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The combination of these factors may be a driving force c. Glycyrrhiza glabra (Licorice root) - Glycyrrhiza
in the extensive pulmonary microvascular damage seen glabra, common name licorice root, has a long history
in severe manifestations of COVID-19. Berberine has of use in Western herbal medicine for viral infections
been shown to downregulate HIF1α. 301-305 and in traditional Chinese medicine (TCM) as a key
In a human trial with 130 acute coronary ingredient for pandemic formulas. It was a component
syndrome subjects receiving percutaneous coronary in TCM formulas for SARS-CoV-1 prevention and
intervention, those receiving 300 mg of berberine treatment. Along with astragalus, it is the most
TID for 30 days had significant reductions in matrix frequently used botanical in TCM formulas for
metalloproteinase (MMP)-9, intercellular adhesion SARS-CoV-2 prevention in China. Multiple clinical
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molecule (ICAM)-1, vascular cell adhesion molecule trials have demonstrated its effectiveness as a part of
(VCAM)-1, C-reactive protein, IL-6 and monocyte TCM formulas for CoV-1 and H1N1. Numerous
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chemoattractant protein-1 (MCP-1), all of which are in-vitro studies have shown the major active
inflammatory signaling molecules. constituent of licorice, glycyrrhizin, to be effective
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Goldenseal is often used because its high against SARS-CoV-1. The Th1 promoting
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concentration of berberine. In a study examining the properties of licorice may contribute to its antiviral
inhibition of influenza A by berberine, goldenseal at action and have been reviewed.
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higher dosages was found to be effective at inhibiting A 2003 study published in Lancet looking at two
both growth of influenza A and production of TNFα clinical isolates of coronavirus from patients with
and PGE2. 307 SARS-CoV-1 identified glycyrrhizin to be the most
active component of licorice in inhibiting viral
b. Baicalin-containing Botanical Medicines (Scutellariae replication as compared to ribavirin, 6-azauridine,
baicalensis (SB) and other Scutellaria spp.) - The high pyrazofurin, and mycophenolic acid.
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infectivity rate of SARS-CoV-2 separates it from the A preprint molecular docking study suggests that
genetically similar SARS-CoV-1. Preprint research the major active constituent, glycyrrhizin, can bind the
suggests that one difference might lie in a unique ACE2 receptor, and therefore may have anti-SARS-
furin-like cleavage site on the SARS-CoV-2 Spike CoV-2 activity.
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protein that is absent in SARS-CoV-1. Dengue Licorice is considered a botanical of low toxic
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virus also infects human cells via furin cleavage, and potential and has been safely used in Western and
could be inhibited in vitro and in vivo by application of Eastern herbal medicin for millennia. However,
the flavonoid luteolin. excessive use can exert an aldosterone-like affect
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Evidence for antiviral, antioxidant, and resulting in potassium wasting. Prescribing glycyrrhizin
anti-inflammatory effects of SB has been reviewed. 310,311 in individuals on potassium wasting medications may
The ability of SB to downregulate Th17 cell result in hypokalemia. It’s also important to note that
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differentiation , the major source of IL-17 that induces SARS-CoV-2 itself has been associated with potassium
macrophage IL-6 production , has been reviewed. wasting, as is hydroxychloroquine, a drug gaining
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Compounds isolated from SB have been shown to have some renown as a potential COVID19 therapeutic,
antiviral and Nrf2-promoting antioxidant properties. especially early in the disease process. Clinical
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SB has shown utility in downregulation of NLRP3 considerations for patients with an increased risk for
inflammasomes, 314,315 antimycobacterial and cardiac arrhythmias, either secondary to acquired
anti-inflammatory effects in macrophage infection, conditions or co-morbidities or consequent to inherited
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and anti-H1N1 activity in vitro and in vivo through syndromes, have been reviewed. Thus, while
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induction of IFN-γ producing cells. Activity against glycyrrhizin may be a very important COVID19
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H1N1 and H3N2 infected cells has been show to be intervention, serum potassium should be monitored
associated with upregulation of type 1 interferons. to avoid hypokalemia in vulnerable individuals.
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In children with acute lymphocytic leukemia, Note that while DGL has substantial clinical
administration of SB extract yielded increased research for such conditions as gastric ulcers, this
production of IFNγ in peripheral blood lymphocytes form is not appropriate for COVID-19 as it is
(PBLs), and reduced TNFα and IL-10 production in deglycyrrhizinated, i.e., the antiviral constituent has
bone marrow cells (BMC), in all patients. The been removed.
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increase in immune surveillance (increased IFNγ)
and downregulation of inflammation (reduced d. Echinacea spp. - Extracts of various species of
TNFα) constitute a potentially useful dual effect. echinacea have been used traditionally in North
Other phytochemicals similar to SB have been America for many years and are currently popular for
identified that block the entry of SARS-CoV into the treatment of many types of upper respiratory
host cells. 320 infections. Recent studies have supported its use by
demonstrating that echinacea extracts possess potent

22 Integrative Medicine • Vol. 19, No. S1 • Epub Ahead of Print Yanuck—Immuno-physiological Approach to COVID-19