Tyrosinase, as a key rate-limiting enzyme in the melanin synthesis pathway, has always been a core target in the development of whitening products. In recent years, Phloretin, a natural polyphenol derived from plants such as apples and pears, has emerged in skincare formulations due to its excellent antioxidant and penetration-promoting abilities.
1, Scientific evidence and controversy: Exploring the mechanism by which Phloretin inhibits tyrosinase
The academic consensus on whether Phloretin can inhibit tyrosinase is not entirely consistent, which precisely reflects the rigor and complexity of scientific research.
- Core scientific discovery: a reversible mixed inhibitor
A key study published in 2020 provides solid evidence for the inhibitory activity of Phloretin. The paper "Phloretin as both a substrate and inhibitor of tyrosinase: Inhibition activity and mechanism," published by Jianmin Chen et al. in Food Chemistry, indicates that Phloretin exhibits a clear inhibitory effect on mushroom tyrosinase. The study determined through kinetic analysis that Phloretin is a reversible mixed inhibitor with an IC50 value of 169.36 μ mol/L.[1,5]
'Mixed inhibition' means that Phloretin can bind to both free tyrosinase and enzyme substrate complexes that have already bound to substrates (such as L-tyrosine), thereby blocking the pathway of melanin production at multiple stages. What's even more interesting is that the study also found that Phloretin itself can serve as a substrate for tyrosinase. This unique "substrate inhibitor" dual identity enables it to form stable complexes with the enzyme, as confirmed through fluorescence quenching experiments.[4] This indicates that the interaction between Phloretin and tyrosinase is real and stable, rather than a random experimental phenomenon.
- Analysis of Data Differences and Disputes
Although the above research provides conclusive evidence, we must also acknowledge some conflicting data within the industry. Some research reports indicate that Phloretin did not exhibit inhibitory activity against tyrosinase under specific experimental conditions.[2,3] This difference may be attributed to the following key factors:
①Differences in enzyme sources: The vast majority of in vitro studies utilize mushroom tyrosinase, which exhibits structural and activity differences compared to human tyrosinase. An effective inhibitor of mushroom tyrosinase may have a reduced effect on human tyrosinase, and vice versa. Therefore, Phloretin may exhibit inconsistent performance on enzymes from different sources.
②Raw material purity and specifications: As a plant extract, Phloretin's purity, impurities, and extraction process all affect its biological activity. The activity performance of raw materials provided by different suppliers may vary significantly.
③Experimental conditions: Minor changes in the pH value of the buffer, reaction temperature, substrate concentration, and other testing conditions may cause fluctuations in IC50 values of orders of magnitude, and even lead to opposite conclusions of "effective" or "ineffective".
2, Efficiency Duel: Quantitative Comparison between Phloretin and Classic Inhibitors
The best way to evaluate Phloretin's "strength" is to directly compare it with industry-recognized "gold standards" such as Kojic Acid and Arbutin.
- Phloretin vs. Kojic Acid
The study by Jianmin Chen et al. (2020) mentioned earlier provides a direct comparison. In this experimental system, quercetin was used as a positive control with an IC50 value of 83.11 μ mol/L. Compared with Phloretin's 169.36 μ mol/L, the inhibitory activity of quercetin is approximately twice that of Phloretin. This indicates that, from the perspective of inhibiting tyrosinase activity alone, Phloretin may not be as effective as quercetin.
However, effectiveness is not the only consideration. The study also emphasizes that Phloretin has higher safety. Due to its potential cytotoxicity and stability issues, quercetin is subject to certain limitations in its application. Therefore, Phloretin provides a better balance between safety and efficacy with its "gentle and effective" properties.
- Phloretin vs. arbutin
Studies have shown that in a certain system, the IC50 value of α-arbutin is 243.16 μM. In other studies, the inhibition rate of arbutin on tyrosinase (32%) was significantly lower than that of quercetin (62%). Overall, arbutin is generally considered a milder inhibitor. Although there is a lack of direct comparison, based on the IC50 value of Phloretin 169.36 μ mol/L, its inhibitory ability may theoretically be at the same level as arbutin, or even slightly better. However, this inference requires more direct experimental data to confirm.
Comprehensive evaluation: Phloretin's identity as a tyrosinase inhibitor is established, and its efficacy has been confirmed in academic research, but its strength may be weaker than that of quercetin. Its true market competitiveness lies not only in its single inhibitory effect on tyrosinase, but also in its multifunctionality - strong antioxidant capacity, "booster" effect that promotes the penetration of other active substances, and good safety.
In summary, as a plant extract, Phloretin is positioned as a "powerhouse" rather than an "idol" in the field of whitening. Its value lies not in its unparalleled inhibitory data but in its scientifically proven efficacy, reliable safety, and excellent formula synergy.
For more details about Phloretin and Phlorizin, connect with Serrisha from APPCHEM. (Email: cwj@appchem.cn; +86-138-0919-0407)
Reference
[1]Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism. Not specified. [2020-02-05]
[2]Sustainable and Scalable Enzymatic Production, Structural Elucidation, And Biological Evaluation of Novel Phlorizin Analogs. Laurène Minsat et al. [2024]
[3]Synthèse chimio-enzymatique, purification et caractérisation de molécules analogues aux métabolites secondaires du bois de co-produits de l'arboriculture pour des applications cosmétiques. Laurène MINSAT. [2022-11-10]
[4]EP 4 541 345 A1. European Patent Office.[2025-04-23]
[5]Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism. Jianmin Chen et al.[2018-10-19]
[6]PHLOROTANNINS AND THEIR BIOLOGICAL SIGNIFICANCES. Chitikela P Pullaiah et al.
[7]Tyrosinase inhibitors isolated from Ceratonia siliqua (L.) and Sideroxylon inerme (L.). Saeideh Momtaz. [2007-04]