A sesquiterpene with diverse biological activities
β-Caryophyllene is a sesquiterpene that has been found in plants, including C. sativa, C. indica, and hemp, and has diverse biological activities, including lipid metabolic, antioxidant, anti-neuroinflammatory, anti-proliferative, and antinociceptive properties.1,2,3,4,5,6 It is an agonist of the cannabinoid (CB) receptor CB2 (Ki = 155 nM) that inhibits cAMP production induced by forskolin in CHO-K1 cells expressing CB2 receptors (EC50 = 38 nM).7 β-Caryophyllene is also an agonist of peroxisome proliferator-activated receptor α (PPARα; EC50 = 9.58 ?M in a reporter assay).2 β-Caryophyllene (1 and 2.5 ?M) reduces the production of reactive oxygen species (ROS) in and protects against cytotoxicity of SH-SY5Y cells induced by 1-methyl-4-pheylpyridinium (MPP+).3 It also decreases the β-amyloid burden in the hippocampus and cerebral cortex and improves memory in an APP/PS1 transgenic mouse model of Alzheimer’s disease, decreasing the latency to find the platform in the Morris water maze during training and increasing the time spent in the target quadrant during testing when administered at a dose of 48 mg/kg per day.4 β-Caryophyllene (50 mg/kg) increases the number of entries into and the time spent in the open arms of the elevated plus maze and the time spent immobile in the forced swim test, indicating anxiolytic-like and antidepressant-like activity, effects that can be blocked by the CB2 receptor antagonist AM630 .5
1.Hazekamp, A., Tejkalová, K., and Papadimitriou, S.Cannabis: From cultivar to chemovar II—A metabolomics approach to Cannabis classificationCannabis Cannabinoid Res.1(1)202-215(2016) 2.Wu, C., Jia, Y., Lee, J.-H., et al.trans-Caryophyllene is a natural agonistic ligand for peroxisome proliferator-activated receptor-αBioorg. Med. Chem. Lett.24(14)3168-3174(2014) 3.Wang, G., Ma, W., and Du, J.β-Caryophyllene (BCP) ameliorates MPP+ induced cytotoxicityBiomed. Pharmacother.1031086-1091(2018) 4.Cheng, Y., Dong, Z., and Liu, S.β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 mice through CB2 receptor activation and the PPARγ pathwayPharmacology94(1-2)1-12(2014) 5.Bahi, A., Al Mansouri, S., Al Memari, E., et al.β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in micePhysiol. Behav.135119-124(2014) 6.Paula-Freire, L.I., Andersen, M.L., Gama, V.S., et al.The oral administration of trans-caryophyllene attenuates acute and chronic pain in micePhytomedicine21(3)356-362(2014) 7.Gertsch, J., Leonti, M., Raduner, S., et al.Beta-caryophyllene is a dietary cannabinoidProc. Natl. Acad. Sci. USA105(26)9099-9104(2008)
|
Cell experiment: |
Panel of human cancer cells such as, pancreatic (PANC-1), colorectal (HCT-116 and HT-29), invasive squamous cell carcinoma (ME-180), leukemia (K562), hormone sensitive and invasive breast cancer cell line (MCF-7), and prostatic (PC3) adenocarcinoma cell lines are used. Cells are incubated in a humidified CO2 incubator at 37°C supplied with 5% CO2. Inhibitory effect of β-Caryophyllene on proliferation of the cell lines is tested using the MTT assay. The selectivity index (SI) for the cytotoxicity of β-Caryophyllene is calculated using the ratio of IC50 of β-Caryophyllene on a normal cell line (NIH-3T3) to the IC50 of β-Caryophyllene on cancer cell lines[2]. |
|
Animal experiment: |
Male double transgenic APP/PS1 mice and wild-type littermates are used. The mice are group housed (3 to 5 animals/cage) with a 12:12-hour light/dark cycle and ad libitum access to food and water. In this experiment, animals are orally treated by gavage with 16, 48, or 144 mg/kg of β-Caryophyllene every morning for 10 weeks starting at the age of 7 months. All vehicle solutions are used for the respective control animal treatments and the Morris water maze test is performed[1]. |
|
参考文献: [1]. Cheng Y, et al. β-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 Mice through CB2 receptor activation and the PPARγ pathway. Pharmacology. 2014;94(1-2):1-12. |
|
动态评分
0.0