Apigenin: A Cornerstone Supplement for Cellular Health and Longevity

Apigenin is a powerful bioactive flavonoid found in plants such as chamomile, parsley, and celery. Recognized for its antioxidant, anti-inflammatory, and anticancer properties, apigenin plays a significant role in cellular health and longevity.

This article explores the mechanisms behind apigenin’s impact on health, including its ability to reduce oxidative stress and inflammation, combat cancer, and influence key longevity pathways. Additionally, we’ll examine apigenin’s effects on NAD+ metabolism and autophagy, two essential processes for aging and overall health.

Traditional Uses of Apigenin

Apigenin derives its name from the genus Apium in the Apiaceae (Umbelliferae) family. It is a prominent bioactive compound in chamomile (Matricaria chamomilla), an herb native to Western Asia and Europe.

As a flavonoid glycoside, apigenin is the non-sugar portion of naturally occurring glycosides. Structurally, it is a yellow-colored crystalline compound that was historically used as a natural dye.

Apigenin has been used in traditional medicine for centuries:

• Chamomile – A remedy for insomnia, digestive issues, and inflammation

• Parsley – Known for detoxifying and diuretic properties

• Celery – Traditionally used to reduce blood pressure and inflammation

Ancient civilizations, including the Egyptians and Greeks, unknowingly benefited from apigenin’s properties by consuming chamomile tea for its calming and anti-inflammatory effects.

Although isolated in the 1930s, apigenin remained relatively obscure until the mid-20th century, when polyphenols were recognized for their health benefits. Today, scientific interest in longevity and cellular health has propelled apigenin into the spotlight.

Key reasons for its growing popularity include:

• Supports pathways like NAD+ metabolism and autophagy

• Potent antioxidant and anti-inflammatory effects

• Natural anticancer properties

As more people seek natural alternatives to synthetic drugs, apigenin supplements have gained popularity for their potential to enhance overall health and longevity.

General Health Benefits of Apigenin

Powerful Antioxidant Protection

Apigenin acts as a potent antioxidant, protecting cells from oxidative stress, a major contributor to aging and disease. Oxidative stress occurs when free radicals outnumber the body's ability to neutralize them, leading to cellular damage.

Apigenin combats oxidative stress through multiple mechanisms:

• Free radical scavenging – Neutralizes harmful reactive oxygen species (ROS), stabilizing cellular structures and promoting longevity (1).

• Regulation of oxidant enzymes – Modulates enzymes such as cyclooxygenase, nitric oxide synthase, xanthine oxidase, and lipoxygenase, reducing oxidative damage (2).

• Activation of Nrf2 pathway – Upregulates key antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1), preventing oxidative stress (3).

• Metal chelation – Binds with transition metals (Fe²⁺, Fe³⁺, Cu²⁺) to prevent the formation of harmful free radicals (4).

• Mitochondrial protection – Enhances mitochondrial function, crucial for energy production and longevity (5).

Anti-Inflammatory Effects and Disease Prevention

Chronic inflammation is a major driver of age-related diseases, including cardiovascular conditions, arthritis, and neurodegenerative disorders. Apigenin helps reduce inflammation by:

• Inhibiting pro-inflammatory cytokines and NF-κB, a key regulator of inflammation (6).

• Activating anti-inflammatory pathways, such as p38/MAPK and PI3K/Akt (7).

• Reducing COX-2 activity, further suppressing inflammatory responses (7).

• By lowering inflammation, apigenin helps protect tissues, strengthen the immune system, and reduce the risk of inflammatory diseases.

Apigenin and Its Role in Cancer Prevention

Apigenin has strong anticancer properties, with studies showing its ability to inhibit tumor growth in breast, colon, prostate, and skin cancers (8). It works through multiple mechanisms:

• Induces apoptosis (programmed cell death) in cancer cells, preventing uncontrolled growth.

• Disrupts the cell cycle, slowing cancerous cell replication.

• Inhibits angiogenesis, the formation of new blood vessels that tumors need to grow and spread.

• These mechanisms make apigenin a promising natural compound for cancer prevention and adjunctive therapy.

Apigenin and Longevity Pathways

Regulation of NAD+ Metabolism

NAD+ (nicotinamide adenine dinucleotide) is a crucial coenzyme involved in cellular energy production, DNA repair, and gene expression. However, NAD+ levels decline with age, reducing cellular efficiency and increasing disease risk.

CD38, an enzyme that regulates NAD+ levels, becomes overactive with aging, leading to NAD+ depletion (9).

Apigenin helps preserve NAD+ by:

• Inhibiting CD38 activity, reducing excessive NAD+ breakdown (10).

• Maintaining NAD+ levels, ensuring efficient DNA repair and cellular metabolism (11).

• By sustaining NAD+ levels, apigenin enhances longevity-related processes, including sirtuin activation and autophagy.

Enhancing Autophagy

Autophagy is the cell’s natural recycling process, removing damaged proteins and organelles to maintain cellular health. With age, autophagy declines, leading to cellular dysfunction and disease.

Apigenin enhances autophagy by:

• Activating AMPK/mTOR signaling, boosting autophagic activity (13).

• Promoting cellular integrity and reducing the accumulation of senescent cells (12).

Senolytic Effects: Clearing Senescent Cells

Senescent cells are aged cells that stop dividing but continue secreting inflammatory molecules. They contribute to tissue dysfunction and degenerative diseases.

Apigenin aids in senescent cell clearance by:

• Triggering apoptosis via Fas and TNF receptors (14).

• Reducing SASP (senescence-associated secretory phenotype) secretion (15).

• Enhancing p53 activity, increasing cell death in damaged cells (16).

• Downregulating anti-apoptotic proteins like Bcl-2, making senescent cells more vulnerable (16).

• These properties make apigenin a valuable longevity compound, promoting cellular renewal and reducing age-related damage.

Apigenin and Sleep Optimization

Apigenin is known for its calming effects, making it useful for anxiety reduction and sleep improvement.

It works by:

• Enhancing GABAergic activity, promoting relaxation and better sleep quality (17).

• Regulating inflammation and oxidative stress, supporting circadian rhythm balance (18).

• Chamomile extract, rich in apigenin, has been shown to reduce anxiety and blood pressure, further supporting overall health (19).

Apigenin: Food Sources vs. Supplements

Natural Food Sources

Apigenin is found in many plant-based foods, including (20):

• Celery seeds – 78.65 mg/100 g

• Spinach – 62.0 mg/100 g

• Parsley – 45.04 mg/100 g

• Chamomile – 3 to 5 mg/100 g

Dietary intake of apigenin is estimated at 20-25 mg per day, but achieving therapeutic doses through food alone is difficult, which is why supplements can be beneficial.

Limitations of Dietary Apigenin

• Low bioavailability – Rapid metabolism reduces absorption.

• Difficult to reach therapeutic doses – Large quantities of food are required to meet ideal intakes. For example, to obtain 50 mg of apigenin, one would need to eat over 100 grams of parsley daily—an impractical amount.

Benefits of Apigenin Supplements

• Higher concentration and improved absorption

• Standardized dosing for consistency

• Synergistic effects with other longevity compounds

Final Thoughts: The Future of Apigenin in Longevity Research

As scientific interest in apigenin grows, its role in anti-aging, disease prevention, and cellular health continues to expand. Whether through diet or supplementation, such as Jung'+s Longevity Foundation, incorporating apigenin into a longevity-focused routine offers promising health benefits for years to come.

References:

1. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review (2022). Journal of Food Biochemistry.

2. Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays  (2013). Analytica Chimica Acta.

3. Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway (2020). Cell Stress and Chaperones.

4. Flavonoids and their properties to form chelate complexes (2012). Biotechnology and Food Sciences.

5. Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function (2013). International Journal of Molecular Sciences.

6. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages (1999). Carcinogenesis.

7. Apigenin-mediated modulations of PI3K-Akt and MAPK signaling pathways causes growth Inhibition and cell cycle arrest in human prostate cancer cells (2007). Cancer Research.

8. Apigenin: A promising molecule for cancer prevention (2010). Pharmaceutical Research. 

9. CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism (2017). Cell Metabolism.

10. Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38 (2013). Diabetes.

11. Sirtuin activation as a therapeutic approach against inborn errors of metabolism (2016). Journal of Inherited Metabolic Disease.

12. Apigenin, a natural flavonoid, promotes autophagy and ferroptosis in human endometrial carcinoma Ishikawa cells in vitro and in vivo (2023). Food Science and Human Wellness.

13. The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR/AMPK/ULK1 pathway (2019). Molecular Medicine Reports.

14. The Effects of Apigenin on the Expression of Fas/FasL Apoptotic Pathway in Warm Liver Ischemia-Reperfusion Injury in Rats (2014). BioMed Research International.

15. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells (2017). Geroscience.

16. Apigenin protects gamma-radiation induced oxidative stress, hematological changes and animal survival in whole body irradiated Swiss albino mice (2012). International Journal of Nutrition, Pharmacology, Neurological Diseases.

17. Flavonoids as GABAA receptor ligands: the whole story? (2012). Journal of Experimental Pharmacology.

18. Role of Food Phytochemicals in the Modulation of Circadian Clocks (2019). Journal of Agricultural and Food Chemistry.

19. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial (2016). Phytomedicine.

20. Polyphenols in the Mediterranean Diet: From Dietary Sources to microRNA Modulation (2021). Antioxidants (Basel).