rosemary
A compound found in common kitchen herbs rosemary and sage has inspired a potential new treatment for Alzheimer’s disease, according to research published in February by scientists at Scripps Research Institute.
The study, published in the journal Antioxidants on February 28, details how researchers developed a stable form of carnosic acid—a natural anti-inflammatory and antioxidant compound—and found it improved memory function and reduced brain inflammation in mice with Alzheimer’s-like symptoms.
“By combating inflammation and oxidative stress with this diAcCA compound, we actually increased the number of synapses in the brain,” said senior author Dr. Stuart Lipton, the Step Family Foundation Endowed Chair at Scripps Research and a clinical neurologist in La Jolla, California. “We also took down other misfolded or aggregated proteins such as phosphorylated-tau and amyloid-β, which are thought to trigger Alzheimer’s disease and serve as biomarkers of the disease process.”
The connection between rosemary and memory has historical roots. As Shakespeare wrote in Hamlet, “There’s rosemary, that’s for remembrance.” This literary reference now appears prescient given the latest scientific developments.
From Kitchen Herb to Laboratory Innovation
Carnosic acid works by activating the body’s natural defense system against inflammation—a key factor linked to cognitive decline in Alzheimer’s disease, which affects millions of Americans as the sixth leading cause of death in the United States.
While pure carnosic acid has promising properties, its instability made it impractical as a medication. To overcome this challenge, Lipton collaborated with Dr. Phil Baran, the Dr. Richard A. Lerner Endowed Chair in Scripps Research’s Department of Chemistry, to develop a more stable derivative called diAcCA.
This modified compound is fully converted to carnosic acid in the digestive system before entering the bloodstream, where it can then reach the brain. Importantly, diAcCA has significant advantages over pure carnosic acid, including a longer shelf life and better bioavailability.
Targeted Inflammation Fighting
What makes this compound particularly notable is its selective activation. The drug is activated by the very inflammation it then fights, meaning it only becomes active in areas of the brain experiencing inflammatory damage. This selective approach could potentially limit side effects.
When administered to mice engineered to develop Alzheimer’s-like symptoms, diAcCA achieved therapeutic doses in the brain and led to measurable improvements. Microscopic examination showed increased synaptic density—the connections between nerve cells essential for learning and memory—along with decreased brain inflammation.
The researchers conducted various memory tests with the mice over three months of treatment. “We did multiple different tests of memory, and they were all improved with the drug,” Lipton noted. “And it didn’t just slow down the decline; it improved virtually back to normal.”
Analysis of brain tissue revealed other positive changes: increased neuronal connections and decreased formation of the protein aggregates associated with Alzheimer’s disease.
Safety Profile and Future Potential
The safety profile of diAcCA appears promising. The compound is well-tolerated and even showed beneficial effects on baseline inflammation in the digestive tract during toxicity studies.
Carnosic acid already has a “generally regarded as safe” (GRAS) designation from the U.S. Food and Drug Administration, which could potentially streamline the approval process for human clinical trials of diAcCA.
This new compound might complement existing treatments for Alzheimer’s disease, according to Lipton. “It could make existing amyloid antibody treatments work better by taking away or limiting their side effects” such as brain swelling or bleeding, he explained.
Beyond Alzheimer’s disease, researchers believe diAcCA might have applications for other conditions characterized by inflammation, including type 2 diabetes, heart disease, and Parkinson’s disease.
The Road Ahead
While the results in mice are encouraging, human clinical trials would be the next step to determine whether these benefits translate to people with Alzheimer’s disease. The research team hopes diAcCA can be fast-tracked through clinical trials because of its safety profile.
The study represents a growing scientific interest in compounds derived from natural sources that may help address complex neurological conditions. By building on traditional knowledge of medicinal herbs with modern chemistry and neuroscience, researchers are uncovering new possibilities for treating previously intractable diseases.
This research was supported by multiple grants from the National Institutes of Health and included contributions from several other scientists at Scripps Research and Socrates Biosciences.
For the millions of families affected by Alzheimer’s disease, innovations like diAcCA offer hope that more effective treatments may be on the horizon—treatments that not only slow decline but potentially reverse some of the damage caused by this devastating condition.
The study “diAcCA, a Pro-Drug for Carnosic Acid That Activates the Nrf2 Transcriptional Pathway, Shows Efficacy in the 5xFAD Transgenic Mouse Model of Alzheimer’s Disease” was published in Antioxidants on February 28, 2025.
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