Botanicals

Natural Support for the Fight Against Infections

Andrographis, cat’s claw, humic acid, and monolaurin

In 2020 we became all too aware of how infectious disease seriously threatens the health of people worldwide. Fortunately, there is ongoing investigation of nutrients, herbs, and other natural substances that may help fight common injurious microbes, especially when conventional medicine fails to deliver.[1] In today’s post we’ll discuss four natural substances that may provide infection-fighting benefits: andrographis, cat’s claw, humic acid, and monolaurin.

Andrographis

Also known as King of Bitters, Indian Echinacea, and Kalmegh, andrographis (Andrographis paniculata) is a bitter-tasting herb that has long been used in traditional medicine for the treatment of infections and other maladies.[2],[3]

The main active ingredient, known as andrographolide,[4],[5] has been shown to reduce the infectivity of numerous human viruses, including influenza.[6],[7],[8],[9] The influenza virus enters (and thus infects) our cells by way of the surface protein hemagglutinin. Research suggests that andrographolide may interfere with hemagglutinin and block its binding to cellular receptors, thus protecting us from infection.[6] In this respect, the action of andrographolide may be similar to that of certain established influenza drugs and antibody therapies.[10]

The effects of andrographolide, however, extend beyond its direct antiviral activity. It is among a handful of plant substances that can induce the expression of human β-defensin-3 (HBD3), one of the most efficient antimicrobial peptides in the body.[11] Defensins such as HBD3 play a crucial role in innate immunity.[12] Andrographolide also increases the expression of Nrf2, a master regulator of the antioxidant response.[5],[8],[13] The activation of Nrf2 helps limit oxidative damage during infections,[13] and may help limit viral replication, as shown for the hepatitis C virus.[8]

A reduction in lung inflammation and pathology is an important feature of andrographolide’s mechanism of action.

In a mouse model of influenza, andrographolide treatment was shown to diminish lung pathology, decrease viral loads, and increase survival rate.[14] A reduction in lung inflammation and pathology is an important feature of andrographolide’s mechanism of action.[15],[16] Virus-associated lung inflammation, which occurs when the immune system floods the body with cytokines, can lead to respiratory failure.

A meta-analysis of 33 randomized controlled trials found that andrographis also may help ameliorate the symptoms of acute respiratory tract infections in adults and children.[17] Andrographolide relieves inflammation by inhibiting a key pathway involving NF-κB, which controls the expression of a wide range of pro‐inflammatory signals and contributes to viral pathology.[14],[18],[19] Andrographolide also reduces levels of interleukin (IL)-6,[20] a pro-inflammatory cytokine that is a target for the treatment of severe respiratory infections.[21] Because it suppresses these pathways, andrographolide may help support lung function during respiratory infections.

Cat’s claw

Cat’s claw (Uncaria tomentosa), an herb that grows wild in the Peruvian highlands, has long been used by indigenous tribes in the Amazonian region to treat inflammatory conditions, including arthritis, allergies, and asthma.[22],[23] U. tomentosa contains more than 30 bioactive compounds,[24] including mitraphylline,[25] an alkaloid that has been shown to modulate the body’s immune responses.[26],[27],[28]

Cat’s claw has been shown to increase the ability of white blood cells to ingest and subsequently destroy invaders.

Cat’s claw is one of the few Amazonian herbs shown to increase phagocytic activity, the ability of human white blood cells to ingest and subsequently destroy invaders.[22] Specific studies of U. tomentosa extracts revealed an antibacterial effect against Pseudomonas aeruginosa and Staphylococcus aureus, which are opportunistic pathogens.[29] Infections with respiratory viruses are known to enable secondary infections with pneumonia-causing bacteria like these; cat’s claw may protect against this.[30],[31]

U. tomentosa extracts have been shown to block the infection of human cells by some viruses, including Dengue virus, the most common mosquito-borne viral infection in the world.[32],[33] However, cat’s claw is best known for its anti-inflammatory properties. It modulates inflammation by suppressing levels of NF-κB and tumor necrosis factor (TNF)-α, a master regulator of inflammatory processes.[34],[35],[36] Its pronounced effect on TNF-α may provide a clue as to the utility of cat’s claw in various clinical conditions. For example, anti-TNF antibodies have been used to treat inflammatory conditions such as rheumatoid arthritis (RA), and studies have shown that cat’s claw may ameliorate the symptoms of RA in a similar manner.[37]

When it comes to respiratory infections, the production of TNF is part of the body’s attempt to clear infections. When TNF spirals out of control, however, lung damage can ensue.[38],[39],[40] It’s not surprising, then, that therapies that suppress TNF are under investigation for the treatment of severe respiratory infections.[41] Because cat’s claw not only inhibits TNF, but also ameliorates lung inflammation in mice,[23],[32],[34] it is a promising candidate for human clinical investigations.

Humic acid

Named after humus, the organic component of soil, humic substances arise from the decomposition of animal and plant residues in water, peat, soil, and sediment.[42] Humic substances can be fractionated into humin, humic acid (HA), and fulvic acid.[43],[44]

HA has a plethora of functional groups with binding properties,[45] making it capable of binding a broad spectrum of viruses.[46],[47],[48],[49],[50] Studies of lakes that contain high amounts of HA suggest that viral numbers are lowered by the presence of these substances.[51]

The antiviral effect of humic acid is directed specifically against an early stage of infection – the one in which the virus attaches to our cells.

In mammalian cells, the antiviral effect of HA is directed specifically against an early stage of infection – the one in which the virus attaches to our cells.[46],[47],[48],[49],[50] HA and its synthetic analogues were shown to reduce the infectivity of herpes simplex virus (HSV),[47],[52],[53] hepatitis B virus (HBV),[54] human immunodeficiency virus (HIV),[48],[49],[50],[53] and Coxsackie virus,[55],[56] all of which afflict humans. In a study of HBV, researchers found that HA not only inhibited viral replication, but also caused infected cells to die off, without harming the healthy, uninfected cells.[54]

A component of HA, protocatechuic acid (PCA),[57] has been shown to inhibit the replication of influenza viruses in the laboratory and in animals.[46] In a study of influenza in mice, fewer than 60% of the control animals survived the infection, while nearly all of the animals who were given PCA survived.[58]

Owing to its antimicrobial properties, HA has been used as a feed additive to improve poultry performance and health.[59] In both animals and humans, HA has health-promoting effects on the gut and immune system.[60],[61],[62] Clinical studies in healthy volunteers showed that supplementation with HA increased the concentration of the colonic microbiota by 20% to 30% without altering its diversity, suggesting that it enhanced the growth of existing healthy bacteria.[60] As an added benefit, HA strongly binds organic pollutants and toxic heavy metals.[63],[64],[65],[66],[67] HA may thus play a role in reducing heavy metal concentrations and environment-caused illnesses.

Monolaurin

Monolaurin, a monoglyceride comprising glycerol and lauric acid (C12), occurs naturally in human milk.[68] In fact, monolaurin is thought to be one of the reasons why breast feeding is so healthful for infants.[68],[69],[70]

Monolaurin was first discovered to have antiviral activity over 40 years ago.[71] Since then, numerous laboratory studies have shown that it can suppress the growth and virulence of enveloped viruses, bacteria, and some fungi, including Candida spp.[72],[73],[74],[75] Monolaurin has been shown to have 200 to 400 times more antibacterial activity than lauric acid, a fatty acid found in coconut oil.[68],[75],[76],[77]

Human milk contains approximately 3,000 mcg of monolaurin per ml, compared to 150 mcg per ml in bovine milk, and none in infant formula.[68] The monolaurin in breast milk is thought to suppress the growth of gut pathogens and to encourage the growth of beneficial bacteria, such as lactobacilli. In fact, monolaurin appears to act in a manner similar to that of reutericyclin,[68] a natural antibiotic substance produced by lactobacilli.[78],[79]

Monolaurin has been shown to reduce the infectivity of 14 different enveloped viruses by more than 99.9% in vitro.

As mentioned, monolaurin inhibits “enveloped” viruses, including influenza.[80] Enveloped viruses are those with an outer wrapping or envelope, which comes from the infected cell in a process called “budding off.”[81] The envelope may play a role in helping a virus survive and infect other cells, and monolaurin may counteract this process by helping to disintegrate the envelope.[75],[82] Monolaurin has been shown to reduce the infectivity of 14 different enveloped viruses by more than 99.9% in vitro.[80]

The membrane-destabilizing activity of monolaurin also inhibits bacterial cell growth (bacteriostatic action) and induces bacterial cell death (bactericidal action).[83] Monolaurin has been shown to inhibit the bacteria associated with pneumonia, including Streptococcus pneumoniae (pneumococcus) and Staphylococcus aureus.[76],[84],[85] These bacteria often complicate viral respiratory infections and are associated with more severe disease outcomes.[86]

Last but not least, its beneficial effects on the gut microbiota contribute to monolaurin’s supportive properties.[87] Respiratory viruses can contribute to an imbalanced microbiota and the ensuing diarrhea, and some viruses can even spread to the gastrointestinal tract after a respiratory infection.[88],[89],[90] A healthy microbiota can suppress viral infections,[91] while a microbiota that is dysbiotic (out of balance) can make it easier for viruses to take hold.[92]

Summary

Andrographis, cat’s claw, humic acid, and monolaurin act via distinct mechanisms to reduce viral infectivity, modulate immunity, and/or reduce the inflammation associated with viral infections. Importantly, unlike drugs that have a single mechanism of action, each of these natural substances attacks the problem in a multifaceted way. The evidence to date is compelling, and justifies further clinical investigations of these natural products.

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