May 2026

Polyphenols in herbal medicine

• Week 1: Polyphenols in herbal medicine
• Week 2: Hawthorn – A Heart Feeling Herb
• Week 3: Milk Thistle – Liver First Aid
• Week 4: Goldenrod – The Golden Healer

Polyphenols in herbal medicine

That is why, in herbalism, we don’t speak about the active substance in a herb but about the relationship between its different constituents.

What are polyphenols?

Polyphenols are the largest group of secondary metabolites, with over 8000 phenolic structures currently known, and many others that remain a mystery. 

A benzene ring is a two-dimensional (flat) molecule composed of six carbon atoms, each bonded to a hydrogen atom (C6H6). In the phenolic ring, one hydrogen atom is missing, leaving C6H5 with a lone pair. Creating a molecule that is constantly on the lookout for partners. 

Polyphenols have poly or many phenol rings with two or more aromatic rings, each bearing one or more hydroxyl groups.

Polyphenols are a diverse group of highly complex compounds. They are divided into four subclasses by the number of rings in the molecule, how the rings are connected,

what other functional groups are attached to the basic phenol ring, and the number of hydroxyl groups attached to the phenol skeleton. 

Why did plants develop polyphenols?

When plants first emerged from the premodern swamp, they found a strong energy source, the sun. However, the sun’s energy carries its own risk of damaging DNA. Polyphenols are responsible for the color in plants that reflects the ultraviolet light, thus protecting the plant from sun radiation. 

Some polyphenols (such as lignin) contributed to stronger cell walls, helping plants grow upright toward the sun to maximize exposure.

For insects that don’t have a liver, polyphenols might be toxic because they can’t metabolize and eliminate them. The bright colors of plants that contain polyphenols might serve as a defense mechanism, helping deter insects. However, for some plants, these bright colors attract specific insects toward their flowers. 

When plants are damaged, you see an increase in their flavonoid constituents, which suggests that polyphenols have a role in the plant’s immune system. 

Four subclasses of polyphenols

• Phenolic Acids
• Stilbenes
• Flavonoids 
• Lignans 

In the next part, I am going to geek out about the phytochemistry of these four subclasses. 

Too much?

Hop to the next chapter: Health benefits of polyphenols. 

Phenolic Acids

Phenolic acids are simple single ring structures composed of an aromatic ring and a carboxylic acid group, which makes them very easy to metabolize. They are readily bioavailable because of their small size, which allows easy absorption in the small intestine, followed by further modification in the liver through phase Ⅱ liver detox (methylation, glucuronidation, and sulfation), thereby changing their structure and biological activity.

While phenolic acids that are not bound to fiber can be easily absorbed in the small intestines, phenolic acids that are bound to fiber reach the colon, where they are liberated from the fiber by gut bacteria and absorbed.

Phenolic acids that do reach the colon selectively inhibit pathogenic gram-negative bacteria while being relatively gentle on beneficial anaerobic bacteria. 

Phenolic acid is found in berries, apples, rosemary, sage, coffee, and cereal grains. 

Stilbenes

Stilbenes are a small class of polyphenol but a famous one mainly because they contain resveratrol. Two phenol rings connected by a two-carbon bridge. 

Stilbenes are anti-inflammatory and, hence, promote cellular longevity while stimulating apoptosis, a programmed cell death in cancer cells.  Some examples of stilbenes are grapes and mulberries.

Flavanoids

Flavonoids make up the largest class of polyphenols. Because many of the early identified compounds in this class were isolated from yellow-pigmented plants, the name was derived from the Latin flavus, meaning yellow. 

Different subclasses produce different colors depending on their structure:

Yellow to cream tones – flavonols and flavones, such as quercetin and kaempferol, produce yellow pigmentation. You see this in onion skins, the yellow of chamomile flowers, St. John’s Wort’s yellow blooms, and goldenrod. The presence of flavonols and flavones suggests mast cell stabilization and anti-inflammatory signaling.

Red, purple, blue – anthocyanins are technically a subclass of flavonoids and are responsible for the red-purple-blue spectrum you see in berries, red cabbage, purple corn, and red roses. The same anthocyanin molecule can actually shift color depending on the pH of the cell sap; more acidic environments push toward red, more alkaline toward blue. This is why hydrangea color changes with soil pH. Anthocyanins have a particularly strong affinity for vascular tissue. The research on bilberry and blueberry for retinal health, capillary integrity, and arterial endothelium function 

Pale cream or white coloration suggests the presence of Isoflavones, which bear structural similarity to estrogen and earn their hormonal modulating reputation from that structural feature—not really related to pigmentation at all.

However, many plants contain multiple polyphenols, making it tricky to summarize their actions based on color alone.

Lignans 

Lignans are small structural polymers found in plant cell walls and seeds; rather than being freely dissolved in plant fluids, they give plants their form. They are highly concentrated in seeds (flax seeds), woody stems, whole grains, and fibrous vegetables. 

There is emerging evidence that lignans fermented by gut bacteria produce metabolites that act as phytoestrogens; they bind to estrogen receptors in the body with a much weaker effect than endogenous estradiol, roughly 1,000 to 10,000 times weaker. Therefore, reducing the risk of estrogen dominance breast and uterine cancer. 

Form affects function

Polyphenols are flat, that are mostly fat soluble molecules; therefore, they are easily diffused through the cell membrane into the cell, where they bind to nuclear receptors, affect DNA enzymes, and alter gene expression or the way the body reads and expresses our genes. 

Why is this important?

Different polyphenols activate different transcription factors and affect different gene clusters. A varied polyphenol-rich diet is essentially sending a complex set of signals to your genome simultaneously. This is why ” Eat the rainbow” is such a solid recommendation. 

Gene expression changes take time to translate into meaningful physiological shifts. You’re not getting an immediate pharmacological hit; instead, you’re gradually shifting your cells’ transcriptional landscape. This is why using polyphenols consistently over time is crucial. 

Many of these polyphenols are mildly stressful to cells at the molecular level—they’re often pro-oxidant at the cellular signaling level, even while being antioxidant in vitro. That mild stress is precisely what activates the adaptive gene expression response. Your cells sense a challenge and upregulate their defense and repair machinery. This is the same fundamental logic as exercise—the stress is the signal.

There’s growing evidence that diet-induced epigenetic modifications can be passed to subsequent generations. The implications for thinking about food as medicine across generational timescales are significant.

Health benefits of polyphenols

As you ingest polyphenols, they come in direct contact with the GI tract, where they exert their anti-inflammatory effect. The next organ to interface with these polyphenols is the liver, where they act as hepato-protective. From the liver, polyphenols are carried in the blood; they have profound anti-inflammatory effects and protect the heart, blood vessels, and neurons. Polyphenols leave the body via the urinary tract, where they reduce inflammation in the epithelium (inner lining) of the urinary tract.

In the GI tract

Polyphenols taste bitter, meaning they stimulate digestive enzymes and bile production, as well as liver enzymes and detoxification function. They modify the glycemic index of food, reducing glucose absorption and supporting healthy metabolism. 

While not all tannins are polyphenols, all polyphenols are tannins, meaning they increase tissue tone. This makes polyphenols beneficial for cases of leaky gut and gut inflammation, where the gut’s integrity is disrupted, leading to excess mucus discharge and increased oxidative stress. 

The more complex polyphenols, such as flavonoids attached to glycosides and lignans, do not absorb in the small intestine; instead, they travel to the colon,, where they act as selective prebiotics, feeding beneficial gut bacteria. 

In the liver

When the liver sustains toxic injury—whether from chemicals, drugs, alcohol, several things are happening simultaneously: 

Increased oxidative stress due to the liver trying to metabolize all these toxins. The increase in ROS load during phase 1 cytochrome P450 processing indicates that the liver is essentially burning itself while trying to detoxify. 

Glutathione depletion – the liver’s primary endogenous antioxidant defense is glutathione.  In the presence of liver damage or severe toxicity, glutathione gets consumed rapidly, leading to an increased oxidative burden. When glutathione reserves are depleted, hepatocyte (liver cells) death accelerates dramatically. 

Inflammatory cascade – damaged hepatocytes release damage trigger Kupffer cell activation and inflammatory signaling, which causes secondary damage beyond the initial toxic injury. 

In the cardiovascular system

Blood is the carrier of nutrients, oxygen, hormones, enzymes, and signaling immune cells. All tissues of the body are vascularized; some tissues more than others. Therefore, healthy blood vessels are essential to the function of cells, tissues, and organs. Polyphenols have a profound effect on blood vessel integrity; therefore, they benefit all tissues, particularly in highly vascularized organs such as the heart, liver, kidneys, and brain. 

In piteri dishes, polyphenols act as antioxidants, and at high doses, that might be one of the ways they work. However, it is not the main pathway through which they protect blood vessels, mainly because in the context of herbs or foods, they are not in sufficient amounts to have a significant antioxidant effect. Instead, when they enter the cells, they promote the production of our innate antioxidant glutathione. 

In the nervous system

The connection between gut health, microbiome, and the brain is mind blowing, pan intendended. Polyphenol feeds gut bacteria, which, through fermentation of the pholinic acid, create metabolites that can cross the gut brain barrier. 

These metabolites can reduce brain inflammation, increase BDNF (Brain-derived neurotrophic factor), a protein that protects and supports neuronal growth and plasticity. Some flavonoids inhibit serotonin breakdown; others exhibit GABAergic activity, calming the nervous system. Yet other polyphenols suppress the breakdown of acetylcholine, increasing focus and memory.

Overall, polyphenols have a regenerative effect on the nervous system following trauma, such as stroke. 

Bioavailability 

The best way to use polyphenols is to eat them three to four times a day. When they come in the context of food, their absorption is optimized.  Polyphenols bound to glycosides are water soluble and can be used in smoothies or tea.