Apigenin

Apigenin is a natural compound known as a flavone, a class of flavonoids. It’s recognized for its promising bioactive properties, notably its potential role in promoting longevity and overall health, by virtue of its influence on cellular functions and its antioxidant, anti-inflammatory, and anti-cancer properties.

Apigenin is found abundantly in various plant foods, such as parsley, celery, and chamomile tea. It’s a subject of increasing research interest due to its diverse biological activities and its potential benefits in preventing and managing a range of health conditions, from metabolic disorders to age-related diseases.

Research on apigenin in the context of longevity focuses primarily on its ability to modulate several cellular pathways related to aging. Apigenin is studied for its potential to inhibit CD38, an enzyme that consumes NAD+, a vital coenzyme in cellular energy metabolism and repair processes. ^[1] By potentially maintaining or elevating NAD+ levels, apigenin could play a role in delaying the aging process and mitigating age-related declines in cellular function. Additionally, its antioxidative and anti-inflammatory properties contribute to its role in promoting cellular health and longevity.

Sources of Apigenin

Apigenin is predominantly found in a variety of plant foods, contributing to the beneficial effects of a plant-rich diet. It is also available in supplement form, offering a concentrated source for those seeking to leverage its potential health and longevity benefits.

Common Foods

Apigenin is found in many fruits and vegetables, but parsley, celery, celeriac, and chamomile tea are the most common sources.^[2] Apigenin is particularly abundant in the flowers of chamomile plants, constituting 68% of total flavonoids.^[3] Dried parsley can contain about 45 mg apigenin/gram of the herb, and dried chamomile flower about 3-5 mg/gram.^[4] The apigenin content of fresh parsley is reportedly 215.5 mg/100 grams, which is much higher than the next highest food source, green celery hearts providing 19.1 mg/100 grams. ^[5]

Supplements

For those seeking higher, more concentrated doses of Apigenin, supplements are available, usually in capsule or powder form. However, it's crucial to approach Apigenin supplementation with caution and ideally under professional guidance, considering the optimal dosage, purity, and potential interactions with medications or other supplements have not been fully established. Users are advised to opt for high-quality, tested products to minimize the risk of contaminants and to adhere to recommended dosages to avoid potential adverse effects.

Benefits and Mechanisms of Action

Apigenin is not just a mere component of our diet; research has elucidated its diverse biological activities, depicting its significant role in promoting health and potentially extending lifespan through various mechanisms.

Antioxidant Properties

Oxidative Stress Reduction: Apigenin has potent antioxidant properties, helping neutralize free radicals and reducing oxidative stress, a key contributor to aging and many chronic diseases.
DNA Protection: By minimizing oxidative damage, Apigenin helps in maintaining the integrity of DNA, crucial for cellular function and longevity.

Anti-Inflammatory Effects

Inflammation Modulation: Apigenin can modulate inflammatory pathways, reducing the production of pro-inflammatory cytokines and potentially mitigating inflammation-related conditions and aging processes.

Cellular Pathways and Longevity

NAD+ Booster: Apigenin may inhibit CD38, potentially maintaining or elevating levels of NAD+, vital for cellular energy metabolism and repair processes, and associated with longevity.
Sirtuin Activation: Through its potential impact on NAD+ levels, Apigenin might indirectly activate sirtuins, a family of proteins associated with lifespan extension and improved healthspan.

Cancer Prevention

Cancer Cell Inhibition: Several studies have indicated that Apigenin can inhibit the growth of cancer cells and induce apoptosis, showing promise in cancer prevention and therapy.

Neuroprotective Effects

Neurological Health: Apigenin may have neuroprotective properties, protecting brain cells from damage and potentially reducing the risk of neurodegenerative diseases.

Cardiovascular Health

Cardiovascular Protection: The anti-inflammatory and antioxidative properties of Apigenin are beneficial for cardiovascular health, potentially reducing the risk of cardiovascular diseases.

While the benefits of Apigenin are promising, it is crucial to acknowledge that many studies are in the preliminary stages, predominantly in vitro or animal-based. More comprehensive human clinical trials are needed to validate these findings, determine optimal dosages, and understand the long-term impacts and potential side effects of Apigenin intake. Additionally, further exploration is required to elucidate the full spectrum of Apigenin’s mechanisms of action and its role in health and longevity.

Safety and Dosage

While Apigenin is generally recognized as safe due to its presence in common fruits and vegetables, considerations around its safety and dosage are paramount when contemplating supplemental use or concentrated intake.

General Safety

Natural Sources: Apigenin is found in many fruits, vegetables, and herbs, and consuming it from these natural sources is generally considered safe.
Side Effects: In supplemental or high doses, potential side effects include gastrointestinal discomfort, allergic reactions, or interactions with medications.

Recommended Dosage

Dietary Intake: No formal recommendations exist for dietary intake, but consuming a diet rich in fruits and vegetables containing Apigenin is encouraged.
Supplemental Dosage: There is no established recommended dosage for Apigenin supplements, and any supplemental use should be approached with caution and preferably under medical guidance.

Drug Interactions

Medication Interaction: Apigenin may interact with certain medications, altering their efficacy and metabolism. Consultation with healthcare providers is essential before supplementing, especially for those on medication.

Research Limitations

The majority of the safety and efficacy data on Apigenin come from in vitro and animal studies, necessitating further human studies to confirm its safety profile and establish appropriate dosages for therapeutic uses.

References

↑ Escande C et al.: Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 2013. (PMID 23172919) [PubMed] [DOI] [Full text] Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD(+) metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD(+) levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD(+)ase in mammals. Moreover, CD38 knockout mice have higher NAD(+) levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD(+) levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD(+) levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD(+) levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD(+)-dependent pathways.
↑ The compound in the Mediterranean diet that makes cancer cells 'mortal' Emily Caldwell, Medical Express, May 20, 2013.
↑ Venigalla M et al.: Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease. Neural Regen Res 2015. (PMID 26487830) [PubMed] [DOI] [Full text] Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible.
↑ Shankar E et al.: Plant flavone apigenin: An emerging anticancer agent. Curr Pharmacol Rep 2017. (PMID 29399439) [PubMed] [DOI] [Full text] Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4', 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin's anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.
↑ Flavonoids, http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids

[pmid23172919-1] Escande C et al.: Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes 2013. (PMID 23172919) [PubMed] [DOI] [Full text] Metabolic syndrome is a growing health problem worldwide. It is therefore imperative to develop new strategies to treat this pathology. In the past years, the manipulation of NAD(+) metabolism has emerged as a plausible strategy to ameliorate metabolic syndrome. In particular, an increase in cellular NAD(+) levels has beneficial effects, likely because of the activation of sirtuins. Previously, we reported that CD38 is the primary NAD(+)ase in mammals. Moreover, CD38 knockout mice have higher NAD(+) levels and are protected against obesity and metabolic syndrome. Here, we show that CD38 regulates global protein acetylation through changes in NAD(+) levels and sirtuin activity. In addition, we characterize two CD38 inhibitors: quercetin and apigenin. We show that pharmacological inhibition of CD38 results in higher intracellular NAD(+) levels and that treatment of cell cultures with apigenin decreases global acetylation as well as the acetylation of p53 and RelA-p65. Finally, apigenin administration to obese mice increases NAD(+) levels, decreases global protein acetylation, and improves several aspects of glucose and lipid homeostasis. Our results show that CD38 is a novel pharmacological target to treat metabolic diseases via NAD(+)-dependent pathways.

[2] The compound in the Mediterranean diet that makes cancer cells 'mortal' Emily Caldwell, Medical Express, May 20, 2013.

[pmid26487830-3] Venigalla M et al.: Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease. Neural Regen Res 2015. (PMID 26487830) [PubMed] [DOI] [Full text] Alzheimer's disease is a progressive neurodegenerative disorder, characterized by deposition of amyloid beta, neurofibrillary tangles, astrogliosis and microgliosis, leading to neuronal dysfunction and loss in the brain. Current treatments for Alzheimer's disease primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for Alzheimer's disease patients. This review will provide an overview of the proven antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of curcumin and apigenin and discuss the potential of these compounds for Alzheimer's disease prevention and treatment. We suggest that these compounds might delay the onset of Alzheimer's disease or slow down its progression, and they should enter clinical trials as soon as possible.

[pmid29399439-4] Shankar E et al.: Plant flavone apigenin: An emerging anticancer agent. Curr Pharmacol Rep 2017. (PMID 29399439) [PubMed] [DOI] [Full text] Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4', 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin's anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

[lpi-flav-5] Flavonoids, http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids

[1]

[2]

[3]

[4]

[5]