Study: Oleocanthal Regulates Abnormalities in Receptor Responsible for Alzheimer’s

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The use of oleo­can­thal-based treat­ments for Alzheimer’s dis­ease con­tin­ues to emerge, with the lat­est find­ings from a team of researchers at the University of Louisiana-Monroe.

The polyphe­nol, which gives extra vir­gin olive oil its dis­tinc­tive throat burn­ing sen­sa­tion, has already shown promise in treat­ments for cer­tain types of can­cers and demen­tia.

Alzheimer’s dis­ease, which is the most com­mon form of demen­tia, leads to irre­versible and pro­gres­sive degen­er­a­tion of the brain func­tions, includ­ing mem­ory, per­son­al­ity, cog­ni­tion and other vital func­tions.

In the United States, six mil­lion peo­ple live with Alzheimer’s dis­ease. This fig­ure is pro­jected to rise to 13 mil­lion by 2050 accord­ing to the U.S. Alzheimer’s Association. An esti­mated 50 mil­lion peo­ple around the world live with Alzheimer’s dis­ease.

The lat­est research, pub­lished in Nutrients, inves­ti­gated the inter­ac­tion between oleo­can­thal and the com­ple­men­tary pep­tide C3a recep­tor 1 (C3AR1), which is also involved in other types of neu­rode­gen­er­a­tive dis­eases.

“The com­ple­ment sys­tem is an impor­tant ele­ment of the innate immune sys­tem, which enhances the anti­bod­ies and phago­cytic cells to clear dam­aged cells and path­o­genic microbes,” Khalid El Sayed, a phar­ma­ceu­ti­cal and tox­i­co­log­i­cal sci­ences pro­fes­sor at the University of Louisiana-Monroe and co-author of the study, told Olive Oil Times.

C3AR1 is a reg­u­la­tory hub in the innate immune sys­tem. In Alzheimer’s dis­ease patients, the recep­tor over­works, pro­mot­ing inflam­ma­tion and impair­ing the func­tion of the innate immune sys­tem.

The recep­tor behaves sim­i­larly in patients at risk of devel­op­ing Alzheimer’s dis­ease as well. The researchers said that the receptor’s deac­ti­va­tion leads to a decrease in tau pathol­ogy, which is a key ele­ment in the devel­op­ment of Alzheimer’s dis­ease.

Therefore, ​“the oleo­can­thal mod­u­la­tion [reg­u­la­tion] of C3AR1 is a very impor­tant find­ing that will direct future stud­ies of oleo­can­thal as a plau­si­ble nutraceu­ti­cal for pre­ven­tion and mod­u­la­tion of pre-Alzheimer’s dis­ease neu­rode­gen­er­a­tive con­di­tions,” El Sayed said.

The main focus of the research has been iden­ti­fy­ing new oral for­mu­la­tions which could soon make oleo­can­thal a viable treat­ment for the dis­ease.

“Oleocanthal causes most of the irri­ta­tive, bit­ter and pha­ryn­geal taste of extra vir­gin olive oil,” El Sayed said. ​“It has a sort of highly reac­tive alde­hyde groups, which cause high chem­i­cal and meta­bolic insta­bil­ity.”

“These are chal­lenges that have to be addressed before using oleo­can­thal in human clin­i­cal tri­als,” he added. ​“We devel­oped novel for­mu­la­tions that masked its unde­sired taste atti­tudes and main­tained its chem­i­cal integrity.”

According to El Sayed, extra vir­gin olive oil con­sump­tion is believed to have a role in a lower inci­dence of cog­ni­tive dis­eases in Mediterranean nations, com­pared to other European and American pop­u­la­tions.

“Oleocanthal has been reported to show promis­ing activ­i­ties against the mark­ers of neu­rode­gen­er­a­tive insults that lead to cog­ni­tive dis­eases in vitro and in ani­mal mod­els,” he said.

“Greek extra vir­gin olive oil rich in phe­no­lics [espe­cially oleo­can­thal] have shown promis­ing pro­tec­tive activ­ity against early stages amy­loid patholo­gies that lead to Alzheimer’s dis­ease,” he added.

The research has been based on 5xFAD mice, a stan­dard in Alzheimer’s research; the two new oral for­mu­la­tions found by the researchers have ​“main­tained amy­loid patho­gen­e­sis sup­pres­sive activ­ity by reduc­ing the β‑amyloid accu­mu­la­tion in the mouse brains,” the study reads.

The new for­mu­la­tions, explained the researchers, ​“sig­nif­i­cantly improved its phar­ma­co­dy­nam­ics effects and deliv­ery in Alzheimer’s dis­eases ani­mal mod­els.”

In order for the two new sup­ple­ments to reach the mar­ket, El Sayed said ​“oleo­can­thal has yet to be pre-clin­i­cally tested as a sin­gle entity in Alzheimer’s dis­ease patients so that it can earn inves­ti­ga­tional new drug approval from the Food and Drug Administration.”

“We actu­ally patented our new for­mu­la­tions and have plans to com­mer­cial­ize oleo­can­thal nutraceu­ti­cal and dietary sup­ple­ment using these for­mu­la­tions in the near future,” he added.

However, the research is ongo­ing with pre-clin­i­cal exam­i­na­tions planned.

“We need to under­stand more about the in vivo meta­bolic fate of oleo­can­thal and val­i­date the short and long-term safety for its use, which are top pri­or­i­ties before clin­i­cal test­ing,” El Sayed con­cluded.

• Nutrients
• Alzheimer’s Association
• Bright Focus