Caryophyllene Oxide
Also known as: Caryophyllene oxide, oxidized form of β-caryophyllene
Overview
Caryophyllene oxide (CAS number: 1139-30-6) is a naturally occurring oxygenated sesquiterpene found in the essential oils of various plants, including clove, cannabis, and black pepper. It is an oxidized derivative of β-caryophyllene. This lipophilic compound is primarily investigated for its potential anti-cancer, anti-inflammatory, antioxidant, and neuroprotective properties. Research suggests it modulates biological pathways related to oxidative stress and inflammation. While it shows promise in preclinical studies, particularly for its ability to induce cell death in cancer cells and its antioxidant effects, the research maturity level is still emerging. Most evidence comes from in vitro and animal studies, with limited human clinical trials. Its moderate bioavailability and specific mechanisms of action, such as inducing ferritinophagy-mediated ferroptosis in cancer cells, are areas of ongoing research. Despite its potential, large-scale randomized controlled trials are lacking, and its clinical efficacy and safety in humans remain largely unestablished.
Benefits
Caryophyllene oxide exhibits several potential benefits, primarily demonstrated in preclinical settings. Its most notable effect is anti-cancer activity, specifically inhibiting the proliferation and migration of hepatoma (liver cancer) cells in vitro. Studies show it can reduce hepatoma cell proliferation by approximately 27.7% to 36.1% at 80 μM, without significant toxicity to normal liver cells. This anti-cancer effect is linked to its ability to induce ferritinophagy-mediated ferroptosis, a form of iron-dependent cell death, in liver cancer cells. Beyond cancer, caryophyllene oxide shares some anti-inflammatory and antioxidant properties with its parent compound, β-caryophyllene. These properties may contribute to protecting against oxidative stress and inflammation-related damage. While direct evidence for caryophyllene oxide is limited, its structural similarity to β-caryophyllene suggests potential neuroprotective effects, possibly mediated through cannabinoid receptor 2 (CB2R) activation. However, these neuroprotective benefits are largely inferred and require direct investigation. Currently, there are no robust human clinical data to support these benefits, and the clinical significance in humans remains unestablished.
How it works
Caryophyllene oxide exerts its effects through several proposed biological pathways. In cancer cells, its primary mechanism involves inducing ferritinophagy, which is the autophagic degradation of ferritin. This process leads to ferroptosis, an iron-dependent form of programmed cell death, specifically observed in liver cancer cells. Additionally, caryophyllene oxide demonstrates antioxidant activity by scavenging reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby mitigating oxidative stress. Its anti-inflammatory effects are thought to be similar to those of β-caryophyllene, potentially involving agonism of the cannabinoid receptor 2 (CB2R). Through these mechanisms, caryophyllene oxide influences cancer cell viability, modulates inflammatory pathways, and impacts oxidative stress responses. It may also affect the nervous system via CB2 receptor modulation, though this is largely inferred. Its molecular targets include components of the ferritinophagy pathway and potentially enzymes involved in oxidative stress and inflammation, such as iNOS and COX-2.
Side effects
The safety profile of caryophyllene oxide is not well documented, as direct human safety data are limited. While related compounds like β-caryophyllene are generally regarded as safe in dietary amounts, this cannot be directly extrapolated to caryophyllene oxide, especially at higher, therapeutic concentrations. Common, uncommon, and rare side effects are currently unknown due to a lack of comprehensive clinical studies. There are no documented clinical drug interactions, but potential interactions could exist via cannabinoid receptor pathways or through modulation of oxidative stress enzymes. Specific contraindications for caryophyllene oxide have not been established. Furthermore, there is no data available regarding its safety or effects in special populations such as pregnant or lactating women, pediatric patients, or the elderly. Given the preclinical nature of most research, caution is advised, and further human studies are necessary to fully assess its safety and potential adverse effects.
Dosage
Currently, there are no established human dosing guidelines for caryophyllene oxide. Most research has been conducted in vitro, where effective concentrations typically range from 40 to 160 μM. The minimum effective dose, optimal dosage ranges, and maximum safe dose for human consumption have not been determined. In vitro studies usually involve exposure times of 24-48 hours, but this does not translate directly to human timing considerations. Caryophyllene oxide is typically studied as an isolated compound or as a component within essential oils. Its lipophilic nature suggests it may affect absorption, but specific clinical pharmacokinetic data are lacking. No specific cofactors have been identified as necessary for its activity. Due to the absence of human clinical trials, any use of caryophyllene oxide as a supplement should be approached with extreme caution and under professional guidance.
FAQs
Is caryophyllene oxide safe for human consumption?
Safety data for caryophyllene oxide in humans are very limited. While related compounds are generally safe in food amounts, its clinical safety as a supplement is unconfirmed and requires further research.
Does it have proven anti-cancer effects in humans?
No, there are no clinical trials demonstrating anti-cancer effects in humans. Current evidence is limited to in vitro (cell culture) and animal studies, which show promise but are not conclusive for human application.
Can it be used for neuroprotection?
Potential neuroprotective effects are suggested by studies on the related compound β-caryophyllene, but direct evidence for caryophyllene oxide's neuroprotective capabilities is currently lacking.
How quickly does it work?
In vitro studies show effects within 1-2 days of exposure. However, there is no human data available to determine how quickly it might work in the human body.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9313605/ – This in vitro study investigated caryophyllene oxide's effects on hepatoma cell lines. It found that caryophyllene oxide inhibited the proliferation and migration of liver cancer cells in a dose-dependent manner, with concentrations between 40-160 μM. The mechanism involved ferritinophagy-mediated ferroptosis, and no significant toxicity was observed in normal liver cells. The study highlights caryophyllene oxide's potential as an anti-cancer agent, though it is limited to in vitro findings.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7603190/ – This review summarizes the chemopreventive potential of caryophyllane sesquiterpenes, including caryophyllene oxide. It discusses their antioxidant, anti-inflammatory, and moderate cytotoxic effects on cancer cells at high concentrations. The review suggests the involvement of CB2 receptors in their anti-inflammatory actions. It emphasizes that most data are preclinical and that large-scale human trials are needed.
- https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6199 – This systematic review focuses on the neuropharmacology of β-caryophyllene, highlighting its neuroprotective, anti-inflammatory, and immunomodulatory effects, primarily mediated via the CB2 receptor. While caryophyllene oxide is structurally related, the review notes that direct neuroprotective evidence for caryophyllene oxide itself is limited. It provides indirect support for potential similar effects but underscores the need for specific research on caryophyllene oxide.