caryophyllene and Inflammation

Topics: Animals; Anti-Inflammatory Agents; Chronic Disease; Humans; Inflammation; Inflammation Mediators; Oxidative Stress; Plant Extracts; Polycyclic Sesquiterpenes; PPAR gamma; Receptor, Cannabinoid, CB2

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at 10 mg/mL (50 µL) induced an itch response and dermatitis at 2 weeks in mice, which were sustained for the period of study. Histopathological analysis of skin tissues revealed significant edema and desquamation for β-CP at 10 mg/mL. For CBD and β-CP, we observed a dose-dependent increase in epidermal thickening with profound thickening observed for β-CP at 10 mg/mL. Significant trafficking of CD11b cells was observed in various compartments of the skin in response to treatment with β-CP in a concentration-dependent manner. Mast cell trafficking was restricted to β-CP (10 mg/mL). Mouse proteome profiler cytokine/chemokine array revealed upregulation of complement C5/5a (anaphylatoxin), soluble intracellular adhesion molecule-1 (sICAM-1) and IL-1 receptor antagonist (IL-1RA) in animals dosed with β-CP (10 mg/mL). Moreover, we observed a dose-dependent increase in serum IgE in animals dosed with β-CP. Treatment with β-CP (10 mg/mL) significantly reduced filaggrin expression, an indicator of barrier disruption. In contrast, treatment with CBD at all concentrations failed to evoke scratching and dermatitis in mice and did not result in increased serum IgE. Further, skin tissues were devoid of any remarkable features, although at 10 mg/mL CBD we did observe the accumulation of dermal CD11b cells in skin tissue sections. We also observed increased filaggrin staining in mice repeatedly dosed with CBD (10 mg/mL). Collectively, our studies indicate that repeated exposure to high concentrations of β-CP can induce dermatitis-like pathological outcomes in mice.

Topics: Angioedema; Animals; Cannabidiol; Cannabinoid Receptor Agonists; Cannabis; Complement C5; Complement C5a; Dermatitis; Filaggrin Proteins; Hallucinogens; Humans; Immunoglobulin E; Inflammation; Mice; Pruritus

We have previously shown that bilateral common carotid artery occlusion followed by reperfusion (BCCAO/R) is a model to study early hypoperfusion/reperfusion-induced changes in biomarkers of the tissue physiological response to oxidative stress and inflammation. Thus in this study, we investigate with immunochemical assays if a single dose of beta-caryophyllene (BCP), administered before the BCCAO/R, can modulate the TRPV1, BDNF, and trkB receptor in the brain cortex; the glial markers GFAP and Iba1 were also examined. Frontal and temporal-occipital cortical regions were analyzed in two groups of male rats, sham-operated and submitted to BCCAO/R. Six hours before surgery, one group was gavage fed a dose of BCP (40 mg/per rat in 300 μL of sunflower oil), the other was pre-treated with the vehicle alone. Western blot analysis showed that, in the frontal cortex of vehicle-treated rats, the BCCAO/R caused a TRPV1 decrease, an increment of trkB and GFAP, no change in BDNF and Iba1. The BCP treatment caused a decrease of BDNF and an increase of trkB levels in both sham and BCCAO/R conditions while inducing opposite changes in the case of TRPV1, whose levels became higher in BCCAO/R and lower in sham conditions. Present results highlight the role of BCP in modulating early events of the cerebral inflammation triggered by the BCCAO/R through the regulation of TRPV1 and the BDNF-trkB system.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cerebral Cortex; Inflammation; Male; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Receptor, trkB; Reperfusion; Reperfusion Injury; TRPV Cation Channels

Inflammatory bowel diseases (IBD) are the common health concern in populations across the world. Clinical evidence suggests that IBD, characterized by intestinal inflammation, is associated with neuronal manifestations to a greater extent. In this study, we have investigated the protective effects of Viphyllin™, a standardized black pepper (Piper nigrum) seed extract containing 30% β-caryophyllene against dextran sodium sulfate (DSS)-induced colitis in mice. Oral pretreatment of Viphyllin at the 50 mg and 100 mg/kg doses significantly reversed the clinical symptoms of colitis in mice. Viphyllin markedly inhibited NLRP3 inflammasome activation and improved barrier function in colon tissue. Viphyllin further mitigated the DSS-induced anxiety-like behavior in mice. Interestingly, Viphyllin improved brain antioxidant status and promoted neuronal cell survival in colitis model mice. In conclusion, our findings strongly support the health claims of Viphyllin as a functional ingredient to deal with IBD and related neuronal symptoms. PRACTICAL APPLICATIONS: Prevalence of inflammatory bowel diseases is not uncommon in the modern lifestyle. Gut health is associated with neurological disorders that contribute substantially to the deterioration of quality of life and socioeconomic development. In this research work, the protective action of a black pepper seed extract standardized to 30% β-caryophyllene (Viphyllin) is evaluated against Dextran sodium sulfate-induced experimental colitis model. Here we have demonstrated the beneficial role of Viphyllin in mitigating intestinal inflammation as a function of NLRP3 inflammasome inhibition. Further, the extract improves intestinal barrier function. In an important aspect of the study, we have provided the data on the effect of Viphyllin on neurological symptoms and brain health in colitis model mice.

Topics: Animals; Antioxidants; Anxiety; Colitis; Dextran Sulfate; Inflammasomes; Inflammation; Inflammatory Bowel Diseases; Mice; Nigella sativa; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Piper nigrum; Plant Extracts; Polycyclic Sesquiterpenes; Quality of Life; Seeds; Sulfates

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

Ulcerative colitis is an inflammatory bowel disease characterized by symptoms such as abdominal pain, diarrhea, bleeding, and weight loss. Ulcerative colitis is typically treated with anti-inflammatory drugs; however, these drugs are associated with various side effects, limiting their use. β-Caryophyllene (BCP), a natural compound derived from cloves, has antioxidant, antibacterial, and anti-inflammatory activities. In this study, we aimed to investigate the effects of BCP on colitis in a dextran sulfate sodium (DSS)-induced colitis mouse model. BCP was administered for seven days, followed by 2.5% DSS for additional seven days to induce colitis. Changes in stool weight, recovery of gut motility, colon length, colon histology, myeloperoxidase activity, inflammatory cytokines (TNF-α, IL-1β, IL-6, IgA, and IgG), and the gut microbiota were observed. Administration of BCP increased stool weight, restored gut motility, and considerably increased colon length compared to those in the untreated colitis mouse model. In addition, the amount of mucin and myeloperoxidase activity in the colon increased, whereas the concentrations of IL-1β, IL-6, and TNF-α decreased following the administration of BCP. Furthermore, BCP reduced the abundance of Proteobacteria which can cause intestinal immune imbalance. These results suggest that BCP has a potential to be developed as a preventive agent for colitis.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Interleukin-6; Mice; Peroxidase; Syzygium; Tumor Necrosis Factor-alpha

Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that β-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.

Topics: Animals; Colitis; Colitis, Ulcerative; Dextran Sulfate; Ferroptosis; Inflammation; Mice; Polycyclic Sesquiterpenes

Matrix metalloproteinase 1 (MMP-1) initiates the breakdown of matrix networks by cleaving fibrillar collagen during the pathophysiological progression of skin aging. Ageratum houstonianum ethanol extract (AHE) has been used as a traditional herbal medicine to treat external wounds and skin diseases. However, the mechanism of action underlying A. houstonianum-mediated modulation of skin aging has not been investigated. In this study, we evaluated the effect of AHE on MMP-1 expression in HaCaT keratinocytes. Gene expression was analyzed by Reverse transcription-PCR (RT-PCR), Quantitative real-time PCR (Q-PCR), gene promoter-reporter assay, and immunoblotting. We found that AHE abrogated TNFα-induced MMP1 expression at the transcriptional level via the suppression of ERK1/2 mitogen-activated protein kinase (MAPK)-mediated Early Growth Response 1 (EGR1) expression. We also demonstrated that β-caryophyllene, a cannabinoid receptor 2 (CB2) agonist, is a functional component of the AHE that inhibits TNFα-induced EGR-1 and MMP1 expression. AHE exerts inhibitory activity on TNFα-induced MMP1 expression at the transcription level through EGR-1 downregulation in keratinocytes. β-Caryophyllene is a bioactive ingredient of AHE that is responsible for the inhibition of TNFα-induced EGR1 expression. β-Caryophyllene can be used as a potential agent to prevent inflammation-induced skin aging.

Topics: Ageratum; Early Growth Response Protein 1; Gene Expression Regulation; Humans; Inflammation; Keratinocytes; MAP Kinase Signaling System; Matrix Metalloproteinase 1; Plant Extracts; Polycyclic Sesquiterpenes; Skin Aging; Transcription, Genetic; Tumor Necrosis Factor-alpha

Acute lung injury (ALI) is a pulmonary manifestation of an acute systemic inflammatory response, which is associated with high morbidity and mortality. Accordingly, from the perspective of treating ALI, it is important to identify effective agents and elucidate the underlying modulatory mechanisms. β-Caryophyllene (BCP) is a naturally occurring bicyclic sesquiterpene that has anti-cancer and anti-inflammatory activities. However, the effects of BCP on ALI have yet to be ascertained.. ALI was induced intratracheally, injected with 5 mg/kg LPS and treated with BCP. The bone marrow-derived macrophages (BMDMs) were obtained and cultured then challenged with 100 ng/ml LPS for 4 h, with or without BCP pre-treatment for 30 min.. BCP significantly ameliorates LPS-induced mouse ALI, which is related to an alleviation of neutrophil infiltration and reduction in cytokine production. In vitro, BCP was found to reduce the expression of interleukin-6, interleukin-1β and tumour necrosis factor-α, and suppresses the MAPK signalling pathway in BMDMs, which is associated with the inhibition of TAK1 phosphorylation and an enhancement of MKP-1 expression.. Our data indicate that BCP protects against inflammatory responses and is a potential therapeutic agent for the treatment of LPS-induced acute lung injury.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cells, Cultured; Cytokines; Dual Specificity Phosphatase 1; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Macrophages; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Phosphorylation; Phytotherapy; Plant Extracts; Polycyclic Sesquiterpenes; Sesquiterpenes; Signal Transduction; Tumor Necrosis Factor-alpha

Backgrounds and Objective: Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines with painful conditions are well known as biomarkers in human muscle pain, and they are produced by macrophages. Metaxalone is used as a skeletal muscle relaxant, but the mechanism by which metaxalone acts is unknown. This study was undertaken to investigate whether or not metaxalone exhibits an inhibitory effect on the activity of inflammatory macrophages in vitro.. Mouse macrophage RAW264.7 cells were cultured in Dulbecco's Modification of Eagle's Medium containing 10% fetal bovine serum in the presence of metaxalone. Cell growth was assayed by counting the number of cells attached to culture dishes. Inflammatory cytokines released into the culture medium were analyzed with the ELISA kit.. Metaxalone (1-100 μM) was found to decrease the number of macrophages by inhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro. The combination of metaxalone (0.1 or 1 μM) and β-caryophyllene (10 or 50 μM), which alone did not have a significant effect on the cell number, caused potential effects on the growth and death of RAW264.7 cells. Mechanistically, molecular levels of mitogenactivated protein kinase were decreased by treatment with metaxalone or β- caryophyllene, and each effect was enhanced by their combination. Furthermore, levels of caspase-3 were increased by metaxalone or β-caryophyllene and enhanced by their combination. Notably, productions of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 or prostaglandin E2, which were enhanced by lipopolysaccharide (LPS), were repressed by culturing with metaxalone. Levels of cyclooxygenase (COX)-1, COX-2 and nuclear factor kappa B, which were increased by LPS treatment, were reduced by metaxalone.. Metaxalone was found to suppress the activity of inflammatory macrophages in vitro.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cytokines; Drug Combinations; Drug Synergism; In Vitro Techniques; Inflammation; Inflammation Mediators; Macrophages; Mice; Neuromuscular Agents; Oxazolidinones; Polycyclic Sesquiterpenes; RAW 264.7 Cells

β-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing β-caryophyllene followed by a hydrogel containing nanoemulsified β-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure β-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. β-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high β-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the β-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated β-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated β-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healing activity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the β-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair.

Topics: Animals; Anti-Inflammatory Agents; Emulsions; Hydrogels; Inflammation; Interleukin-1; Male; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Skin; Skin Absorption; Swine; Tumor Necrosis Factor-alpha; Wound Healing

Beta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta- caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.

Topics: Animals; Cell Movement; Cell Proliferation; Female; Hair Follicle; Inflammation; Keratinocytes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Polycyclic Sesquiterpenes; Re-Epithelialization; Receptor, Cannabinoid, CB2; Sesquiterpenes; Sex Factors; Skin; Wound Healing

Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects. The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors. Wistar rats were fed a high-fat diet and administered 10% fructose for 12 weeks. Treatment with pioglitazone, BCP, BCP + CB2R antagonist, AM630, or BCP + PPAR-γ antagonist, BADGE was started from the 9th week and continued till the 12th week. BCP significantly ameliorated all diet-induced alterations in a CB2R-dependant manner as it improved glycemic parameters, dyslipidemia, and vascular oxidative stress and inflammation. It also downregulated proatherogenic adhesion molecule (VCAM-1) and restored vascular eNOS/iNOS expression balance. PPAR-γ was involved in BCP-evoked suppression of vascular inflammation, VCAM-1 and restoration of normal vascular eNOS/iNOS balance thus normal NO level. Furthermore, part of BCP hypolipidemic effects (lowering total cholesterol, LDL, VLDL) involved both CB2R and PPAR-γ receptors. BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation.

Topics: Animals; Diet; Dyslipidemias; Inflammation; Male; Pioglitazone; Polycyclic Sesquiterpenes; PPAR alpha; Protective Agents; Rats; Rats, Wistar; Receptor, Cannabinoid, CB2; Sesquiterpenes

The present study investigates the cardioprotective effect of β-caryophyllene against doxorubicin-induced acute cardiotoxicity in rats. Doxorubicin (12.5 mg/kg) and β-caryophyllene (25, 50 or 100 mg/kg) were administered intraperitoneally to male albino Wistar rats. Doxorubicin-treated rats showed elevated levels of creatine kinase-MB in serum and oxidative stress in the myocardium as evidenced by decreased superoxide dismutase, catalase and glutathione with a concomitant rise in malondialdehyde levels. Doxorubicin also induced pro-inflammatory cytokines release following activation of the nuclear factor kappa-B and elevated expressions of inducible nitric oxide synthase and cyclooxygenase-2 in the myocardium. Additionally, doxorubicin also increased expression of γ-H2AX, a marker of DNA damage as well as increased expression of proapoptotic (Bax, p53, and active caspase-3) proteins along with the decreased expression of anti-apoptotic protein, Bcl2 in the myocardium. The histological and ultrastructural studies further revealed edema, inflammation and structural degeneration of cardiomyocytes following doxorubicin injection. However, treatment with β-caryophyllene showed significant cardioprotective effects as evidenced by favorable improvement of biochemical and molecular parameters along with remarkable preservation of cardiomyocytes in histological and ultrastructural studies. Results of the present study demonstrate that β-caryophyllene has potential to protect heart against doxorubicin-induced acute cardiotoxicity in rats. Moreover, the antioxidant and free radical scavenging properties of β-caryophyllene was confirmed by in vitro assays. Provided the anticancer and chemosensitizing properties of β-caryophyllene, the cardioprotective effects of β-caryophyllene are suggestive of its multiple properties that provides an additional basis of its possible therapeutic application in chemotherapy-associated cardiotoxicity.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Cytokines; Cytoprotection; Diet; DNA Damage; Dose-Response Relationship, Drug; Doxorubicin; Hydroxyl Radical; Inflammation; Lipid Peroxidation; Male; Myocardium; NF-kappa B; Oxidative Stress; Polycyclic Sesquiterpenes; Rats; Rats, Wistar; Superoxides

The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).. Two groups of adult Wistar rats were used, sham-operated and submitted to BCCAO/R. In both groups, 6 h before surgery, half of the rats were gavage-fed with a single dose of BCP (40 mg/per rat in 300 μl of sunflower oil as vehicle), while the second half were pre-treated with the vehicle alone. HPLC, Western Blot and immunohistochemistry were used to analyze cerebral cortex and plasma.. After BCCAO/R, BCP prevented the increase of lipoperoxides occurring in the vehicle-treated rats in both cerebral cortex and plasma. In the frontal cortex, BCP further prevented activation of the endocannabinoid system (ECS), spared the docosahexaenoic acid (DHA), appeared to prevent the increase of cyclooxygenase-2 and increased the peroxisome-proliferator activated receptor-alpha (PPAR-alpha) protein levels, while, in plasma, BCP induced the reduction of arachidonoylethanolamide (AEA) levels as compared to vehicle-treated rats.. Collectively, the pre-treatment with BCP, likely acting as agonist for CB2 and PPAR-alpha receptors, modulates in a beneficial way the ECS activation and the lipoperoxidation, taken as indicative of oxidative stress. Furthermore, our results support the evidence that BCP may be used as a dietary supplement to control the physiological response to the hypoperfusion/reperfusion-induced oxidative stress.

Topics: Animals; Brain Ischemia; Carotid Artery Diseases; Carotid Artery, Common; Endocannabinoids; Frontal Lobe; Hippocampus; Humans; Inflammation; Oxidative Stress; Polycyclic Sesquiterpenes; Rats; Reperfusion Injury; Sesquiterpenes

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 current study investigated the action of β-caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β-caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Fabaceae; Gluconeogenesis; Humans; Inflammation; Liver; Oxidative Stress; Plant Oils; Polycyclic Sesquiterpenes; Rats; Reactive Oxygen Species; Sesquiterpenes

β-Caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo are reported to involve activation of cannabinoid CB. In this study, we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS.. Chronic treatment with BCP alleviated the chronic and binge alcohol-induced liver injury and inflammation by attenuating the pro-inflammatory phenotypic `M1` switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules intercellular adhesion molecule 1, E-Selectin and P-Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation and PPAR-α signalling). These protective effects of BCP against alcohol-induced liver injury were attenuated in CB. Given the safety of BCP in humans, this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.. This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Topics: Acetylation; Animals; Brain; Chemical and Drug Induced Liver Injury; E-Selectin; Ethanol; Fatty Liver; Inflammation; Intercellular Adhesion Molecule-1; Kupffer Cells; Liver; Male; Mice; Mice, Knockout; Neutrophil Infiltration; P-Selectin; Polycyclic Sesquiterpenes; PPAR alpha; Receptor, Cannabinoid, CB2; Sesquiterpenes

Oxidative and inflammatory stress has been implicated in the onset and progression of diabetes mellitus and its complications. The present study was designed to evaluate the effect of β-Caryophyllene (BCP) on hyperglycemia mediated oxidative and inflammatory stress in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in experimental rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5). Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes and the levels of non-enzymic antioxidants were decreased while increases in the levels of lipidperoxidative markers, protein carbonyls and conjugated dienes were observed in pancreatic tissues of diabetic rats. An elevation of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were observed in plasma and pancreatic tissues of diabetic rats. Intragastric administration of BCP (200 mg/kg b.w) for 45 days significantly decreased glucose and increased insulin levels in diabetic rats. BCP administration significantly restored antioxidant status and decreased proinflammatory cytokines in diabetic rats. These findings were supported by histological and immunohistochemical studies. Thus, we conclude that oral administration of BCP effectively rescued β-cells by mitigating hyperglycemia through enhancing insulin release and also averted oxidative/inflammatory stress in pancreatic tissue of diabetic rats. The efficacy of BCP was compared with glibenclamide, a standard antidiabetic drug.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Diabetes Mellitus, Experimental; Hyperglycemia; Hypoglycemic Agents; Inflammation; Interleukin-6; Male; Oxidative Stress; Polycyclic Sesquiterpenes; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha

Trans-caryophyllene is a sesquiterpene present in many medicinal plants' essential oils, such as Ocimum gratissimum and Cannabis sativa. In this study, we evaluated the antinociceptive activity of trans-caryophyllene in murine models of acute and chronic pain and the involvement of trans-caryophyllene in the opioid and endocannabinoid systems. Acute pain was determined using the hot plate test (thermal nociception) and the formalin test (inflammatory pain). The chronic constriction injury (CCI) of the sciatic nerve induced hypernociception was measured by the hot plate and von Frey tests. To elucidate the mechanism of action, mice were pre-treated with naloxone or AM630 30 min before the trans-caryophyllene treatment. Afterwards, thermal nociception was evaluated. The levels of IL-1β were measured in CCI-mice by ELISA. Trans-caryophyllene administration significantly minimized the pain in both the acute and chronic pain models. The antinociceptive effect observed during the hot plate test was reversed by naloxone and AM630, indicating the participation of both the opioid and endocannabinoid system. Trans-caryophyllene treatment also decreased the IL-1β levels. These results demonstrate that trans-caryophyllene reduced both acute and chronic pain in mice, which may be mediated through the opioid and endocannabinoid systems.

Topics: Acute Pain; Administration, Oral; Analgesics; Animals; Cannabis; Chronic Pain; Formaldehyde; Hot Temperature; Hyperalgesia; Inflammation; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Naloxone; Ocimum; Oils, Volatile; Phytotherapy; Plant Extracts; Polycyclic Sesquiterpenes; Sesquiterpenes

The antinociceptive and antispasmodic properties of the essential oil of OCIMUM micranthum (EOOM) were characterized. In mice, EOOM (15-100 mg · kg (-1), p. o.) reduced both the writhing responses induced by acetic acid and the licking-time induced by formalin, being inert on the hot plate test. In rat trachea, EOOM relaxed sustained contractions induced by KCl or carbachol (CCh). Its constituents, ( E)- [( E)-MC] and ( Z)-methyl cinnamate [( Z)-MC], reproduced several effects of EOOM. Inhaled as aerosol, EOOM prevented tracheal hyperresponsiveness to KCl or CCh in ovalbumin-sensitized animals after antigen challenge. Thus, EOOM exerts peripheral analgesia in nociception of inflammatory origin and has antispasmodic actions on rat airways under an inflammatory environment. Its effects are mainly due to ( E)-MC, which makes this substance potentially interesting for studies involving conjunctly smooth muscle cells, nociception, and inflammation. Other EOOM constituents also appear to be involved in its pharmacological actions.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Inflammation; Male; Mice; Nociceptive Pain; Ocimum; Oils, Volatile; Parasympatholytics; Phytotherapy; Plant Oils; Polycyclic Sesquiterpenes; Rats; Sesquiterpenes