Latest Research Progress on the Anti-Aging Effects of Ellagic Acid
Aging is accompanied by the decline of physiological functions of the body, triggering various chronic diseases. Therefore, finding effective anti-aging intervention methods is of great significance. Ellagic acid, as a natural polyphenol dilactone, exists in many plants and has various biological activities such as antioxidant and anti-inflammatory effects, exerting anti-aging effects at the cellular, tissue and systemic levels. This review systematically expounds its plant sources, physicochemical properties, current application progress and future development directions, aiming to provide a theoretical basis for in-depth research and development applications in this field.
Keywords: Ellagic acid; anti-aging; antioxidant; anti-inflammatory; autophagy
1. Introduction
With the intensification of global aging, it is urgent to find safe and effective anti-aging strategies. Ellagic acid from natural sources has attracted much attention due to its wide existence in fruits such as blueberries, strawberries, pomegranates and nuts, as well as its significant anti-aging activity. This substance can not only play a role through direct absorption, but its intestinal metabolite urolithin A can promote mitochondrial autophagy, showing multiple anti-aging effects at the cellular, tissue and systemic levels, providing a natural solution for improving the health of the elderly.
2. Physicochemical Properties and Biological Metabolism of Ellagic Acid
Ellagic acid is a natural polyphenolic compound widely present in the plant kingdom. It contains four phenolic hydroxyl groups and two lactone groups, which give it strong antioxidant activity. Under alkaline conditions, the lactone ring is easy to open to form ellagic acid salt with better water solubility. However, its sensitivity to light and heat makes it easy to degrade during processing. At present, its stability and bioavailability can be significantly improved through nano-encapsulation or structural modification. After oral administration, part of ellagic acid is hydrolyzed into gallic acid in the gastrointestinal tract, and part is absorbed into the blood circulation in its original form. The unabsorbed ellagic acid enters the colon and is metabolized by intestinal microorganisms into urolithins and other products, which can promote mitochondrial autophagy and improve mitochondrial function.
3. Mechanisms of Ellagic Acid in Systematically Delaying Aging
3.1 Antioxidant Effect
As a powerful natural antioxidant, ellagic acid can directly scavenge reactive oxygen species, with a scavenging rate 3-5 times higher than that of vitamin C. At the same time, it can up-regulate the expression of many endogenous antioxidant enzymes by activating related signaling pathways. Studies have found that ellagic acid can reduce the expression level of 8-hydroxydeoxyguanosine, a marker of oxidative damage in senescent cells, and can effectively protect the mitochondrial membrane potential. In the D-galactose-induced aging mouse model, the antioxidant capacity of brain tissue is increased by 2.3 times. These effects together constitute the core mechanism of ellagic acid in delaying aging related to oxidative stress.
3.2 Anti-Inflammatory Effect
Chronic low-grade inflammation, as one of the core biological characteristics of aging, significantly promotes the process of cellular senescence by continuously activating inflammation-related signaling pathways. Ellagic acid intervention can significantly reduce the serum CRP expression level in aging model mice and reduce the infiltration of inflammatory cells in liver tissue, and its mechanism involves the negative regulation of relevant signaling pathways. In addition, in the animal model of Alzheimer's disease, ellagic acid can effectively inhibit the abnormal activation of microglia, reducing the density of GFAP-positive cells in the hippocampus by 55%, which fully confirms its effect of delaying aging related to neuroinflammation.
3.3 Activation of Autophagy
The activation of autophagy, as a key target for anti-aging intervention, can effectively inhibit the occurrence and development of various aging-related phenotypes by regulating the protein homeostasis network and organelle renewal mechanism. Ellagic acid enhances autophagic activity, promotes the selective clearance of damaged mitochondria and protein aggregates. In the aging model, it reduces the accumulation of abnormal proteins and reduces the level of related genes. At the same time, it enhances the function of the autophagy-lysosome system. In the liver tissue of D-galactose-induced aging mice, the autophagic flux is restored to 70-80% of that in the young state, showing its multi-target activation of autophagy to play an anti-aging role.
3.4 Epigenetic Modification
Epigenetic mechanisms such as the dynamic balance of DNA methylation modification, the precise regulation of histone post-translational modification, and the non-coding RNA-mediated regulation of gene expression together constitute the key molecular switches that regulate the aging process, directly determining the expression characteristics of aging-related genes. Existing studies have shown that ellagic acid can inhibit the pro-aging signaling pathway by up-regulating the expression of aging-related miRNAs. In addition, in the D-galactose-induced aging model, ellagic acid treatment can effectively restore the genome-wide DNA hydroxymethylation level and significantly improve the epigenetic modification status of telomere-related proteins, exerting the anti-aging effect mediated by epigenetic reprogramming.
4. Safety Research on Clinical Application of Ellagic Acid
Ellagic acid shows multi-target effects in clinical anti-aging applications, and is currently mainly studied through interventions such as pomegranate extract. Clinical trials show that daily supplementation of pomegranate extract containing ellagic acid (370mg/capsule) for 12 weeks can significantly reduce inflammatory markers in the elderly and improve systolic blood pressure; in terms of skin anti-aging, the cream containing ellagic acid can significantly improve skin brightness, reduce density and fade wrinkles after 4 weeks of use. In addition, urolithin A, a metabolite of ellagic acid, shows a dose-dependent anti-inflammatory effect in human trials, which can enhance muscle function but does not significantly affect mitochondrial biogenesis. Ellagic acid has a unique antioxidant-anti-inflammatory-metabolic regulation multiple anti-aging mechanism, making it occupy an important position in the development of functional anti-aging products.
5. Experimental Analysis of Safety Threshold of Ellagic Acid
Safety research data show that ellagic acid has good tolerance at the recommended clinical dose (≤500mg/day), and the adverse reaction spectrum is mainly mild gastrointestinal symptoms, showing a dose-response relationship; basic toxicology tests show that its acute toxicity threshold is high (rat LD50>2000mg/kg), and no organ-specific damage is observed in medium-term toxicity observation, but the long-term medication safety and pharmacokinetic parameters in high-risk groups need to be further clarified.
6. Application Value of Ellagic Acid in Anti-Aging Health Products and Health Maintenance Systems
Ellagic acid shows diversified values in anti-aging applications due to its excellent antioxidant properties, stimulation of collagen production and inhibition of melanin formation: as a key active ingredient, it can be formulated into various anti-aging skin care products such as essences and creams, effectively improving signs of skin aging; as a functional additive in sunscreen formulations, it can synergize with traditional sunscreens to enhance anti-photoaging effects; in the field of health food, it can be processed into capsules, tablets and other forms to delay the aging process by regulating the redox state of the body. In addition, by daily consumption of fruits rich in ellagic acid or fortified functional foods, a complete anti-aging system covering professional care and daily nutrition is built for consumers.
7. Conclusion
Ellagic acid shows multi-level protective effects in the field of anti-aging. Studies have shown that this substance has significant anti-aging effects at the cellular, tissue and system levels, making it of great value in the development of anti-aging drugs, the addition of functional foods and the application of cosmetic raw materials. Current basic research has provided a solid theoretical basis for its practical application, but future research still needs to further explore and optimize its bioavailability. With the solution of these key scientific issues, ellagic acid is expected to become an important functional ingredient in the field of anti-aging, providing innovative solutions for delaying the aging process and preventing and treating aging-related diseases.
References
[1] Zeb A. Ellagic acid in suppressing in vivo and in vitro oxidative stresses[J]. Mol Cell Biochem, 2018, 448(1-2): 27-41.
[2] Derosa G, Maffioli P, Sahebkar A. Ellagic Acid and Its Role in Chronic Diseases[J]. Adv Exp Med Biol, 2016, 928: 473-479.
[3] Fu H, Li W, Liu J, et al. Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/β-catenin signaling pathway[J]. J Ethnopharmacol, 2024, 330: 118227.
[4] Wang X, Zhou X, Zhang X. Effects of Ellagic Acid on Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis[J]. J Nutr Metab, 2024, 2024: 5558665.
[5] Alfei S, Zuccari G. Ellagic Acid: A Green Multi-Target Weapon That Reduces Oxidative Stress and Inflammation to Prevent and Improve the Condition of Alzheimer's Disease[J]. Int J Mol Sci, 2025, 26(2): 844.
