Cnidium officinale (CO) and Angelica gigas (AG) are traditional medicinal herbs widely recognized in East Asian medicine for their diverse biological activities. Both herbs contain the bioactive compound ferulic acid (FA), a potent phenolic antioxidant known for its significant dermatological and cosmetic benefits, including skin-whitening, anti-inflammatory, antioxidant, and UV-protective effects. FA is particularly effective in skin brightening by downregulating tyrosinase activity and inhibiting melanin synthesis, making it a promising ingredient for hyperpigmentation therapies.
Despite its therapeutic potential, FA’s efficacy is significantly hindered by its poor water solubility and low bioavailability, which necessitates the development of alternative formulation strategies to improve its stability and absorption. Traditional extraction methods for CO and AG often result in limited yields and can be solvent-intensive. To address these challenges, hot-melt extrusion (HME) was considered as a potential solution. HME is an established continuous, solvent-free, and eco-friendly processing technology that has been widely adopted in the pharmaceutical industry to enhance the solubility and bioavailability of poorly water-soluble compounds. Its alignment with green chemistry principles—by eliminating organic solvents, reducing processing steps, and enabling scalable, energy-efficient production—made it an attractive approach to improve the biofunctional performance of FA-enriched CO and AG extracts for cosmetic applications.
Methods
The study optimized the hot-melt extrusion (HME) process for Cnidium officinale (CO) and Angelica gigas (AG) powders using a twin-screw extruder to prepare HME-CO and HME-AG. Quantitative high-performance liquid chromatography (HPLC) was employed to analyze the ferulic acid (FA) content in both untreated and HME-treated extracts. Structural and morphological changes were characterized using Fourier-transform infrared (FT-IR) spectroscopy, field emission-scanning electron microscopy (FE-SEM), field emission-transmission electron microscopy (FE-TEM), and dynamic light scattering (DLS). The cosmetic efficacy was then evaluated through antioxidant activity assessments (DPPH and ABTS assays), anti-melanogenic activity in B16F10 melanoma cells, and in vitro wound-healing effects in HaCaT keratinocytes, following cytotoxicity assessments.
Key Findings
• Significant Increase in Ferulic Acid (FA) Content: HME processing led to a substantial enhancement in FA concentration, with a 22.7-fold increase in CO (from 330.07 ± 7.37 µg/g to 7479.66 ± 170.37 µg/g) and a 4.4-fold increase in AG (from 528.58 ± 2.89 µg/g to 2339.20 ± 21.85 µg/g). This is attributed to the destruction of cross-linked structures and ester bonds within plant cell walls by the high temperature, pressure, and mechanical shear forces of HME.
• Improved Particle Morphology and Size Reduction: FE-SEM and FE-TEM analyses revealed that HME treatment resulted in substantial morphological changes, including smoother surface topology, reduced particle size (e.g., HME-CO at 350.3 d. nm from >700 d. nm; HME-AG at 400.3 d. nm from >700 d. nm), and more uniform, densely packed structures with diminished surface porosity and improved dispersibility.
• Molecular and Structural Alterations: FT-IR spectroscopy confirmed that HME induced measurable alterations in the molecular environment of CO and AG, suggested by spectral shifts and reduced peak intensities, indicative of changes in hydrogen bonding networks and matrix interactions that could increase the accessibility and extractability of functional components like FA.
• Enhanced Antioxidant Activity: HME-treated samples showed significantly elevated radical scavenging activity in both DPPH and ABTS assays. HME-CO’s DPPH IC50 value (589.4 ± 13.7 µg/mL) was 2.21-fold lower than untreated CO (1304.3 ± 74.7 µg/mL), and HME-AG’s DPPH IC50 (299.6 ± 21.2 µg/mL) was 2.03-fold lower than native AG (606.8 ± 15.9 µg/mL).
• Potent Anti-Melanogenic Effects: HME-CO and HME-AG demonstrated significantly greater inhibitory effects on α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis in B16F10 cells, reducing melanin production to 39.9% and 44.8% respectively, compared to 68.4% and 66.4% for their non-processed counterparts.
• Accelerated Wound Healing Efficacy: In HaCaT keratinocytes, HME-treated groups promoted superior wound closure. HME-CO achieved 96.2 ± 0.3% wound closure and HME-AG achieved 98.2 ± 0.1% wound closure at 48 hours, significantly outperforming untreated controls and CO/AG groups.
• Low Cytotoxicity: HME extracts exhibited no cytotoxicity up to 500 µg/mL in B16F10 melanocytes and no cytotoxicity at any tested concentration in HaCaT keratinocytes, where they even increased cell proliferation at higher concentrations.
Conclusion
This research successfully demonstrates the novel application of hot-melt extrusion (HME) technology to enhance the bioavailability and functional properties of Cnidium officinale (CO) and Angelica gigas (AG) extracts for cosmetic purposes. To the best of the authors’ knowledge, this is the first study applying HME to CO and AG extracts for such applications. The process significantly increased ferulic acid content and improved particle morphology, leading to enhanced antioxidant, anti-melanogenic, and wound-healing activities.
The findings underscore HME’s utility as a green, solvent-free, and scalable processing technology capable of enhancing the physicochemical characteristics and biological efficacy of herbal materials. This research offers promising opportunities for the development of next-generation functional cosmetics and therapeutic formulations. The results specifically support the potential application of HME-processed CO and AG as active ingredients designed to enhance skin brightening and accelerate skin regeneration, highlighting their future integration into advanced cosmetic products and regenerative treatment approaches for hyperpigmentation and skin repair.
Link to the study: https://www.mdpi.com/2079-9284/12/5/197
