The team presented evidence that carnosic acid has a unique effect on inhibiting the potent inflammatory pathway active in other diseases, including acute COVID-19 and Alzheimer’s disease, and reviewed the evidence from previous studies.
“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 found evidence that carnosic acid activates an anti-inflammatory, antioxidant signaling cascade called the Nrf2 pathway, and found evidence that it reduces Alzheimer-like symptoms in mouse models of the disease known to have encephalitis.
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 disease.
The researchers also reviewed evidence from other investigators’ studies showing that carnosic acid inhibits inflammation in other disease models. They suggested that this effect may be effective against inflammation found in COVID-19, as well as in some cases of post-COVID syndrome known as the long covid, which includes cognitive difficulties often referred to as “brain fog.”
Additionally, the scientists also described a COVID-19 infection-blocking experiment conducted by Oh. He showed that the carnosic acid can directly block SARS-CoV-2’s ability to infect cells, with progressively greater infection-blocking activity at higher doses using a standard infectivity assay.
Although research is preliminary, researchers suggest that carnosic acid, although a safe and relatively inactive compound, has this antiviral effect because it is converted into its active form by inflammation and oxidation found at the site of infection.
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, the compound modifies the ACE2 receptor for SARS-CoV-2, thereby making the receptor immobile and thereby preventing infection.
“Carnosic acid represents a ‘pathologically activated therapeutic’ in preclinical models of disease ยinactive 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.
The researchers Lipton and Satoh hold patents for the use of carnosic acid derivatives for degenerative diseases.
The research was supported in part by the National Institutes of Health (R35 AG071734, RF1 AG057409, R01 AG056259, R01 AG066750, R01 AG073418, R01 DA048882, R01 NS086890, R56 AG065372, and DP1 DA041722), the California Institute for Regenerative Medicine, and Fast Grants.
Source: Medindia
