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Apigenin: A potent antioxidant and anti-inflammatory flavonoid

Article
July 2, 2022
By
Ehab Naim, MBA.

apigenin has several biological characteristics, such as anticancer, antimicrobial, anti-inflammatory, antihypertensive, cardioprotective, antioxidant, and hepatoprotective properties .

Compound description

Apigenin is a naturally occurring flavonoid (a polyphenolic compound produced by plants) present in different fruits, vegetables, and herbs, like orange, garlic, parsley, chamomile, and celery (1, 2). The literature indicates that apigenin has several biological characteristics, such as anticancer, antimicrobial, anti-inflammatory, antihypertensive, cardioprotective, antioxidant, and hepatoprotective properties (1, 3).

 

Properties

Recent years have shown a growth in research investigating apigenin in vitro and in vivo health properties. Therapeutic actions of this bioactive compound have been shown to be driven by its properties, influencing mechanisms like these related to cell cycle arrest and apoptosis (4). It downregulates several cyclin-dependent kinases (protein kinases that play many roles in the cell cycle and are involved in longevity).

The antioxidant properties of apigenin are driven by its capacity to increase the expression of enzymes that fight oxidative stress, like superoxide dismutase (4). In addition, it has been found to alleviate oxidative stress resulting from cellular senescence (irreversible cell cycle arrest and a hallmark of aging) by promoting NAD+ (nicotinamide adenine dinucleotide, a molecule playing a central role in metabolism) and inhibiting CD-38 (a glycoprotein molecule that plays roles in cellular signaling and is involved in NAD metabolism) (4-7).

As an anti-inflammatory, apigenin potentially decreases the expression of several pro-inflammatory cytokines and pathways, like interleukins and tumor necrosis factor-alpha (4). The bioactive molecule has also been shown to increase nitric oxide (a molecule naturally produced in the body and plays a role in blood circulation by influencing blood vessels) levels by inhibiting the enzyme responsible for its breakdown (2).

Based on the abovementioned properties, apigenin has the potential to fight the aging process and promote longevity by acting on several pathways involved in the aging process (8, 9).

 

Use as a supplement

The literature has highlighted the importance of apigenin in improving cardiovascular health. In this context, preclinical studies emphasize that apigenin intake reduces blood pressure via multiple mechanisms (1, 4). Research has also indicated that apigenin has a potential role in lowering low-density lipoprotein (LDL or bad cholesterol), which is responsible for developing heart diseases. Furthermore, in vitro and  in vivo studies have consolidated the potential of apigenin as a protective bioactive compound for the myocardium by preventing ischemic injury (1, 4).

Research indicates apigenin may have hepatoprotective roles through its antioxidant capacity, anti-inflammatory functions, and several other roles. However, results regarding benefits in this domain are inconclusive and require further investigation (1, 10).

The benefits of apigenin could be observed across other organs. For example, preclinical studies have shown that apigenin exerts beneficial effects in animal models suffering from respiratory conditions like asthma and acute lung injury (1, 10). Other studies have shown that apigenin benefits the endocrine system, as it was found to possess pancreas-protecting effects. In addition to the previous, the literature indicates that it may exert protective effects on brain cells and may protect joints and bones by increasing mineralization and decreasing inflammation. This leads to a reduced chance of developing osteoporosis and arthritis (1). Research has also indicated that the molecule shows promising anticancer and antimicrobial effects (1, 2).

In clinical studies, apigenin has been tested and shown promising results in treating Alzheimer’s disease (enhanced cognitive function), insomnia (improved daytime functioning and sleep), knee osteoarthritis (decreased analgesic use), anxiety (reduced anxiety, body weight, and arterial blood pressure), and depression (reduced depression as measured by Hamilton depression rating scale) (4).

The typical recommended apigenin dose in literature is 900mg (11). In our Marketplace under the vendor DoNotAge, you can find apigenin as capsules (Pure Apigenin). Pure Apigenin provides the body with 500mg of the bioactive molecule per serving (serving is two capsules).

 

Side effects

The literature indicates that apigenin has an acceptable safety profile (12). However, the latter requires further validation and research. Moreover, the poor bioavailability and chemical instability of the bioactive molecule has been highlighted. It is recommended to use this supplement only after consulting a licensed healthcare professional, like a physician or pharmacist.

References

1.            Zhou X, Wang F, Zhou R, Song X, Xie M. Apigenin: A current review on its beneficial biological activities. Journal of Food Biochemistry. 2017;41(4):e12376.

2.            Wang M, Firrman J, Liu L, Yam K. A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota. BioMed Research International. 2019;2019:7010467.

3.            Kim JK, Park SU. Recent insights into the biological functions of apigenin. EXCLI journal. 2020;19:984-91.

4.            Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The Therapeutic Potential of Apigenin. International journal of molecular sciences. 2019;20(6):1305.

5.            Li BS, Zhu RZ, Lim S-H, Seo JH, Choi B-M. Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis. The American Journal of Chinese Medicine. 2021;49(05):1235-50.

6.            Ogura Y, Kitada M, Xu J, Monno I, Koya D. CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD(+)/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats. Aging. 2020;12(12):11325-36.

7.            Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, 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;62(4):1084-93.

8.            Mumpuni E, Mulatsari E. Molecular Docking and Toxicity Test of Apigenin Derivative Compounds as an Anti-Aging Agent. Journal of Applied Chemical Sciences. 2018;5(1):409-13.

9.            López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.

10.          Kashyap P, Shikha D, Thakur M, Aneja A. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review. J Food Biochem. 2022;46(4):e13950.

11.          DeRango-Adem EF, Blay J. Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers? Frontiers in Pharmacology. 2021;12.

12.          Miguel FG, Cavalheiro AH, Spinola NF, Ribeiro DL, Barcelos GRM, Antunes LMG, et al. Validation of a RP-HPLC-DAD Method for Chamomile (<i>Matricaria recutita</i>) Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti-Inflammatory Effect. Evidence-Based Complementary and Alternative Medicine. 2015;2015:828437.

 

Compound description

Apigenin is a naturally occurring flavonoid (a polyphenolic compound produced by plants) present in different fruits, vegetables, and herbs, like orange, garlic, parsley, chamomile, and celery (1, 2). The literature indicates that apigenin has several biological characteristics, such as anticancer, antimicrobial, anti-inflammatory, antihypertensive, cardioprotective, antioxidant, and hepatoprotective properties (1, 3).

 

Properties

Recent years have shown a growth in research investigating apigenin in vitro and in vivo health properties. Therapeutic actions of this bioactive compound have been shown to be driven by its properties, influencing mechanisms like these related to cell cycle arrest and apoptosis (4). It downregulates several cyclin-dependent kinases (protein kinases that play many roles in the cell cycle and are involved in longevity).

The antioxidant properties of apigenin are driven by its capacity to increase the expression of enzymes that fight oxidative stress, like superoxide dismutase (4). In addition, it has been found to alleviate oxidative stress resulting from cellular senescence (irreversible cell cycle arrest and a hallmark of aging) by promoting NAD+ (nicotinamide adenine dinucleotide, a molecule playing a central role in metabolism) and inhibiting CD-38 (a glycoprotein molecule that plays roles in cellular signaling and is involved in NAD metabolism) (4-7).

As an anti-inflammatory, apigenin potentially decreases the expression of several pro-inflammatory cytokines and pathways, like interleukins and tumor necrosis factor-alpha (4). The bioactive molecule has also been shown to increase nitric oxide (a molecule naturally produced in the body and plays a role in blood circulation by influencing blood vessels) levels by inhibiting the enzyme responsible for its breakdown (2).

Based on the abovementioned properties, apigenin has the potential to fight the aging process and promote longevity by acting on several pathways involved in the aging process (8, 9).

 

Use as a supplement

The literature has highlighted the importance of apigenin in improving cardiovascular health. In this context, preclinical studies emphasize that apigenin intake reduces blood pressure via multiple mechanisms (1, 4). Research has also indicated that apigenin has a potential role in lowering low-density lipoprotein (LDL or bad cholesterol), which is responsible for developing heart diseases. Furthermore, in vitro and  in vivo studies have consolidated the potential of apigenin as a protective bioactive compound for the myocardium by preventing ischemic injury (1, 4).

Research indicates apigenin may have hepatoprotective roles through its antioxidant capacity, anti-inflammatory functions, and several other roles. However, results regarding benefits in this domain are inconclusive and require further investigation (1, 10).

The benefits of apigenin could be observed across other organs. For example, preclinical studies have shown that apigenin exerts beneficial effects in animal models suffering from respiratory conditions like asthma and acute lung injury (1, 10). Other studies have shown that apigenin benefits the endocrine system, as it was found to possess pancreas-protecting effects. In addition to the previous, the literature indicates that it may exert protective effects on brain cells and may protect joints and bones by increasing mineralization and decreasing inflammation. This leads to a reduced chance of developing osteoporosis and arthritis (1). Research has also indicated that the molecule shows promising anticancer and antimicrobial effects (1, 2).

In clinical studies, apigenin has been tested and shown promising results in treating Alzheimer’s disease (enhanced cognitive function), insomnia (improved daytime functioning and sleep), knee osteoarthritis (decreased analgesic use), anxiety (reduced anxiety, body weight, and arterial blood pressure), and depression (reduced depression as measured by Hamilton depression rating scale) (4).

The typical recommended apigenin dose in literature is 900mg (11). In our Marketplace under the vendor DoNotAge, you can find apigenin as capsules (Pure Apigenin). Pure Apigenin provides the body with 500mg of the bioactive molecule per serving (serving is two capsules).

 

Side effects

The literature indicates that apigenin has an acceptable safety profile (12). However, the latter requires further validation and research. Moreover, the poor bioavailability and chemical instability of the bioactive molecule has been highlighted. It is recommended to use this supplement only after consulting a licensed healthcare professional, like a physician or pharmacist.

References

1.            Zhou X, Wang F, Zhou R, Song X, Xie M. Apigenin: A current review on its beneficial biological activities. Journal of Food Biochemistry. 2017;41(4):e12376.

2.            Wang M, Firrman J, Liu L, Yam K. A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota. BioMed Research International. 2019;2019:7010467.

3.            Kim JK, Park SU. Recent insights into the biological functions of apigenin. EXCLI journal. 2020;19:984-91.

4.            Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, et al. The Therapeutic Potential of Apigenin. International journal of molecular sciences. 2019;20(6):1305.

5.            Li BS, Zhu RZ, Lim S-H, Seo JH, Choi B-M. Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis. The American Journal of Chinese Medicine. 2021;49(05):1235-50.

6.            Ogura Y, Kitada M, Xu J, Monno I, Koya D. CD38 inhibition by apigenin ameliorates mitochondrial oxidative stress through restoration of the intracellular NAD(+)/NADH ratio and Sirt3 activity in renal tubular cells in diabetic rats. Aging. 2020;12(12):11325-36.

7.            Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, 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;62(4):1084-93.

8.            Mumpuni E, Mulatsari E. Molecular Docking and Toxicity Test of Apigenin Derivative Compounds as an Anti-Aging Agent. Journal of Applied Chemical Sciences. 2018;5(1):409-13.

9.            López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.

10.          Kashyap P, Shikha D, Thakur M, Aneja A. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review. J Food Biochem. 2022;46(4):e13950.

11.          DeRango-Adem EF, Blay J. Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers? Frontiers in Pharmacology. 2021;12.

12.          Miguel FG, Cavalheiro AH, Spinola NF, Ribeiro DL, Barcelos GRM, Antunes LMG, et al. Validation of a RP-HPLC-DAD Method for Chamomile (<i>Matricaria recutita</i>) Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti-Inflammatory Effect. Evidence-Based Complementary and Alternative Medicine. 2015;2015:828437.

 

Article reviewed by
Dr. Ana Baroni MD. Ph.D.
SCIENTIFIC & MEDICAL ADVISOR
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Dr. Ana Baroni MD. Ph.D.

Scientific & Medical Advisor
Quality Garant

Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.

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