Naringenin — Structure, Sources, Health Benefits, and Supplements

Ani Harutyunyan | Обновлено: Июль 09, 2024

Introduction

The naturally occurring flavonoid naringenin is primarily found in citrus fruits, such as grapefruits, oranges, and lemons. Naringenin, well-known for its strong anti-inflammatory and antioxidant qualities, has drawn interest due to possible health advantages. This bioactive substance modulates multiple metabolic processes and aids in the defense of cells against oxidative stress.

In this article, we shall cover all there is to know about naringenin, with particular attention to its structure, mechanism of action, food sources, and effects on human health.

Содержание

Naringenin Structure

Metabolism

Recommended Intake

Foods Rich in Naringenin

Naringenin Supplements

Health Benefits

Inflammation

Cardiovascular Health

Anti-HCV Therapy

Neurological Health

Diabetes

Cancer

Weight Management

Pregnancy

Interactions With Medications

Historical Background

Summary

References

Naringenin Structure

With the chemical formula of C15H12O5, naringenin is a polyphenol belonging to the flavonoid class and the flavanone subgroup, to be precise. Polyphenols are naturally occurring compounds found in plants characterized by the presence of multiple phenol units.

Naringenin’s distinctive flavanone backbone comprises three rings: a heterocyclic pyran ring in the center, surrounded by two aromatic benzene rings (1).

The distinct configuration of hydroxyl or -OH groups at the rings' positions 5, 7, and 4' characterizes naringenin chemically. These hydroxyl groups are essential to this phytochemical's unique bioactive qualities and antioxidant action. naringenin structure

Naringenin is easily confused with naringin. Also commonly present in citrus fruits, naringin is a flavonoid glycoside with a bitter taste. Naringenin lacks carbohydrates, while naringin’s chemical structure consists of a flavanone backbone to which two sugar molecules are connected, indicating that it is a glycoside.

Naringenin is a metabolite of naringin in the human body. It is poorly absorbed in the gastrointestinal tract, where intestinal bacteria usually convert it into its aglycone form, naringenin (2).

Metabolism

The complex mechanism of naringenin's metabolism, which involves several organs and enzymatic pathways, is essential to the compound's bioactivity and possible therapeutic uses in humans.

The human body extensively metabolizes naringenin through phase I and phase II enzymatic activities. These are the two main stages of metabolism, usually responsible for detoxifying and eliminating drugs and toxins.

Naringenin is first absorbed in the small intestine, where cytochrome P450 enzymes may subject it to phase I metabolism, resulting in hydroxylation and other changes. Phase II metabolism after that mostly takes place in the liver, where enzymes like sulfotransferases (SULTs) and UDP-glucuronosyltransferases (UGTs) help naringenin proceed through conjugation events like glucuronidation, sulfation, and methylation (3, 4). These changes make the molecule more soluble, making it easier for the bile and urine to excrete. Naringenin can also be further metabolized by the gut bacteria, which can change its biological effects and bioavailability.

Naringenin can be found in the lungs, trachea, gastrointestinal tract, liver, and kidneys, where it can modulate the activity of cells, leading them to activate various biochemical pathways (2).

Recommended Intake

As with other flavonoids, naringenin's recommended consumption is not clearly defined because dietary habits vary widely, and there is no dietary reference intake.

Epidemiological research, however, suggests that consuming 500mg to 1 gram of flavonoids, including naringenin, daily is linked to a number of health advantages, such as improved cardiovascular health, anti-inflammatory properties, and increased antioxidant capacity (5).

Foods Rich in Naringenin

Numerous fruits and vegetables are rich in naringenin. The most notable sources are citrus fruits, with grapefruits topping the list, especially white ones, which have the highest content (6). Lemons and oranges are also good sources of naringenin, so they complement any diet that aims to increase this compound's health benefits.

In addition to citrus fruits, other fruits with significant naringenin content include tomatoes (which are actually berries), cherries, and blueberries (7). Not only do these fruits enhance the taste of food, but they also increase the amount of this beneficial flavonoid that is consumed.

Foods	Naringenin Content /mg per 100g/	Average Serving Size
Grapefruit	25-35	1 medium (230g)
Orange	2-6	1 medium (140g)
Lemon	2-11	1 medium (65g)
Tomato	0.9-1.3	1 medium (123g)
Cherry	0.5-1	1 cup (154g)
Pistachio	0.5-1	1 oz (28g)
Blueberry	0.1-0.2	1 cup (148g)
Parsley	0.5	1/4 cup (15g)

These values are approximate and can vary based on the variety and growing conditions of the fruits.

Naringenin is also present in smaller amounts in bergamot, cocoa, water mint, and some types of beans (6).

Naringenin Supplements

Pure naringenin supplements are hard to find; however, this flavanone is commonly included in antioxidant or citrus supplements. These can come in the form of tablets, capsules, powders, or soft gels.

The doses of these commercially available supplements mostly fall between 200 and 500 mg per serving, while the naringenin content within can be at around 50mg.

Health Benefits

The health benefits of flavonoids are well known. Naringenin is a potent antioxidant that lowers the risk of chronic illnesses, including heart disease and some types of cancer, by reducing oxidative stress. Because inflammation is a prevalent element in many chronic illnesses, its anti-inflammatory effects help ameliorate inflammation and improve general health. Naringenin has also demonstrated promise in enhancing metabolic health, which includes improved control over blood sugar and cholesterol levels. Thus, including foods high in naringenin in your diet can have a major positive impact on your health, both restorative and protective.

Below, we will discuss these beneficial effects of naringenin in depth.

Inflammation

Naringenin has a variety of mechanisms to produce strong anti-inflammatory effects.

One important mechanism is its capacity to inhibit pro-inflammatory cytokines, including interleukins (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α) (8). Naringenin has the ability to decrease these cytokines, which in turn helps lower inflammation. Furthermore, naringenin inhibits nuclear factor-kappa B (NF-κB), a transcription factor essential for controlling inflammation.

Naringenin significantly reduces the expression of many inflammatory mediators by blocking NF-κB from translocating to the cell nucleus and activating inflammatory genes. Naringenin can also block the cyclooxygenase-2 (COX-2) enzyme, which lowers the production of prostaglandins, hormone-like molecules that play a large role in inflammation (2).

Cardiovascular Health

Strong antioxidants like naringenin aid in the neutralization of free radicals, lowering oxidative stress and preventing cardiovascular system damage. Additionally, this flavonoid has anti-inflammatory properties that help reduce blood vessel inflammation, which is a major contributing factor to the development of atherosclerosis.

Moreover, it has been discovered that naringenin enhances lipid metabolism by raising levels of high-density lipoprotein (HDL) cholesterol and decreasing levels of low-density lipoprotein (LDL) cholesterol and triglycerides (9). These lipid-modulating properties improve blood flow and lower the risk of heart attacks and strokes by preventing plaque formation in arteries.

Naringenin also promotes endothelial function, which raises cardiovascular efficiency and dilates blood vessels (10).

Anti-HCV Therapy

Naringenin's multiple mechanisms of action, including suppression of viral assembly, secretion, and replication, have drawn interest in it as a possible anti-HCV (Hepatitis C virus) treatment (11).

Naringenin inhibits the virus's release from infected cells, which lowers the viral load in the bloodstream and is one of the main ways it fights HCV. This flavonoid also disrupts the HCV replication cycle by blocking the enzyme NS5B polymerase, which is essential for the synthesis of viral RNA.

Naringenin also affects liver cells' lipid metabolism, reducing the supply of lipids needed by HCV for assembly and reproduction. It further obstructs the creation of lipoviral particles, which are necessary for HCV infectivity, by downregulating the production of apolipoprotein B (12).

Neurological Health

Because naringenin can pass across the blood-brain barrier, it can directly have neuroprotective effects. By neutralizing free radicals, naringenin helps reduce oxidative stress in the brain, shielding neurons from harm and lowering the risk of neurodegenerative illnesses like Parkinson's and Alzheimer's (13).

Also, it prevents the activation of microglia, the immune cells that live in the brain, and are crucial in the development of neuroinflammation (14).

Naringenin has been shown to improve synaptic plasticity and neurogenesis, two functions essential for memory and learning (15).

This phytochemical promotes the release of neurotrophic factors and modulates signaling pathways to support neuron survival and function. These combined activities highlight naringenin's potential as a therapeutic agent for maintaining cognitive function and avoiding neurological diseases.

Diabetes

Because naringenin decreases insulin resistance, blood sugar levels are lowered, and cell absorption of glucose is improved (16).

By raising high-density lipoprotein (HDL) cholesterol and decreasing triglycerides and low-density lipoprotein (LDL) cholesterol, naringenin's capacity to regulate lipid metabolism contributes to diabetes control. This control of lipids aids in preventing cardiovascular complications that are frequently linked to diabetes. Naringenin also affects the activity of enzymes involved in the metabolism of carbohydrates, which helps stabilize blood glucose levels (17).

Cancer

The possible use of neringenin in the prevention and treatment of cancer has drawn interest. It alters several signaling pathways linked to the spread of cancer, including those regulating cell division, death, and metastasis. It has been demonstrated that naringenin causes cell cycle arrest and induces programmed cell death (apoptosis), suppressing cancer cell proliferation (18). It also inhibits the action of enzymes involved in angiogenesis, the formation of new blood vessels to support the growth and metastasis of tumors, and tumor invasion (19).

Naringenin has shown promise against various cancer types in preclinical research and experimental settings. According to research, naringenin can stop tumor growth and spread in animal models and prevent the growth of cancer cells in the breast, prostate, colon, lung, and liver (20, 21).

Furthermore, naringenin has demonstrated the potential to avert UV-induced DNA damage, a factor pertinent to preventing skin cancer (19).

Although these results are encouraging, more research, including clinical trials, is required to completely clarify the therapeutic potential of naringenin against various human cancer types.

Weight Management

It has been discovered that naringenin inhibits the synthesis of cholesterol and fatty acids by blocking important enzymes like HMG-CoA reductase and fatty acid synthase (FAS). Furthermore, it increases fat burning by stimulating AMP-activated protein kinase (AMPK), an essential energy enzyme in cells, stimulating fatty acid oxidation (22).

Through its effects on the central nervous system, naringenin also affects appetite regulation. It has been shown to regulate the production of hormones involved in hunger and satiety signals, such as adiponectin and leptin (23).

Pregnancy

Naringenin is generally considered safe when consumed in moderate amounts as part of a balanced diet during pregnancy. However, limited research on the effects of naringenin supplementation during pregnancy is available, so caution is advised. Pregnant individuals should consult with their healthcare provider before taking naringenin supplements to ensure safety for both maternal and fetal health.

Interactions With Medications

Citrus fruits, certain supplements, and naringenin affect liver enzymes involved in drug metabolism and can interact with several drugs.

Naringenin suppresses the activity of cytochrome P450 enzymes, specifically CYP3A4, which are responsible for metabolizing various drugs, such as antibacterial, anticancer, and blood pressure drugs. Therefore, using naringenin along with other medications may raise the levels of those medications in the blood, which could have negative consequences or change their effectiveness.

A well-known interaction is with statin drugs, which are used to reduce cholesterol. Because naringenin can prevent statins from being metabolized, blood levels of these medications may rise, increasing the possibility of adverse effects such as muscle damage (24). Similarly, naringenin may interfere with immunosuppressants, anticoagulants, blood pressure medicines, and sedatives, among other drugs.

Historical Background

Naringenin has a rich historical background. Although citrus fruits have long been known for their therapeutic benefits, scientists didn't identify and analyze their constituents until the 1930s. Albert Szent-Györgyi, a Hungarian scientist who won the 1937 Nobel Prize in Physiology or Medicine for his research on vitamin C, was the one who initially found and isolated naringenin in the early 1930s (25, 26).

The name "naringenin" likely originates from the Sanskrit word for orange, "narang."

With developments in analytical chemistry and pharmacology in subsequent decades, scientists clarified the range of pharmacological characteristics of naringenin, including anti-inflammatory and antioxidant activities, as well as possible roles in preventing cancer and cardiovascular health.

Naringenin is still a highly investigated topic in science today, with studies being conducted to determine its medicinal potential and possible uses in various industries, such as medicine, functional foods, and dietary supplements.

Summary

Naringenin, a flavonoid phytochemical abundant in citrus fruits, has potent anti-inflammatory and antioxidant properties, offering potential health benefits. It modulates metabolic processes and protects cells from oxidative stress.

Rich sources of naringenin include grapefruits, oranges, and lemons.

Discovered in the 1930s by Albert Szent-Györgyi, naringenin has since been studied extensively for its diverse pharmacological effects, including anti-inflammatory, antioxidant, and potential anticancer properties.

Its consumption has various health benefits, including cardiovascular and neurological health and potential anti-HCV therapy. However, caution is advised regarding interactions with certain medications, such as statins.

References

Автор статьи: Ani Harutyunyan

Специальность: General Medicine at YSMU

Обновлено: Июль 09, 2024

Проверено Victoria Mazmanyan