caryophyllene and Edema

Inflammation is a complex biological response involving the immune, autonomic, vascular, and somatosensory systems that occurs through the synthesis of inflammatory mediators and pain induction by the activation of nociceptors. Staphylococcus aureus, the main cause of bacteremia, is one of the most common and potent causes of inflammation in public health, with worse clinical outcomes in hospitals. Antioxidant substances have been evaluated as alternative therapeutic analgesics, antioxidants, anti-inflammatory agents, antitumor agents, and bactericides. Among these, we highlight the essential oils of aromatic plants, such as β-caryophyllene (BCP), and polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). The objective of this study was to evaluate the biological activities of BCP-DHA association in in vitro and in vivo experimental models of antinociception and inflammation. To determine the anti-inflammatory effects, monocytes isolated from the peripheral blood of adult male volunteers were infected with methicillin-resistant S. aureus and incubated with treatment for cytokine dosage and gene expression analysis. Antinociceptive effects were observed in the three models when comparing the control (saline) and the BCP-DHA treatment groups. For this purpose, the antinociceptive effects were evaluated in animal models using the following tests: acetic acid-induced abdominal writhing, paw edema induced by formalin intraplantar injection, and von Frey hypernociception. There was a significant reduction in the GM-CSF, TNFα, IL-1, IL-6, and IL-12 levels and an increase in IL-10 levels in the BCP-DHA treatment groups, in addition to negative regulation of the expression of the genes involved in the intracellular inflammatory signaling cascade (IL-2, IL-6, IRF7, NLRP3, and TYK2) in all groups receiving treatment, regardless of the presence of infection. Statistically significant results (p < 0.05) were obtained in the acetic acid-induced abdominal writhing test, evaluation of paw edema, evaluation of paw flinching and licking in the formalin intraplantar injection model, and the von Frey hypernociception test. Therefore, BCP and DHA, either administered individually or combined, demonstrate potent anti-inflammatory and antinociceptive effects.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Docosahexaenoic Acids; Edema; Formaldehyde; Inflammation; Interleukin-6; Methicillin-Resistant Staphylococcus aureus; Plant Extracts

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.. 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 β-caryophyllene.. 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.. The tested substances have a clinically safe profile, additionally the EOCC and β-caryophyllene presented relevant anti-inflammatory activity. This study supports the hypothesis that β-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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Carrageenan; Croton; Cyclohexanols; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Eucalyptol; Inflammation; Male; Mice; Monoterpenes; Oils, Volatile; Plant Extracts; Plant Leaves; Polycyclic Sesquiterpenes; Sesquiterpenes; Toxicity Tests, Acute

The leaves of Alchornea floribunda and Alchornea cordifolia are used traditionally as topical anti-inflammatory agents. In this study, two highly lipophilic fractions AFLF and ACLF isolated from A. floribunda and A. cordifolia leaves respectively were investigated for topical anti-inflammatory effects using xylene-induced mice ear oedema as a model of inflammation. AFLF and ACLF at 5 mg per ear showed significant (p < 0.01) topical anti-inflammatory effect with oedema inhibitions of 64.0% and 79.0% at 2 h, respectively. When compared to indomethacin (5 mg per ear), these fractions showed significantly (p < 0.05) higher topical anti-inflammatory effect. Gas chromatography-mass spectrometry analysis revealed that AFLF is composed mainly of long chain saturated and unsaturated hydrocarbons (18.78%) and their oxygenated derivatives (1.89%); while ACLF is rich in volatile oils eugenol (21.26%) and cadinol (4.76%), and other constituents like, nanocosaine (36.86%) and steroid derivatives, ethyl iso-allocholate (4.59%) and 3-acetoxy-7,8-epoxylanostan-1-ol (15.86%). Analysis of the volatile oil (ACV) extracted from the fresh leaves of A. cordifolia revealed the presence of high concentrations of eugenol (41.7%), cadinol (2.46%), Caryophylene (1.04%), Linalool (30.59%) and (E)-α-bergamotene (4.54%). These compounds could be contributing to the topical anti-inflammatory effects of A. floribunda and A. cordifolia leaf extracts.

Topics: Acyclic Monoterpenes; Administration, Topical; Animals; Anti-Inflammatory Agents; Bridged Bicyclo Compounds; Edema; Eugenol; Euphorbiaceae; Gas Chromatography-Mass Spectrometry; Hydrocarbons; Mice; Monoterpenes; Oils, Volatile; Plant Extracts; Plant Leaves; Polycyclic Sesquiterpenes; Sesquiterpenes; Skin; Species Specificity

The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor (K(i) = 155 +/- 4 nM) and that it is a functional CB(2) agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB(2) receptor, showing ligand pi-pi stacking interactions with residues F117 and W258. Upon binding to the CB(2) receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB(2) receptors, providing evidence that this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis.

Topics: Administration, Oral; Animals; Binding Sites; Binding, Competitive; Cannabinoids; Cannabis; Carrageenan; Cells, Cultured; Computational Biology; Diet; Edema; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Ligands; Lipopolysaccharides; Mice; Monocytes; Oils, Volatile; Polycyclic Sesquiterpenes; Receptor, Cannabinoid, CB2; Sesquiterpenes; Signal Transduction; Tumor Necrosis Factor-alpha

The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNFalpha, without affecting IL-1beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFalpha production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases.

Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Carrageenan; Cordia; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Edema; Interleukin-1beta; Mice; Monocyclic Sesquiterpenes; Neutrophils; Oils, Volatile; Peroxidase; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha

alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS.. The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors.. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK.. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cell Nucleus; Cordia; Cytosol; Edema; Electrophoretic Mobility Shift Assay; Foot; Interleukin-1beta; Lipopolysaccharides; Male; Mitogen-Activated Protein Kinases; Neutrophil Infiltration; Neutrophils; NF-kappa B; Oils, Volatile; Peroxidase; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Receptor, Bradykinin B1; Reverse Transcriptase Polymerase Chain Reaction; Sesquiterpenes; Tumor Necrosis Factor-alpha; Up-Regulation

This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse paw oedema, while only alpha-humulene was able to diminish the oedema formation caused by histamine injection. Also, both compounds had important inhibitory effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression, induced by the intraplantar injection of carrageenan in rats. The anti-inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were comparable to those observed in dexamethasone-treated animals, used as positive control drug. All these findings indicate that alpha-humulene and (-)-trans-caryophyllene, derived from the essential oil of C. verbenacea, might represent important tools for the management and/or treatment of inflammatory diseases.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Brazil; Cordia; Cyclooxygenase 2; Dexamethasone; Dinoprostone; Edema; Interleukin-1beta; Male; Medicine, Traditional; Mice; Monocyclic Sesquiterpenes; Nitric Oxide Synthase Type II; Oils, Volatile; Plant Components, Aerial; Plants, Medicinal; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha