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Article

Eco-Friendly Enhancement of Ferulic Acid-Rich Extracts from Cnidium officinale and Angelica gigas via Hot-Melt Extrusion for Skin Brightening and Regeneration

by
Yoo-Na Jeon
1,2,†,
Han-Sol You
2,†,
So-Hee Jang
2 and
Jong-Suep Baek
1,2,*
1
BeNatureBioLab, Chuncheon 24206, Republic of Korea
2
Department of Bio-Health Convergence, Kangwon National University, Chuncheon 24341, Republic of Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cosmetics 2025, 12(5), 197; https://doi.org/10.3390/cosmetics12050197
Submission received: 16 July 2025 / Revised: 5 August 2025 / Accepted: 21 August 2025 / Published: 10 September 2025
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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Abstract

Cnidium officinale (CO) and Angelica gigas (AG) are traditional herbal medicines known for their bioactive compound ferulic acid (FA), which exerts skin-whitening, anti-inflammatory, antioxidant, and UV-protective effects. However, conventional extraction yields are limited and often require solvent-intensive processes. In this study, an eco-friendly hot-melt extrusion (HME) process was applied to enhance the FA content and extractability from CO and AG. Process optimization significantly improved particle morphology and reduced size, as confirmed by Fourier transform-infrared spectroscopy (FT-IR) and field emission-scanning electron microscopy (FE-SEM) analysis. Quantitative High-performance liquid chromatography (HPLC) analysis showed increased FA content in HME-treated extracts, which corresponded to enhanced biological efficacy. The HME extracts exhibited no cytotoxicity up to 500 µg/mL in B16F10 melanocytes and significantly inhibited α-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis. In HaCaT keratinocytes, the HME group promoted superior wound closure at 24 and 48 h, indicating accelerated skin regeneration. These findings support HME as a sustainable and effective strategy for developing natural ingredient-based cosmetic formulations targeting hyperpigmentation and skin repair.

1. Introduction

Cnidium officinale (CO) and Angelica gigas (AG) are well-established traditional medicinal herbs widely utilized in East Asian medicine for their broad spectrum of biological activities. CO, a perennial plant belonging to the Apiaceae family, is predominantly cultivated in Korea, China, and Japan and has been historically used to manage conditions such as angiogenesis, menstrual disorders, inflammation, and skin diseases [1,2,3,4,5]. Its rhizome contains a diverse range of bioactive constituents, including coumarins, polyphenols, flavonoids, and notably, ferulic acid (FA), all of which contribute to its antioxidant, anti-inflammatory, anticancer, and antifungal properties [6]. Recent studies have shown that CO extract has antioxidant, skin-moisturizing, and whitening activities and has the potential as a cosmetic ingredient that can inhibit collagen decomposition by reducing the expression of MMP1, which decomposes skin collagen [7,8].
AG, often referred to as Korean Angelica, also belongs to the Apiaceae family and is valued for its dried root, traditionally prescribed for gynecological ailments, anemia, and pain management [9,10,11]. AG is particularly rich in furanocoumarin-based compounds such as decursin and decursinol angelate, which have demonstrated potent antioxidative, anticancer, and antitumor effects [12,13]. More recently, AG extract has been reported to increase skin collagen synthesis, inhibit melanin synthesis, and have anti-wrinkle effects in vitro and clinical trials, highlighting its potential for cosmetic development [14,15,16].
Among the key active compounds in both CO and AG, FA has garnered significant attention in dermatological and cosmetic applications. As a potent phenolic antioxidant, FA mitigates oxidative stress, suppresses inflammation, and exhibits UV-protective, skin-whitening, and anti-aging properties [17,18]. In particular, FA is recognized for its skin-brightening effects by downregulating tyrosinase activity and inhibiting melanin synthesis, making it a promising ingredient in hyperpigmentation therapies [19]. However, the therapeutic potential of FA is significantly limited by its poor water solubility and low bioavailability, prompting the development of alternative formulation strategies to improve its stability and absorption [20,21,22].
To overcome these limitations, a hot-melt extrusion (HME) approach was utilized as a continuous, solvent-free processing technology to enhance the solubility, stability, and biofunctional performance of FA-enriched CO and AG extracts. HME is a continuous, solvent-free, and eco-friendly processing technology widely adopted in the pharmaceutical industry to enhance the solubility and bioavailability of poorly water-soluble compounds [23]. By eliminating organic solvents, reducing processing steps, and enabling scalable, energy-efficient production, HME aligns with green chemistry principles and sustainable manufacturing practices [24,25,26]. While prior research has explored HME for improving functional delivery of certain herbal extracts (e.g., ginseng, mulberry leaf, Haematococcus pluvialis) [27,28,29], to the best of our knowledge, this is the first study applying HME to CO and AG extracts for cosmetic applications, highlighting the novelty of our approach.
In this study, we optimized the HME process for CO and AG and analyzed the resultant changes in FA content using high-performance liquid chromatography (HPLC). Structural alterations were assessed through Fourier-transform infrared (FT-IR) spectroscopy, while particle morphology was examined via field-emission scanning electron microscopy (FE-SEM). The cosmetic efficacy of the HME-treated extracts was further evaluated through their melanin-inhibitory activity in B16F10 melanoma cells and wound-healing effects in HaCaT keratinocytes. This research highlights the utility of HME as a green and scalable platform for developing next-generation natural product-based ingredients with enhanced skin benefits, offering significant promise for cosmetic and therapeutic applications.

2. Materials and Methods

2.1. Materials

Cnidium officinale and Angelica gigas were purchased from Samhong Herbal Medicine Co. (Seoul, Republic of Korea). Gallic acid (G7384), quercetin (Q4951), melanin, and α-melanocyte stimulating hormone (α-MSH) were obtained from Sigma-Aldrich (St. Louis, MO, USA). Arbutin was obtained from TCI (Tokyo, Japan). Human keratinocyte cell line HaCaT and mouse melanoma cell line B16F10 were purchased from the Korean Cell Line Bank (Seoul, Republic of Korea). Dulbecco’s modification of Eagle’s medium (DMEM), phosphate-buffered saline (PBS), penicillin-streptomycin, and fetal bovine serum (FBS) were purchased from Thermo Fisher Scientific (Waltham, MA, USA). Di-methyl sulfoxide (DMSO) for cell culture was purchased from Gen DEPOT (Altair, TX, USA). Cell counting kit-8 (CCK-8) assay kits were purchased from Abcam (Cambridge, UK).

2.2. Preparation of CO, HME-CO, AG, and HME-AG

CO and AG powders were treated with HME to prepare HME-CO and HME-AG. The extruder (STS-25HS, co-rotating intermeshing twin-screw extruder, Pyeongtaek, Republic of Korea) was used, and the extruder was made with a twin-screw extruder and a die (1 mm) at an injection speed of 40 g/min and 150 rpm. Then, the extrudates were dried using freeze-drying. The freeze-dried samples were obtained in powder form through a grinder. The compositions of the formulations are shown in Table 1 and Table 2. Ferulic acid was added to promote the antioxidant, skin-whitening, and regenerative effects of CO and AG [30]. Lecithin was used to improve bioavailability by enhancing the dispersibility and solubility of hydrophobic ingredients, and ascorbyl palmitate was used to enhance stability by acting as an antioxidant that prevents lipid oxidation [31,32]. All formulations were extracted by sonication with distilled water (50 mL per gram) at 40 °C for 1 h. The extracts were filtered through filter paper and were evaporated.

2.3. HPLC Analysis for FA Quantification

Before HPLC analysis, each sample was filtered using a hydrophobic syringe filter with a pore size of 0.45 μm. Analysis was performed on an Agilent 1200 Series system equipped with a diode array detector (DAD; Agilent Technologies, Waldbronn, Germany). Ferulic acid analysis followed a previously established protocol, with minor modifications made in this study. The specific analytical conditions are summarized in Table 3 [33].

2.4. Characterization

To observe physical properties, CO, HME-CO, AG, and HME-AG were analyzed using Transmission electron microscopy (TEM) equipped with an energy-dispersive spectroscope (EDS [JEM-2100F, JEOL, Tokyo, Japan]) and Scanning Electron Microscopy (SEM) (S-4800, Hitachi, Japan). The particle size was measured using Dynamic light scattering (DLS) (Zetasizer Nano ZS, Malvern Instruments, Malvern, UK). The functional characteristics of the samples were analyzed in FT-IR spectroscopy, which was performed using a Thermo Scientific instrument (iN10/iS50, Waltham, MA, USA). The spectra were acquired over a wavenumber range of 4000–400 cm−1, employing the attenuated total reflection (ATR) mode for analysis.

2.5. Assessment of Antioxidant Activity Through DPPH and ABTS Methods

For the 2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, 0.4 mM ABTS solution was mixed with 2.4 mM potassium persulfate at a 1:1 ratio and allowed to react in the dark for 16 h. The resulting ABTS solution was diluted with distilled water and adjusted to an absorbance of 0.7 at 734 nm. Subsequently, 100 µL of the sample and 100 µL of the prepared ABTS solution were combined in a 96-well plate and incubated in the dark for 20 min.
For the DPPH assay, 100 µL of 0.1 mM DPPH methanolic solution was mixed with 100 µL of the sample under dark conditions and allowed to react for 20 min. The absorbance was recorded at 734 nm (ABTS) and 517 nm 2,2-Diphenyl-1-picrylhydrazyl (DPPH) using a microplate reader, and the IC50 values of each sample were calculated based on the obtained data [34].

2.6. Cytotoxicity

B16F10 cells and HaCaT cells were maintained in DMEM supplemented with 10% FBS and 1% P/S at 37 °C in a humidified atmosphere containing 5% CO2. Cell viability was evaluated using the CCK-8 assay. Briefly, B16F10 cells and HaCaT cells were seeded in 96-well plates at a density of 2 × 104 cells per well and incubated for 24 h to allow cell attachment. Following this, 10 µL of the test samples at various concentrations was added to each well and incubated for another 24 h. Subsequently, 10 µL of CCK-8 reagent was introduced, and after a 1 h incubation period, absorbance was recorded at 450 nm using a microplate reader. The percentage of cell viability was determined using the formula: (Absorbance of sample/Absorbance of control) × 100.

2.7. Assessment of Anti-Melanogenic Activity in B16F10 Cells

B16F10 melanoma cells were seeded in 6-well plates (2 × 105 cells/well, 3 mL medium) and incubated overnight to allow attachment. Cells were subsequently exposed to the samples with or without 100 nM α-MSH for 72 h. After treatment, cells were washed with PBS and lysed in 800 µL of 1 N NaOH containing 10% DMSO at 80 °C for 1 h. Absorbance was measured at 405 nm using a microplate reader, and melanin content was quantified using a standard curve generated from synthetic melanin [35].

2.8. In Vitro Scratch Assay for Wound Healing

HaCaT keratinocytes were seeded in 6-well plates at a density of 2 × 105 cells/well and cultured in DMEM supplemented with 10% FBS and 1% penicillin-streptomycin until reaching approximately 90% confluence. A linear scratch was created across the cell monolayer using a sterile 200 μL pipette tip, followed by two PBS washes to remove detached cells. The medium was then replaced with DMEM containing the samples (CO, HME-CO, AG, or HME-AG). Images of the wound area were captured at 0, 24, and 48 h post-scratch using an inverted phase-contrast microscope. The percentage of wound closure was quantified using Image J software (Version 1.53, National Institutes of Health, Bethesda, MD, USA) by calculating the remaining wound area at each time point relative to the initial area at 0 h [36].

2.9. Statistical Analysis

All data were obtained through three replicate experiments, and the results of the analysis are presented as the mean ± standard deviation. Statistical significance was measured through two-way analysis of variance (ANOVA).

3. Results and Discussion

3.1. Determination of FA Content by HPLC

To assess the impact of HME on the FA content in CO and AG, quantitative analysis was conducted using HPLC. The comparative FA levels before and after HME treatment are presented in Figure 1.
Significant increases in FA content were observed in both CO and AG following HME processing (*** p < 0.001). In CO, the FA concentration increased from 330.07 ± 7.37 μg/g in the untreated sample to 7479.66 ± 170.37 μg/g in the HME-CO, reflecting an approximate 22.7-fold enhancement (Figure 1A). Similarly, in AG, FA levels rose from 528.58 ± 2.89 μg/g to 2339.20 ± 21.85 μg/g after HME, corresponding to a 4.4-fold increase (Figure 1B).
The significant increase in FA content is likely due to the destruction of cross-linked structures and ester bonds within the plant cell wall by the high temperature, pressure, and mechanical shear forces applied during the HME process [37]. In particular, HME has been previously reported to enhance the solubility and availability of phenolic compounds, such as FA, without the use of organic solvents, thereby improving efficiency and sustainability [38].

3.2. FE-SEM and FE-TEM

FE-SEM was employed to observe the microstructural alterations of CO, HME-CO, AG, and HME-AG at magnifications of ×50, ×500, and ×1000 (Figure 2).
The raw CO and AG samples exhibited irregular particle shapes with non-uniform size distributions, rough surfaces, and porous textures. In contrast, HME-processed samples showed substantial morphological changes, including smoother surface topology, reduced particle size, and more uniform, densely packed structures. Notably, at ×1000 magnification, surface porosity was markedly diminished in both HME-CO and HME-AG.
These morphological changes were also observed in TEM analysis. TEM images of CO and AG revealed highly aggregated, heterogeneous morphologies. Conversely, HME-CO and HME-AG exhibited spherical nanoparticles, relatively uniform particle sizes, and improved dispersibility. This confirms that HME processing reduced particle size, achieved amorphization, and ensured uniform dispersibility. DLS analysis supported the TEM results, demonstrating that HME was involved in particle size reduction. The particle sizes of CO and AG were found to be greater than 700 d. nm, whereas the particle sizes of HME-CO and HME-AG were 350.3 d. nm and 400.3 d. nm, respectively (Table 4).
These changes are attributed to the mechanical and thermal effects of the HME process, where high shear force and elevated temperature facilitate particle fragmentation and structural compaction [39]. The resulting reduction in particle size and surface roughness is likely to increase the specific surface area, thereby enhancing the release and solubility of embedded active compounds such as FA.
Collectively, these findings suggest that HME can serve as an effective microstructural engineering tool to optimize the physical characteristics of herbal materials and improve the bioavailability of their bioactive constituents.

3.3. FT-IR

FT-IR spectroscopy was performed to investigate the structural changes in major functional groups of CO and AG before and after HME treatment. The spectral results are presented in Figure 3A.
In the native CO spectrum, characteristic absorption bands were observed at 3296 cm−1 (O–H stretching), 2931, and 2916 cm−1 (C–H symmetric and asymmetric stretching), 1635 cm−1 (C=C stretching), and 990 cm−1 (C–O stretching). Following HME processing, HME-CO exhibited notable spectral shifts and reduced peak intensities. The attenuation of the O–H stretching band at 3296 cm−1 suggests alterations in hydrogen bonding or a reduction in moisture content [40]. The C–H stretching bands showed slight shifts, which may be indicative of lipid structure modification or decreased lipophilic affinity due to protein-lipid complex disruption [41]. Additionally, the diminished C=C stretching peak at 1635 cm−1 implies a reduction in conjugated double bonds or weakening of intermolecular hydrogen bonding, likely resulting from thermal and mechanical stress during extrusion [42].
Similar spectral trends were observed in AG and HME-AG (Figure 3B). The AG spectrum showed peaks at 3289 cm−1 (O–H stretching), 2916 and 2849 cm−1 (C–H stretching), 1728 and 1627 cm−1 (C=O and C=C stretching), 1133 and 991 cm−1 (C–O stretching). Upon HME treatment, these peaks exhibited changes in both position and intensity. In particular, enhanced signals at 1728 and 1627 cm−1 may reflect increased exposure or reconfiguration of carbonyl-containing moieties due to the breakdown of polymeric or glycosidic linkages under high shear and thermal conditions [43].
These spectral modifications confirm that the HME process induces measurable alterations in the molecular environment of CO and AG, potentially increasing the accessibility and extractability of functional components such as FA by modifying hydrogen bonding networks and matrix interactions.

3.4. Determination of Antioxidant Activity by DPPH and ABTS Assays

3.4.1. DPPH

The antioxidant capacities of CO, HME-CO, AG, and HME-AG were assessed using the DPPH radical scavenging assay. The results, expressed as IC50 values, are summarized in Figure 4.
HME treatment led to a substantial improvement in antioxidant activity for both CO and AG. The IC50 value of HME-CO (589.4 ± 13.7 μg/mL) was significantly lower than that of untreated CO (1304.3 ± 74.7 μg/mL), reflecting a 2.21-fold enhancement (Table 5). Similarly, HME-AG exhibited a marked increase in antioxidant capacity, with an IC50 of 299.6 ± 21.2 μg/mL compared to 606.8 ± 15.9 μg/mL in native AG—indicating a 2.03-fold improvement.
These results suggest that the enhanced antioxidant effects observed after HME processing may be attributed to the increased release and bio accessibility of phenolic compounds, including FA. The improved particle uniformity and structural breakdown achieved through the HME process likely facilitate more effective radical scavenging. This trend is consistent with previous studies reporting enhanced antioxidant properties in natural products following HME-induced modification [44].

3.4.2. ABTS

To further evaluate the antioxidant properties of CO and AG, the ABTS radical scavenging assay was conducted, and the IC50 values were determined (Figure 5 and Table 5). All samples demonstrated a concentration-dependent increase in antioxidant activity, with HME-treated samples exhibiting generally enhanced scavenging effects.
In the case of CO, the IC50 value slightly decreased from 778.26 ± 2.79 μg/mL in the untreated sample to 699.66 ± 29.44 μg/mL in HME-CO, indicating a modest improvement following HME processing. In contrast, AG showed a more pronounced enhancement, with the IC50 value significantly reduced from 862.78 ± 2.18 μg/mL to 491.49 ± 8.41 μg/mL after HME treatment (HME-AG).
Interestingly, the extent of improvement in antioxidant activity observed in the ABTS assay was less dramatic for CO compared to the DPPH assay. This discrepancy may be attributed to differences in the reaction mechanisms of the two assays: DPPH is primarily sensitive to lipophilic antioxidants, whereas ABTS can interact with both hydrophilic and lipophilic radicals. Similar patterns have been reported in previous studies, suggesting that the antioxidant profile of CO may be more reactive toward DPPH radicals than ABTS [45].

3.5. Cell Viability (%)

The cytotoxicity of CO, HME-CO, AG, and HME-AG was evaluated using the CCK-8 assay (Figure 6). Cell viability was dose-dependently assessed to determine an appropriate concentration for subsequent biological assays.
In B16F10 cells, HME-CO exhibited low cytotoxicity, maintaining cell viability above 80% at all tested concentrations. In contrast, CO exhibited cytotoxicity, with cell viability dropping sharply to 64.11% at 1000 μg/mL.
For AG and HME-AG, cell viability remained above 80% at concentrations up to 500 μg/mL. However, viability decreased slightly at 1000 μg/mL, with viability rates of 79.16% and 76.17% for AG and HME-AG, respectively.
Based on these results, 500 μg/mL was selected as a relatively safe and non-cytotoxic concentration for subsequent assays, including melanin inhibition and wound healing evaluation.
In HaCaT cells, CO, HME-CO, AG, and HME-AG did not exhibit cytotoxicity at any concentration tested. Furthermore, HME-CO and HME-AG were found to increase cell proliferation compared to the untreated control at increasing concentrations. Based on these results, the concentration used in the wound healing activity assay was selected as 1000 μg/mL.

3.6. Evaluation of Anti-Melanogenesis Effect in B16F10 Cells

The effects of different formulations on melanin production were assessed using α-MSH-stimulated B16F10 melanoma cells (Figure 7). Arbutin is a β-D-glucopyranoside of hydroquinone (4-hydroxyphenol) and a structural derivative of hydroquinone. It inhibits tyrosinase, a key enzyme in melanin synthesis, thereby blocking the dopaquinone production step. Consequently, melanin biosynthesis is inhibited, reducing pigmentation. In this study, arbutin was used as a positive control, and the results confirmed a melanin synthesis rate of 33.78%, validating the reliability of the experiment [46]. In comparison, CO and AG reduced melanin production to 68.4% and 66.4% of the α-MSH-stimulated control, respectively. Notably, HME-CO and HME-AG demonstrated significantly greater inhibitory effects, decreasing melanin production to 39.9% and 44.8%, respectively (*** p < 0.001).
These results indicate that HME processing substantially enhances the melanin-inhibitory activities of CO and AG. This enhancement appears to be due to the increased solubility and bioavailability of key lipophilic components, such as ligustilide and decoursine, which are uniformly dispersed during the HME process. This process may also promote nano- or micro-sized particle formation, enhancing cellular uptake and membrane permeability [47]. Such regulation of melanin production is highly relevant for cosmetic applications, particularly in managing hyperpigmentation issues such as melasma, post-inflammatory pigmentation, and UV-induced skin darkening.
Overall, these findings suggest that HME is a promising approach to enhance the skin-brightening efficacy of herbal ingredients, supporting their potential use in the cosmetic industry for pigmentation management and skin tone improvement.

3.7. In Vitro Wound Healing Assay

For CO-based samples, the wound closure rate at 24 h was 51.9 ± 0.8% in the untreated control group, 53.5 ± 3.7% in the CO group, and significantly increased to 71.7 ± 1.4% in the HME-CO group (Figure 8). After 48 h, the closure rates further increased to 79.5 ± 1.5% (control), 89.1 ± 1.2% (CO), and 96.2 ± 0.3% (HME-CO), respectively.
For AG-based treatments, the wound closure rates at 24 h were 36.3 ± 0.8% (control), 38.7 ± 1.0% (AG), and 58.6 ± 0.9% (HME-AG). At 48 h, HME-AG treatment resulted in near-complete closure (98.2 ± 0.1%), outperforming both AG (81.4 ± 1.5%) and control (75.3 ± 0.9%).
These findings indicate that HME processing enhances the wound-healing efficacy of CO and AG by improving solubility, dispersion, and cellular uptake of bioactive constituents, leading to faster keratinocyte migration and tissue repair.
Given the traditional use of CO and AG in oriental medicine for improving blood circulation, reducing inflammation, and supporting tissue regeneration [48], the results of this study highlight the potential of HME-processed herbal materials as effective topical agents for skin repair and regeneration [49], providing a scientific basis for their potential integration into regenerative treatment approaches.
Table 6 provides a comparative summary of key quantitative results for FA content, melanin production rate, and wound closure rate for all tested formulations.

4. Conclusions

In this study, HME technology was effectively employed to improve the bioavailability and functional properties of CO and AG. Quantitative HPLC analysis confirmed a substantial increase in FA content by 22.66-fold in CO and 4.4-fold in AG following HME processing. Complementary FT-IR, FE-SEM, and FE-TEM analyses revealed chemical and morphological alterations, including enhanced particle uniformity and reduced porosity, which likely contributed to improved solubility and extraction efficiency of bioactive constituents.
The functional enhancements achieved through HME were further supported by antioxidant assays (DPPH and ABTS), which showed significantly elevated radical scavenging activity in HME-treated samples. Additionally, melanin inhibition assays demonstrated that HME-CO and HME-AG more effectively suppressed α-MSH-induced melanin synthesis in B16F10 cells compared to their non-processed counterparts. Wound healing studies using HaCaT keratinocytes confirmed accelerated re-epithelialization in the HME-treated groups, with significant improvements in closure rates at both 24 and 48 h.
Taken together, the findings underscore the utility of HME as a green, solvent-free processing technology capable of enhancing the physicochemical characteristics and biological efficacy of herbal materials. The results support the potential application of HME-processed CO and AG as active ingredients specifically designed to enhance skin brightening and accelerate skin regeneration, offering promising opportunities for next-generation functional cosmetics and therapeutic formulations.

Author Contributions

Conceptualization, Y.-N.J., H.-S.Y., and J.-S.B.; methodology, Y.-N.J., H.-S.Y., and S.-H.J.; software, Y.-N.J. and S.-H.J.; validation, H.-S.Y., S.-H.J., and J.-S.B.; formal analysis, Y.-N.J., H.-S.Y., and S.-H.J.; investigation, Y.-N.J. and H.-S.Y.; resources, Y.-N.J. and H.-S.Y.; data curation, Y.-N.J., H.-S.Y., and S.-H.J.; writing—original draft preparation, Y.-N.J. and H.-S.Y.; writing—review and editing, J.-S.B.; visualization, Y.-N.J., H.-S.Y., and S.-H.J.; supervision, J.-S.B.; project administration, J.-S.B.; funding acquisition, J.-S.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (MSIT) (grant number RS-2023-00262645), and by the Technology Development Program funded by the Ministry of SMEs and Startups (MSS, Korea) (grant number S3312539).

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The datasets supporting this article’s conclusions are available from the corresponding author upon reasonable request.

Conflicts of Interest

Yoo-Na Jeon and Jong-Suep Baek, the authors are employees of BeNatureBioLab Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Yang, K.M.; Ge, Y.; Palanisamy, S.; Zhang, Y.; Kou, F.; Yelithao, K.; Jeong, D.; You, S.; Lim, S.-B. Cnidium officinale polysaccharide enhanced RAW 264.7 cells activation and NK-92 cells cytotoxicity against colon cancer via NF-κB and MAPKs signaling pathways. Int. J. Biol. Macromol. 2023, 253, 127605. [Google Scholar] [CrossRef]
  2. De la Cruz, J.; Kim, D.-H.; Hwang, S.G. Anti cancer effects of Cnidium officinale Makino extract mediated through apoptosis and cell cycle arrest in the HT-29 human colorectal cancer cell line. Asian Pac. J. Cancer Prev. 2014, 15, 5117–5121. [Google Scholar] [CrossRef]
  3. Jeong, J.B.; Park, J.H.; Lee, H.K.; Ju, S.Y.; Hong, S.C.; Lee, J.R.; Chung, G.Y.; Lim, J.H.; Jeong, H.J. Protective effect of the extracts from Cnidium officinale against oxidative damage induced by hydrogen peroxide via antioxidant effect. Food Chem. Toxicol. 2009, 47, 525–529. [Google Scholar] [CrossRef]
  4. Lee, Y.M.; Lee, Y.-R.; Kim, C.-S.; Jo, K.; Sohn, E.; Kim, J.S.; Kim, J. Cnidium officinale extract and butylidenephthalide inhibits retinal neovascularization in vitro and in vivo. BMC Complement Altern. Med. 2016, 16, 231. [Google Scholar] [CrossRef]
  5. Belete, M.T.; Kim, S.E.; Gudeta, W.F.; Igori, D.; Kwon, J.A.; Lee, S.-H.; Moon, J.S. Deciphering the virome of Chunkung (Cnidium officinale) showing dwarfism-like symptoms via a high-throughput sequencing analysis. Virol. J. 2024, 21, 86. [Google Scholar] [CrossRef]
  6. Ma, J.; Liu, W.; Wang, X.; Lu, C.; Hao, Z.; Wang, Y.; Ding, Y.; Li, Y. Cnidium officinale Makino: Phytology, Phytochemistry, Toxicology, Pharmacology and Prescriptions (1967–2023). Chem. Biodivers. 2024, 21, e202301639. [Google Scholar] [CrossRef]
  7. Kim, Y.-J.; Kim, Y.-J. Inhibition effect of Cnidium officinale Makino extracts on MMP1 expression in human dermal fibroblasts. Asian J. Beauty Cosmetol. 2018, 16, 131–138. [Google Scholar] [CrossRef]
  8. Ku, J.M.; Hong, S.H.; Kim, H.I.; Kim, M.J.; Mok, K.; Shin, Y.C.; Ko, S.-G. Cnidium officinale Makino promotes skin health via anti-inflammation processes in various skin cell lines. Res. Squar. 2020. [Google Scholar] [CrossRef]
  9. Sowndhararajan, K.; Kim, S. Neuroprotective and cognitive enhancement potentials of Angelica gigas Nakai root: A review. Sci. Pharm. 2017, 85, 21. [Google Scholar] [CrossRef] [PubMed]
  10. He, Z.; Wang, Y.; Chen, Y.; Geng, F.; Jiang, Z.; Li, X. Angelica gigas Nakai: An overview on its chemical composition and pharmacological activity. Biochem. Syst. Ecol. 2023, 111, 104717. [Google Scholar] [CrossRef]
  11. Zhang, J.; Li, L.; Jiang, C.; Xing, C.; Kim, S.-H.; Lu, J. Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its major pyranocoumarin compounds. Anticancer Agents Med. Chem. 2012, 12, 1239–1254. [Google Scholar] [CrossRef]
  12. Park, S.I.; Heo, S.H.; Lee, J.; Shin, M.S. Extraction of active compounds from Angelica gigas using supercritical carbon dioxide and its physiological activity. J. Converg. Inf. Technol. 2021, 11, 206–212. [Google Scholar] [CrossRef]
  13. Kim, S.-A.; Oh, H.-K.; Kim, J.-Y.; Hong, J.-W.; Cho, S.-I. A review of pharmacological effects of Angelica gigas, Angelica sinensis, Angelica acutiloba and their bioactive compounds. J. Korean Med. 2011, 32, 1–24. [Google Scholar]
  14. Kang, J.W.; Cho, H.E.; Choi, H.M.; Lee, I.C. Anti-wrinkle properties of Angelica gigas Nakai root extracts using mineral-rich water. J. Cosmet. Dermatol. 2023, 22, 328–334. [Google Scholar] [CrossRef] [PubMed]
  15. Kim, Y.A.; Park, S.H.; Kim, B.Y.; Kim, A.H.; Park, B.J.; Kim, J.J. Inhibitory effects on melanin production of demethylsuberosin isolated from Angelica gigas Nakai. Korean J. Pharmacogn. 2014, 45, 209–213. [Google Scholar]
  16. Kang, J.; Nam, G.; Yoon, Y.; Kim, G.; Bae, S.; Lee, H.; Bae, S.; Cha, Y.; Cho, H.; Cho, H. Suppression of matrix metallopeptidase-3 expression in human dermal fibroblasts by decursin from Angelica gigas Nakai root extracts fermented with Jeju lava seawater. Asian J. Beauty Cosmetol. 2021, 19, 65–76. [Google Scholar] [CrossRef]
  17. Cao, Y.-j.; Zhang, Y.-m.; Qi, J.-p.; Liu, R.; Zhang, H.; He, L.-c. Ferulic acid inhibits H2O2-induced oxidative stress and inflammation in rat vascular smooth muscle cells via inhibition of the NADPH oxidase and NF-κB pathway. Int. Immunopharmacol. 2015, 28, 1018–1025. [Google Scholar] [CrossRef]
  18. Kumar, N.; Pruthi, V. Potential applications of ferulic acid from natural sources. Biotechnol. Rep. 2014, 4, 86–93. [Google Scholar] [CrossRef]
  19. Park, H.-J.; Cho, J.-H.; Hong, S.-H.; Kim, D.-H.; Jung, H.-Y.; Kang, I.-K.; Cho, Y.-J. Whitening and anti-wrinkle activities of ferulic acid isolated from Tetragonia tetragonioides in B16F10 melanoma and CCD-986sk fibroblast cells. J. Nat. Med. 2018, 72, 127–135. [Google Scholar] [CrossRef]
  20. Han, X.; Wei, T.; Jiang, H.; Li, W.; Zhang, G. Enhanced water solubility, stability, and in vitro antitumor activity of ferulic acid by chemical conjugation with amino-β-cyclodextrins. J. Mat. Sci. 2020, 55, 8694–8709. [Google Scholar] [CrossRef]
  21. Das, S.; Wong, A.B. Stabilization of ferulic acid in topical gel formulation via nanoencapsulation and pH optimization. Sci. Rep. 2020, 10, 12288. [Google Scholar] [CrossRef]
  22. Rezaei, A.; Varshosaz, J.; Fesharaki, M.; Farhang, A.; Jafari, S.M. Improving the solubility and in vitro cytotoxicity (anticancer activity) of ferulic acid by loading it into cyclodextrin nanosponges. Int. J. Nanomed. 2019, 14, 4589–4599. [Google Scholar] [CrossRef]
  23. Patil, H.; Vemula, S.K.; Narala, S.; Lakkala, P.; Munnangi, S.R.; Narala, N.; Jara, M.O.; Williams, R.O.; Terefe, H.; Repka, M.A. Hot-Melt Extrusion: From Theory to Application in Pharmaceutical Formulation—Where Are We Now? AAPS PharmSciTech 2024, 25, 37. [Google Scholar] [CrossRef] [PubMed]
  24. Lee, H.Y.; Ryu, S.; You, H.S.; Jeon, Y.N.; Jin, M.; Cho, C.-W.; Baek, J.-S. Enhanced antioxidant and anti-inflammatory effects of bee pollen and honey hybrid formulation by hot-melt extrusion. Food Hydrocoll. Health 2023, 4, 100167. [Google Scholar] [CrossRef]
  25. Ryu, S.-J.; You, H.-S.; Lee, H.-Y.; Baek, J.-S. Manufacture of mesoporous silica coated multi-walled carbon nanotubes containing silver nanoparticles synthesized by Angelica gigas Nakai using hot-melt extrusion for enhanced antimicrobial activities. Colloids Surf. A Physicochem. Eng. Asp. 2024, 693, 134023. [Google Scholar] [CrossRef]
  26. Ashour, E.A.; Majumdar, S.; Alsheteli, A.; Alshehri, S.; Alsulays, B.; Feng, X.; Gryczke, A.; Kolter, K.; Langley, N.; Repka, M.A. Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine. J. Pharm. Pharmacol. 2016, 68, 989–998. [Google Scholar] [CrossRef]
  27. Go, E.J.; Ryu, B.R.; Gim, G.J.; Lee, H.Y.; You, H.S.; Kim, H.B.; Lee, H.T.; Lee, J.Y.; Shim, M.S.; Baek, J.-S. Hot-melt extrusion enhances antioxidant effects of mulberry on probiotics and pathogenic microorganisms. Antioxidants 2022, 11, 2301. [Google Scholar] [CrossRef]
  28. Luo, Y.; Xu, L.; Xu, M.; Tao, X.; Ai, R.; Tang, X. Improvement of dissolution and bioavailability of Ginsenosides by hot melt extrusion and cogrinding. Drug Dev. Ind. Pharm 2013, 39, 109–116. [Google Scholar] [CrossRef]
  29. You, H.-S.; Jang, Y.-S.; Sathiyaseelan, A.; Ryu, S.-J.; Lee, H.-Y.; Baek, J.-S. Antibiofilm and Anticancer Activity of Multi-Walled Carbon Nanotubes Fabricated with Hot-Melt Extruded Astaxanthin-Mediated Synthesized Silver Nanoparticles. Int. J. Nanomed. 2025, 20, 343–366. [Google Scholar] [CrossRef] [PubMed]
  30. Li, G.; Lee, Y.Y.; Lu, X.; Chen, J.; Liu, N.; Qiu, C.; Wang, Y. Simultaneous loading of (−)-epigallocatechin gallate and ferulic acid in chitosan-based nanoparticles as effective antioxidant and potential skin-whitening agents. Int. J. Biol. Macromol. 2022, 219, 333–345. [Google Scholar] [CrossRef] [PubMed]
  31. Majchrzak, O.; Makiej, A.; Lopes Silva, C.; Jordan, O.; Borchard, G.; Marcinkowska, A.; Płatkiewicz, J.; Zgoła-Grześkowiak, A.; Kaczorek, E.; Smułek, W. Enhancing Formulation Stability: A Comparative Study of Ascorbic Acid and Ascorbyl Palmitate as Antioxidants in Nanoemulsions of Natural Products. ACS Appl. Nano Mater. 2025, 8, 12306–12313. [Google Scholar] [CrossRef]
  32. Ameta, R.K.; Soni, K.; Bhattarai, A. Recent advances in improving the bioavailability of hydrophobic/lipophilic drugs and their delivery via self-emulsifying formulations. Colloids Interfaces 2023, 7, 16. [Google Scholar] [CrossRef]
  33. Shin, D.H.; Cho, H.J.; Park, S.H.; Jeong, S.W.; Park, C.-W.; Han, K.; Chung, Y.B. HPLC analysis of ferulic acid and its pharmacokinetics after intravenous bolus administration in rats. J. Biomed. Transl. Res. 2016, 17, 1–7. [Google Scholar] [CrossRef]
  34. Kim, H.-B.; You, H.-S.; Ryu, S.-j.; Lee, H.-Y.; Baek, J.-S. Green synthesis of silver nanoparticles from mulberry leaf through hot melt extrusion: Enhanced antioxidant, antibacterial, anti-inflammatory, antidiabetic, and anticancer properties. Food Hydrocoll. Health 2024, 6, 100184. [Google Scholar] [CrossRef]
  35. Zhang, L.; Meng, S.; Yan, B.; Chen, J.; Zhou, L.; Shan, L.; Wang, Y. Anti-proliferative, pro-apoptotic, anti-migrative and tumor-inhibitory effects and pleiotropic mechanism of theaflavin on B16F10 melanoma cells. Onco Targets Ther. 2021, 14, 1291–1304. [Google Scholar] [CrossRef] [PubMed]
  36. Han, K.; Sathiyaseelan, A.; Lu, Y.; Kim, K.M.; Wang, M.-H. Agar/carboxymethyl cellulose composite film loaded with hydroxyapatite nanoparticles for bone regeneration. Cellulose 2024, 31, 9319–9334. [Google Scholar] [CrossRef]
  37. Go, E.-J.; Ryu, B.-R.; Ryu, S.-J.; Kim, H.-B.; Lee, H.-T.; Kwon, J.-W.; Baek, J.-S.; Lim, J.-D. An enhanced water solubility and stability of anthocyanins in mulberry processed with hot melt extrusion. Int. J. Mol. Sci. 2021, 22, 12377. [Google Scholar] [CrossRef]
  38. Wang, W.; Kang, Q.; Liu, N.; Zhang, Q.; Zhang, Y.; Li, H.; Zhao, B.; Chen, Y.; Lan, Y.; Ma, Q. Enhanced dissolution rate and oral bioavailability of Ginkgo biloba extract by preparing solid dispersion via hot-melt extrusion. Fitoterapia 2015, 102, 189–197. [Google Scholar] [CrossRef]
  39. Saerens, L.; Vervaet, C.; Remon, J.P.; De Beer, T. Process monitoring and visualization solutions for hot-melt extrusion: A review. J. Pharm. Pharmacol. 2014, 66, 180–203. [Google Scholar] [CrossRef]
  40. Hofstetter, K.; Hinterstoisser, B.; Salmén, L. Moisture uptake in native cellulose–the roles of different hydrogen bonds: A dynamic FT-IR study using Deuterium exchange. Cellulose 2006, 13, 131–145. [Google Scholar] [CrossRef]
  41. Chen, J.; Li, L.; Zhou, X.; Li, B.; Zhang, X.; Hui, R. Structural characterization and α-glucosidase inhibitory activity of polysaccharides extracted from Chinese traditional medicine Huidouba. Int. J. Biol. Macromol. 2018, 117, 815–819. [Google Scholar] [CrossRef] [PubMed]
  42. Robert, M.S. Spectroscopy of Organic Compounds; Free Academy: Norwich, UK, 2008. [Google Scholar]
  43. Azad, M.O.K.; Kang, W.S.; Lim, J.D.; Park, C.H. Bio-fortification of Angelica gigas Nakai nano-powder using bio-polymer by hot melt extrusion to enhance the bioaccessibility and functionality of nutraceutical compounds. Pharmaceuticals 2019, 13, 3. [Google Scholar] [CrossRef]
  44. Azad, M.O.K.; Kim, W.W.; Jin, C.W.; Kang, W.S.; Park, C.H.; Cho, D.H. Development of a polymer-mediated soybean nanocomposite by hot melt extrusion to improve its functionality and antioxidant properties. Foods 2019, 8, 41. [Google Scholar] [CrossRef]
  45. Balakrishnan, K.; Casimeer, S.C.; Ghidan, A.Y.; Al Antary, T.M.; Singaravelu, A. Exploration of antioxidant, antibacterial activities of green synthesized hesperidin loaded PLGA nanoparticles. Biointerface Res. Appl. Chem. 2021, 11, 14520–14528. [Google Scholar] [CrossRef]
  46. Eradati, N.; Tajabadi, F.; Ahmadi-Ashtiani, H.R.; Rezazadeh, S.; Taherian, M.; Rastegar, H. Optimization of Cleaning and Analytical Method for Determination of Arbutin, Hydroquinone and Kojic Acid in Cosmetic Products. J. Med. Plants 2020, 20, 50–59. [Google Scholar] [CrossRef]
  47. Lee, S.Y.; Nam, S.; Choi, Y.; Kim, M.; Koo, J.S.; Chae, B.-J.; Kang, W.-S.; Cho, H.-J. Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus. Appl. Sci. 2017, 7, 902. [Google Scholar] [CrossRef]
  48. Lü, J.; Jiang, C.; Drabick, J.J.; Joshi, M.; Perimbeti, S. Angelica gigas Nakai (Korean Dang-gui) Root Alcoholic Extracts in Health Promotion and Disease Therapy—Active Phytochemicals and In Vivo Molecular Targets. Pharm. Res. 2025, 42, 25–47. [Google Scholar] [CrossRef] [PubMed]
  49. Gao, N.; Guo, M.; Fu, Q.; He, Z. Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid. Asian J. Pharm. Sci. 2017, 12, 66–72. [Google Scholar] [CrossRef]
Cosmetics 12 00197 g001
Figure 1. Comparison of FA contents in (A) CO and HME-CO, and (B) AG, and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as *** p < 0.001.
Figure 1. Comparison of FA contents in (A) CO and HME-CO, and (B) AG, and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as *** p < 0.001.
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Cosmetics 12 00197 g002
Figure 2. (A) FE-SEM and (B) FE-TEM images at different magnifications of CO, HME-CO, AG, and HME-AG.
Figure 2. (A) FE-SEM and (B) FE-TEM images at different magnifications of CO, HME-CO, AG, and HME-AG.
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Cosmetics 12 00197 g003
Figure 3. FT-IR analysis of (A) CO and HME-CO, and (B) AG, and HME-AG.
Figure 3. FT-IR analysis of (A) CO and HME-CO, and (B) AG, and HME-AG.
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Cosmetics 12 00197 g004
Figure 4. DPPH radical scavenging (%) of (A) CO and HME-CO, and (B) AG and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 4. DPPH radical scavenging (%) of (A) CO and HME-CO, and (B) AG and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as * p < 0.05, ** p < 0.01, and *** p < 0.001.
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Cosmetics 12 00197 g005
Figure 5. ABTS radical scavenging (%) of (A) CO and HME-CO, and (B) AG and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 5. ABTS radical scavenging (%) of (A) CO and HME-CO, and (B) AG and HME-AG. The data are expressed as the mean ± standard deviation (SD, n = 3), and difference evaluations are shown as * p < 0.05, ** p < 0.01, and *** p < 0.001.
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Cosmetics 12 00197 g006
Figure 6. Cell viability of B16F10 melanoma cells (A) and HaCaT keratinocytes (B) following 24 h exposure to various concentration of CO, HME-CO, AG, and HME-AG. Results are expressed as mean ± SD (n = 3).
Figure 6. Cell viability of B16F10 melanoma cells (A) and HaCaT keratinocytes (B) following 24 h exposure to various concentration of CO, HME-CO, AG, and HME-AG. Results are expressed as mean ± SD (n = 3).
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Cosmetics 12 00197 g007
Figure 7. Inhibitory effects of (A) CO and HME-CO and (B) AG and HME-AG on melanin production in α-MSH-stimulated B16F10 melanoma cells. Arbutin was used as a positive control. Data are presented as mean ± standard deviation (n = 3), and statistical significance is indicated as *** p < 0.001.
Figure 7. Inhibitory effects of (A) CO and HME-CO and (B) AG and HME-AG on melanin production in α-MSH-stimulated B16F10 melanoma cells. Arbutin was used as a positive control. Data are presented as mean ± standard deviation (n = 3), and statistical significance is indicated as *** p < 0.001.
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Cosmetics 12 00197 g008
Figure 8. Wound healing assay evaluating the effects of CO and HME-CO (A,B) and AG and HME-AG (C,D) on HaCaT keratinocyte migration. Representative images of scratch closure were captured at 0, 24, and 48 h after treatment (A,C), and the percentage of wound closure was quantified using Image J software (Version 1.53, National Institutes of Health, Bethesda, MD, USA) (B,D). Dashed lines indicate the initial scratch boundaries. The yellow scale bar shown in A and C represents 200 μM. Data are expressed as mean ± standard deviation (n = 3), and statistical significance is indicated as *** p < 0.001.
Figure 8. Wound healing assay evaluating the effects of CO and HME-CO (A,B) and AG and HME-AG (C,D) on HaCaT keratinocyte migration. Representative images of scratch closure were captured at 0, 24, and 48 h after treatment (A,C), and the percentage of wound closure was quantified using Image J software (Version 1.53, National Institutes of Health, Bethesda, MD, USA) (B,D). Dashed lines indicate the initial scratch boundaries. The yellow scale bar shown in A and C represents 200 μM. Data are expressed as mean ± standard deviation (n = 3), and statistical significance is indicated as *** p < 0.001.
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Table 1. Composition of HME-CO.
Table 1. Composition of HME-CO.
HME-CO
CO93.3
FA0.2
Lecithin3
Ascorbyl palmitate3.5
Total100 (%)
Table 2. Composition of HME-AG.
Table 2. Composition of HME-AG.
HME-AG
AG93.3
FA0.2
Lecithin3
Ascorbyl palmitate3.5
Total100 (%)
Table 3. HPLC analysis condition.
Table 3. HPLC analysis condition.
InstrumentAgilent 1200 Series HPLC System
ColumnKinetex 5 µm C18 100 Å LC Column 250 × 4.6 mm
Detector (Wavelength)diode array detector (325 nm)
Solvent A-
Solvent BWater: Methanol (55: 45), pH 2.8
Flow rate0.7 mL/min
Oven25 °C
Injection volume10 µL
Isocratic elution system
Time (min)%A%B
Initial0100
10 m0100
Table 4. Particle sizes of CO, HME-CO, AG, and HME-AG.
Table 4. Particle sizes of CO, HME-CO, AG, and HME-AG.
COHME-COAGHME-AG
Size (d. nm)752.3 ± 97.8350.3 ± 39.9746.1 ± 77.2400.3 ± 47.3
Table 5. IC50 values (μg/mL) of CO, HME-CO, AG, and HME-AG.
Table 5. IC50 values (μg/mL) of CO, HME-CO, AG, and HME-AG.
COHME-COAGHME-AG
DPPH1304.3 ± 74.7589.4 ± 13.7606.8 ± 15.9299.6 ± 21.2
ABTS778.2 ± 22.7699.6 ± 19.4862.7 ± 12.1491.4 ± 8.4
Table 6. Key quantitative results of CO, HME-CO, AG, and HME-AG.
Table 6. Key quantitative results of CO, HME-CO, AG, and HME-AG.
COHME-COAGHME-AG
FA contents (μg/g)330.1 ± 7.47479.6 ± 170.4528.5 ± 2.92339.2 ± 21.8
Melanin production rate (%)68.4 ± 3.239.9 ± 0.566.4 ± 4.344.8 ± 4.8
Wound closure rate (%) (48 h)89.1 ± 1.296.2 ± 0.381.4 ± 1.598.2 ± 0.1
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Jeon, Y.-N.; You, H.-S.; Jang, S.-H.; Baek, J.-S. Eco-Friendly Enhancement of Ferulic Acid-Rich Extracts from Cnidium officinale and Angelica gigas via Hot-Melt Extrusion for Skin Brightening and Regeneration. Cosmetics 2025, 12, 197. https://doi.org/10.3390/cosmetics12050197

AMA Style

Jeon Y-N, You H-S, Jang S-H, Baek J-S. Eco-Friendly Enhancement of Ferulic Acid-Rich Extracts from Cnidium officinale and Angelica gigas via Hot-Melt Extrusion for Skin Brightening and Regeneration. Cosmetics. 2025; 12(5):197. https://doi.org/10.3390/cosmetics12050197

Chicago/Turabian Style

Jeon, Yoo-Na, Han-Sol You, So-Hee Jang, and Jong-Suep Baek. 2025. "Eco-Friendly Enhancement of Ferulic Acid-Rich Extracts from Cnidium officinale and Angelica gigas via Hot-Melt Extrusion for Skin Brightening and Regeneration" Cosmetics 12, no. 5: 197. https://doi.org/10.3390/cosmetics12050197

APA Style

Jeon, Y.-N., You, H.-S., Jang, S.-H., & Baek, J.-S. (2025). Eco-Friendly Enhancement of Ferulic Acid-Rich Extracts from Cnidium officinale and Angelica gigas via Hot-Melt Extrusion for Skin Brightening and Regeneration. Cosmetics, 12(5), 197. https://doi.org/10.3390/cosmetics12050197

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