FERULIC ACID

The goal of this study was to create and optimize a topical cream based on cubosomes for improved dermal delivery and stability of ferulic acid, a strong antioxidant with anti-hyperpigmentation properties that is limited by low photostability and skin permeability. Improving the stability of ferulic acid and regulating its skin distribution is crucial for its successful application in cosmeceutical formulations. Cubosomal nanocarriers offer a viable way to enhance photostability, solubility, and sustained release, improving therapeutic efficacy while preserving skin safety. Glyceryl monooleate and Poloxamer 407 were used to create ferulic acid-loaded cubosomes. The effects of almond oil and Sepineo P600 on viscosity and drug content were assessed using the Box-Behnken design to optimize cream formulation. Particle size analysis, entrapment efficiency, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rheological investigations were all part of the characterization. To clarify release mechanisms, kinetic models were fitted to in vitro release data. Tyrosinase inhibition studies evaluated the effectiveness of anti-hyperpigmentation, while MTT and RT-PCR assays were used to assess biocompatibility. The optimized formulation developed nanosized particles with thixotropic flow behavior, skin-compatible pH, and high entrapment efficiency. Diffusion-controlled delivery was indicated by release following first-order and Higuchi kinetics, although super case-II transport was suggested by Korsmeyer-Peppas analysis ( n  = 1.105). The cream showed moderate tyrosinase inhibition, TNF-α expression suppression, and non-cytotoxic behavior. Ferulic acid's potential as a safe and efficient cosmeceutical for skin-brightening applications is supported by the cubosomal cream's significant improvements in solubility, photostability, and prolonged dermal application.

Psoriasis is skin inflammation caused by an immune system dysfunction, involving a complex interaction between immune cells and keratinocytes. The aim of this study was to develop nanoemulsion (NE) based hydrogel containing ferulic acid, a poorly water-soluble compound and evaluate its effect on imiquimod induced psoriasis like skin inflammation. Ferulic acid nanoemulsion (FA-NE) was prepared by ultra-sonication method. Castor oil, Tween-80 and propylene glycol were selected for NE preparation as oil phase surfactant and cosurfactant respectively based on solubility. The NE particle size (29.8 ± 0.49 nm) was within colloidal range, polydispersity index (0.21 ± 0.02) showed homogenous NE, zeta potential (28.5 ± 0.57 mV) indicated stable NE. Entrapment efficiency (96.26 ± 0.33%) and pH (6.8 ± 0.15) was also in suitable range. The rheological study results of FA-NE hydrogel indicated pseudoplastic behavior. The pH and spreadibility were 6.2 ± 0.15 and 8.2 ± 0.89 respectively, suitable for topical application. The optimized FA-NE hydrogel was tested on male Wistar rats (100-150 g) divided into five groups (n = 5). Psoriasis like disease was induced by applying 5% imiquimod (IMQ) cream for 7 days on the shaved dorsal skin of four groups (except normal group) and psoriasis area severity index (PASI) scoring were calculated. The application of optimized FA-NE hydrogel dramatically reduced TNF-α, IL-6, IL-17 A, IL-23, superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase biomarkers when compared to the disease group. These results were consistent with the in-silico docking studies with highest docking score observed with TNF-α. The treatment group's spleen index reduced significantly. Histopathological findings showed increased capillaries, skin thinning, small dermal projections, and inflammatory cells around blood vessels with 5% IMQ cream application and FA-NE hydrogel greatly reduced these psoriatic changes. Immunohistochemical Ki-67 analysis demonstrated that disease control rats expressed more protein than normal, treatment, and standard animals. The FA-NE hydrogel effectively reduced inflammation and oxidative stress in a rat model of psoriasis, suggesting its potential as a topical treatment.

Psoriasis is a chronic autoimmune inflammatory dermatosis with a global prevalence exceeding 3%. Available therapeutic approaches for psoriasis, encompassing topical formulations, monoclonal antibodies, and phototherapy, seldom elicit full clinical remission in practice, yet are plagued by exorbitant costs or impractical administration protocols. To enhance the therapeutic efficacy of ferulic acid (FA), a widely used naturally occurring antioxidant, a series of short-chain fatty acids (SCFAs) were selected for the structural modification of FA, thereby endowing the covalent conjugate with enhanced antioxidant activity, as well as potent immunomodulatory and cell cycle regulatory properties. Using an imiquimod (IMQ)-induced psoriasis-like mouse model, pentanoylated ferulic acid methyl ester (PentFAMe) was identified as the most potent candidate compound, exhibiting the highest efficacy. Its therapeutic effects and underlying mechanism were further elucidated through in vivo and in vitro approaches. Compared with the parent compounds, the conjugate PentFAMe exhibits superior and more comprehensive pharmacological activity. The activity of PentFAMe is substantially higher than the individual component likely to be formed in vivo upon hydrolysis. Pentanoic acid alone displays potent anti-proliferative and anti-inflammatory activities via suppression of HDAC3/6 expression. PentFAMe exerts superior effects by inhibiting HDAC3/6 expression, thereby restoring acetylation levels of H3K27 and NF-κB p65. Meanwhile, PentFAMe surpassed ferulic acid in its ability to activate the antioxidant Nrf2 pathway. Furthermore, effective Nrf2 activation inhibited NF-κB phosphorylation, resulting in a notable decrease in proinflammatory cytokine and chemokine expression. PentFAMe, as a component in an oral formulation, is both cost-effective and convenient, offering a novel potential lead compound against psoriasis.

The aryl hydrocarbon receptor (AHR) has expanded beyond its classical role and is increasingly recognized for its involvement in mediating the biological effects of cosmetic bioactives. Increasing evidence indicates that key cosmetic compounds, including resveratrol, ferulic acid, and curcumin, exert part of their effects through AHR activation, rather than solely via classical nuclear factor erythroid 2related factor 2 (NRF2) and nuclear factor kappa B (NF-κB)mediated pathways. Based on a comprehensive review of existing studies, AHR regulates multiple pathways relevant to skin function, including collagen synthesis, melanogenesis, barrier integrity, and metabolic signaling, highlighting its role as an integrative hub coordinating complex skin responses. This review frames AHR not merely as a xenobiotic sensor but as a transcription factor integrating multiple signals from environmental and bioactive inputs. Finally, we discuss how emerging tools, including AI-driven modeling and synthetic biology, may expand opportunities for future AHR-focused research and help inform more tailored skincare strategies.

Electrospun poly(ε-caprolactone) (PCL) membranes incorporating Triticum vulgare extract (TVE) were developed as biomimetic scaffolds for periodontal regeneration. Using a ternary solvent system, two experimental formulations (µF-P10 and µF-P10T1) were fabricated and compared against a commercial dermal matrix. SEM analysis revealed bimodal fiber distributions (0.77-1.74 µm) and a surface porosity of 29.86% for TVE-loaded membranes, significantly higher than that of the commercial control (25.26%). FT-IR confirmed that the PCL chemical integrity was preserved, while mechanical testing showed that extract incorporation reinforced the matrix, increasing the Young's modulus from 2.90 × 10 3 Pa to 3.54 × 10 3 Pa. UHPLC-MS identified ferulic acid as the primary bioactive component (90%), with release kinetics following a first-order model (R 2 = 0.998) over 48 h. Biological assays with human gingival fibroblasts (HGF) confirmed non-cytotoxicity (>70% viability). While both membranes supported healing, the µF-P10 formulation showed superior performance, with 80.2% proliferation and 60.6% wound closure, approaching control levels. These findings demonstrate that PCL-TVE electrospun scaffolds effectively combine favorable morphology and controlled release, offering a promising alternative for subepithelial connective tissue regeneration.

Skin pigmentation disorders present a significant therapeutic challenge, often arising from disturbances in melanin metabolism that lead to uneven pigmentation and skin damage. Tyrosinase (TYR), the key enzyme in melanin biosynthesis, serves as a crucial therapeutic target for managing hyperpigmentation and pigmentary skin diseases. In this study, we performed structure-based virtual screening of a comprehensive library of FDA-approved drugs and chemical active agents against tyrosinase and selected top-ranked compounds based on predicted binding affinities and favorable binding poses for experimental validation. In vitro assays confirmed that nine compounds inhibited mushroom tyrosinase (mTYR) with IC 50 values of 6.3-23.4 μM. Among them, rosmarinic acid (compound 1) and ferulic acid (compound 3) also inhibited human tyrosinase (hTYR) with IC 50 values of 7.8 ± 0.4 and 9.3 ± 0.5 μM, respectively. Enzyme kinetic analysis indicated a competitive inhibition mechanism against mTYR for the most active compounds. In α-melanocyte stimulating hormone (MSH)-stimulated B16F10 cells, the selected hits produced measurable anti-melanogenic effects within the tested concentration range, with cellular IC 50  = 37.8-108.1 μM. Additionally, molecular dynamics simulations of rosmarinic acid in complex with hTYR confirmed a stable binding mode characterized by persistent coordination within the dicopper active site. These findings identify repurposable small-molecule scaffolds with tyrosinase-inhibitory activity and highlight rosmarinic acid as a promising lead for further development. Although the present study is limited to in vitro enzymatic and cellular evaluation, it provides a useful foundation for future validation in human skin-derived systems and in vivo models.

Integrated skincare (ISC) combines dermocosmetics with medical aesthetic procedures to improve outcomes. However, guidance on selecting appropriate active ingredients across different procedure types and phases remains limited. To provide international guidance on appropriate ISC actives for use with aesthetic procedures. In a simplified Delphi study, 14 experts evaluated 44 actives for use across four procedure categories (ablative energy-based, non-ablative energy-based, non-energy-based procedures with or without skin barrier disruption) at four time points (pretreatment, peri-treatment, aftercare, and follow-up ≥ 1 week post-procedure). The panelists also ranked their top five preferred actives for each procedure category and time point. Ceramides, cholesterol, hyaluronic acid, niacinamide, and peptides were deemed appropriate across all procedure categories and all time points. Azelaic acid, benzoyl peroxide, cysteamine, glycolic acid, hydroquinone, lactic acid, retinoids, and salicylic acid were identified as unsuitable for use on treatment day. Ceramides and hyaluronic acid were highly ranked for pre-treatment, peri-treatment and aftercare, while retinoids and ferulic acid were highly ranked for pretreatment and followup. Vitamin C was ranked in the top 5 across all procedure categories and time points, except at pretreatment for non-energy-based without skin barrier damage. Safety and tolerability are primary considerations when selecting ISC actives. Ingredients with higher irritation potential, such as retinoids and acids, should be avoided during the healing phase (on treatment day and during short-term aftercare) due to risk of irritation, as well as post-inflammatory hyperpigmentation in skin of color.

Ferulic acid (FA), a natural bioactive compound, faces severe limitations in health-promoting applications due to its poor water solubility and low bioavailability. Different from physical encapsulation of FA in hydrogels, this study develops sodium deoxycholate (NaDC)-FA supramolecular hydrogels through direct assembly of NaDC with FA. The prepared NaDC-FA hydrogels contain 20-80 mM FA, which are about 5-20 times FA amount in the saturated solution. Experimental studies of phase behavior, scanning electron microscopy, small-angle X-ray diffraction, fourier transform infrared and Raman spectra, together with computational simulation reveal that as FA concentration increases from 20 mM to 30 mM, the flexible nanofibers are gradually assembled into homogeneous hydrogel networks via the hydrophobic interaction and hydrogen bonding. Above 30 mM FA, high amount of FA promotes the formation of more rigid and densely packed networks in NaDC-FA hydrogels, where excessive FA-FA interactions disrupt the structural homogeneity of the hydrogels. The different microstructures of NaDC-FA hydrogels contribute to the appearance, melting temperature, and viscoelastic properties of the hydrogels as well as the transdermal permeation behavior of FA. The porcine skin permeation measurement suggests that the cumulative permeation amount of FA in NaDC-FA hydrogels with 50 mM FA is 7.1-fold relative to a saturated FA solution, indicating that the co-permeation of NaDC can reduce the free energy barrier for the transdermal permeation of FA. Moreover, bioactive FA loaded in NaDC-FA hydrogels achieves superior long-lasting free radical scavenging activity owing to the confined microenvironment of fibrous hydrogel networks.

This study reports the formulation and biofunctional evaluation of ferulic acid (FA)-loaded films using native (NFS) and carboxymethylated (MFS) finger millet starch for advanced wound management. Successful structural modification (degree of substitution: 0.17 ± 0.05) was confirmed via 1 H NMR, ATR-FTIR, and CHN elemental analysis. X-ray diffraction revealed a reduction in relative crystallinity (25.5% to 21%) following etherification, while thermogravimetric analysis (TGA) demonstrated a structural degradation shift (T max ) from 302 °C to 228 °C indicated thermal stability exceeding 150 °C. Compared to the native matrix, MFS exhibited superior solubility, bioadhesion, and prolonged matrix integrity during extended 6-h swelling studies. Crucially, kinetic modeling of in-vitro dissolution profiles revealed that optimized 10% FA-loaded MFS films provided highly sustained drug release governed by Super Case-II transport (Korsmeyer-Peppas, n = 1.20). This robust, crosslinked hydrogel network successfully suppressed the rapid burst release and anomalous matrix erosion (n = 0.81) observed in unmodified native films. In-vivo excision wound models demonstrated that 10% MFSFA films significantly accelerated healing, achieving 97.06% wound contraction by day 12. Histopathological and biochemical evaluations confirmed advanced epithelial regeneration, restored dermal appendages, and elevated hydroxyproline deposition (5.06 mg/g) comparable to standard povidone‑iodine treatment. These findings establish chemically modified finger millet starch as a highly stable, structurally tunable biopolymer platform for the sustained topical delivery of antioxidant therapeutics.

Current alopecia treatments have side effects and limited efficacy, highlighting the need for better alternatives. Estrogen and estrogen receptor alpha (ERα)-targeting therapies have shown promise in addressing female-pattern hair loss, outperforming some conventional options. This study investigated the hair growth-promoting effects of Cnidium officinale extract (COE) and its active compound, ferulic acid (FA), focusing on their role in activating ERα. Using human dermal papilla cells (DPCs) and cultured human hair follicles, we assessed cell proliferation, mitochondrial function, gene expression, and protein levels including transcriptome analysis. Both COE and FA significantly enhanced DPCs proliferation and mitochondrial activity, and extended hair follicle length during the anagen (growth) phase. Transcriptomic comparisons between FA- and estrogen-treated cells revealed upregulation of genes involved in energy metabolism, particularly those related to ATP regeneration. FA also elevated c-JUN mRNA expression, indicating estrogen-like ERα activation, and increased the expression of MAPK pathway-associated proteins, along with key growth factors. Additionally, co-treatment with FA and NMN, a cellular activity regulator, enhanced mitochondrial activity in a concentration-dependent manner beyond NMN alone. These findings suggest that COE and FA stimulate hair growth by enhancing DPCs function, with FA’s ERα-activating properties offering potential as a novel therapeutic option for alopecia.

Pharmaceutical, cosmetic, and food industries have contributed to the increasing interest in herbal phytochemicals. Salvia , a multifunctional culinary herb, meets phytotherapeutic requirements in the treatment of heartburn, excessive sweating, flatulence, and mouth, throat, and skin inflammatory conditions. Salviae folium is used in conductive education, i.e., a unique rehabilitation method for individuals with neurological and motor disorders designed to help in learning to perform activities independently. The comparative analysis of bioactive chemical compounds in S. officinalis , S. officinalis subsp. lavandulifolia , and S. sclarea herb showed that S. officinalis had the highest concentration of exogenous amino acids (53 mg·g -1 DW), with a predominance of lecithin and phenylalanine, and endogenous amino acids were dominated by aspartic and glutamic acids. S. officinalis subsp. lavandulifolia was the richest source of omega-3, omega-6, and omega-9 fatty acids, followed by S. officinalis and S. sclarea . The vitamin C content was 4.9 ( S. sclarea )-14.4 mg·100 g -1 DW ( S. officinalis ). Phenolic acids were dominated by rosmarinic acid ( S. officinalis > S. officinalis sub. lavandulifolia > S. sclarea ) and ferulic acid ( S. officinalis > S. sclarea > S. officinalis sub. lavandulifolia ). Salvia sclarea is a rich source of p -coumaric acid. Among non-phenolic organic acids, the highest content of quinic and malic acids was found in S. sclarea and S. officinalis , respectively. The level of o -dihydroxyphenols was 2140 ( S. officinalis )-2222 mg CAE·100·g -1 DW ( S. sclarea) . The flavonoid content was 610 ( S. officinalis subsp. lavandulifolia )-347 mg RU·100 g -1 DW ( S. sclarea ). Flavonoids, flavonols, and flavanones were dominated by apigenin, kaempferol, and hesperidin, respectively. These metabolites may be potential components in phytotherapeutic products.