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Active Compound in Rosemary May Be Neuroprotective


Caroline Cassels
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November 15, 2007 — New research suggests carnosic acid (CA), the active ingredient in the herb rosemary, is neuroprotective, without producing the serious adverse effects characteristic of many agents used to treat neurodegenerative disease.

Two studies, led by Stewart Lipton, MD, PhD, from the Burnham Institute for Medical Research, in La Jolla, California, and Takumi Satoh, MD, PhD, from Iwate University, in Japan, which are published in the October 2007 issue of Nature Reviews Neuroscience and online November 8 in the Journal of Neurochemistry, show that CA activates a novel signaling pathway that protects brain cells from free radical damage, seen in stroke and other neurodegenerative conditions such as Parkinson's and Alzheimer's diseases.

In animal experiments, the investigators found CA is activated by the free radical damage but otherwise remains innocuous, a finding that may signal a major breakthrough in the development of drugs to treat neurodegenerative disease.

"Clinical use of potential neuroprotective treatments has been limited owing to serious side effects. These include cognitive problems, hallucinations, and even coma, all of which can occur as a result of interference of the drugs with normal brain function," Dr. Lipton writes in Nature Reviews Neuroscience. "Indeed, because the brain is a complex organ that is capable of many intricate functions, it has proved difficult to develop drugs for the treatment of neurodegenerative disorders that do not interfere with the normal functioning of the nervous system."

No Negative Effects

According to the investigators, animal experiments showed CA activates the Keap1/Nrf2 transcriptional pathway by binding to specific Keap1 cysteine residues, protecting neurons from oxidative stress and excitotoxicity. The study also suggests that CA may protect the brain against middle cerebral artery ischemia/reperfusion.

Dr. Lipton said this new type of agent, known as a pathological-activated therapeutic (PAT) drug, "works though a mechanism known as redox chemistry, in which electrons are transferred from 1 molecule to another to activate the body's own defense system.

"Moreover, unlike most new drugs, this type of compound may well be safe and clinically tolerated because it is present in a naturally occurring herb that is known to get into the brain and has been consumed by people for over a thousand years," he added.

Used since the Middle Ages to treat disorders of the nervous system and to ward off sickness, the exact chemical pathways by which rosemary works have, until now, been unknown.

However, the identification of CA and its potential beneficial effect in the brain should lead to the development of better and more effective neuroprotective agents. Drs. Satoh and Lipton have filed a US patent application for a whole series of novel compounds that show even greater benefits than rosemary itself.

According to Dr. Satoh, within the next few years, the research team hopes to improve upon rosemary's beneficial effects. "We can do even better in protecting the brain from terrible disorders such as Alzheimer's and Lou Gehrig's disease, perhaps even slowing down the effects of normal aging by developing new and improved cousins to the active ingredient in rosemary," he said.

J Neurochem. Published online November 8, 2007. Abstract

Nature Rev Neurosci. 2007;8:803-808. Abstract