Luteolin, the Super Supplement for Regulating Inflammation

It’s safe to say that we have all experienced some sort of inflammation in the body while trying to recover from an illness or infection.

However, for many of us, this inflammation can persist for long periods of time and make us more vulnerable to developing more dangerous, even life-threatening diseases.

For that reason, it is incredibly important to regulate the level of inflammation in the body to prevent or reduce the risk of developing any other diseases.

What if we told you that a substance called luteolin plays an essential role in regulating inflammation?

In this article, we’ll be discussing what makes luteolin so important to fighting chronic inflammation.

But first, we have to figure out:

What is Inflammation?

As we have previously mentioned, inflammation naturally occurs as a part of the body’s defense mechanism. 

In inflammation, the immune system recognizes harmful stimuli such as bacteria and viruses within the body, and removes them in order to kickstart the healing process.

There are two types of inflammation: acute and chronic.

What do they mean?

Acute inflammation may be caused by tissue damage because of toxic compounds, microbial invasion, or trauma.

This type of inflammation begins quickly and becomes severe after a short time. 

Symptoms of acute inflammation may last for a few days, including acute pneumonia and cellulitis, which is a serious bacterial infection that causes redness and swelling in the skin.

There is also a transitional stage between acute and chronic inflammation called subacute inflammation, which may last for 2 to 6 weeks.

Chronic Inflammation

Causes

Now, we come to chronic inflammation, which we’ll be putting a lot of focus on in this article.

This inflammation is slow and long-term, lasting anywhere from several months to even years.

Usually, the extent and effects of chronic inflammation depend on what causes it, as well as the body’s ability to repair itself from the damage and overcome it.

Let’s take a closer look at the causes of chronic inflammation:

1. The body is unable to eliminate pathogens that cause acute inflammation

• Mycobacterium tuberculosis – the pathogen that causes tuberculosis

 

1. Protozoa – may exist as free-living organisms or bacteria

1. Fungi – includes living organisms such as yeasts and molds

1. Parasites that are able to resist your body’s defenses and remain in bodily tissues for an extended length of time

1. Your body is exposed to a low level of a specific irritant or foreign materials that cannot be broken down enzymatically or through the process of phagocytosis.

1. These include substances or industrial chemicals that may be inhaled over a long period, such as silica dust.

1. Phagocytosis is the process by which living cells known as phagocytes ingest harmful foreign particles, bacteria, and dying or dead cells, and kill microbes.

1. You are suffering from an autoimmune disorder in which your immune system has become sensitized to the normal components of the body, and attacks your healthy tissues

1. This may lead to the development of diseases such as rheumatoid arthritis and systemic lupus erythematosus, or SLE.

1. Rheumatoid arthritis is the most common form of autoimmune arthritis caused by improper functioning of the immune system, and results in pain and swelling in the joints of the hands and feet.

1. Systemic lupus erythematosus is an autoimmune disorder in which the immune system unknowingly attacks the body’s own healthy tissues, which may affect the kidneys, joints, skin, and brain, among other organs.

1. You have repeatedly experienced episodes of acute inflammation

1. However, in the case of diseases such as tuberculosis and rheumatoid arthritis, chronic inflammation is an independent bodily response and does not follow acute inflammation.

1. There are inflammatory and biochemical inducers that cause oxidative stress and mitochondrial dysfunction in the body. These inducers include the increased production of:

1. Free radicals such as the hydroxyl radical (OH–) and superoxide anion (O2-).

1. Advanced glycation end products, or AGE’s – harmful compounds that are produced from cooking foods at high temperatures and buildup in the body as you age, which could increase the risk of insulin resistance and developing type-2 diabetes.

1. Uric acid, or urate, crystals – when deposited into the joints, they cause the pain and swelling associated with gout.

1. Oxidized lipoproteins – usually refers to oxidized low-density lipoproteins, or LDL-cholesterol, which may lead to atherosclerosis

1. Homocysteine – may lead to neuronal damage and the development of neurodegenerative diseases such as Alzheimer’s disease.

Statistics

Did you know that diseases caused by chronic inflammation are the most significant cause of death on Earth?

According to the World Health Organization (WHO), chronic diseases are ranked at the top for its threat level to human health.

According to the Rand Corporation, in 2014, almost 3 in every 5 Americans had at least one chronic condition. 

More than 2 in every 5 Americans had multiple chronic conditions. 

Twelve percent of American adults had at least 5 chronic conditions.

Sounds scary, doesn’t it?

Let’s look at some worldwide statistics:

Three of five people who die do so because of chronic inflammatory conditions including, but not limited to, diabetes, obesity, stroke, chronic respiratory conditions, and heart conditions.

Clearly, chronic inflammation presents a great risk of harm to your overall health and well-being, and must be addressed as soon as possible.

On that note, let’s get into: 

What is Luteolin?

• Plant Compound found in certain fruits, vegetables, and herbs.
• Powerful Anti-Inflammatory Properties.
• Strong Anti-oxidative Properties.
• Anti-allergic Effects.

Luteolin is a bioflavonoid that is found in certain fruits, vegetables, and medicinal herbs. 

For reference:

A bioflavonoid is a biologically active compound in the human body that serves as an antioxidant that protects against free radical damage. 

Free radicals cause oxidative stress and damage the cell membranes and DNA, and could even kill off cells. 

Bioflavonoids help lessen or even prevent the damage that free radicals can cause. 

Luteolin is one of the most important biologically active antioxidant compounds that helps to repair and protect the cells.

Let’s dive deeper into what makes luteolin so special.

Chinese traditional medicine incorporates plants that are rich in luteolin to help treat various diseases, including hypertension and inflammatory disorders.

This is due to luteolin’s biochemical properties as a pro-oxidant or antioxidant, which results in multiple biological effects such as anti-allergic and anti-inflammatory effects.

Let us explain:

Pro-oxidants induce oxidative stress by either producing reactive oxygen species, which are a type of free radicals, or inhibiting antioxidant system activity.

Whether luteolin exhibits pro-oxidant or antioxidant properties depends on the concentration and source of the free radicals present, as well as the context and microenvironment of the cell.

For example:

When the concentration of iron ions in a cell is low, measured at less than 50 micromoles per liter, luteolin will behave as an antioxidant.

When the concentration of iron ions in a cell is high, measured at more than 100 micromoles per liter, luteolin will behave as an pro-oxidant.

Luteolin possesses natural compounds that protect our immune system by neutralizing free radicals. 

Additionally, it is also able to relieve inflammation at the deepest levels by turning off the genes that create inflammation and oxidative stress, which are shown by wrinkles and skin lesions. 

Luteolin also inhibits the activity of mast cells, which play important roles in allergy by increasing the activity of anti-allergic cells called regulatory T-cells. 

As if that weren’t enough, it also helps protect the brain and stimulate cognition by addressing neurological functions like memory, learning, and motor skills. 

To that point, individuals with autoimmune disorders and inflammatory conditions that affect the nervous system have shown improvements with luteolin supplementation. 

In addition, research shows that luteolin supplementation improves tolerance for high intensity exercise. 

What Does Research Have to Say About Luteolin Benefits?

Let’s take a look at what the research says about how luteolin benefits inflammation and other disorders.

Inflammation

As we have previously discussed, chronic inflammation may lead to the development of more harmful conditions such as arthritis and chronic obstructive pulmonary disease, among others.

For reference:

Chronic obstructive pulmonary disease is a common lung disease that makes it difficult to breathe. It may manifest itself as chronic bronchitis, which results in long-term coughing with mucus, or emphysema, which results in lung damage over time.

In the inflammation process, white blood cells called macrophages are activated by different molecules, which include cytokines from the body and toxins from pathogens.

For those who don’t know:

Cytokines are small proteins that help immune cells and host tissue cells communicate with each other. 

They help regulate the immune response in the body.  

Anyways:

Lipopolysaccharide, or LPS, is a component of the outer membrane of Gram-negative bacteria, and is a common endotoxin. It is also a trigger for inflammation.

The activated macrophages begin to aggressively produce inflammatory molecules, including tumor necrosis factor α, or TNFα, interleukins, or ILs, and free radicals, or reactive oxygen species and reactive nitrogen species.

This then leads to the recruitment of immune cells such as neutrophils and lymphocytes to the site of infection to clear out the pathogens.

Sounds good, right?

WRONG.

The continuous production of the inflammatory molecules during chronic inflammation is what is primarily responsible for the development of dangerous, life-threatening diseases.

So where does luteolin fit into this?

The anti-inflammatory effect of luteolin comes from its suppression of the production of cytokines, as well as their signal transduction pathways.

For reference:

Signal transduction pathways are the chains of molecules that relay signals within a cell to trigger a cellular response.

So what does this mean?

By suppressing cytokine production and the signal transduction pathways associated with those cytokines, luteolin is able to limit the number of macrophages that are activated. 

As a result, this helps decrease the production of inflammatory molecules that lead to the development of chronic inflammatory diseases.

In addition, luteolin has also been shown to suppress the lipopolysaccharide-stimulated pathways of nuclear factor kappa B, or NF-κB, and mitogen-activated protein kinase, or MAPK.

These are two major pathways that are involved in the activation of macrophages, and in the responses of tissue epithelial and stromal cells to TNFα, ILs, and other inflammation mediators.

It is the suppression of such pathways that underlines the main mechanism of the anti-inflammatory effect of luteolin on acute and chronic inflammation.

Cardiovascular Disease

A study published by Frontiers in Pharmacology discovered that luteolin improves heart function by decreasing myocardial apoptosis, reducing myocardial infarct size, and enhancing left ventricular ejection fraction.

Let’s explore these in greater individual detail. 

For starters, in general, several studies have shown a positive correlation between high dietary intake of luteolin and a reduced risk of acute myocardial infarction, also known as a heart attack.

Luteolin helps relieve ischemia-reperfusion injury by inhibiting apoptosis.

Before we go any further, let’s define those terms.

Ischemia-reperfusion injury is a condition in which blood flow is restored to the damaged cardiac muscle, or myocardium, after a period of reduced blood flow or lack of oxygen supply.

However, the period of reduced blood flow or lack of oxygen makes it so that, instead of restoring normal cardiac function, the restored blood flow actually causes oxidative stress, resulting in inflammation and oxidative damage to the tissues.

Apoptosis is a type of programmed cell death that naturally occurs as part of an organism’s growth of development.

Back to luteolin:

Luteolin has been shown to activate the anti-apoptosis key protein AKT, which has been proven to regulate the apoptotic process in ischemia-reperfusion injury.

Additionally, it increases the expression of BCL-2, an apoptosis suppressor protein, decreases the expression of BAX, a pro-apoptotic member of the BCL-2 protein family, and increases the BCL-2/BAX ratio.

Sounds good, right? It gets better.

Research has shown that calcium ion overload is a major mechanism of myocardial ischemia-reperfusion injury.

By activating the PI3/AKT signaling pathway, luteolin is indirectly able to improve the activity of SERCA2a.

Let us explain:

SERCA2a is an important protein that is involved with the uptake of calcium ions from the cytosol, or intracellular fluid, into the sarcoplasmic reticulum.

The sarcoplasmic reticulum is an intracellular system of saclike membranes that is responsible for storing calcium ions.

Dysfunction of the SERCA2a protein has been linked to the impairment of systolic/diastolic function.

Therefore, luteolin is involved with helping avoid heart ventricular dysfunction.

In addition, when tested on living cells with myocardial ischemia-reperfusion injury, luteolin was shown to decrease infarct size, apoptosis, and the release of lactate dehydrogenase, also known as lactic acid.

For reference: 

High levels of lactic acid indicate tissue damage.

As if that weren’t enough, luteolin’s role in regulating members of the MAPK family, which we previously mentioned in the inflammation section, improves the function of the cardiac muscle cells.

It’s pretty clear that luteolin may have potent cardiovascular benefits.

Neurocognitive Disorders

In one study published in the Neurochemical Research journal, researchers were able to show that luteolin has potential in improving cognitive dysfunction by inhibiting neuroinflammation.

Let’s get into it.

The researcher investigated the effects of luteolin on neurocognitive disorders through cognitive deficits following chronic cerebral hypoperfusion, or CCH.

Chronic cerebral hypoperfusion is a major cause of vascular dementia and Alzheimer’s disease, which are the two most common forms of dementia in elderly adults.

It may be caused by other disorders that affect the cerebral vascular system, such as hypertension, diabetes, and atherosclerosis. 

Individuals who have chronic cerebral hypoperfusion may suffer from cognitive deficits to various degrees.

Neuroinflammation and oxidative stress are both heavily involved in cognitive deficits following chronic cerebral hypoperfusion.

Researchers showed that chronic cerebral hypoperfusion: 

For reference:

Malondialdehyde is a biomarker for oxidative stress.

Superoxide dismutase is an enzyme that is essential to the antioxidant defense against free radicals, specifically oxygen radicals, in the body.

Glutathione peroxidase is a family of enzymes whose main role is to protect the body from oxidative stress and damage.

Also, CCH caused overactivation of microglia, which help oversee the brain’s environment and are activated in response to such factors as proteins naturally produced within the body, and toxins that come from the external environment.

The lack of regulation of microglial activation is a contributing mechanism to the neuronal damage experienced as a symptom of neurodegenerative diseases.

Furthermore, CCH caused astrogliosis, which is an abnormal increase in glial cells of the brain and spinal cord due to the death of neurons due, in part, to neurodegenerative diseases.

As if that weren’t enough, chronic cerebral hypoperfusion caused dysfunction in learning and short-term memory and a deficiency in long-term potentiation, the long-term increase in strength of the synapses between neurons that is essential to learning and memory.

Finally, we get to luteolin’s role in this study.

Luteolin supplementation reversed all of the changes induced by CCH.

Luteolin inhibited the microglial overactivation and astrogliosis, especially in the cortex and hippocampus parts of the brain. It also improved the dysfunction in short-term memory and learning, as well as the deficiency in long-term potentiation.

The researchers believe that luteolin is a potent anti-inflammatory agent that protects cognitive functioning and synaptic plasticity due to chronic cerebral hypoperfusion.

In another study, researchers suggested that the antioxidant and cytoprotective effects of luteolin are related to the nuclear factor erythroid 2-related factor 2-pathway, also known as the Nrf2 pathway.

The Nrf2 pathway is involved in the body’s anti-inflammatory process by organizing the recruitment of inflammatory cells. 

It also uses the antioxidant response elements in the body to control the expression of detoxifying genes and enzymes, such as glutathione peroxidase, which exert their anti-inflammatory effects to protect cells from oxidative damage.

Clearly, luteolin shows great potential in helping treat neurocognitive disorders.

Food Sources of Luteolin

If you’re looking to increase your levels of luteolin, then you could look to eating certain foods.

Luteolin is found in fresh vegetables such as:

• Celery

• Broccoli

• Kale

• Parsley

• Artichoke Leaves

• Bell Peppers

• Khlorabi

Fruits such as:

• Apples with Skin

• Pumpkins

• Grapes

• Lemons

• Oranges

Herbs such as:

• Thyme

• Basil

• Parsley

• Oregano

• Chamomile tea 

Why You Should Supplement Luteolin?

Luteolin is a major promoter of antioxidant benefits. It has the power to manage, prevent, reduce, and even eliminate inflammation and help many of the diseases associated with inflammation. 

Luteolin also helps provide nervous system and memory support in addition to its antioxidant abilities. 

Although it is naturally occurring in plants as a bioflavonoid, you may still want to optimize the medicinal properties of luteolin by increasing your intake of it through the use of high-quality supplements.

Now, we’d like to hear from you:

Have you ever heard of luteolin before? If so, what did you know about it prior to reading this article?

Please let us know in the comments below.