From the PROMED bulletin
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[2] Carnosic acid (rosemary)
Date: Tue 1 Feb 2022
Source: Scripps [edited]
https://www.scripps.edu/news-and-events/press-room/2022/20220201-lipton-rosemary-covid19.html
A team co-led by scientists at Scripps Research has found evidence
that a compound contained in the medicinal and culinary herb rosemary
could be a 2-pronged weapon against the SARS-CoV-2 coronavirus that
causes COVID-19.
The scientists, in experiments described in a paper published 6 Jan
2022 in the journal Antioxidants, found that the compound, carnosic
acid, can block the interaction between the SARS-CoV-2 outer “spike”
protein and the receptor protein, ACE2, which the virus uses to gain
entry to cells.
The team also presented evidence, and reviewed evidence from prior
studies, that carnosic acid has a separate effect in inhibiting a
powerful inflammatory pathway — a pathway that is active in severe
COVID-19 as well as in other diseases including Alzheimer’s.
“We think that carnosic acid, or some optimized derivative, is worth
investigating as a potentially cheap, safe, and effective treatment
for COVID-19 and some other inflammation-related disorders,” says
study senior author Stuart Lipton, MD, PhD, Professor and Step Family
Foundation Endowed Chair in the Department of Molecular Medicine and
founding co-director of the Neurodegeneration New Medicines Center at
Scripps Research.
In a 2016 study, Lipton and colleagues showed that carnosic acid
activates an anti-inflammatory, antioxidant signaling cascade called
the Nrf2 pathway, and found evidence that it reduces Alzheimer’s-like
signs in mouse models of that disease, which is known to feature brain
inflammation.
For the new study, Lipton, along with Chang-ki Oh, PhD, and Dorit
Trudler, PhD, respectively a staff scientist and postdoctoral fellow
in the Lipton lab, and first author Takumi Satoh, PhD, of the Tokyo
University of Technology, described their further studies of this
anti-inflammatory effect on the immune cells that drive inflammation
in COVID-19 and Alzheimer’s. The researchers also reviewed evidence
from other investigators’ studies indicating that carnosic acid
inhibits inflammation in other disease models. They proposed that this
effect could be beneficial against the inflammation observed in
COVID-19 and in some cases of the post-COVID syndrome known as long
COVID, whose reported symptoms include cognitive difficulties often
described as “brain fog.”
Additionally, the scientists described a COVID-19 infection-blocking
experiment conducted by Oh. Using a standard infectivity assay, he
showed that carnosic acid can directly block SARS-CoV-2’s ability to
infect cells, with progressively greater infection-blocking activity
at higher doses.
While the research is preliminary, the researchers propose that
carnosic acid has this antiviral effect, despite being a safe and
relatively unreactive compound, because it is converted to its active
form by the inflammation and oxidation found at sites of infection. In
that active form, they suggest, the compound modifies the ACE2
receptor for SARS-CoV-2 — making the receptor impregnable to the
virus and thereby blocking infection.
“Carnosic acid represents a ‘pathologically activated therapeutic’ in
preclinical models of disease — inactive and innocuous in its normal
state, but converted to an active form where it needs to be active,”
Lipton says.
Lipton and his colleagues are now working with Scripps Research
chemists, including Phil Baran and Ben Cravatt, professors in the
Department of Chemistry, to synthesize and test more potent
derivatives of carnosic acid with improved drug characteristics for
potential use in inflammation-related disorders.
Lipton and Satoh hold patents for the use of carnosic acid derivatives
for degenerative diseases.
—
Communicated by:
Mary Marshall
[…Because CA has been shown to not only act systemically but also to
penetrate the blood-brain barrier and reach the brain parenchyma to
exert neuroprotective effects, we discuss the evidence that CA or
rosemary extracts containing CA may represent an effective
countermeasure against both acute and chronic pathological events
initiated by SARS-CoV-2 infection as well as other chronic
neurodegenerative diseases including AD and PD.
References
———-
1. Satoh T, Trudler D, Oh CK, Lipton SA. Potential Therapeutic Use of
the Rosemary Diterpene Carnosic Acid for Alzheimer’s Disease,
Parkinson’s Disease, and Long-COVID through NRF2 Activation to
Counteract the NLRP3 Inflammasome. Antioxidants 2022, 11, 124;
https://doi.org/10.3390/antiox11010124
2. Lipton SA, Rezaie T, Nutter A, et al. Therapeutic advantage of
pro-electrophilic drugs to activate the Nrf2/ARE pathway in
Alzheimer’s disease models. Cell Death Dis. 2016 Dec 1;7(12):e2499;
https://doi.org/10.1038/cddis.2016.389.
– Mod.LK]