Japanese and American Scientists Finds That Carnosic Acid From The Herb Rosemary Can Be Used To Treat COVID-19, Long COVID And Other Diseases
: Scientists Tokyo University of Technology-Japan, the Scripps Research Institute-USA and the University of California San Diego School of Medicine,-USA have found that that the phytochemical compound Carnosic Acid that is extracted from the common herb Rosemary can be used to treat COVID-19, Long COVID and other inflammatory and also neurodegenerative diseases.
The herb Rosemary (Rosmarinus officinalis [family Lamiaceae]), a plant of economic and gustatory repute, has been employed in traditional medicines in many countries for decades.
Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid.
The study focuses on the potential applications of carnosic acid (CA) and carnosol (CS), for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome.
Carnosic acid exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation.
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study team also proposes that carnosic acid may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed “long-COVID.”
It has been found that one factor that contributes to COVID-19 disease severity is the cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells.
Also, neurological aftereffects such as anxiety and “brain fog” are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects.
Because carnosic acid 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, the study team explored we the evidence that carnosic acid or rosemary extracts containing carnosic acid 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 Alzheimer’s disease (AD) and Parkinson’s disease (PD).
The study findings were published in the peer reviewed journal: Antioxidants.
The study team 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 study findings also presented evidence, and reviewed evidence from prior studies, that carnosic acid has a separate effect in inhibiting a powerful inflammatory pathway ie a pathway that is active in severe COVID-19 as well as in other diseases including Alzheimer's. https://pubs.acs.org/doi/abs/10.1021/jf104837w
Senior author Dr Stuart Lipton, MD, Ph.D., 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 said, "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.”
Dr Lipton and colleagues 2016 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. https://pubmed.ncbi.nlm.nih.gov/27906174/
In this new study, Dr Lipton, along with Dr Chang-ki Oh, Ph.D., and Dr Dorit Trudler, Ph.D., respectively a staff scientist and postdoctoral fellow in the Lipton lab, and first author Dr Takumi Satoh, Ph.D., 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 study team also reviewed evidence from other investigators' studies indicating that carnosic acid inhibits inflammation in other disease models.
The researchers 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."
Furthermore, the study team described a COVID-19 infection-blocking experiment conducted by Dr Oh.
Utilizing 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.
Although, the research is preliminary, the study team proposes 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.
The study team suggests that in that active form, the compound modifies the ACE2 receptor for SARS-CoV-2, making the receptor impregnable to the virus and thereby blocking infection.
Dr Lipton further added, "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."
The study team 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 study team concluded, “Carnosic acid is a safe pro-electrophilic drug (PED) that activates the KEAP1/NRF2 transcriptional pathway, leading to the sustained induction of phase 2 antioxidant and anti-inflammatory enzymes. Carnosic acid exerts neuroprotective and anti-inflammatory effects and has been proposed to be a potential therapeutic against chronic neurodegenerative disorders, such as AD and PD, and acute and chronic effects of infections such as SARS-CoV-2. The use carnosic acid in particular as an NRF2 activator and anti-inflammatory has gained wide attention due to the virtual absence of side effects and its relatively low economic cost compared to other strategies. The health-promoting effects of carnosic acid have been demonstrated in multiple animal models against chronic neurodegenerative disorders. Moreover, inhibition of the NLRP3 inflammasome by carnosic acid represents an important molecular target in limiting IL-1β pro-inflammatory cytokine production. This study review also highlights the role of the NLRP3 inflammasome in neurological diseases such as AD and PD/LBD, and in the pathogenesis of COVID-19 including so-called ‘long-COVID’ symptoms. Carnosic acid appears to inhibit the manifestations of SARS-CoV-2 infection by two mechanisms, one at the point of viral entry, possibly through covalent binding to the ACE2 receptor protein, and the other by ameliorating cytokine storm through the inhibition of NLRP3 inflammasome activation
. Thus, carnosic acid represents a potential therapeutic for COVID-19 as well as for neurodegenerative disorders like AD and PD/LBD.”
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