1. Introduction
The growing demand for natural ingredients in cosmetic formulations has led to the increased use of plant-derived antioxidants, such as quercetin, a flavonoid with known antioxidant and anti-inflammatory properties. Given the rising interest in cosmeceuticals, there is a pressing need for advanced, accurate methods to detect these compounds in cosmetic matrices and track their absorption, bioavailability, and potential metabolic transformations in the skin [
1,
2].
Flavonoids, found in a variety of plant-based foods, are well-known for their potent antioxidant activity. Present in abundant quantities in fruits and vegetables, like leafy greens, berries, and citrus fruits, flavonoids play a critical role in neutralizing free radicals and preventing damage to vital cellular structures, such as DNA, lipids, and proteins. Additionally, phenolic acids contribute significantly to antioxidant defense by acting as reducing agents, quenching reactive oxygen species (ROS), and chelating metal ions, further enhancing their protective properties [
3,
4,
5,
6].
Among these, quercetin has been extensively studied for its broad pharmacological effects. Known for its antioxidant properties, quercetin helps protect skin cells from oxidative damage caused by external factors, such as UV radiation and pollution. Its rapid absorption into the skin allows for immediate protection, making it a valuable ingredient in topical formulations aimed at safeguarding skin health [
7,
8].
Beyond its antioxidant action, quercetin exhibits a range of therapeutic benefits, including anti-inflammatory effects that can calm irritated skin and reduce redness. It also shows promise in regulating blood pressure, improving vascular function, and even addressing obesity. These diverse biological activities highlight quercetin’s potential not only as a cosmetic ingredient, but also as a therapeutic agent in managing oxidative stress-related chronic conditions [
3,
9].
However, integrating flavonoids like quercetin into cosmetic products poses challenges related to their stability, bioavailability, and skin penetration. Flavonoids are prone to degradation when exposed to light, heat, or air, potentially reducing their effectiveness unless properly stabilized. To address these concerns, various delivery systems—such as liposomal encapsulation and nanoparticles—have been explored to enhance the bioavailability and stability of flavonoids, ensuring their deeper penetration into the skin for more pronounced effects [
10,
11].
In parallel, advancements in electrochemical detection methods have enabled precise measurement of quercetin and other flavonoids in plant extracts, offering insights into their concentration and bioactivity. These developments are essential for optimizing extraction processes and improving formulation techniques, ensuring that cosmeceuticals contain effective levels of bioactive compounds [
12,
13,
14].
While numerous techniques, such as high-performance liquid chromatography (HPLC) and spectrophotometry, have been used to detect quercetin in botanical extracts, these methods primarily focus on its precursors without addressing how quercetin or its metabolites are processed after topical application in cosmetics. This gap in the knowledge limits our understanding of how quercetin interacts with the skin and potentially enters the systemic circulation, where its metabolites could exert additional therapeutic effects [
15].
In this study, we present a novel approach using amperometric microsensors to detect quercetin in cosmetic formulations and track its metabolic behavior after topical application. This method offers a sensitive, real-time alternative to conventional techniques, enabling the detection of quercetin’s bioavailability, its transformation into active metabolites, and its potential therapeutic effects when applied to the skin.
This study aims to extend the application of electrochemical detection to quercetin, a flavonoid with significant cosmetic potential, extracted from
Ginkgo biloba essential oil. Three novel amperometric microsensors were designed, based on graphite (G) and carbon nanoparticles (CNs), with configurations including both unmodified and modified versions using chitosan (CHIT) and cobalt(II) tetraphenylporphyrin (Co(II)TPP). Differential pulse voltammetry (DPV) was chosen as the primary electrochemical method for detecting quercetin, building upon the protocol by Van Staden et al. (2014) [
16], initially developed for serotonin detection in biological fluids and adapted here for quercetin in a botanical matrix. The selection of chitosan and Co(II)TPP was based on their proven stability and effectiveness in acidic environments, crucial for the analysis of quercetin in essential oils.
By optimizing these electrochemical detection techniques, this study aims to ensure the precise measurement of quercetin and facilitate its incorporation into cosmeceutical products, further enhancing the analysis of plant-based bioactive compounds.
Quercetin, a widely studied flavonoid found in various fruits, vegetables, and medicinal plants, has garnered significant attention for its antioxidant and therapeutic properties. Known for its ability to scavenge free radicals, quercetin helps protect the body from oxidative stress, a key factor in aging and the development of chronic diseases like cardiovascular disorders and cancer. While its biological effects have been extensively explored in previous studies, the focus of this research lies in the development of electrochemical detection methods to quantify quercetin in complex matrices such as essential oils [
8,
17].
The main challenge in detecting quercetin within such matrices is the compound’s complex chemical nature, which can complicate its extraction and analysis. As quercetin is sensitive to environmental factors like light and heat, its incorporation into essential oils requires accurate and reliable methods to ensure the compound remains stable and detectable. Furthermore, understanding the best techniques for quantifying quercetin, especially in botanical formulations, is critical for optimizing its use in therapeutic and cosmetic applications. This study addresses these challenges by developing novel amperometric microsensors to enhance the precision and sensitivity of quercetin detection, providing a valuable tool for future research and product development in the field of cosmeceuticals and natural health products.
The accurate quantification of quercetin in cosmetic products is essential for ensuring consistent product quality and efficacy. The ability to measure trace amounts of quercetin and its metabolites is critical for product formulation, quality control, and ensuring that these compounds exert the desired antioxidant and anti-inflammatory effects on the skin [
17].
The goal of this study is to develop a highly sensitive electrochemical approach for detecting quercetin in Ginkgo biloba essential oil, providing a robust tool for quantifying both the parent compound and its metabolites in cosmeceutical formulations. Through this method, we aim to advance the field of metabolite science, shedding light on quercetin’s absorption, metabolism, and bioactivity in cosmetic applications.
Ginkgo biloba, one of the oldest living tree species, is native to China but has also been cultivated in other parts of Asia, Europe, and North America. It is commonly known as the “maidenhair tree” due to the distinctive fan-shaped leaves. The plant has been revered in traditional medicine for centuries, with a long history of use in both Eastern and Western herbal practices [
18].
Various parts of the
Ginkgo biloba tree, including the leaves, seeds, and bark, have been used in traditional medicine, though it is primarily the leaves that are exploited for their medicinal properties. Ginkgo leaf extracts are rich in bioactive compounds, notably flavonoids, terpenoids, and ginkgolides, which are thought to contribute to the plant’s therapeutic effects. These extracts are commonly used in modern medicine, particularly in the treatment of cognitive disorders, circulatory problems, and as an antioxidant agent. They have been extensively researched for their potential neuroprotective, anti-inflammatory, and cardioprotective benefits [
19,
20].
In the cosmetic industry,
Ginkgo biloba extracts are utilized for their skin-protective properties. The antioxidants, particularly flavonoids like quercetin, are valued for their ability to neutralize free radicals, which helps to reduce oxidative stress and protect the skin from environmental damage, such as UV radiation and pollution. As such,
Ginkgo biloba extract is frequently incorporated into skincare products aimed at anti-aging, skin hydration, and improving skin elasticity [
21].
In countries where
Ginkgo biloba grows naturally, such as China and parts of Japan, the plant is also used in folk medicine. Traditional uses of the plant include treatment for respiratory issues, as a general tonic, and for its purported benefits in improving memory and mental function [
22]. The growing interest in
Ginkgo biloba’s secondary metabolites, particularly in the context of their antioxidant properties, has further expanded its applications in both medicine and cosmetics worldwide [
23].
Adding a discussion of the plant’s widespread use in traditional and modern medicine will provide valuable context for understanding its relevance in the study of secondary metabolites, particularly quercetin, and its role in health and skincare products.
4. Discussion
The results of this study demonstrate that quercetin (Q) was successfully assayed in Ginkgo biloba essential oil, with recovery rates reaching up to 97.4%. Among the different microsensors tested, the graphite and carbon nanoparticle (G-CN) sensor yielded the highest recovery, followed by the chitosan (CHIT)/G-CN and cobalt(II) tetraphenylporphyrin (Co(II)TPP)/G-CN sensors.
In this research, three distinct amperometric microsensors were developed to evaluate the electrochemical characteristics of quercetin in Ginkgo biloba oil. The base sensors, composed of graphite (G) and carbon nanoparticles (CNs), provided a robust and conductive platform. Modifications with chitosan (CHIT) and Co(II)TPP enhanced their sensitivity and selectivity. Chitosan, a biopolymer derived from chitin, was chosen for its biocompatibility and capacity to improve electron transfer, making it an ideal material for biosensor applications. Similarly, Co(II)TPP, a metalloporphyrin, was selected to improve electrocatalytic activity, enabling the detection of quercetin at lower concentrations.
The differential pulse voltammetry (DPV) technique applied in this study was particularly effective for detecting quercetin due to its high resolution and sensitivity. DPV works by applying a series of potential pulses to the electrochemical cell, allowing for the detection of current changes as quercetin undergoes oxidation or reduction. This method is well-suited for detecting low concentrations of analytes, which is essential in cosmeceutical and pharmaceutical research, where the precise quantification of active compounds is critical. Previous studies have demonstrated DPV’s effectiveness in detecting flavonoids like quercetin, where sensitivity and selectivity are crucial for analyzing complex biological samples [
29,
30,
31]. Similarly, other research has employed DPV for monitoring antioxidant levels in pharmaceutical and food matrices [
32,
33,
34], highlighting the method’s potential for trace-level analysis.
In our study, the CHIT/G–CN microsensor exhibited the highest sensitivity, with a detection limit of 1.22 × 10−7 mol/L. This high sensitivity makes it particularly suitable for detecting quercetin in complex botanical matrices, such as Ginkgo biloba oil, where active compound concentrations may vary. The G–CN and Co(II)TPP/G–CN sensors also performed well, with detection limits of 5.64 × 10−8 mol/L and 9.80 × 10−8 mol/L, respectively. These detection limits are within the range required for practical applications in cosmeceutical formulations, where even trace amounts of quercetin can have significant biological effects.
Achieving low detection limits is critical for ensuring the efficacy of cosmeceutical products. Quercetin, when applied topically, must penetrate the skin barrier and reach the deeper layers of the epidermis to exert its antioxidant and anti-inflammatory effects. Reliable methods for measuring its concentration in formulations are essential for product development and quality control. The recovery rates and relative standard deviation (RSD) values obtained in this study (97.4% ± 0.43) further demonstrate the accuracy and precision of the microsensors, providing confidence in their real-world applicability.
While our approach offers promising results, it is important to consider the advantages of electrochemical detection in comparison with other established methods for quercetin analysis. High-performance liquid chromatography (HPLC), mass spectrometry, and spectrophotometry are all widely used for the quantification of quercetin. HPLC is known for its high accuracy and ability to separate quercetin from complex matrices, but it requires expensive equipment and skilled personnel. Mass spectrometry provides detailed structural information but is similarly costly and time-consuming. Spectrophotometry offers a simpler, faster alternative, but its sensitivity is often lower than that of electrochemical methods. In contrast, electrochemical detection provides a sensitive, cost-effective, and portable solution for quercetin analysis. The use of DPV in this study offers superior sensitivity, particularly at low concentrations, and the microsensors developed here are more affordable and accessible compared to traditional analytical techniques.
Despite its advantages, electrochemical detection does have limitations. The sensitivity of the microsensors can be affected by matrix interferences in real-world samples, and the stability of the sensors over time may need to be improved. Furthermore, the performance of these sensors could be enhanced by optimizing the materials used in sensor construction or exploring alternative modifications. Future research could focus on improving sensor stability and exploring additional modifications to increase selectivity and reduce the influence of matrix interferences.
The findings of this study also open the door to further research into the use of quercetin and other flavonoids in regenerative medicine and therapeutic treatments. As the interest in natural, plant-based compounds grows, innovative methods for harnessing their potential are essential. The combination of advanced electrochemical techniques with sustainable sourcing, as demonstrated in this study, offers a promising avenue for developing cosmeceuticals that are not only effective, but also environmentally responsible. Quercetin has already shown regenerative properties in skin cell renewal and wound healing [
35], and the use of electrochemical techniques may further enhance our understanding of its role in these processes. Additionally, the research by Sasounian et al. (2023) emphasizes the importance of combining natural compounds with sustainable practices, advocating for eco-friendly and effective skincare solutions [
36].
In conclusion, this study contributes to the growing body of research on natural antioxidants in cosmeceuticals, particularly focusing on quercetin’s electrochemical behavior in Ginkgo biloba essential oil. The development of highly sensitive microsensors provides valuable tools for detecting and quantifying quercetin in botanical extracts, enabling its integration into next-generation skincare products. By combining the therapeutic potential of plant-derived compounds with advanced electrochemical analysis, we can create innovative solutions that promote both human health and environmental sustainability.
The novelty of this work lies in the development of innovative amperometric microsensors for the precise detection of quercetin in Ginkgo biloba essential oil, a complex botanical matrix. Key aspects of the novelty include:
Design of new microsensors: this study introduces three novel amperometric microsensors based on graphite (G) and carbon nanoparticles (CNs), with modifications using chitosan (CHIT) and cobalt(II) tetraphenylporphyrin (Co(II)TPP). These modifications enhance the sensors’ sensitivity, selectivity, and electrocatalytic activity, making them highly effective for detecting quercetin at low concentrations.
Use of differential pulse voltammetry (DPV): this study applies the DPV technique to quercetin detection in a botanical matrix, demonstrating the high resolution and sensitivity of this electrochemical method, which is well-suited for trace-level analysis in complex samples, like plant extracts. This represents a novel application of DPV for quercetin in cosmeceutical and pharmaceutical contexts.
Enhanced detection limits: this study achieves exceptionally low detection limits (down to 1.22 × 10−7 mol/L for the CHIT/G-CN sensor), which is important for accurately measuring quercetin in cosmeceutical formulations, where even trace amounts of quercetin can have significant biological effects.
Exploration of electrochemical sensors for flavonoids in botanical extracts: while electrochemical methods for flavonoids are not new, this work specifically targets quercetin, a prominent antioxidant, in Ginkgo biloba oil, providing insights into its electrochemical behavior and offering a reliable tool for monitoring its bioavailability and effectiveness in skincare applications.
Potential for sustainable, eco-friendly cosmeceuticals: by combining cutting-edge electrochemical techniques with sustainable sourcing practices (like using plant-derived compounds), this work addresses the growing demand for natural, eco-friendly skincare solutions, paving the way for the development of regenerative medicines and therapeutic treatments based on plant antioxidants like quercetin.
The detection of quercetin in cosmetics can play a significant role in the development of metabolite science for several reasons, despite quercetin typically being used in unchanged form in cosmetic products. Here’s how the study of quercetin’s presence, quantification, and behavior in cosmetics can contribute to metabolite science:
1. Understanding quercetin’s bioavailability and metabolism
While quercetin in cosmetics is applied in its unchanged form, it is well-documented that, once absorbed through the skin, quercetin undergoes metabolic transformations. These transformations are crucial for its therapeutic effects, as the metabolites of quercetin often exhibit different or enhanced biological activities compared to the parent compound. For example, quercetin is metabolized into various conjugates (e.g., glucuronides, sulfates, and methylated forms) within the skin and other tissues, which can affect its antioxidant, anti-inflammatory, and cardioprotective properties.
By developing accurate methods to measure quercetin in cosmetics, this study opens the door to monitoring its metabolism and bioavailability after topical application. Knowing how quercetin behaves in the skin, including how it is metabolized into active forms, provides essential information for optimizing the efficacy of quercetin-based cosmeceuticals and advancing personalized skincare. This is critical in metabolite science, as understanding the biotransformation of quercetin within skin cells (and other organs) leads to improved formulations and better therapeutic outcomes.
2. Linking cosmetic applications with systemic effects
The metabolites of quercetin have shown activity in other organs beyond the skin. For example, quercetin metabolites are involved in regulating blood pressure, modulating vascular function, and providing anti-inflammatory effects. By detecting quercetin in cosmetic formulations, researchers can track its percutaneous absorption and systemic distribution, enabling a better understanding of how topical quercetin may influence the body’s metabolism beyond just the skin.
3. Improved development of topical therapies
Accurate detection of quercetin in cosmetic products could enhance the development of topical therapies that are not just aimed at skin benefits, but also take into account the systemic effects of quercetin metabolites. If quercetin’s metabolites are found to significantly impact other organs, such as the heart or liver, this could open up new directions for cosmeceutical formulations that provide multi-organ benefits, which is a growing trend in the skincare and pharmaceutical industries.
4. Link between cosmetics and metabolite profiling
While quercetin itself is applied in unchanged form, studying its metabolite profiles after skin absorption could lead to better formulations and formulations that actively contribute to skin health and systemic wellbeing. With improved detection methods for quercetin in cosmetics, researchers can build detailed profiles of its metabolites, contributing to the advancement of metabolite science by linking topical application to systemic metabolic effects.
5. Potential for personalized skin care
The development of detection systems for quercetin in cosmetics can ultimately help scientists better understand individual variations in metabolism—how different people metabolize quercetin and how this may affect the efficacy of topical treatments. This could eventually contribute to personalized skincare solutions, where consumers are provided with products tailored to their specific metabolic profiles, improving their overall health and skincare results.
While quercetin is used in its unchanged form in cosmetics, studying its metabolism and detection through improved electrochemical sensors will significantly contribute to metabolite science. This research will allow a deeper understanding of how quercetin and its metabolites interact with the skin and other organs, contributing to more effective topical therapies, personalized skincare, and the advancement of metabolomics. The ability to measure quercetin and its metabolites in complex matrices, like cosmetics, is a key step toward integrating metabolite science with cosmetic product development and therapeutic applications.