Formulation of Ascorbic Acid and Betaine-based Therapeutic Deep Eutectic System for Enhanced Transdermal Delivery of Ascorbic Acid.

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.

Study of the soothing effects of troxerutin in alleviating skin sensitivity.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined. AIMS: We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments. METHODS: For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 µM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin- and heat-induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices. RESULTS: Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin-treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin-induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin- and heat-related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation. CONCLUSIONS: Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.

Substantial Confinement of Crystal Growth of Organic Crystalline Materials in Metal-Organic Membrane Microshells.

This study proposes a robust microshell encapsulation system in which a metal-organic membrane (MOM), consisting of phytic acids (PAs) and metal ions, intrinsically prevents the molecular crystal growth of organic crystalline materials (OCMs). To develop this system, OCM-containing oil-in-water (O/W) Pickering emulsions were enveloped with the MOM, in which anionic pulp cellulose nanofiber (PCNF) primers electrostatically captured zinc ions at the O/W interface and chelated with PA, thus producing the MOM with a controlled shell thickness at the micron scale. We ascertained that the MOM formation fills and covers ∼75% of the surface pore size of PCNF films, which enhances the interfacial modulus by 2 orders of magnitude compared to that when treated with bare PCNFs. Through a feasibility test using a series of common OCMs, including ethylhexyl triazone, avobenzone, and ceramide, we demonstrated the excellent ability of our MOM microshell system to stably encapsulate OCMs while retaining their original molecular structures over time. These findings indicate that our MOM-reinforced microshell technology can be applied as a platform to substantially confine the crystal growth of various types of OCMs.

Penetration rates into the stratum corneum layer: A novel quantitative indicator for assessing skin barrier function.

BACKGROUND: The stratum corneum (SC), the outermost layer of the skin epidermis, acts as an effective bi-directional barrier, preventing water loss (inside-outside barrier) and entry of foreign substances (outside-inside barrier). Although transepidermal water loss (TEWL) is a widely-used measure of barrier function, it represents only inside-outside protection. Therefore, we aimed to establish a non-invasive method for quantitative evaluation of the outside-inside barrier function and visually present a skin barrier model. MATERIALS AND METHODS: Skin barrier damage was induced by applying a closed patch of 1% sodium dodecyl sulfate to the forearms of eight participants; they were instructed to apply a barrier cream on a designated damaged area twice daily for 5 days. The SC barrier was evaluated by measuring TEWL and fluorescein sodium salt penetration rate before, immediately after, and 5 days after damage. The penetration rate was assessed using tape-stripping (TS) technique and fluorescence microscopy. RESULTS: The rates of fluorescein sodium salt penetration into the lower layers of SC differed significantly based on the degree of skin barrier damage. The correlation between penetration rate and TEWL was weak after two rounds of TS and became stronger after subsequent rounds. Five days after skin barrier damage, the penetration rate of all layers differed significantly between areas with and without the barrier cream application. CONCLUSION: Our findings demonstrated that the penetration rate was dependent on skin barrier conditions. The penetration rate and corresponding fluorescence images are suitable quantitative indicators that can visually represent skin barrier conditions.

Fine Wrinkle Improvement through Bioactive Materials That Modulate EDAR and BNC2 Gene Expression.

Skin aging is a multifaceted biological phenomenon influenced by a combination of intrinsic or extrinsic factors. There is an increasing interest in anti-aging materials including components that improve skin wrinkles. Despite the availability of several such wrinkle-improving materials, the demand for ingredients with outstanding efficacy is increasing. Therefore, this study aimed to explore the mechanisms of wrinkle-related genes reported in previous genome-wide association studies (GWASs), identify materials that regulate these genes, and develop an effective anti-wrinkle formula containing the active ingredients that regulate the expression of these genes. We selected two candidate genes, EDAR and BNC2, that are reportedly related to periorbital wrinkles. We investigated their functions in the skin through in vitro experiments using human skin cell lines (keratinocytes and fibroblasts). Moreover, we identified ingredients that regulate the expression of these two genes and confirmed their efficacy through in vitro experiments using the skin cell lines. Finally, we developed a formula containing these ingredients and confirmed that it enhanced dermal collagen in the 3D skin and improved fine wrinkles under the eyes more effectively than retinol in humans, when applied for 8 weeks. Our results are significant and relevant, as we have discovered a special formula for wrinkle improvement with reliable efficacy that surpasses the efficacy of retinol and does not cause side-effects such as skin irritation.

Image-based investigation of lip aging features in a large number of Korean women.

BACKGROUND: The lips play a significant role in shaping facial aesthetics. Due to the distinct attributes of lips in contrast to other facial skin, a unique approach is imperative for managing lip aging. We analyzed lip characteristics (morphology, wrinkles, and color) to investigate visual changes and distinctive attributes of aging lips. METHODS: By utilizing image data processing methods, including facial landmark detection, pattern recognition, and color quantification, we extracted 11 lip characteristic indices (four morphological indices, four wrinkle indices, and three color indices) from high-resolution images of 1000 Korean women aged 20-69. Correlation tests were conducted to assess the relationship between lip characteristic indices and age, and also between lip morphological and wrinkle indices. RESULTS: Lip height significantly decreased, while lip width and lip ratio (lip width divided by the sum of the upper and lower lip height) significantly increased with aging. Lip wrinkles significantly increased with aging, whereas lip colors (redness and yellowness) decreased. The lip wrinkle indices, which are segmented for the first time in this study, exhibited significant correlations with lip width, and three of them additionally were correlated with lip ratio (p < 0.05). The results imply such morphological changes can be associated with wrinkle formation of human lips. CONCLUSION: The indices suggested in this study can be used for assessing lip aging characteristics, and the study results can contribute to deeper understanding of lip aging.

Skin aging-related microbial types separated by Cutibacterium and α-diversity.

BACKGROUND: Studies on the skin microbiome have been conducted to uncover the relationship between skin microbes and the host. However, most of these studies have primarily focused on analyzing individual microbial compositions, which has resulted in a limited understanding of the overall relationship. METHODS: We analyzed the facial skin characteristics and microbial profiles of 100 healthy Korean female volunteers using the V1-V2 region of the 16S ribosomal RNA gene. RESULTS: The two most prominent features of the facial skin microbiome, the proportion of Cutibacterium and α-diversity, were associated with most of the skin characteristics. Based on clustering results, we proposed four types of facial skin microbiome: type C for Cutibacterium, type B for balanced, type CB for those between types C and B, and type O for others. Type C, which has a high proportion of Cutibacterium, showed high levels of pigmentation, wrinkles, pores, and sagging pores, indicating a tendency for severe skin aging. Type B, which has no dominant species and high microbial diversity, had lower values for pigmentation and wrinkles indicating less severe skin aging. Type CB was an intermediate type between type C and type B in terms of microbial composition and the level of skin aging. Type O dominated by microorganisms other than Cutibacterium, had high levels of sebum and pores but low levels of wrinkles. CONCLUSION: We proposed a criterion for classifying facial skin microbial types, each of which showed distinct facial skin aging features. Our simplified microbial types will contribute to a better understanding of facial skin microbial studies.

Longitudinal study of the interplay between the skin barrier and facial microbiome over 1 year.

Skin is a diverse ecosystem that provides a habitat for microorganisms. The skin condition and the skin microbiome interact each other under diverse environmental conditions. This study was conducted on 10 study participants for a one-year, from September 2020 to August 2021, to investigate the variability of skin microbiome and skin biophysical parameters [TEWL, hydration, and elasticity (R5)] according to season, and to understand the interplay between skin microbiome and skin characteristics. We identified that Cutibacterium, Corynebacterium, Staphyloccocus, unclassified genus within Neisseriaceae, and Streptococcus were major skin microbial taxa at the genus level, and fluctuated with the seasons. Cutibacterium was more abundant in winter, while Corynebacterium, Staphylococcus, and Streptococcus were more abundant in summer. Notably, Cutibacterium and skin barrier parameter, TEWL, exhibited a co-decreasing pattern from winter to summer and showed a significant association between Cutibacterium and TEWL. Furthermore, functional profiling using KEGG provided clues on the impact of Cutibacterium on the host skin barrier. This study enhances our understanding of the skin microbiome and its interplay with skin characteristics and highlights the importance of seasonal dynamics in shaping skin microbial composition.

Anti-Inflammatory Artificial Extracellular Vesicles with Notable Inhibition of Particulate Matter-Induced Skin Inflammation and Barrier Function Impairment.

Particulate matter (PM) exposure disrupts the skin barrier, causing cutaneous inflammation that may eventually contribute to the development of various skin diseases. Herein, we introduce anti-inflammatory artificial extracellular vesicles (AEVs) fabricated through cell extrusion using the biosurfactant PEGylated mannosylerythritol lipid (P-MEL), hereafter named AEVP-MEL. The P-MEL has anti-inflammatory abilities with demonstrated efficacy in inhibiting the secretion of pro-inflammatory mediators. Mechanistically, AEVP-MEL enhanced anti-inflammatory response by inhibiting the mitogen-activated protein kinase (MAPK) pathway and decreasing the release of inflammatory mediators such as reactive oxygen species (ROS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines in human keratinocytes. Moreover, AEVP-MEL promoted increased expression levels of skin barrier proteins (e.g., involucrin, IVL) and water-proteins (e.g., aquaporin 3, AQP3). In vivo studies revealed that repeated PM exposure to intact skin resulted in cutaneous inflammatory responses, including increased skin thickness (hyperkeratosis) and mast cell infiltration. Importantly, our data showed that the AEVP-MEL treatment significantly restored immune homeostasis in the skin affected by PM-induced inflammation and enhanced the intrinsic skin barrier function. This study highlights the potential of the AEVP-MEL in promoting skin health against PM exposure and its promising implications for the prevention and treatment of PM-related skin disorders.

Bacteria detection and species identification at the single-cell level using super-resolution fluorescence imaging and AI analysis.

The skin microbiome is thought to play a critical role in maintaining skin health and protecting against infection. While most microorganisms that live on the skin are harmless or even beneficial, some can cause skin infections or other health problems, emphasizing the importance of diagnosis of the composition and diversity of the skin flora. However, conventional diagnostic methods for evaluation of the skin microbiome are not sensitive enough to detect bacteria at low concentrations and suffer from poor specificity, thus limiting early diagnosis of bacterial infections. In this study, we developed novel approaches for bacterial species detection and identification methods with single-cell sensitivity using super-resolution microscopy and AI-based image analysis: a protein quantification-based method and an AI-based bacterial image analysis method. We demonstrate that these methods can differentiate between common bacterial members of the skin flora, including Staphylococcus aureus and Staphylococcus epidermidis, and different ribotypes of Cutibacterium acnes, both in purified bacterial samples and in scaling skin samples. The advantages of these methods, including the lack of time-consuming amplification or purification steps and single-cell level detection sensitivity, allow early diagnosis of bacterial infections, even from bacterial samples at extremely low concentrations, thus showing promise as a next-generation platform for microbiome detection as single-cell diagnostics.

Escin Activates Canonical Wnt/ß-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3ß in Cultured Human Dermal Papilla Cells.

Abnormal inactivation of the Wnt/ß-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt/ß-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt/ß-catenin signaling, resulting in increased ß-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear ß-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3ß, a key regulator of the Wnt/ß-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3ß protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt/ß-catenin signaling pathway and downregulates GSK-3ß protein expression by facilitating the proteasomal degradation of GSK-3ß in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities.

Genome-scale metabolic modeling and in silico analysis of opportunistic skin pathogen Cutibacterium acnes.

Cutibacterium acnes, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes, which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes, iCA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti-C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.

Iris Pallida Extract Alleviates Cortisol-Induced Decrease in Type 1 Collagen and Hyaluronic Acid Syntheses in Human Skin Cells.

Excessive endogenous or exogenous levels of the stress hormone cortisol have negative effects on various tissues, including the skin. Iris pallida (IP), used in traditional medicine and perfumes, exhibits biological activities, such as antioxidant and anti-inflammatory activities. In this study, we aimed to investigate the inhibitory effect of IP extract (IPE) on cortisol activity in human skin cells. We found that IPE alleviated the cortisol-induced decrease in the levels of procollagen type 1 and hyaluronic acid (HA), which were significantly recovered by 106% and 31%, respectively, compared with cortisol-induced reductions. IPE also rescued the suppression of the gene expression of COL1A1 and the HA synthases HAS2 and HAS3 in cortisol-exposed cells. Moreover, IPE blocked the cortisol-induced translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus as effectively as the GR inhibitor mifepristone. Analysis using a high-performance liquid chromatography-diode-array detector system revealed that irigenin, an isoflavone, is the main component of IPE, which restored the cortisol-induced reduction in collagen type 1 levels by 82% relative to the cortisol-induced decrease. Our results suggest that IPE can act as an inhibitor of cortisol in human skin cells, preventing cortisol-induced collagen and HA degradation by blocking the nuclear translocation of the GR. Therefore, IPE may be used as a cosmetic material or herbal medicine to treat stress-related skin changes.

Visualizing extracellular vesicle biogenesis in gram-positive bacteria using super-resolution microscopy.

BACKGROUND: Recently, bacterial extracellular vesicles (EVs) have been considered to play crucial roles in various biological processes and have great potential for developing cancer therapeutics and biomedicine. However, studies on bacterial EVs have mainly focused on outer membrane vesicles released from gram-negative bacteria since the outermost peptidoglycan layer in gram-positive bacteria is thought to preclude the release of EVs as a physical barrier. RESULTS: Here, we examined the ultrastructural organization of the EV produced by gram-positive bacteria using super-resolution stochastic optical reconstruction microscopy (STORM) at the nanoscale, which has not been resolved using conventional microscopy. Based on the super-resolution images of EVs, we propose three major mechanisms of EV biogenesis, i.e., membrane blebbing (mechanisms 1 and 2) or explosive cell lysis (mechanism 3), which are different from the mechanisms in gram-negative bacteria, despite some similarities. CONCLUSIONS: These findings highlight the significant role of cell wall degradation in regulating various mechanisms of EV biogenesis and call for a reassessment of previously unresolved EV biogenesis in gram-positive bacteria.

Enhancement of Efficacy of Retinoids through Enhancing Retinoid-Induced RAR Activity and Inhibiting Hydroxylation of Retinoic Acid, and Its Clinical Efficacy on Photo-Aging.

Retinoids, one of the most robust bioactive materials, have been widely used to improve various dermatological and pathological conditions. The body has an endogenous mechanism that modulates the exogenous retinoid above physiological concentrations, which limits the bioavailability or pharmacological efficacy of retinoids. Considering that most retinoids trigger extensive irritation in users, it is necessary to enhance the pharmacological efficacy of retinoids, thereby achieving a higher efficacy at a lower dosage. Here, we present approaches for enhancing the efficacy of retinol by enhancing retinoid-induced RAR gamma (RAR-γ) activity and inhibiting the hydroxylation of retinoic acid. Using both in vitro and ex vivo experiments, retinoid boosters were demonstrated to enhance pharmacological efficacy. A small pilot study was conducted to investigate the efficacy for improvement of facial wrinkles, whose results revealed that these boosters could enhance the pharmacological efficacy of topical applications of both retinol and retinoic acid for cosmetic use. These results promote not only a higher compliance among retinoids users, but also provide significant insights into the mechanisms underlying the action of retinoids.

Sugar-Triggered Burst Drug Releasing Poly-Lactic Acid (PLA) Microneedles and Its Fabrication Based on Solvent-Casting Approach.

Microneedles have emerged as a novel transdermal delivery tool that enables the delivery of various products such as drugs, vaccines, or cosmetic ingredients. Although the demand for solid microneedles composed of biocompatible polymer is increasing, the manufacture of microneedles using poly-lactic acid (PLA) with rapid drug-releasing is yet to be established and the process is still in its infancy. Here, we propose a novel strategy for the fabrication of PLA solid microneedles which enable a drug to be burst-released based on a solvent-casting process. This approach offers extreme simplicity, broad geometric capability, cost-effectiveness, and scalability based on high fidelity-replicas. It was verified that microneedles of various heights (250-500 µm) could be fabricated with appropriate mechanical strength to penetrate the stratum corneum layer of skin. By adding sugar in the composition of PLA microneedle, it was observed that both hydrophilic and hydrophobic drugs can be rapidly released within 30 min. Our burst drug-releasing PLA microneedle having both characteristics of solid microneedle and soluble microneedle and its fabrication approach based on solvent-casting will contribute to getting microneedle technology close to commercialization and beyond existing technical limitations.

Two newly developed indices evaluating facial skin aging.

BACKGROUND: Skin assessment methodologies have focused mainly on intuitive aging characteristics, including facial wrinkles and pigmented spots, and usually adopt pattern recognition algorithms. Recently, distinct methods of interpreting skin aging, such as the detection of facial landmarks and age prediction using machine learning techniques, have been conducted. MATERIALS AND METHODS: We defined two indices that represent the severity of facial aging. The first index was the ratio of the bizygomatic distance and bigonial distance. The second index was the ratio of the degrees of the near mandible. The indices extracted from two-dimensional frontal face images were intended to show the deformation of the facial skin downward with aging progress. To validate whether these proposed indicators can represent facial aging, we conducted correlation tests with age and facial skin characteristics and performed association tests between the indices and facial skin characteristics, adjusted for age. RESULTS: The indices showed strong correlations with age (r = 0.557 and 0.464, respectively) and facial skin characteristics. Although there were correlations between the indices and facial skin features, the associations between the indices and facial skin characteristics adjusted for age were weak or not significant. This suggests that the newly developed indices are appropriate for evaluating facial skin aging and distinct from typical measurements. CONCLUSION: We suggest two novel indices for evaluating facial aging based on frontal face images. The indices exhibited strong correlations with age and representative facial skin characteristics. The newly developed values can be differentiated indicators of facial aging compared with general skin features.

Anti-Hair Loss Effect of Adenosine Is Exerted by cAMP Mediated Wnt/ß-Catenin Pathway Stimulation via Modulation of Gsk3ß Activity in Cultured Human Dermal Papilla Cells.

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/ß-catenin pathway by modulating the activity of Gsk3ß in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3ß was increased. Furthermore, the expression of ß-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/ß-catenin signaling through the activation of the adenosine receptor and Gsk3ß plays a critical role in transmitting the signals from the adenosine receptor to ß-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.

Antiandrogenic activity of Riboflavin 5'-phosphate (FMN) in 22Rv1 and LNCaP human prostate cancer cell lines.

The androgen receptor is a hormone activated transcription factor that regulates the development and maintenance of male characteristics and represents one of the most well-established drug targets, being implicated not only in prostate cancer but also in many non-cancerous human diseases including androgenetic alopecia, acne vulgaris, and hirsutism. In this study, the antiandrogenic effects of FMN were investigated in 22Rv1 and LNCaP prostate cancer cells. FMN inhibited dihydrotestosterone (DHT)-induced protein expression of androgen receptor in 22Rv1cells. In another prostate cancer LNCaP cells, FMN decreased the protein level of DHT-induced prostate specific antigen (PSA). In addition, FMN downregulated DHT-induced mRNA expression of androgen regulated genes in both cell lines, showing less prominent inhibition in 22Rv1cells where androgen receptor had been significantly decreased by FMN. FMN was found to bind androgen receptor, demonstrating that it acted as a competitive androgen receptor antagonist. FMN increased the phosphorylation of Akt in 22Rv1 cells and this increment was abrogated by PI3K inhibitor wortmannin, resulting in a rescued androgen receptor protein level which was decreased by FMN. Additionally, FMN was found to increase the mRNA and protein level of E3 ligase mouse double minute 2. Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.