Apigenin’s Antioxidant Molecular Mechanism
A Multi-Dimensional Defense System for Free Radical Scavenging
The generation of free radicals is an inevitable process in living organisms. Respiration, environmental pollutants, and ultraviolet radiation all contribute to the production of superoxide anions (O₂⁻), hydroxyl radicals (・OH), and DPPH radicals. When these free radicals accumulate in large quantities, exceeding the body’s ability to eliminate them, they trigger oxidative stress and cause severe damage to cells and tissues. Apigenin, a flavonoid compound, is rich in phenolic hydroxyl groups within its molecular structure, acting as sophisticated “free radical scavengers.”
For example, in cell experiments, when cells are induced to produce large amounts of hydroxyl radicals by substances such as hydrogen peroxide, the addition of apigenin rapidly donates hydrogen atoms, combining with hydroxyl radicals and converting them into harmless substances such as water. This significantly reduces intracellular hydroxyl radical levels and mitigates damage to cellular DNA. Research data demonstrates that apigenin’s scavenging rate for hydroxyl radicals increases in a dose-dependent manner with increasing concentrations. In one study, a certain concentration of apigenin reduced the production of 8-hydroxydeoxyguanosine (8-DHG) in oxidative stress-induced DNA damage by 30%, demonstrating its protective effect on DNA.
In the presence of superoxide anion radicals, apigenin can dismutate superoxide anion radicals through electron transfer, generating oxygen and hydrogen peroxide. The resulting hydrogen peroxide is then decomposed into water and oxygen by intracellular enzymes such as catalase, thereby mitigating the oxidative stress response induced by superoxide anion radicals. In an in vitro chemical simulation system, apigenin’s scavenging rate against superoxide anion radicals increased significantly with increasing concentration, demonstrating its potent scavenging ability. Regarding DPPH free radicals, apigenin can donate hydrogen atoms to facilitate single-electron pairing in DPPH free radicals, causing them to discolor. This simple and effective method accurately measures apigenin’s free radical-scavenging ability in experiments evaluating its antioxidant capacity. By directly scavenging various free radicals in multiple ways, apigenin blocks free radical chain reactions, mitigating the harmful effects of oxidative stress on the body at its source.
Metal Ion Chelation and Oxidative Reaction Inhibition
Although present in minute quantities in the body, transition metal ions such as iron and copper play a key role in many redox reactions. In particular, in the Fenton reaction, iron ions catalyze hydrogen peroxide to produce highly reactive hydroxyl radicals, a key pathway for oxidative damage to biomolecules. Apigenin acts as a “metal ion guardian,” chelating with metal ions like iron and copper to form stable chelates.
When apigenin chelates with iron ions, the activity of the iron ions is greatly reduced, making them ineffective in catalyzing the Fenton reaction and thereby preventing the generation of large amounts of hydroxyl radicals. In in vitro models, the addition of apigenin reduced iron-induced lipid peroxidation by 45%. Lipid peroxidation refers to a series of oxidative reactions of unsaturated fatty acids in biological membranes, mediated by free radicals and other factors, leading to structural and functional damage to cell membranes. By chelating metal ions, apigenin successfully prevents them from participating in the lipid peroxidation chain reaction. This acts like a strong “protective film” on biological membranes, maintaining their integrity and fluidity, and ensuring that cells can carry out normal physiological activities such as material exchange and signal transmission. This effect not only protects normal cellular function at the cellular level but is also crucial for maintaining the health of entire tissues and organs.
Activation and Regulation of the Antioxidant Enzyme System
Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) are key components of the body’s antioxidant defense system. SOD catalyzes the dismutation of superoxide anion radicals, converting them into hydrogen peroxide and oxygen; GSH-Px and CAT are primarily responsible for decomposing hydrogen peroxide into water and oxygen, thereby preventing the further generation of more damaging hydroxyl radicals. Apigenin can precisely regulate the gene expression and activity of these antioxidant enzymes by activating the Nrf2/ARE signaling pathway. When the body is exposed to oxidative stress, apigenin can induce Nrf2 to dissociate from its binding to Keap1, allowing it to enter the cell nucleus and bind to the antioxidant response element (ARE), initiating the transcription of genes encoding antioxidant enzymes such as SOD, GSH-Px, and CAT, thereby increasing their synthesis. In animal experiments, when apigenin was administered to animals with oxidative damage, researchers were surprised to find that SOD activity in the liver tissue increased by 25% and GSH-Px activity by 20%. This suggests that apigenin can significantly enhance the body’s antioxidant defenses, providing a more comprehensive and sustained defense against oxidative stress through the endogenous antioxidant enzyme system. This activation of the antioxidant enzyme system allows apigenin to go beyond simply scavenging free radicals in its antioxidant process, stimulating antioxidant “potential” within the cell, providing strong support for maintaining the body’s redox balance.
The Core Role of Apigenin in Anti-Aging
The Core Role of Apigenin in Anti-Aging(I) Molecular Regulatory Mechanisms of Cellular Senescence
Targeting PRDX6 to Inhibit the Senescence-Associated Secretory Phenotype (SASP)
Cellular senescence is accompanied by the emergence of the senescence-associated secretory phenotype (SASP). The SASP secretes a large number of inflammatory factors and proteases, negatively impacting surrounding tissues and cells and accelerating the aging process. Zhang Weidong’s team at Shanghai University of Traditional Chinese Medicine has conducted in-depth research on this mechanism. Through a series of experiments, they discovered that Apigenin acts like a precise “molecular key” that directly binds to peroxiredoxin 6 (PRDX6). PRDX6 has multiple intracellular activities, among which phospholipase A2 (PLA2) activity is closely linked to the generation of the SASP.
When apigenin binds to PRDX6, it acts like a “pause button” on PRDX6’s PLA2 activity, effectively inhibiting it. This inhibition triggers a series of subsequent chain reactions. The researchers further demonstrated through protein interaction experiments and signaling pathway analysis that apigenin disrupts the interaction between the heat shock protein HSPA8 and the ATM/p38MAPK signaling pathway. The ATM/p38MAPK signaling pathway plays a key role in the expression of SASP factors induced by the DNA damage response (DDR). By blocking this critical link, apigenin significantly reduced the expression of SASP factors (such as IL-6 and TNF-α). In cell experiments, senescent cells treated with apigenin saw a 40% and 35% decrease in IL-6 and TNF-α secretion, respectively. This clearly demonstrates apigenin’s inhibitory effect on the SASP, reducing the disruption of tissue homeostasis by senescent cells and slowing the aging process at the cellular level.
Regulating the Balance between the Cell Cycle and Apoptosis
A key characteristic of cellular senescence is the disruption of the balance between the cell cycle and apoptosis. If abnormally proliferating cells are not promptly cleared, this can disrupt the tissue environment and accelerate aging. Apigenin plays a crucial role in regulating this balance. By inducing the p53/p21 pathway, it acts like a “checkpoint” in the cell cycle, forcing senescent cells into a cell cycle arrest state and preventing further abnormal proliferation. Furthermore, apigenin precisely regulates the expression of apoptosis-related proteins. It inhibits the expression of the anti-apoptotic protein Bcl-2, acting like a “brake” on apoptosis, making it easier for cells to initiate apoptosis and induce apoptosis in those cells that have already proliferated and become senescent.
To verify this effect, researchers conducted in vitro experiments using a senescent human skin fibroblast model. The degree of cell senescence was assessed by measuring the number of β-galactosidase-positive cells. The results showed that apigenin treatment reduced the number of β-galactosidase-positive cells by 35%. This data strongly demonstrates that apigenin can effectively delay the process of cellular senescence. By maintaining a balance between the cell cycle and apoptosis, it keeps cells in a relatively youthful and healthy state, effectively safeguarding the normal function of tissues and organs.
(II) Multi-Organ System Anti-Aging Protection Effects
Delaying Skin Aging and Skin Barrier Repair
As the largest organ in the human body, the skin is directly exposed to the external environment and is one of the areas most susceptible to aging. With aging, collagen in the skin gradually degrades, reducing elastic fibers, leading to sagging and wrinkles. The skin barrier function also deteriorates, weakening its ability to resist external stimuli. Apigenin demonstrates significant efficacy in delaying skin aging and repairing the skin barrier.
Regarding collagen metabolism, apigenin can inhibit the activity of matrix metalloproteinase (MMP-1), an enzyme that degrades collagen. Research data shows that apigenin inhibits MMP-1 by up to 40%, significantly slowing collagen degradation and maintaining skin elasticity and firmness. Apigenin also promotes the synthesis of hyaluronic acid, a powerful moisturizing agent that retains moisture in the skin, making it appear more hydrated and plump. In a UV-induced damage model, UV exposure leads to increased keratinocyte apoptosis, accelerating photoaging. However, apigenin treatment reduced keratinocyte apoptosis by 28%, effectively delaying the formation of photoaging-related wrinkles. This series of effects suggests that apigenin protects the skin from multiple levels, maintaining its youthful appearance and strengthening the skin barrier function, providing better protection against environmental aggressors.
Improvement of Metabolic Aging
With aging, the body’s metabolic function gradually declines, leading to increasingly prominent problems such as impaired fat metabolism and insulin resistance, which are key manifestations of metabolic aging. In a mouse model of high-fat diet-induced aging, researchers found that apigenin can activate the AMPK pathway, essentially revitalizing the cell’s energy metabolism “engine” and promoting fatty acid oxidation. Experimental data showed that apigenin treatment reduced serum triglycerides (TG) by 22% and low-density lipoprotein (LDL-C) by 18%, demonstrating that apigenin can effectively regulate blood lipid levels and reduce fat accumulation. Insulin resistance is another key issue associated with metabolic aging. It can lead to abnormal blood sugar regulation and increase the risk of diseases such as diabetes. Apigenin also plays a positive role in improving insulin resistance by increasing the expression of the glucose transporter GLUT4 by 25%. GLUT4 is a key protein responsible for transporting glucose into cells. Increased expression of GLUT4 enhances the cells’ ability to uptake and utilize glucose, thereby improving insulin resistance and stabilizing blood sugar levels. These results suggest that apigenin can comprehensively improve issues associated with metabolic aging, delaying the aging of metabolic organs, maintaining normal metabolic function, and providing strong support for overall health.
Neuroprotection and Cognitive Function Maintenance
The brain, the “headquarters” of the human body, faces the risk of neurodegeneration with aging. Problems such as amyloid-β (Aβ) deposition and tau protein hyperphosphorylation can lead to neuronal damage and cognitive decline, resulting in symptoms such as memory loss and cognitive impairment, which seriously impact quality of life. Apigenin, thanks to its unique molecular structure and bioactivity, is able to cross the blood-brain barrier, acting like a brave “guardian” and entering the brain to exert powerful neuroprotective effects. Apigenin can scavenge free radicals in the central nervous system, reducing oxidative stress-induced neuronal damage and providing a relatively “clean” living environment for neurons. It also inhibits the deposition of amyloid-β (Aβ), preventing Aβ aggregation into neurotoxic oligomers and fibrils, and reducing its toxic effects on neurons. Regarding Tau protein, apigenin can inhibit its hyperphosphorylation, maintaining its normal function and safeguarding the structural and functional stability of neurons. In Parkinson’s disease models, apoptosis of dopaminergic neurons is a key factor in the development and progression of Parkinson’s disease. The intervention of apigenin reduced the apoptosis rate of dopaminergic neurons by 30%. This result shows that apigenin has great potential in preventing neurodegenerative diseases. By protecting neurons and maintaining the normal function of the brain, it effectively improves memory and cognitive functions, keeping the brain “young”. It has important research value and application prospects for the prevention and treatment of neurodegenerative diseases such as Alzheimer’s disease.
Research Progress on Apigenin’s Antioxidant and Anti-Aging Effects
Cutting-Edge Scientific Discoveries
Apigenin continues to yield exciting new advances in the field of antioxidants and anti-aging. A study published in Advanced Science in 2025 revealed a novel mechanism of action and remarkable efficacy of apigenin in anti-aging.
Through carefully designed experiments, researchers defined apigenin as a senomorph—a regulator of senescent cell function. This discovery is highly significant, opening up a new understanding of apigenin’s effects. During the experiment, the researchers established a mouse model of premature aging and observed a series of surprising changes by administering apigenin to these mice.
In terms of exercise endurance, mice treated with apigenin showed a significant improvement, with exercise endurance increasing by 20% compared to the untreated group. This suggests that apigenin can effectively improve the physical function of aging mice, enabling them to exhibit greater capacity for physical activity. The mice also performed exceptionally well in cognitive tests, performing significantly better than the control group in cognitive tasks like maze tests and finding their way around more quickly. This suggests that apigenin has a positive protective and improving effect on brain function, potentially helping to slow cognitive aging.
The researchers also delved into the effects of apigenin on age-related diseases. They found that apigenin significantly reduced muscle atrophy, maintaining muscle strength and mass in mice. Regarding vascular sclerosis, apigenin inhibited the thickening and hardening of blood vessel walls, reducing the risk of cardiovascular disease. These results suggest that apigenin, by regulating the function of senescent cells, can intervene in multiple aspects of age-related diseases, providing novel targets and approaches for the prevention and treatment of age-related diseases and potentially playing an important role in future clinical treatments.
Clinical Application Potential
Currently, clinical research on apigenin as an antioxidant focuses primarily on its adjunctive treatment for chronic diseases, demonstrating its significant potential. In the treatment of atherosclerosis, clinical studies have shown that combining apigenin with statins can produce a synergistic effect. Statins are commonly used to treat cardiovascular disease, primarily by lowering blood lipids to reduce atherosclerotic cardiovascular events. Apigenin, with its antioxidant and anti-inflammatory properties, can scavenge free radicals within blood vessels, mitigate oxidative stress damage to endothelial cells, and inhibit inflammation, reducing the stimulation of inflammatory factors on the blood vessel wall.
When used together, apigenin enhances the protective effects of statins on the endothelium. Clinical data show that patients in the combined treatment group experienced significant improvements in endothelial function, with increased levels of nitric oxide secreted by endothelial cells. Nitric oxide is a key vasodilator that helps maintain vascular elasticity and dilation. Furthermore, inflammatory markers such as C-reactive protein were significantly reduced in patients’ blood, indicating that the inflammatory response was effectively controlled, further reducing the risk of atherosclerosis progression and providing a more effective treatment option for cardiovascular disease.
In the anti-aging field, a major challenge facing apigenin is its low bioavailability, which limits its effectiveness in the body. However, researchers have made significant breakthroughs in nanodelivery systems, offering hope for addressing this issue. Among them, liposome carriers are a commonly used nano-delivery system, which uses phospholipids and other materials as the main materials to form double-layer membrane vesicles similar to the cell membrane structure. After encapsulating apigenin inside the liposomes, the stability of apigenin can be effectively improved, and its degradation and inactivation in the gastrointestinal tract can be reduced. The structure of liposomes makes it easier for cells to take up apigenin, and through fusion with the cell membrane or endocytosis, apigenin is accurately delivered to the inside of the cell, thereby improving the bioavailability of apigenin. At present, the nano-delivery system of apigenin is in the preclinical research stage. Although it is still some distance away from clinical application, these preliminary research results have laid a solid foundation for the application of apigenin in the anti-aging field. Once successfully applied in clinical practice, it will provide a new and powerful means to delay aging and improve the quality of life of the elderly.
Scientific Applications and Future Outlook
(I) Dietary Intake and Supplementation Recommendations
In our daily lives, we can consume apigenin through a variety of dietary choices to enjoy its health benefits. Celery is one of the most familiar apigenin-rich foods, containing approximately 15mg per 100g. Whether it’s a cold celery salad, wash and cut fresh celery into sections, add appropriate seasonings and mix well for a refreshing and delicious dish that preserves the celery’s original flavor while maximizing its apigenin intake. Or stir-frying celery with shredded pork, combining celery and shredded pork, is a nutritious and excellent choice. In addition to celery, chamomile tea is also a good source of apigenin. A cup of chamomile tea on a busy afternoon not only soothes the mind and body but also replenishes apigenin. The apigenin in chamomile is fully released and absorbed by the body when brewed with hot water. Parsley is also rich in apigenin. It’s often used as a garnish or side dish in Western cuisine. We can make full use of it when we consume it. For example, adding some fresh parsley to a salad not only adds flavor but also increases apigenin intake.
To achieve optimal health benefits, the recommended daily intake of apigenin is 50-100mg. This intake is based on extensive scientific research and experimental results. Within this range, apigenin can best exert its antioxidant and anti-aging effects, helping us maintain a healthy state. For certain populations, such as the elderly and those with chronic illnesses, increasing apigenin intake may offer greater benefits. However, before adjusting your diet or supplement dosage, it’s best to consult a doctor or nutritionist.
When taking apigenin in the form of a dietary supplement, pay special attention to the product’s quality and purity. It’s recommended to choose a standardized extract with a purity of ≥95%. This high-purity extract ensures sufficient and effective apigenin. Taking it after a meal is a good option. This is because the presence of food in the gastrointestinal tract after a meal can slow the absorption of apigenin, allowing it to be more fully absorbed and utilized, thereby increasing its absorption rate and enhancing its effectiveness.
(II) Precautions and Research Directions
Although apigenin has a good safety profile, there are still some precautions to take during its use. In particular, for those taking anticoagulants (such as warfarin), apigenin may interact with these medications. Warfarin is a commonly used anticoagulant that exerts its anticoagulant effect by inhibiting the synthesis of vitamin K-dependent coagulation factors. Apigenin has certain antioxidant and antiplatelet effects. When used in combination with warfarin, it may enhance the anticoagulant effect of warfarin and increase the risk of bleeding. Therefore, patients taking anticoagulants should consult their doctor before considering apigenin supplementation. The doctor will comprehensively assess the risks and benefits based on the patient’s specific circumstances, including their medical condition and medication regimen, and provide professional advice.
Looking forward, there are many areas of apigenin’s antioxidant and anti-aging potential that warrant further research. Regarding major aging-related diseases such as Alzheimer’s disease and cardiovascular disease, while some studies have shown that apigenin has potential for preventing and treating these conditions, further large-scale, high-quality clinical studies are needed to further validate its efficacy. For example, in the case of Alzheimer’s disease, although previous studies have found that apigenin can inhibit β-amyloid deposition and reduce neuroinflammation, clinical trials are still needed to clarify the optimal dosage, treatment duration, and safety of apigenin in humans, providing a solid scientific basis for the development of new treatment strategies.
In terms of delivery technology, developing efficient delivery systems is also a key focus for future research. Currently, one of the main challenges facing apigenin is its low bioavailability, which limits its effective use in the body. The development of novel delivery systems, such as nanoparticles and liposomes, is expected to improve apigenin’s stability, solubility, and cellular uptake, enabling it to more precisely reach its target site and fully exert its antioxidant and anti-aging benefits. These novel delivery systems can protect apigenin from the damaging effects of the gastrointestinal environment, increase its circulation time and concentration in the body, and pave the way for its widespread application in pharmaceuticals and health supplements.
