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  • Writer's pictureTravis Cesarone

Three flavonoids that protect anandamide

Updated: Jan 31, 2023

An international team from the Universities of Calgary, Maryland, and Islamabad found three flavonoids that protect the endocannabinoid known as anandamide (AEA.) They used a computer analysis known as an in silico study to identify three active compounds. Finally, the team validated their results by testing mice.


We now know that flavonoids affect the endocannabinoid system and contribute to the entourage effect. And while the exact mechanism of action successfully hid from researchers.


How flavonoids protect endocannabinoids


Biochanin-A

Biochanin-A, courtesy of Wiki.


The international team elucidated a cannabimimetic mechanism. Computer data indicated three isoflavonoids that bind to and inhibit an enzyme known as FAAH. They tested Genistein, Biochanin-A, and 7-hydroxyflavone on mice to confirm their results.


FAAH primarily facilitates Anandamide’s degradation. Flavonoids tested in the study, therefore, protect the endocannabinoid by reducing enzymatic metabolism. All three compounds have a similar binding strength, although Biochanin-A is the most potent FAAH inhibitor.


The three flavonoids affected FAAH with a potency comparable to arch-5HT, an endogenous inhibitor. The researchers further compared the flavonoids with the exogenous inhibitor — fluoxetine. 7-hydroxyflavone’s hydrogen bonds do, however, bind to a unique part of the receptor. The researchers suggested this binding site can destabilize the receptor.



7-hydroxyflavone

7-hydroxyflavone, courtesy of Pubchem.


Flavonoids and anandamide levels

Researchers analyzed blood samples from the mice after a swim test. The three flavonoids increase anandamide levels while reducing corticosterone. Motor movement also slightly slowed following a dose of either flavonoid equally for males and females.


Each flavonoid only slightly reduced locomotion, but Genistein, Biochanin-A, and 7-hydroxyflavone significantly knocked down depressive-like symptoms. Biochanin-A also attenuates oxidative stress in mice with Parkinson’s Disease.



Genistein

Genistein, courtesy of Wiki.


Previous research found flavonoids affect CB1 receptor activity, but the exact mechanism remained elusive. Three flavonoids might, at least, contribute to the ensemble effect by protecting the endocannabinoid, anandamide.


CBD, like the three flavonoids, blocks anandamide metabolism by inhibiting FAAH. Further human studies can confirm the current in silico analysis and mouse study. Moreover, pharmacokinetic research can better quantify flavonoid metabolism.


Sources

  1. Zada, W., VanRyzin, J. W., Perez-Pouchoulen, M., Baglot, S. L., Hill, M. N., Abbas, G., Clark, S. M., Rashid, U., McCarthy, M. M., & Mannan, A. (2022). Fatty acid amide hydrolase inhibition and N-arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants. Pharmacology research & perspectives, 10(5), e00999.

  2. Zada, W., VanRyzin, J. W., Perez-Pouchoulen, M., Baglot, S. L., Hill, M. N., Abbas, G., Clark, S. M., Rashid, U., McCarthy, M. M., & Mannan, A. (2022). Fatty acid amide hydrolase inhibition and N-arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants. Pharmacology research & perspectives, 10(5), e00999.



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