Beta-Caryophyllene – Terpenes and Cannabinoid Research

ß-Caryophyllene Properties and Effects

Beta-caryophyllene is associated with the following properties and effects:

1. Anti-microbial
   
   
   
   1. Anti-fungal (against onychomycosis) (D. Yang et al., 2000)
   
   
   
   


2. Gastro-protective (in cases of dyspepsia) (Hyun Ik Shim et al., 2019)


3. Wound healing agent (L. Gushiken et al., 2022)

Selective CB2 receptor agonist without psychoactivity (via low-efficacy or “weak” binding of CB2, with more binding occurring at high nanomolar or micromolar doses)

Antidepressant, anxiolytic, stress-reducing (via CB2 signaling, serotonergic, GABAergic modulation, and nitrergic systems)

Immune-modulation, anti-inflammatory, antioxidant (via CB2 receptor activation, peroxisome proliferator-activated receptors (PPARs), activation of ERK1/2 and JNK1/2 kinases, inhibit the toll-like receptor CD-14/TLR4/MD2 axis, increasing levels of IL-10 and GPx while decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1β, IL-6, IL-8, NF-κB, TGF-β, and KIM-1 in addition to other markers of oxidative stress and inflammation)

Neuroprotective (spasms, seizures, epilepsy, MS); may help reduce brain damage in models of ischemic stroke and cerebral ischemia-reperfusion injury; may protect from Alzheimer’s Disease, Parkinson’s Disease, and Vascular Dementia in preclinical models (via CB2 receptor activity, involvement of benzodiazepine-GABAAergic, serotonergic and nitrergic systems, rescuing neurons, inducing neuritogenesis, inhibiting microglial activation, diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor, NF-κB-mediated signaling, reducing reactive oxygen species, protecting against blood-brain-barrier breakdown, decreasing the release of proinflammatory cytokines, regulation of TRPV1 and the BDNF-trkB system, suppressing ferroptosis by activation of the NRF2/HO-1 signaling pathway, protects dopaminergic neurons by partially inducing antioxidant effects via NQO1 activation, elevating acetylcholinesterase and catalase levels, lowered lipid peroxidation, and antagonizing Aβ’s neurotoxicity via inhibition of JAK2-STAT3-BACE1 signaling pathway)

May protect against binge drinking or chronic alcohol consumption-induced alcoholic steatohepatitis, nonalcoholic fatty liver disease, and steatosis (via attenuating oxidative stress, vascular inflammation, and hepatic metabolic pathways by activating CB2, relieving liver stress caused by hypercholesterolemia, reduces voluntary alcohol intake and conditioned place preference in mice)

Analgesic effects in cases of inflammatory pain, neuropathic pain, osteoarthritis, acid burns, and inflammation; may hamper OA cartilage degeneration without producing tolerance for the analgesic effects (via CB2 receptors, TRPV1 ion channels and opioid receptor activation, in addition to anti-inflammatory mechanisms)

Gastroprotective may be beneficial in cases of colitis, and IBD (via dual activation of CB2 and PPAR-γ pathways, leading to attenuation of gut inflammatory cells and markers in mice)

It may be protective against type-2 diabetes and diabetic cardiomyopathy, including attenuating oxidative stress and improving cardiac functions. In addition, it may modulate insulin secretion and reduce hyperglycemia.

Combining 1,8-cineole and β-caryophyllene synergistically reverses cardiac hypertrophy in isoprenaline-induced H9c2 cells and mice.

Mice treated with beta-caryophyllene and L-arginine had significantly normalized hemodynamic parameters and decreased glucose, cardiac markers, IL-6, and TNF-α levels.

β-caryophyllene significantly lowered serum total cholesterol, low-density lipoprotein, and the atherogenic index and significantly increased high-density lipoprotein levels in mice (via scavenging ROS, leading to deactivation of HMG-CoA reductase and inhibition of endogenous cholesterol synthesis, attenuating glucose-stimulated insulin secretion mediated by Arf6, inhibition of NF-ĸβ, improving oxidative stress, inflammation, glycemia, and dyslipidemia by CB2/PPAR-γ, inhibiting vascular inflammation, adhesion molecules and restoring vascular eNOS/iNOS, modulating endothelial dysfunction via inhibition of IRF-1 and VCAM-1, and regulating PTGS2, TNF, IL-6, AKT1, NOS2, CAT, and P13K-AKT)

Anti-bacterial effects in tuberculosis, leprosy, Staphylococcus aureus, S. mutans, MRSA, Bacillus cereus, Pseudomonas aeruginosa, E. coli, H. pylori, and M. pneumoniae.

It might be beneficial during the hyper-inflammatory phase of sepsis (via potential alteration in bacterial membrane permeability, inhibiting NF-κB signal transduction in mice, CB2 activation, inhibiting biofilm formation, and other possible antibacterial mechanisms yet to be explored further)

Anti-fungal (Candida albicans, Aspergillus niger) may protect against fungal skin infections (via anti-dermatophyte activity comparable to ciclopiroxolamine and sulconazole)

It may have anti-cancer properties and anti-proliferative effects in kidney, colon, pancreatic, melanoma, multiple myeloma, lymphoma, triple-negative breast cancer cells (via CB2 receptor activation, downregulating the cell cycle, and inhibiting NF-ҡ B, MAPK, PI3K/AKT/mTOR/S6K1 and STAT3 pathways to suppress cell proliferation and enhance apoptosis)

May produce a synergistic/organ-protective effect with specific chemotherapy agents (e.g., Paclitaxel, Cisplatin); May mitigate Paclitaxel-induced peripheral neuropathy and prevent cisplatin-induced nephrotoxicity (via suppressing p38 MAPK/NF-kB stimulation and cytokine production, mitigating inflammation, oxidative/nitrosative stress, apoptosis, and enhancing the efficacy of some chemotherapeutics such as Paclitaxel and Doxorubicin)

Last reviewed by Dr. Abraham Benavides, M.D., 06-23-2022