Euphol, a novel cannabinoid agonist, it has anti-inflammatory action, it can prevent experimental autoimmune encephalomyelitis in mice, it also prevents inflammatory and neuropathic persistent pain in rodents. Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression.
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Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression.[Pubmed: 23969579
Euphorbia tirucalli is a long‑established treatment for a wide variety of cancers. However, the mechanism of its anticancer effect is yet to be elucidated.
METHODS AND RESULTS:
In the present study, we examined the anticancer effect of Euphol, a tetracyclic triterpene alcohol isolated from the sap of Euphorbia tirucalli, in T47D human breast cancer cells. Following the treatment of cells with different doses of Euphol for 24, 48 and 72 h, the cell proliferation, cell cycle, and mRNA and protein levels of cell cycle regulatory molecules were analyzed, respectively. Treatment of the cells with Euphol resulted in decreased cell viability, which was accompanied by an accumulation of cells in the G1 phase. Further studies demonstrated that Euphol treatment downregulated cyclin D1 expression and the hypophosphorylation of Rb. Furthermore, this effect was correlated with the downregulation of cyclin‑dependent kinase 2 (CDK2) expression and the upregulation of the CDK inhibitors p21 and p27. Reduced expression levels of cyclin A and B1 were also observed, corresponding to the decreased distribution of cells in the S and G2/M phases, respectively.
These findings indicated that Euphol is an active agent in Euphorbia tirucalli that exerts anticancer activity by arresting the cell cycle of cancer cells.
Neuropharmacology. 2012 Sep;63(4):593-605.
Euphol, a tetracyclic triterpene produces antinociceptive effects in inflammatory and neuropathic pain: the involvement of cannabinoid system.[Pubmed: 22613837
Persistent pains associated with inflammatory and neuropathic states are prevalent and debilitating diseases, which still remain without a safe and adequate treatment. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action.
METHODS AND RESULTS:
Here, we assessed the effects and the underlying mechanisms of action of Euphol in preventing inflammatory and neuropathic pain. Oral treatment with Euphol (30 and 100 mg/kg) reduced carrageenan-induced mechanical hyperalgesia. Likewise, Euphol given through the spinal and intracerebroventricular routes prevented mechanical hyperalgesia induced by carrageenan. Euphol consistently blocked the mechanical hyperalgesia induced by complete Freund's adjuvant, keratinocyte-derived chemokine, interleukin-1β, interleukin-6 and tumor necrosis factor-alpha associated with the suppression of myeloperoxidase activity in the mouse paw. Oral treatment with Euphol was also effective in preventing the mechanical nociceptive response induced by ligation of the sciatic nerve and also significantly reduced the levels and mRNA of cytokines/chemokines in both paw and spinal cord tissues following i.pl. injection of complete Freund's adjuvant. In addition, the pre-treatment with either CB₁R or CB₂R antagonists, as well as the knockdown gene of the CB₁R and CB₂R, significantly reversed the antinociceptive effect of Euphol. Interestingly, even in higher doses, Euphol did not cause any relevant action in the central nervous system.
Considering that few drugs are currently available for the treatment of chronic pain states, the present results provided evidence that Euphol constitutes a promising molecule for the management of inflammatory and neuropathic pain states.
Biochem Pharmacol. 2012 Feb 15;83(4):531-42.
Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for the underlying mechanisms.[Pubmed: 22155310
Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action. However there are no reports about the effects and mechanisms of Euphol in experimental autoimmune encephalomyelitis (EAE), an established model of MS.
METHODS AND RESULTS:
Here we report the effects and the underlying mechanisms of action of Euphol in EAE. Euphol (1-10mg/kg) was administered orally at different time-points of EAE. Immunological and inflammatory responses were evaluated by real-time PCR, Western blot and flow cytometry assays. We provide evidence that Euphol significantly attenuates neurological signs of EAE. These beneficial effects of Euphol seem to be associated with the down-regulation of mRNA and protein expression of some pro-inflammatory mediators such as TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the CNS. Furthermore, in vitro, Euphol consistently inhibited the T cell-mediated immune response including the production of T(H)1 and T(H)17 cytokines in spleen cells of untreated EAE animals. Likewise, oral Euphol treatment inhibited the infiltration of T(H)17 myelin-specific cells into the CNS through the adhesion molecule, lymphocyte function-associated antigen 1 (LFA-1).
Our findings reveal that oral administration of Euphol consistently reduces and limits the severity and development of EAE. Therefore, Euphol might represent a potential molecule of interest for the treatment of MS and other T(H)17 cell-mediated inflammatory diseases.