| Title |
Anti-inflammatory ω-3 endocannabinoid epoxides
|
|---|---|
| Published in |
Proceedings of the National Academy of Sciences of the United States of America, July 2017
|
| DOI | 10.1073/pnas.1610325114 |
| Pubmed ID | |
| Authors |
Daniel R. McDougle, Josephine E. Watson, Amr A. Abdeen, Reheman Adili, Megan P. Caputo, John E. Krapf, Rodney W. Johnson, Kristopher A. Kilian, Michael Holinstat, Aditi Das |
| Abstract |
Clinical studies suggest that diets rich in ω-3 polyunsaturated fatty acids (PUFAs) provide beneficial anti-inflammatory effects, in part through their conversion to bioactive metabolites. Here we report on the endogenous production of a previously unknown class of ω-3 PUFA-derived lipid metabolites that originate from the crosstalk between endocannabinoid and cytochrome P450 (CYP) epoxygenase metabolic pathways. The ω-3 endocannabinoid epoxides are derived from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to form epoxyeicosatetraenoic acid-ethanolamide (EEQ-EA) and epoxydocosapentaenoic acid-ethanolamide (EDP-EA), respectively. Both EEQ-EAs and EDP-EAs are endogenously present in rat brain and peripheral organs as determined via targeted lipidomics methods. These metabolites were directly produced by direct epoxygenation of the ω-3 endocannabinoids, docosahexanoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA) by activated BV-2 microglial cells, and by human CYP2J2. Neuroinflammation studies revealed that the terminal epoxides 17,18-EEQ-EA and 19,20-EDP-EA dose-dependently abated proinflammatory IL-6 cytokines while increasing anti-inflammatory IL-10 cytokines, in part through cannabinoid receptor-2 activation. Furthermore the ω-3 endocannabinoid epoxides 17,18-EEQ-EA and 19,20-EDP-EA exerted antiangiogenic effects in human microvascular endothelial cells (HMVEC) and vasodilatory actions on bovine coronary arteries and reciprocally regulated platelet aggregation in washed human platelets. Taken together, the ω-3 endocannabinoid epoxides' physiological effects are mediated through both endocannabinoid and epoxyeicosanoid signaling pathways. In summary, the ω-3 endocannabinoid epoxides are found at concentrations comparable to those of other endocannabinoids and are expected to play critical roles during inflammation in vivo; thus their identification may aid in the development of therapeutics for neuroinflammatory and cerebrovascular diseases. |
X Demographics
The data shown below were collected from the profiles of 37 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 12 | 32% |
| United Kingdom | 3 | 8% |
| Japan | 2 | 5% |
| Austria | 1 | 3% |
| Netherlands | 1 | 3% |
| Iceland | 1 | 3% |
| New Zealand | 1 | 3% |
| France | 1 | 3% |
| Unknown | 15 | 41% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 25 | 68% |
| Practitioners (doctors, other healthcare professionals) | 5 | 14% |
| Scientists | 5 | 14% |
| Science communicators (journalists, bloggers, editors) | 2 | 5% |
Mendeley readers
The data shown below were compiled from readership statistics for 202 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 202 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 34 | 17% |
| Researcher | 30 | 15% |
| Student > Master | 22 | 11% |
| Student > Bachelor | 22 | 11% |
| Student > Doctoral Student | 15 | 7% |
| Other | 34 | 17% |
| Unknown | 45 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 32 | 16% |
| Agricultural and Biological Sciences | 20 | 10% |
| Chemistry | 15 | 7% |
| Neuroscience | 15 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 12 | 6% |
| Other | 48 | 24% |
| Unknown | 60 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 176. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 December 2023.
All research outputs
#229,103
of 25,457,297 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#4,317
of 103,135 outputs
Outputs of similar age
#4,844
of 325,638 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#87
of 957 outputs
Altmetric has tracked 25,457,297 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 103,135 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 39.5. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 325,638 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 957 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.