β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties

Abstract

Natural bicyclic sesquiterpenes, β‐caryophyllene (BCP) and β‐caryophyllene oxide (BCPO), are present in a large number of plants worldwide. Both BCP and BCPO (BCP(O)) possess significant anticancer activities, affecting growth and proliferation of numerous cancer cells. Nevertheless, their antineoplastic effects have hardly been investigated in vivo. In addition, both compounds potentiate the classical drug efficacy by augmenting their concentrations inside the cells. The mechanisms underlying the anticancer activities of these sesquiterpenes are poorly described. BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB 2), but not cannabinoid receptor type 1 (CB 1). In opposite, BCP oxidation derivative, BCPO, does not exhibit CB 1/2 binding, thus the mechanism of its action is not related to endocannabinoid system (ECS) machinery. It is known that BCPO alters several key pathways for cancer development, such as mitogen‐activated protein kinase (MAPK), PI3K/AKT/mTOR/S6K1 and STAT3 pathways. In addition, treatment with this compound reduces the expression of procancer genes/proteins, while increases the levels of those with proapoptotic properties. The selective activation of CB 2 may be considered a novel strategy in pain treatment, devoid of psychoactive side effects associated with CB 1 stimulation. Thus, BCP as selective CB 2 activator may be taken into account as potential natural analgesic drug. Moreover, due to the fact that chronic pain is often an element of cancer disease, the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. This review is focused on anticancer and analgesic activities of BCP and BCPO, the mechanisms of their actions, and potential therapeutic utility.

Actividad antiproliferativa de aceites esenciales de plantas cultivadas en Colombia

“…El análisis por cromatografía identificó β-cariofileno, α-copaeno y pineno (α y β) como constituyentes mayoritarios de los AEs de Piper. Se ha demostrado que el β-cariofileno y óxido de cariofileno tienen potente actividad anticancerígena (Fidyt et al, 2016); y el α-copaeno, β-pineno, α-pinene y otros monoterpenos inhiben la proliferación de una amplia variedad de células cancerígenas (Zhao et al, 2017;Scotti et al, 2017). El linalol se identificó como el componente mayoritario (37 %) del AE de P. cumanese y esto podría explicar su baja citotoxicidad observada en células humanas renales (HEK293) y hepáticas (HepG-2).…”

Short-term efficacy of a fixed association of Palmitoylethanolamide and other phytochemicals as add-on therapy in the management of chronic pain in elderly patients: a real-world retrospective study

“…18,[29][30][31] β-Caryophyllene is a member of sesquiterpene lactone found in large amounts in Piper Nigrum (black pepper) and other plants, 32 with analgesic, antidiabetic, hepatoprotective and neuroprotective properties. 33,34 Whilst myrrh has a Mu opioid effect, β-Caryophyllene is a selective cannabinoid receptor (CB) 2 receptor agonist, thus it does not have the psychotropic effects typical of other cannabinoids that Nausea 4 (8.5%) 3 (6%) 1 (2%) 8 (17%) 7 (15%) 0 (0%) 0 (0%) 7 (15%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Vomiting 1 (2%) 0 (0%) 1 (2%) 2 (4%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) Dizziness 9 (19%) 1 (2%) 1 (2%) 1 (2%) 8 (17%) 0 (0%) 0 (0%) 8 (17%) 5 (11%) 0 (0%) 0 (0%) 5 (11%) 4 (8.5%) 0 (0%) 0 (0%) 4 (8.5%) Drowsiness 4 (8.5%) 2 (4%) 1 (2%) 7 (15%) 5 (11%) 1 (2%) 0 (0%) 6 (13%) 3 (6%) 0 (0%) 0 (0%) 3 (6%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Dry mouth 4 (8.5%) 2 (4%) 1 (2%) 7 (15%) 5 (11%) 0 (0%) 0 (0%) 5 (11%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 1 (2%) 0 (0%) 0 (0%) 1 (2%) Itch 6 (13%) 0 (0%) 1 (2%) 7 (15%) 4 (8.5%) 1 (2%) 0 (0%) 5 (11%) 3 (6%) 2 (4%) 0 (0%) 5 (11%) 3 (6%) 0 (0%) 0 (0%) 3 (6%) Other 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) AE, adverse event. bind to CB1.…”

Anti‐inflammatory activity of β‐caryophyllene combined with docosahexaenoic acid in a model of sepsis induced by Staphylococcus aureus in mice

“…NF‐ κ B is a transcription factor responsible for regulating the expression of large numbers of genes involved in cell proliferation, apoptosis, chemotaxis, and inflammation. COX‐2 is one of the enzymes involved in the cascade of arachidonic acid, which causes pro‐inflammatory metabolites . Another interesting factor is that the reduction of COX‐2 and iNOS expression contributes to the suppression of the activation of NF‐ κ B, and both BCP and DHA are potent inhibitors of these enzymes .…”

“…COX‐2 is one of the enzymes involved in the cascade of arachidonic acid, which causes pro‐inflammatory metabolites . Another interesting factor is that the reduction of COX‐2 and iNOS expression contributes to the suppression of the activation of NF‐ κ B, and both BCP and DHA are potent inhibitors of these enzymes . β ‐Caryophyllene and DHA still have in common the ability to activate the gamma‐peroxisome proliferator‐activated receptor (PPAR‐ γ ) pathway, capable of inhibiting NF‐ κ B activation and the synthesis of proinflammatory cytokines, such as IL‐1 and TNF‐ α …”