As global awareness of holistic health continues to rise, women’s wellness has emerged as one of the fastest-growing and most dynamic sectors.
By 2026, hormonal balance and ovarian health are set to become central pillars in the dietary supplement markets across both China and Western countries – fueling innovation, scientific research, and product development like never before.
At the forefront of this transformation are three naturally derived bioactive compounds – urolithin A, S-equol, and fisetin – each backed by compelling science and clinical potential. These ingredients are redefining how we support ovarian function and combat reproductive aging, offering women a proactive, science-driven approach to long-term vitality.
Ovarian health: More than fertility
The ovaries are far more than reproductive organs. They serve as master regulators of hormonal equilibrium, metabolic health, and even the broader aging process. Yet modern lifestyles – marked by chronic stress, environmental toxins, and circadian disruption – are increasingly linked to premature ovarian aging, hormonal imbalances, and related health challenges.
This reality has shifted the focus toward cellular-level interventions that preserve ovarian reserve, enhance follicular quality, and sustain endocrine harmony. Enter urolithin A, S-equol, and fisetin: a powerful trio of natural compounds now recognized as key allies in ovarian longevity.
The science behind the trio: How each ingredient supports ovarian health
1. Urolithin A: The cellular conductor of rhythm and repair
Urolithin A is a gut-derived metabolite produced from ellagitannins found in pomegranates, nuts, and berries. Far beyond its well-known benefits, urolithin A acts as a sophisticated cellular conductor – orchestrating circadian rhythms, DNA integrity, and cellular energy metabolism to support ovarian function.
Research shows that urolithin A upregulates core clock genes like Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), ensuring precise timing in follicle development and hormone secretion.1 It also activates DNA repair pathways (eg, PARP1), shielding ovarian cells from oxidative damage.2 Additionally, urolithin A enhances fatty acid oxidation and glucose homeostasis, providing oocytes with cleaner, more efficient energy.3
Together, these mechanisms help slow the decline of ovarian reserve and improve the follicular microenvironment. In 2025, a landmark study explored how urolithin A supplementation significantly improved ovarian health in aging mice. Results showed urolithin A reduced follicular atresia and increased the proportion of healthy, viable follicles.4
2. S-equol: The smart estrogen modulator
S-equol is a bioactive metabolite formed by specific gut bacteria from soy isoflavones. Often described as a natural selective estrogen receptor modulator (SERM), it offers intelligent, context-dependent estrogenic activity.
When estrogen levels are low – as during perimenopause – S-equol binds to estrogen receptors (particularly ERβ) to deliver mild estrogen-like benefits, easing symptoms like hot flashes and mood swings. Conversely, when estrogen is excessive, it exerts anti-estrogenic effects, helping mitigate risks associated with hormonal overstimulation.5
This selective action stems from its high affinity for the ERβ receptor, which is widely distributed in the ovaries, bones, cardiovascular system, and other tissues, playing roles in regulating inflammation, cell proliferation, and apoptosis.
Clinical trials confirm that daily supplementation with just 10mg of S-equol significantly improves menopausal symptom scores in perimenopausal women while supporting bone density and skin elasticity. Its dependence on gut microbiota also highlights the future potential of personalized nutrition and probiotic co-interventions.5,6
3. Fisetin: The precision senolytic for ovarian rejuvenation
Found naturally in strawberries, apples, and other fruits, fisetin is a potent flavonoid celebrated as a senolytic – a compound that selectively clears senescent zombie cells. As ovaries age, these dysfunctional cells accumulate, secreting inflammatory cytokines and enzymes that degrade the ovarian microenvironment.
Fisetin targets these cells by modulating key senescence pathways (including p53 and p21) and inhibiting pro-survival proteins, triggering their apoptosis without harming healthy tissue. The result? Reduced inflammation, restored stem cell activity, and a rejuvenated niche for oocyte development.
Studies demonstrate that fisetin not only reduces ovarian senescent cell burden but also improves oocyte quality and extends reproductive lifespan – making it a cornerstone of advanced ovarian anti-aging strategies.7
Turning science into trusted solutions
While the science is promising, translating these actives into safe, effective, and bioavailable products remains a critical challenge. Bonerge is leading the charge by combining rigorous ingredient standards with cutting-edge delivery technologies.
As an active contributor to industry standards, Bonerge has implemented rigorous quality controls across its portfolio of science-backed actives. The company proudly launched its proprietary branded ingredients: StanYouth® urolithin A, EquoYouth™ S-equol, and BeFisetin® fisetin – each developed with purity, traceability, and clinical relevance in mind.
Notably, Bonerge is the first company globally to secure US self-affirmed GRAS (Generally Recognized As Safe) status for both fisetin and S-equol, reinforcing its leadership in safety validation and setting a new benchmark for ingredient integrity – from raw material sourcing to final product delivery.
Moreover, the company invests heavily in human clinical trials, partnering with research institutions to generate real-world evidence that validates every efficacy claim.
Breaking bioavailability barriers: Where innovation meets nutrition
Natural actives like urolithin A and fisetin offer powerful health benefits – but their efficacy is often limited by poor absorption. Classified as BCS Class IV compounds, these ingredients suffer from low solubility and low permeability, resulting in suboptimal bioavailability after oral intake. This means consumers may need higher doses to achieve desired effects – reducing efficiency and increasing cost.
To overcome this challenge, Bonerge leverages its advanced formulation platform to deliver two innovative delivery systems designed for maximum absorption and practical consumer use.
Water-soluble nano-lipid carrier technology
This innovative system encapsulates urolithin A and fisetin into nano-sized lipid carriers (200 to 300 nm) using proprietary solid lipid encapsulation technology. These nanocarriers dramatically enhance dissolution in the gastrointestinal tract by enabling dual absorption pathways – transcellular and paracellular transport – thereby significantly boosting bioavailability.
Moreover, the water-dispersible nature allows active ingredients to rapidly dissolve and uniformly disperse in aqueous solutions, making them ideal for integration into protein powders, beverages, and ready-to-mix formats – expanding formulation versatility and enhancing consumer experience.
In comparative testing, conventional fisetin powder remains largely insoluble in water, forming clumps that settle quickly. In contrast, Bonerge’s nano-lipid fisetin solution disperses instantly and evenly in water, maintaining stability without sedimentation – delivering consistent performance every time.
Self-emulsifying softgel system
This micro-emulsion capsule transforms upon contact with gastrointestinal fluids, forming nano-droplets (100 to 500 nm) within minutes. The emulsion prevents aggregation, maximizes membrane contact, and allows co-delivery with synergistic lipids like DHA, krill oil, or CoQ10 – enhancing both efficacy and consumer experience.
In real-world testing, commercially available urolithin A softgels fail to disperse in water, sinking as oily clumps with poor absorption potential. By contrast, Bonerge’s softgel instantly creates a uniform, milky emulsion – even in room-temperature water – making it ideal for liquid-based regimens and significantly improving reliability across diverse user habits.
Redefining healthy aging – from cells to life
Supporting ovarian health is no longer just about fertility – it’s a profound investment in a woman’s lifelong vitality, resilience, and autonomy. Urolithin A, S-equol, and fisetin offer a scientifically grounded, multi-dimensional strategy: restoring cellular rhythm, balancing hormones intelligently, and clearing aging-related cellular debris.
With Bonerge’s commitment to ingredient integrity, clinical validation, and advanced delivery science, these once-laboratory-only compounds are now becoming accessible, reliable tools for everyday wellness.
Looking ahead, the convergence of personalized nutrition, microbiome science, and senotherapeutics will unlock even more precise approaches to ovarian care. And as women gain deeper control over their biological timelines, they’ll be better equipped to thrive – not just survive – through every stage of life.
References
- Kuatov, R.; et al. Urolithin A Modulates PER2 Degradation via SIRT1 and Enhances the Amplitude of Circadian Clocks in Human Senescent Cells. Nutrients. 2024 Dec 25;17(1):20.
- Shi, W.; et al. Urolithin A Protects Porcine Oocytes from Artificially Induced Oxidative Stress Damage to Enhance Oocyte Maturation and Subsequent Embryo Development. Int J Mol Sci. 2025 Mar 26;26(7):3037.
- Toney, A M.; et al. Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis. Obesity (Silver Spring). 2019 Apr;27(4):612-620.
- Wang, W.; et al. Urolithin A Protects Ovarian Reserve Via Inhibiting PI3K/Akt Signaling and Preventing Chemotherapy-Induced Follicle Apoptosis. Biology (Basel). 2025 Jul 8;14(7):829.
- Ishiwata N.; et al. New equol supplement for relieving menopausal symptoms: randomized, placebo-controlled trial of Japanese women. Menopause.2009 Jan-Feb;16(1):141-8.
- Tousen, Y.; et al. Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial. Randomized Controlled Trial Menopause. 2011 May;18(5):563-74.
- Moustafa, PE.; et al. Fisetin mitigates letrozole-induced polycystic ovarian syndrome in rats: crosstalk of AMPK/PI3K/AKT-mediated-Nrf2 antioxidant defense mechanism and the inflammasome NLRP3/NF-κB P65/IL-1β signaling pathways. Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):8077-8088.
