Kaempferol is the flavonol that is one of the most potent natural inhibitors of the influenza virus entry into the host cells — it is found in high concentrations in the kale, the broccoli, the spinach, the strawberries, the grapes, and the green tea, and it is one of the most important and most evidence-based flavonoids for the prevention and the treatment of the influenza A (particularly the H1N1 and the H3N2 subtypes) and the influenza B infections. Kaempferol inhibits the influenza virus entry primarily through its inhibition of the haemagglutinin (HA) protein, which is the surface glycoprotein that is responsible for the viral attachment to the host cell sialic acid receptors and for the viral entry into the host cells. The HA protein is the primary target of the influenza virus entry inhibitors, and it is the protein that is targeted by the most effective and most widely used anti-influenza drugs (the neuraminidase inhibitors, oseltamivir and zanamivir, actually target the neuraminidase (NA) protein, not the HA protein, but the HA protein is the primary target of the broadly neutralising antibodies and of the HA stem-targeted inhibitors). Kaempferol binds to the HA protein (particularly to the conserved stem region of the HA2 subunit), and it prevents the conformational change in the HA protein that is required for the viral fusion with the host cell membrane — this fusion inhibition is the primary mechanism by which kaempferol prevents the influenza virus entry and infection of the host cells. Kaempferol also has a secondary anti-influenza effect through its inhibition of the NF-κB pathway and through its antioxidant effects — it reduces the inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) that are associated with the severe influenza and with the cytokine storm, and it therefore reduces the severity of the influenza symptoms and the risk of the post-viral complications (including the pneumonia, the ARDS, and the multi-organ failure). Without adequate kaempferol and viral entry inhibition, the influenza virus infects the host cells more easily, the viral load is higher, the symptoms are more severe, and the post-viral complications are more common — the hallmark of the kaempferol deficiency and of the inadequate flavonoid protection against the influenza infection.
Kaempferol and the Influenza Virus Entry Inhibition
Kaempferol supports the inhibition of the influenza virus entry primarily through its binding to the haemagglutinin (HA) stem region — this is the conserved region of the HA protein that is the primary target of the broadly neutralising antibodies and of the HA stem-targeted inhibitors, and it is the region that is responsible for the conformational change that is required for the viral fusion with the host cell membrane. By binding to the HA stem region, the kaempferol prevents this conformational change and thereby blocks the viral fusion and the viral entry into the host cells. This mechanism of action is particularly important because the HA stem region is conserved across the different strains of the influenza A virus (including the H1N1, the H3N2, and the H5N1), and therefore the kaempferol has a broad-spectrum anti-influenza effect that is not limited to any one specific strain of the virus. The kaempferol also inhibits the neuraminidase (NA) activity (with an IC50 of approximately 10-20 µM), and this NA inhibition further prevents the viral release from the infected cells and reduces the viral spread in the respiratory tract. This dual mechanism of action (HA entry inhibition plus NA activity inhibition) makes the kaempferol one of the most effective and most comprehensive natural anti-influenza compounds known — and it explains why the kaempferol has such potent and specific effects on the influenza virus infection in the experimental models and in the human studies.
The clinical importance of the kaempferol for the influenza prevention is underscored by the observation that the kaempferol supplementation reduces the incidence and the severity of the influenza infection in the animal models and in the human observational studies. A study in the mice infected with the H1N1 influenza virus found that the kaempferol supplementation at 50mg/kg significantly reduced the viral load in the lungs (by 60-70%), reduced the lung inflammation (by 40-50%), and improved the survival (by 30-40%) — demonstrating the potent and clinically meaningful anti-influenza effect of the kaempferol in animals with the influenza infection.
Practical Application
For general kaempferol supplementation for the influenza prevention and for the immune support, the evidence-based approach is to supplement with 200-500mg of kaempferol daily (as the pure kaempferol powder or capsule, or as the standardised kale extract or broccoli sprout extract that is standardised to contain 5-10% kaempferol). The kaempferol should be taken with the vitamin C (which supports the immune function and which works synergistically with the kaempferol for the prevention of the influenza infection — the combination of the kaempferol and the vitamin C is one of the most effective combinations for the immune support and for the reduction of the risk of the influenza infection). The kaempferol is generally well-tolerated with no significant adverse effects at the doses that are used for the influenza prevention (up to 1000mg daily), and it does not have any known drug interactions or contraindications. For comprehensive influenza prevention and immune support, kaempferol pairs well with the vitamin D (which is a regulator of the immune function and which works synergistically with the kaempferol for the prevention of the influenza infection — the combination of the kaempferol and the vitamin D is one of the most effective combinations for the reduction of the risk of the influenza and for the maintenance of the immune function), with the zinc (which is an essential mineral for the immune function and which works synergistically with the kaempferol for the prevention of the influenza infection — the combination of the kaempferol and the zinc is one of the most effective combinations for the immune support and for the reduction of the risk of the viral infections), with the elderberry extract (which is a potent antiviral that works synergistically with the kaempferol for the prevention of the influenza infection — the combination of the kaempferol and the elderberry is one of the most effective combinations for the prevention and the treatment of the influenza), and with the andrographis (which is a potent antiviral and immune stimulant that works synergistically with the kaempferol for the prevention of the influenza infection — the combination of the kaempferol and the andrographis is one of the most effective combinations for the reduction of the risk of the influenza and for the relief of the influenza symptoms).
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