Caryophyllene oxide

Antiinflamm Antiallergy Agents Med Chem. 2014 Mar;13(1):45-55.

Beta caryophyllene and caryophyllene oxide, isolated from Aegle marmelos, as the potent anti-inflammatory agents against lymphoma and neuroblastoma cells.[Pubmed: 24484210]

Aegle marmelos (Indian Bael) is a tree which belongs to the family of Rutaceae. It holds a prominent position in both Indian medicine and Indian culture.
METHODS AND RESULTS:
We have screened various fractions of Aegle marmelos extracts for their anticancer properties using in vitro cell models. Gas chromatography-Mass spectrometry (GC-MS) was employed to analyze the biomolecules present in the Aegle marmelos extract. Jurkat and human neuroblastoma (IMR-32) cells were treated with different concentrations of the fractionated Aegle marmelos extracts. Flow cytometric analysis revealed that optimal concentration (50 μg/ml) of beta caryophyllene and Caryophyllene oxide fractions of Aegle marmelos extract can induce apoptosis in Jurkat cell line. cDNA expression profiling of pro-apoptotic and anti-apoptotic genes was carried out using real time PCR (RT-PCR). Down-regulation of anti-apoptotic genes (bcl-2, mdm2, cox2 and cmyb) and up-regulation of pro-apoptotic genes (bax, bak1, caspase-8, caspase-9 and ATM) in Jurkat and IMR-32 cells treated with the beta caryophyllene and Caryophyllene oxide fractions of Aegle marmelos extract revealed the insights of the downstream apoptotic mechanism. Furthermore, in-silico approach was employed to understand the upstream target involved in the induction of apoptosis by the beta caryophyllene and Caryophyllene oxide fractions of Aegle marmelos extract.
CONCLUSIONS:
Herein, we report that beta caryophyllene and Caryophyllene oxide isolated from Aegle marmelos can act as potent anti-inflammatory agents and modulators of a newly established therapeutic target, 15-lipoxygenase (15-LOX). Beta caryophyllene and Caryophyllene oxide can induce apoptosis in lymphoma and neuroblastoma cells via modulation of 15-LOX (up-stream target) followed by the down-regulation of anti-apoptotic and up-regulation of pro-apoptotic genes.

Phytomedicine. 2010 Feb;17(2):149-51.

Analgesic and anti-inflammatory activity of Caryophyllene oxide from Annona squamosa L. bark.[Pubmed: 19576741]

Caryophyllene oxide was isolated from an unsaponified petroleum ether extract of the bark of Annona squamosa and studied for its analgesic and anti-inflammatory activity.
METHODS AND RESULTS:
Caryophyllene oxide at the doses of 12.5 and 25mg/kg body wt. and unsaponified petroleum ether extract at a dose of 50mg/kg body wt. showed significant central as well as peripheral analgesic, along with anti-inflammatory, activity.
CONCLUSIONS:
These activities of Caryophyllene oxide were comparable with the standard drug used in the respective experiments.

Cancer Lett. 2011 Dec 22;312(2):178-88

β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation.[Pubmed: 21924548]

Both PI3K/AKT/mTOR/S6K1 and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis, and metastasis of tumor cells.
METHODS AND RESULTS:
In the present report, we investigated the effects of β-Caryophyllene oxide (CPO), a sesquiterpene isolated from essential oils of medicinal plants such as guava (Psidium guajava), oregano (Origanum vulgare L.), cinnamon (Cinnamomum spp.) clove (Eugenia caryophyllata), and black pepper (Piper nigrum L.) on the PI3K/AKT/mTOR/S6K1 and MAPK activation pathways in human prostate and breast cancer cells. We found that CPO not only inhibited the constitutive activation of PI3K/AKT/mTOR/S6K1 signaling cascade; but also caused the activation of ERK, JNK, and p38 MAPK in tumor cells. CPO induced increased reactive oxygen species (ROS) generation from mitochondria, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and TUNEL staining, loss of mitochondrial membrane potential, release of cytochrome c, activation of caspase-3, and cleavage of PARP. Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented CPO-induced apoptosis. Subsequently, CPO also down-regulated the expression of various downstream gene products that mediate cell proliferation (cyclin D1), survival (bcl-2, bcl-xL, survivin, IAP-1, and IAP-2), metastasis (COX-2), angiogenesis (VEGF), and increased the expression of p53 and p21. Interestingly, we also observed that CPO can significantly potentiate the apoptotic effects of various pharmacological PI3K/AKT inhibitors when employed in combination in tumor cells.
CONCLUSIONS:
Overall, these findings suggest that CPO can interfere with multiple signaling cascades involved in tumorigenesis and used as a potential therapeutic candidate for both the prevention and treatment of cancer.

Mycopathologia. 1999 Nov;148(2):79-82.

Use of caryophyllene oxide as an antifungal agent in an in vitro experimental model of onychomycosis.[Pubmed: 11189747]

Caryophyllene oxide, an oxygenated terpenoid, well known as preservative in food, drugs and cosmetics, has been tested in vitro as an antifungal against dermatophytes. Its antifungal activity has been compared to ciclopiroxolamine and sulconazole, commonly used in onychomycosis treatment and chosen because of their very different chemical structures.
METHODS AND RESULTS:
So, a new model has been tested, utilizing sheep hoof plates in order to simulate human nails, which are almost unobtainable for in vitro tests. Three protocols were utilized: pre-treatment, simultaneous treatment and post-treatment.
CONCLUSIONS:
Among these, the post-treatment method was the best to simulate antifungal therapy, as it permitted testing and comparing the efficiency of different antifungal drugs.

Pest Manag Sci. 2014 May;70(5):757-62.

Acaricidal activities of β-caryophyllene oxide and structural analogues derived from Psidium cattleianum oil against house dust mites.[Pubmed: 23861316 ]

BACKGROUND: This study was to evaluate the acaricidal activities of an active compound isolated from Psidium cattleianum and structural analogues against Dermatophagoides farinae and D. pteronyssinus. β-Caryophyllene oxide was isolated using chromatographic techniques.
METHODS AND RESULTS:
Based on the 50% lethal concentration (LD50) values against D. farinae using the fumigant method, β-Caryophyllene oxide (1.36 μg cm(-2)) was ～ 7.52 times more toxic than benzyl benzoate (10.23 μg cm(-2)), followed by α-caryophyllene (1.75 μg cm(-2)) and β-caryophyllene (3.13 μg cm(-2)). Against D. pteronyssinus, β-Caryophyllene oxide (1.38 μg cm(-2)) was ～ 7.22 times more toxic than benzyl benzoate (9.96 μg cm(-2)), followed by α-caryophyllene (1.71 μg cm(-2)) and β-caryophyllene (3.58 μg cm(-2)). In the contact toxicity method against D. farinae, β-Caryophyllene oxide (0.44 μg cm(-2)) was ～ 17.27 times more active than benzyl benzoate (7.60 μg cm(-2)), followed by α-caryophyllene (0.67 μg cm(-2)) and β-caryophyllene (0.91 μg cm(-2)). Against D. pteronyssinus, β-Caryophyllene oxide (0.47 μg cm(-2)) was ～ 13.06 times more effective than benzyl benzoate (6.14 μg cm(-2)), followed by α-caryophyllene (1.71 μg cm(-2)) and β-caryophyllene (3.58 μg cm(-2)).
CONCLUSIONS:
β-Caryophyllene oxide and structural analogues have potential for development as preventive agents for the control of house dust mites.