The Anti-Aging Potential of Natural of Fisetin : A Natural Compound with senotherapeutic which is studied to extend health and lifespan

Fisetin as senolytic activator, helps selective elimination of senescent cells

Fisetin, a natural compound found in fruits like strawberries and apples, garners attention for its potent anti-aging and senolytic properties. Particularly notable is its capacity to eliminate senescent cells prevalent in aging, reducing their harmful impact on surrounding healthy cells and mitigating inflammaging. As a senolytic, fisetin stands out for its effectiveness, surpassing other compounds like quercetin in destroying senescent cells.

Mice studies indicate fisetin’s ability to extend lifespan, even when administered later in life. Beyond acting as a senolytic, fisetin inhibits the mTOR pathway associated with aging, mimicking fasting benefits. It also combats oxidative stress and inflammaging by inhibiting pro-inflammatory enzymes, showcasing fisetin as a promising candidate for enhancing longevity and overall health in the aging process.

Fisetin as senolytic activator, helping elimination of senescent cells

Notably, fisetin offers benefits for skin health. By reducing the production of matrix metalloproteinases (MMPs), enzymes that break down collagen and elastin, fisetin helps to preserve the integrity of the extracellular matrix, which keeps the skin firm and youthful. This property makes fisetin a potential agent in reducing the formation of wrinkles and signs of skin aging.

Furthermore, fisetin positively impacts brain function and aging. It has been shown to enhance memory formation and cognitive abilities in animal models, suggesting its potential as a cognitive enhancer.

While the research on fisetin’s anti-aging effects is still evolving, its impressive range of benefits makes it a compound of considerable interest in longevity research. However, it is important to note that most studies have been conducted on animal models. Further research is needed to fully understand the effects of fisetin in humans and enhance our comprehension of its potential impact on human longevity.

Fisetin as senolytic activator, helping elimination of senescent cells

With its antioxidant prowess, Fisetin effectively combats harmful free radicals, curbing oxidative stress and cellular damage linked to diseases and aging. Simultaneously, it showcases anti-inflammatory prowess, inhibiting the production of cytokines and prostaglandins, potentially benefiting conditions tied to chronic inflammation like cardiovascular diseases, neurodegenerative disorders, and certain cancers.

In the realm of neuroprotection, Fisetin shines, safeguarding neurons from oxidative stress, reducing brain inflammation, and enhancing memory and cognitive function, particularly evident in preclinical studies on Alzheimer’s and Parkinson’s models. Turning towards its anti-cancer potential, Fisetin exhibits promise by inhibiting cancer cell growth, inducing apoptosis, and thwarting the formation of blood vessels crucial for tumor support. Despite these encouraging findings, comprehensive research is imperative for a nuanced understanding of its efficacy and safety in human cancer treatment.

Beyond these realms, preliminary studies hint at additional benefits, including anti-diabetic effects, enhanced insulin sensitivity, protection against age-related macular degeneration (AMD) by curbing retinal oxidative stress, and a potential role in promoting longevity through the activation of aging-associated cellular pathways.

Fisetin extract

Understanding the pharmacokinetics of fisetin is crucial for determining its in vivo effects.

Revealing rapid absorption and metabolism, studies show that the body predominantly forms sulfate and glucuronide metabolites from fisetin. Intravenous administration in rats showed a quick absorption of fisetin, with subsequent transformation into glucuronides and sulfates. Upon oral administration, there was a transient presence of the parent form; nevertheless, over time, glucuronides and sulfates gradually became predominant in the system.

Fisetin injected intraperitoneally in mice exhibited plasma levels peaking at 15 minutes, followed by a half-life of 3.12 hours. Tissue distribution indicated higher levels in the kidney, intestine and liver. Detect metabolites, including glucuronide conjugates and a 3′-methoxylated metabolite named geraldol, where geraldol accumulates more in tumors, showing enhanced cytotoxic effects. Biliary excretion studies in rats demonstrated the presence of sulfates and glucuronide conjugates, with sulfates being the main metabolites. Due to its notable high affinity, Fisetin’s biliary excretion experiences influence from P-glycoprotein. Consequently, this interaction not only shapes but also plays a crucial role in determining the dynamic process of Fisetin’s elimination through the biliary system.

Assay of Fisetin, method of analysis

A Comparison between HPLC External Standard Method and HPLC Area Normalization Method

To determine Fisetin concentration in extracts or formulations, researchers commonly employ analytical methods like High-Performance Liquid Chromatography (HPLC). Two commonly used approaches in HPLC analysis are the External Standard Method and the Area Normalization Method. In this article, we will explore the differences between these two methods for the assay of Fisetin.

External Standard Method

The External Standard Method involves preparing a calibration curve using known concentrations of a Fisetin standard solution. For an accurate analysis, run a high-purity standard solution (e.g., Fisetin 98%) through the HPLC system, ensuring meticulous calibration. Subsequently, record the peak area or height, providing essential data for precise quantification and analysis. Generate a calibration curve by plotting the concentration of the standard solution against its respective peak area or height. Compare the peak area or height of the sample to the calibration curve to determine the Fisetin concentration. This method offers a direct quantification of Fisetin in the sample and is relatively straightforward to perform.

Area Normalization Method

Conversely, in the Area Normalization Method, the calculation involves determining the percentage of Fisetin in a given sample relative to the total peak area of all components detected in the chromatogram. Within this methodological approach, the emphasis shifts towards prioritizing relative quantification, thereby eschewing reliance on a specific absolute concentration value. Run the sample through the HPLC system to obtain a chromatogram, showing peaks corresponding to different compounds. To determine the percentage of Fisetin in the sample, start by calculating the area under the Fisetin peak. Subsequently, after obtaining the individual area, divide this specific area by the total area of all peaks, and then multiply the result by 100 for an accurate representation. This method does not require the use of a standard solution and offers a simple means of estimating the relative abundance of Fisetin in the sample.

Moreover, due to its unique properties, Fisetin emerges as a promising candidate for anti-aging interventions. This distinctiveness makes it compelling for further research and potential applications in enhancing longevity and overall well-being. Particularly beneficial when absolute concentration is not imperative, it significantly facilitates comparing Fisetin content among various samples or formulations. Furthermore, it allows researchers to draw meaningful insights into the relative distribution of Fisetin across diverse contexts.

Efficacy and safety

Frequently, Fisetin supplements target a 98% purity level, crucial for efficacy and safety. This commitment ensures a potent and reliable product with concentrated Fisetin for optimal dosage and effectiveness. Studied for various pharmacokinetic applications, including antioxidant and anti-inflammatory effects, researchers actively explore its bioavailability and potential benefits, advising consultation with healthcare professionals for proper guidance.

Similar to other natural compounds, Fisetin may interact with medications or supplements, necessitating caution and healthcare consultation, particularly for those with existing medical conditions. A proactive approach ensures comprehensive understanding and personalized guidance for safe health regimens. Assaying Fisetin involves diverse HPLC methods, each with advantages and limitations, requiring careful selection based on analysis goals.

Fisetin, a promising anti-aging senolytic, shows initial promise, but research relies heavily on cells and animal models, lacking sufficient human studies. Further exploration of dosage, bioavailability, and long-term effects in humans is crucial for a nuanced understanding of Fisetin’s potential benefits and risks.

Few of the important references to study:

  1. Huang, H.-C., Liao, C.-C., Hsiao, P.-C., & Wang, Y.-J. (2018). Fisetin attenuates glycolytic metabolism and inhibits pancreatic cancer cell proliferation. Frontiers in Pharmacology, 9, 643.
  • Mehta, R. G., Williamson, E., Patel, M. K., & Koeffler, H. P. (2015). Simultaneous targeting of multiple cancer signaling pathways by a naturally occurring compound, fisetin. Cancer Research, 75(9 Supplement), 2106.
  • Mehta, R. G., Patel, M. K., Majumdar, A. P., & Chen, J. (2017). Fisetin, a natural flavonoid, targets chemoresistant human pancreatic cancer AsPC-1 cells through DR3-mediated inhibition of NF-κB. International Journal of Oncology, 50(5), 1849-1857.
  • Chao, P.-C., Hsu, C.-C., Yin, M.-C., & Lin, Y.-H. (2002). Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Research, 22(1A), 11-15.
  • Shia, C.-S., Ju, D.-T., Shen, J.-J., Yang, C.-C., Kuo, C.-D., Lin, M.-W., … & Wu, C.-H. (2009). Fisetin protects against ischemia/reperfusion-induced acute kidney injury in mice by promoting autophagy and regulating IL-33/ST2 signaling. Journal of Nutritional Biochemistry, 20(11), 925-933.
  • Touil, Y. S., Fellous, A., Scherman, D., & Chabot, G. G. (2011). Flavonoids binding to ROCK1 kinase domain: A new insight in Fas signaling modulation. Biochemical and Biophysical Research Communications, 411(3), 568-573.