action of Croton rhamnifolioides essential oil in mice.

BACKGROUND: Croton rhamnifolioides Pax is a plant species that have been used in the folk medicine to treat ulcers, inflammations and hypertension. However, despite the relevant data obtained from ethnopharmacological studies, the pharmacological properties endorsing the efficacy of this plant to treat ulcer remain to be elucidated. HYPOTHESIS/PURPOSE: The present study aimed to characterize the chemical profile and evaluate the gastroprotective activity of the essential oil obtained from C. rhamnifolioides Pax (OECC) in mice. METHODS: The essential oil of Croton rhamnifolioides was obtained by hydrodistillation and analyzed by gas-phase chromatography coupled to mass spectrometry (GC/MS). The median lethal dose was determined employing an acute toxicity test. The gastroprotective activity of the OECC was investigated using animal models of gastric ulcer induced by the administration of absolute ethanol, acidified ethanol or indomethacin. Mechanisms of action were investigated using the physical barrier test and by in vivo evaluation of the involvement of the following molecular pathways: nitric oxide, ATP - dependent potassium channels, α2 - noradrenergic receptors, capsaicin - sensitive afferent neurons and opioid receptor. RESULTS: We identified the presence of 21 compounds in OECC, including spathulenol and 1,8 - cineole as major constituents. In orally administered mice, OECC caused no significant toxicity. OECC significantly prevented gastric lesions in all mice models. The barrier test demonstrated that the gastroprotective activity of OECC occurs in a systemic dimension. Our results demonstrated that the gastroprotective effect of OECC involves mechanisms that are related to modulation of opioid receptors and nitric oxide. CONCLUSION: In conclusion, OECC demonstrated significant gastroprotective activity associated with low toxicity, providing scientific evidences that C. rhamnifolioides have the potential for the development of new antiulcer drugs.