Effect Of Β-caryophyllene Research Articles

Effect of β-Caryophyllene on oxidative stress, glucose metabolism in the skeletal muscle of high fat diet and fructose-induced type-2 diabetic adult male rats.

Skeletal muscle is where the majority of insulin-stimulated whole-body glucose elimination takes place under normal circumstances. A significant risk factor for metabolic diseases is high dietary fat consumption, which also increases stored fat mass. Natural solutions with anti-diabetic effectiveness and fewer side effects are becoming more popular as a result of the conventional pharmacological treatments' numerous negative side effects and high rates of secondary failure. Cannabis and a variety of culinary herbs and spices may include the naturally occurring sequiterpene β-caryophyllene. Among other things, it has antioxidant, anti-inflammatory, and anti-lipidemic properties. However, it is not yet known how β-caryophyllene affects the uptake and oxidation of glucose. Determining if β -caryophyllene has anti-diabetic properties in type-2 diabetes brought on by a high-fat diet was the objective of the current investigation. A sufficient dose of β-caryophyllene (200 mg/kg b.w.t., orally for 30 days) was given to type-2 diabetic rats fed a high-fat diet and given fructose as an inducer of diabetes to assess its anti-diabetic activity. The treatment of diabetes-induced rats with β -Caryophyllene restored the altered levels of blood glucose, serum insulin as well as the lipid parameters, oxidative stress markers, antioxidant enzymes. Our findings show that β-caryophyllene improves glycemia control by enhancing glucose absorption and oxidation in the skeletal muscle of type-2 diabetic rats. From the present findings, it is evident that β -caryophyllene can be used as an anti-diabetic drug.

Effects of β-caryophyllene and oxygen availability on cholesterol and fatty acids in breast cancer cells.

Hypoxia is a common feature of most solid tumors, one that favors tumor progression and limits treatment effectiveness. Targeting hypoxia has long been a goal in cancer therapy, by identifying factors that reverse or ameliorate the effects of hypoxia on cancer cells. We, and others, have shown that β-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells. We have further shown that non-cytotoxic concentrations of BCP affect cholesterol and lipid biosynthesis in hypoxic hBrC cells at both transcriptional and translational levels. This led us to hypothesize that BCP may reverse the hypoxic phenotype in hBrC cells. To test this, we determined the effect of BCP on hypoxic sensitive pathways, including oxygen consumption, glycolysis, oxidative stress, cholesterol and fatty acid biosynthesis, and ERK activation. While each of these studies revealed new information on the regulation by hypoxia and BCP, only the lipidomic studies showed reversal of hypoxic-dependent effects by BCP. These later studies showed that hypoxia-treated samples lowered monounsaturated fatty acid levels, shifting the saturation ratios of the fatty acid pools. This signature was ameliorated by sub-lethal concentrations of BCP, possibly through an effect on the C:16 fatty acid saturation ratios. This is consistent with BCP-induced upregulation of the stearoyl-CoA desaturase (SCD) gene, observed previously. This suggests that BCP may interfere with the lipid signature modulated by hypoxia which could have consequences for membrane biosynthesis or composition, both of which are important for cell replication.

The effect of β-caryophyllene on food addiction and its related behaviors: A randomized, double-blind, placebo-controlled trial

Food addiction (FA) is a psychological construct that may be involved in the etiology of obesity. The cannabinoid system is involved in the addictive-like food preferences by acting on the dopaminergic pathway of the brain. β-caryophyllene is a dietary cannabinoid that is a cannabinoid type 2 (CB2) receptor agonist. This study explored the impacts of β-caryophyllene supplementation on eating behavior, appetite, mental health, anthropometric parameters, body composition, and some hormones related to appetite in women with obesity diagnosed with FA. Women with obesity and FA, diagnosed by the Yale Food Addiction Scale Score (YFAS-S) ≥3, were randomly allocated to receive a β-caryophyllene softgel (n = 26) (100 mg/daily with meal) or placebo (n = 26) for 8 weeks. Anthropometric measurements, body composition, eating behavior, biochemical markers, dietary intake, appetite, stress, anxiety, and depression were evaluated during the study period. β-caryophyllene administration significantly reduced YFAS-S compared to the placebo group (changes in FA score: 1.5 ± 0.9 vs. - 0.7 ± 1.4; corrected P = 0.05). Serum levels of orexin-A significantly decreased in the β-caryophyllene group (p = 0.02); however, no significant difference was observed compared to the placebo group (corrected P = 0.09). β-caryophyllene supplementation had no significant effect on body composition, anthropometric indices, appetite, eating behavior, dietary intake, physical activity level, mental health, and levels of oxytocin and neuropeptide Y (NPY), compared to the placebo. β-caryophyllene supplementation may have beneficial effects on improving YFAS-S in women with obesity diagnosed with FA. Trial registrationIranian Registry of Clinical Trials identifier: IRCT20200914048712N1.

Evaluation of the effect of β-Caryophyllene on oxidative stress in BALB / c mice with streptozotocin-induced diabetes

Evaluation of the effect of β-Caryophyllene on oxidative stress in BALB / c mice with streptozotocin-induced diabetes

Dexmedetomidine Associated Lung Cancer Proliferation and Tumor Growth is Prevented by β-Caryophyllene: Role of AMPK Activation and PGC-1α/TFAM Over Expression

Background: Dexmedetomidine has been reported to induce anti-apoptotic effects and metastatic progression in lung cancer. In the current investigation, the effect of β-Caryophyllene on dexmedetomidine induced cell proliferation and apoptosis of lung cancer cells and tumor growth in mice was studied. Methods: A549 cell line was cultured with either dexmedetomidine alone or together with β-Caryophyllene for 24 h and analysed for cell proliferation with MTT assay. ELISA based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of target proteins. The induction of experimental lung tumor in rat model was achieved through the injection of A549 tumor cells subcutaneously into the middle left side of the mice after anesthetization with pentobarbital (35 mg/kg) at 2.8 × 106 cells in 400 μl of PBS. Result: We found that β-Caryophyllene exerts the anti-proliferative effects on A549 cells. Furthermore, β-Caryophyllene significantly prevents apoptotic cell death and causes up-regulation of PGC-1α and TFAM compared to dexmedetomidine treated cells. We observed that β-Caryophyllene suppressed tumor development in mice significantly compared to dexmedetomidine treated group without changing body weight.

Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by β-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions.

Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)-dependent and IgE-independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G-protein-coupled receptors(GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO-1signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO-1signalling axis in pseudo-allergic reaction. In the present study, we evaluated the anti-pseudo-allergic effects of β-caryophyllene, an FDA-approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO-1 axis signalling pathway. Compound 48/80 (C48/80)-induced systemic and cutaneous anaphylaxis-like shock in BALB/c mice was performed to assess the efficacy of β-caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)-6, tumour necrosis factor (TNF), IL-1β, IgE, ovalbumin (OVA)-IgE and APN and western blotting for protein expression of Nrf2/HO-1 and AdipoR1-AdipoR2. BCP dose-dependently inhibited systemic and cutaneous anaphylaxis-like shock induced by C48/80. BCP dose-dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose-dependently activated the Nrf2/HO-1 and AdipoR1-AdipoR2signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2-Nrf2/HO-1 axis pathway agonist that may suppress the IgE-independent pathway towards allergic response to secretagogues.

Sesquiterpenes and sesquiterpenoids harbor modulatory allosteric potential and affect inhibitory GABAA receptor function in vitro.

Naturally occurring compounds such as sesquiterpenes and sesquiterpenoids (SQTs) have been shown to modulate GABAA receptors (GABAA Rs). In this study, the modulatory potential of 11 SQTs at GABAA Rs was analyzed to characterize their potential neurotropic activity. Transfected HEK293 cells and primary hippocampal neurons were functionally investigated using electrophysiological whole-cell recordings. Significantly different effects of β-caryophyllene and α-humulene, as well as their respective derivatives β-caryolanol and humulol, were observed in the HEK293 cell system. In neurons, the concomitant presence of phasic and tonic GABAA R configurations accounts for differences in receptor modulation by SQTs. The in vivo presence of the γ2 and δ subunits is important for SQT modulation. While phasic GABAA receptors in hippocampal neurons exhibited significantly altered GABA-evoked current amplitudes in the presence of humulol and guaiol, negative allosteric potential at recombinantly expressed α1 β2 γ2 receptors was only verified for humolol. Modeling and docking studies provided support for the binding of SQTs to the neurosteroid-binding site of the GABAA R localized between transmembrane segments 1 and 3 at the (+ α)-(- α) interface. In sum, differences in the modulation of GABAA R isoforms between SQTs were identified. Another finding is that our results provide an indication that nutritional digestion affects the neurotropic potential of natural compounds.

Effect of β-caryophyllene from Cloves Extract on Helicobacter pylori Eradication in Mouse Model.

New antibacterial treatments against Helicobacter pylori are needed as H. pylori is acquiring antibiotic resistance. β-caryophyllene is a natural bicyclic sesquiterpene, with anti-inflammatory and antimicrobial effects. This study investigates the effects of H-002119-00-001 from β-caryophyllene on the eradication of H. pylori in a mouse model, and its effects on the inflammation of the gastric mucosa. To evaluate the anti-H.pylori efficacy of β-caryophyllene, a total of 160 mice were divided into eight groups (n = 10 each) and were administered different treatments for 2 and 4 weeks. H. pylori eradication was assessed using a Campylobacter-like organism (CLO) test and H. pylori qPCR of the gastric mucosa. The levels of inflammation of gastric mucosa were assessed using histology and immunostaining. H-002119-00-001 decreased bacterial burden in vitro. When H-002119-00-001 was administered to mice once daily for 2 weeks, cure rates shown by the CLO test were 40.0%, 60.0%, and 70.0% in groups 6, 7, and 8, respectively. H. pylori levels in gastric mucosa decreased dose-dependently after H-002119-00-001 treatment. H-002119-00-001 also reduced levels of inflammation in gastric mucosa. H-002119-00-001 improved inflammation and decreased bacterial burden in H. pylori-infected mouse models. H-002119-00-001 is a promising and effective therapeutic agent for the treatment of H. pylori infection.

Efficacy of β-caryophyllene for periodontal disease related factors

ObjectiveThis study aimed to investigate the antimicrobial activity of β-caryophyllene against periodontopathogens as well as its inhibitory effects on the expression of inflammatory cytokines and production of volatile sulfur compounds by lipopolysaccharide and periodontopathogenic enzymes, respectively. DesignThe antimicrobial activity of β-caryophyllene againstPorphyromonas gingivalis, Tannerella forsythia, and Treponema denticola was investigated via a susceptibility assay using a microplate reader. THP-1 cells were treated with lipopolysaccharide in the presence or the absence of β-caryophyllene, and the expression and production of inflammatory cytokines were then analyzed by a real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After fluorescence-labelling lipopolysaccharide, the effect of β-caryophyllene on the binding of lipopolysaccharide to the cell wall was investigated via flow cytometry. The spent culture media of P. gingivalis was shaken with or without β-caryophyllene and gaseous volatile sulfur compounds (VSCs) were measured by a gas chromatograph. Resultsβ-caryophyllene showed strong the antimicrobial activity against periodontopathogens. It also reduced lipopolysaccharide-induced expression and production of cytokines, thereby inhibiting the binding of lipopolysaccharide-binding to toll-like receptors by interfering with the complex of lipopolysaccharide and CD14 or lipopolysaccharide-binding protein. β-caryophyllene also inhibited the emission of gaseous VSCs produced byP. gingivalis. Conclusionsβ-caryophyllene may improve periodontal health via antimicrobial activity against periodontopathogens, reducing inflammation caused by lipopolysaccharide, and by neutralizing VSCs.

Effects of β-caryophyllene on arginine ADP-ribosyltransferase 1-mediated regulation of glycolysis in colorectal cancer under high-glucose conditions.

Type2 diabetes mellitus (T2DM) is associated with an increased risk of the development of colorectal cancer(CRC). A previous study revealed that the levels of arginine-specific mono-ADP-ribosyltransferase1 (ART1) in CRC tissues from patients with T2DM were higher than in non-diabetic patients. Hyperglycemia, which is a risk factor of cancer, is a common feature of T2DM; however, the effects of ART1 on glycolysis and energy metabolism in CRC cells under high-glucose conditions remains to be elucidated. β-caryophyllene (BCP) has been reported to exert anticancer and hypoglycemic effects. In the present study, CT26 cells were cultured under a high-glucose conditions and the expression levels of relevant factors were detected by western blotting. Cell Counting Kit-8 assay, flow cytometry, Hoechst33258 staining, ATP assay and lactic acid assay were used to detect the proliferation, apoptosis and energy metabolism of CT26 cells. To observe the effects of ART1 and BCP on tumor growth invivo, CT26 cell tumors were successfully transplanted into BALB/c mice with T2DM. The results demonstrated that overexpression of ART1 may increase glycolysis and energy metabolism in CT26 CRC cells under high glucose conditions by regulating the protein kinaseB/mammalian target of rapamycin/c‑Myc signaling pathway and the expression of glycolytic enzymes. BCP inhibited the effects induced by ART1, which may be due to a BCP-induced reduction in the expression levels of ART1 via nuclear factor-κB. Therefore, ART1 may be considered a therapeutic target for the treatment of diabetic patients with CRC.

Enzymes that hydrolyze adenine nucleotides in a model of hypercholesterolemia induced by Triton WR-1339: protective effects of β-caryophyllene.

Purinergic system has been proven to play a critical role in the inflammatory process and to represent an important therapeutic target to improve the immune response during hypercholesterolemia. β-caryophyllene, a phytocannabinoid compound, has a powerful hypolipidemic and anti-inflammatory actions. However, the effects of β-caryophyllene on seric enzymes of purinergic system have not been evaluated. The purpose of this study was to investigate whether β-caryophyllene is able to ameliorate the seric activities of NTPDase and adenosine deaminase (ADA) in a model of hypercholesterolemia induced by Triton WR-1339. The activities of NTPDase and ADA were evaluated enzymatically, and the seric levels of β-caryophyllene were evaluated by high-performance liquid chromatography. We found that treatment with β-caryophyllene ameliorates the enzymatic activities of NTPDase and ADA in serum of hypercholesterolemic rats, in a concentration-dependent manner. These results indicated that β-caryophyllene treatment could improve the immune response during hypercholesterolemia through purinergic pathway.

Effects of β-caryophyllene and Murraya paniculata essential oil in the murine hepatoma cells and in the bacteria and fungi 24-h time–kill curve studies

Context: Orange Jessamine [Murraya paniculata L. (Rutaceae)] has been used worldwide in folk medicine as an anti-inflammatory, antibiotic and analgesic. Objective: The objective of this study is to investigate the in vitro antioxidant, cytotoxic, antibacterial and antifungal activity and the time-kill curve studies of orange jessamine essential oil and β-caryophyllene, as well as the chemical composition of the essential oil. Material and methods: The cytotoxic activity of M. paniculata and β-caryophyllene (7.8–500 μg/mL) was evaluated using the MTT assay on normal fibroblasts and hepatoma cells. The minimal inhibitory concentration and time–kill curves (24 h) were evaluated against those of Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Enterococcus faecallis, Aspergillus (niger, fumigates and parasiticum) and F. solani by the broth microdilution method. The antioxidant activity was measured by the DPPH and ABTS assays. Chemical composition was evaluated by GC/MS analyses. Results: GC/MS analyses identified 13 compounds, with β-caryophyllene as the major compound. The oil exhibited moderate antibacterial activity (MIC <1.0 mg/mL) and strong antifungal activity. Time–kill curve studies showed that either the essential oil or β-caryophyllene presented rapid bacterial killing (4 h for S. aureus) and fungicidal effect (2-4 h for F. solani); however, both displayed weak free radical scavenger capacity. The cytotoxic activity exhibited a prominent selective effect against hepatoma cancer cells (IC50 value =63.7 μg/mL) compared with normal fibroblasts (IC50 value =195.0 μg/mL), whereas the β-caryophyllene showed low cytotoxicity. Discussion and conclusion: The experimental data suggest that the activities of M. paniculata essential oil are due to the synergistic action among its components.

The combination of β-caryophyllene, baicalin and catechin synergistically suppresses the proliferation and promotes the death of RAW267.4 macrophages in vitro.

β-caryophyllene, which is a constituent of many essential oils, has been known to be a selective agonist of the cannabinoid receptor type-2 and to exert cannabimimetic anti-inflammatory effects in animals. The effects of β-caryophyllene on macrophages have not been investigated to date. This study was undertaken to determine whether β-caryophyllene exerts suppressive effects on mouse RAW267.4 macrophages invitro in comparison with other botanical molecules that exert antioxidant and anti-inflammatory effects. The proliferation of RAW267.4 cells was suppressed by culture with β-caryophyllene (50, 100 and 200µg/ml of medium) or curcumin(100 and 200µg/ml). Culture with baicalin(1-200µg/ml) or (+)-catechin (1-200µg/ml) did not exert an effect on RAW267.4 cells. The combination of β-caryophyllene(1 or 10µg/ml) with either curcumin(1or 10µg/ml), baicalin (1 or 10µg/ml) or (+)-catechin (1 or 10µg/ml) did not exert any suppressive effects on cell proliferation. Of note, the combination of all three agents, β-caryophyllene, baicalin and (+)-catechin at the concentration of either 1 or 10µg/ml was found to exert synergistic suppressive effects on cell proliferation. Moreover, the combination of β-caryophyllene, baicalin and (+)-catechin synergistically promoted the death of RAW267.4 cells. Such an effect was blocked by culture with caspase-3 inhibitor. The combination of the three agents decreased the protein levels of Akt, mitogen-activated protein kinase(MAPK) and cyclooxygenase(COX)-1 or-2. On the whole, this study demonstrates that the combination of β-caryophyllene, baicalin and (+)-catechin exerts synergistic suppressive effects on macrophages invitro. This composition may be a useful as an anti-inflammatory treatment strategy.