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Article

Impact of Kickxia elatine In Vitro-Derived Stem Cells on the Biophysical Properties of Facial Skin: A Placebo-Controlled Trial

by
Anastasia Aliesa Hermosaningtyas
1,2,*,
Anna Kroma-Szal
3,
Justyna Gornowicz-Porowska
3,*,
Maria Urbanska
3,
Anna Budzianowska
2 and
Małgorzata Kikowska
2
1
Doctoral School, Poznan University of Medical Sciences, 70 Bukowska St., 60-812 Poznan, Poland
2
Laboratory of Pharmaceutical Biology and Biotechnology, Department and Division of Practical Cosmetology and Skin Disease Prophylaxis, Poznan University of Medical Sciences, Collegium Pharmaceuticum, 3 Rokietnicka St., 60-806 Poznan, Poland
3
Department and Division of Practical Cosmetology and Skin Disease Prophylaxis, Poznan University of Medical Sciences, Collegium Pharmaceuticum, 3 Rokietnicka St., 60-806 Poznan, Poland
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2025, 15(15), 8625; https://doi.org/10.3390/app15158625
Submission received: 1 July 2025 / Revised: 25 July 2025 / Accepted: 1 August 2025 / Published: 4 August 2025
(This article belongs to the Special Issue Biological Activities of Medicinal Plants and Their Potential Applications)
Browse Figures
Versions Notes

Abstract

The growing demand for natural and sustainable skincare products has driven interest in plant-based active ingredients, especially from in vitro cultures. This placebo-controlled study investigated the impact of a facial cream containing 2% Kickxia elatine (L.) Dumort cell suspension culture extract on various skin biophysical parameters. The cream was applied to the cheek once daily for six weeks on 40 healthy female volunteers between the ages of 40 to 49. The evaluated skin parameters including skin hydration, transepidermal water loss (TEWL), erythema intensity (EI), melanin intensity (MI), skin surface pH, and skin structure, wrinkle depth, vascular lesions, and vascular discolouration. The results indicated that significant improvements were observed in skin hydration (from 40.36 to 63.00 AU, p < 0.001) and there was a decrease in TEWL score (14.82 to 11.76 g/h/m2, p < 0.001), while the skin surface pH was maintained (14.82 to 11.76 g/h/m2, p < 0.001). Moreover, the K. elatine cell extract significantly improved skin structure values (9.23 to 8.50, p = 0.028), reduced vascular lesions (2.72 to 1.54 mm2, p = 0.011), and lowered skin discolouration (20.98% to 14.84%, p < 0.001), indicating its moisturising, protective, brightening, and soothing properties. These findings support the potential use of K. elatine cell extract in dermocosmetic formulations targeting dry, sensitive, or ageing skin.

1. Introduction

Since antiquity, plant-derived substances have constituted a foundational component of cosmetic and dermatological practices, with civilisations such as those in ancient Egypt, Greece, and Rome utilising herbal extracts, essential oils, and floral preparations in their beauty regimens. The enduring presence of botanicals in cosmetic applications can be attributed to their recognised pharmacological, olfactory, and aesthetic properties. Contemporary botanical formulations synthesise historical ethnobotanical insights with modern scientific methodologies to develop cosmetic products that are both efficacious and aligned with sustainability principles [1,2,3]. Plant-based ingredients in cosmetics offer a range of advantages that align with both consumer expectations and sustainability goals. Owing to their natural composition and abundance of bioactive compounds, plant extracts are generally well-tolerated by the skin. Sourced from renewable resources, they also contribute to reducing environmental impact and support circular economy practices. Their multifunctionality allows formulators to create simpler, more natural products without compromising on performance. Moreover, the use of botanical components promotes ethical sourcing and strengthens social responsibility by supporting fair trade and local communities. Importantly, their natural origin fosters consumer trust, as users increasingly seek clean, plant-based alternatives they perceive as safer and more transparent [4,5]. The European cosmetic (beauty and personal care) market comprised 24% of the global market in 2023, up to EUR 96 billion. It is worth mentioning that natural and organic cosmetics products dominated, representing 80% of the total sales in Europe. The exponential growth of natural beauty products is expected at an average of 5.7% per year by 2028 [6]. This growth is driven by increasing consumer awareness of the environmental, social, and economic impacts of product life cycles, leading to a higher demand for eco-friendly ingredients and sustainable formulations. European consumers are increasingly seeking natural and organic cosmetic products that align with their values of sustainability and health consciousness [7].
In this context, recent advances in plant cell culture technology present a highly promising extension of these advantages. It enables the production of bioactive compounds in a controlled, standardised, and sustainable manner, independent of geographic or seasonal limitations [8,9]. Bringing plant cell biomass products from the laboratory to commercial usage presents promising opportunities. Yet, it is inevitable that there are challenges throughout this process. A key focus is on scale-up optimisation; for example, using bioreactors to facilitate cost-effective and efficient production while maintaining the purity and potency of the plant-based ingredients [10]. Furthermore, regulation has to constantly evolve to set clear guidelines and approval processes for customers’ safety [11]. In this way, in vitro cultures produce extracts that are safe, free from contaminants and pesticides, and genetically consistent, which ensures both regulatory compliance and high-quality outcomes aligned with good manufacturing practices. By combining the benefits of traditional botanical actives with the precision and reliability of biotechnology, plant cell culture represents the next frontier in natural and sustainable cosmetic formulation [12,13,14]. Plant stem cells, especially from meristematic tissues, might be potentially useful to treat skin problems, since they can withstand oxidative stress and support cell vitality. Recent research has shown that plant stem cells are abundant in antioxidants and bioactive compounds, which help in reducing inflammation and delaying the skin ageing process. Using plant stem cells in cosmetic products was found to promote regeneration, improve elasticity, and contribute to a more youthful skin appearance. It is worth noting that in cosmetic formulations, the term “plant stem cells” often refers to extracts derived from calli and cell suspensions cultured under in vitro conditions [9,15,16].
Given the short market lifespan of many cosmetic products—shaped by changing trends and evolving consumer awareness—the cosmetics industry is in constant search of new, biologically active substances, particularly those of plant origin. In this pursuit, increasing attention is being directed toward phytocosmetics and phytocosmeceuticals, which incorporate active plant-based ingredients known for their therapeutic and functional benefits [17]. These formulations often utilise extracts or compounds isolated from traditional terrestrial plants as well as in vitro plant cultures, offering a sustainable and innovative source of high-efficacy bioactives [12,18].
Kickxia elatine (L.) Dumort (syn. Antirrhinum elatine L.), a member of the Plantaginaceae family, has long been recognised in traditional medicine for its therapeutic properties. According to Potter’s New Cyclopaedia of Botanical Drugs and Preparations—where it is listed under its synonym Linaria elatine—the plant exhibits notable astringent and haemostatic activity. A recommendation was written to prepare an infusion of K. elatine herb, 1 ounce to 1 pint, for internal use and topical application (wounds) [19]. Historically, it has been used to support wound healing, alleviate haemorrhages and excessive lacrimation, as well as to manage conditions such as plantar hyperhidrosis [20,21,22,23]. Recently, attention has also been drawn to its potential cytotoxic activity, suggesting the presence of tentatively identified biologically active constituents with therapeutic relevance [24]. Despite these traditional applications, the influence of K. elatine on skin physiology is still unclear. This knowledge gap, coupled with its ethnobotanical relevance, drew attention and became the foundation for research into its potential dermocosmetic applications. This study aims to evaluate the effects of a facial cream containing a 2% Kickxia elatine (L.) Dumort cell suspension culture extract on selected biophysical parameters of facial skin, namely skin hydration, transepidermal water loss (TEWL), erythema index (EI), melanin index (MI), skin surface pH, as well as structural features including wrinkle depth, vascular lesions, and skin discolouration.

2. Materials and Methods

The Local Ethics Committee of Poznan University of Medical Sciences approved this study under decision number 698/24, 5 December 2024, Poznan, Poland. Participants obtained written informed consent before this study.

2.1. Cell Suspension Culture

The calli of K. elatine were previously established on Murashige and Skoog (MS) solid media supplemented with 2.0 mg L−1 3,6-dichloro-2-methoxybenzoic acid (Dicamba, Dic; Sigma-Aldrich, St Louis, MO, USA) and 2.0 mg L−1 2,4-dichlorophenoxyacetic acid (2,4-D; Sigma-Aldrich, St Louis, MO, USA) [24]. For cell biomass production, the calli were transferred into MS liquid media with the same variation and concentration of growth regulators. The cell suspension culture was established from a root-derived, homogeneous, and stabilised callus line. The resulting suspension culture was free of contamination, exhibited an appropriate cell density, and had a characteristic yellow colouration. The cultured cells were predominantly round or oval in shape, varied in size, and demonstrated a natural tendency to form aggregates. The cell suspension culture was maintained in a controlled room at 20 ± 2 °C with a 16:8 h photoperiod and was shaken at 110 RPM. For the study, a uniform biomass of cell suspension from the ninth passage was selected. The fresh biomass from passage nine was then dried at 30 °C for three days or until complete dryness.

2.2. Preparation of the Cream Containing K. Elatine Cell Suspension Extract

The dried K. elatine cell biomass was soaked three times with 70% ethanol (Chempur, Piekary Śląskie, Poland), assisted with an ultrasonic bath at 80 °C. The extract was filtered and the solvent was evaporated using Rotavapor® R−100 (BUCHI, Flawil, Switzerland) at 40 ± 1 °C.

2.3. Cream Preparation

Two types of creams were prepared for this study: (1) placebo and (2) cream containing K. elatine cell extract at a capacity of 20 g per participant. Celugel hydroxyethylcellulose mucilage (Actifarm®, Warsaw, Poland) was used as the cream base and placebo. The base contained water, glycerol, and hydroxyethylcellulose as the gelling agent. A total of 2 g of K. elatine cell extract, 2 g of sterile distilled water, and 96 g of Celugel were thoroughly mixed and homogenised in a mortar to produce the cream. The placebo and the tested cream were transferred to a dark glass cosmetic container (Figure 1).

2.4. Study Group and Skin Biophysical Parameter Evaluation

The effect of the cream containing K. elatine cell extract on skin biophysical parameters was assessed in a randomised and placebo-controlled study involving 40 participants. Eligible participants were healthy adult females aged 40 to 49 years. Exclusion criteria included pregnancy or breastfeeding, the presence of skin diseases, and the use of systemic medications with strong pharmacological activity. The block randomisation method was applied to ensure the size of each group (placebo and treatment) was similar throughout the entire study.
Skin biophysical parameters assessed in this study included skin hydration, transepidermal water loss (TEWL), erythema intensity, melanin intensity, skin surface pH, and skin structure, following a previously described protocol [25]. Non-invasive skin approaches were used to measure the parameters using the Courage & Khazaka MPA-9 (Courage+Khazaka electronic GmbH, Cologne, Germany) and Nati Skin Analyzer (Beauty of Sciences, Wroclaw, Poland). The Corneometer® CM 825 probe (Courage+Khazaka electronic GmbH, Cologne, Germany) was used to measure the electrical capacitance of the stratum corneum (skin hydration) by operating at 40–75 Hz. TEWL was measured using the Tewameter® TM 300 (Courage+Khazaka electronic GmbH, Cologne, Germany). Erythema index and melanin index were evaluated using the Mexameter® MX 18 probe (Courage+Khazaka electronic GmbH, Cologne, Germany). The Skin-pH-meter PH 908 probe (Courage+Khazaka electronic GmbH, Cologne, Germany) was used to assess the acidity of the skin surface. Lastly, the sebum level and luminosity of the skin surface were determined using Sebumeter® SM 815 and Skin-Glossymeter GL 200 (Courage+Khazaka electronic GmbH, Cologne, Germany), respectively. The Nati Skin Analyzer evaluates skin parameters physically and optically using UV and white light. Skin structure, wrinkle depth, vascular lesions, and discolouration were analysed using the Nati Skin Analyzer. The device grades the parameters using red, yellow, and green spectra (Figure 2B). The colours correspond to numerical scores based on specific skin parameter evaluations (Table 1).
The tests were performed in a controlled environment at 22 ± 3 °C and a relative humidity of 45 ± 2%. The measurements were carried out on a designated area (left cheek) to ensure repeatability (Figure 2A). The probes were placed on the skin surface, and each parameter was assessed in three technical replications at baseline and after six weeks of application. The results were calculated and presented as mean ± standard deviation (SD).
Furthermore, the sensory evaluation of the cream containing K. elatine cell extract was assessed through surveys that the participants completed during the final measurement (six weeks after application). The evaluated attributes included the following: colour, consistency, fragrance notes, fragrance intensity, cream texture, spreadability, absorption, effectiveness, and overall characteristics. A 5-point scale was used to evaluate colour and fragrance notes, ranging from (1) very unpleasant, (2) unpleasant, (3) neutral, (4) pleasant, to (5) very pleasant. A similar range scale was applied to spreadability, absorption, efficiency, and overall characteristics of the creams (1—very bad, 2—bad, 3—medium, 4—good, 5—excellent). Moreover, fragrance intensity and cream consistency were evaluated using a 3-point scale: (1) not intense enough, (2) appropriate, and (3) too intense for fragrant intensity; and (1) too runny, (2) appropriate, and (3) too thick for cream consistency.

2.5. Statistical Analysis

All statistical analyses were performed using the R programming language [26] in R Studio Software version 2025.5.0.496 [27]. Additionally, the dplyr [28], tidyr [29], purrr [30], and broom [31] packages were used. The Shapiro–Wilk test assesses the normality of the data. The differences before and after cream application were calculated using the paired t-test or Wilcoxon test, depending on the normality results. The p-value of <0.05 was considered statistically significant. Effect size (Cohen’s d) is used to quantify the size of the mean differences in the TEWL values between the placebo and treatment groups on the last biophysical parameter assessment. The measurements were considered small, medium, and large when the value reached 0.2, 0.5, and 0.8, respectively. If the value was greater than 1.0, then it was considered substantial [32].

3. Results

In total, 40 female volunteers, with an average age of 45.28 ± 3.95 years, participated in this study. To evaluate the effects of the tested formulations, key skin parameters—including facial skin hydration, transepidermal water loss (TEWL), erythema index (EI), melanin index (MI), and skin pH—were measured before and after the six-week application period using the Courage & Khazaka MPA-9 device. In addition, the Nati Skin Analyzer was employed to assess deeper dermatological features such as skin structure integrity, wrinkle depth, vascular lesions, and pigmentation irregularities.
While both formulations led to a significant increase in skin hydration, the cream with K. elatine demonstrated a more pronounced effect, with values rising from 40.36 to 63.00 AU (p < 0.001). Healthy skin is considered sufficiently moisturised when the probe shows > 40 AU in normal room conditions (20 °C and 40–60% air humidity) [33]. In comparison, the placebo group showed a smaller increase (47.81 to 57.68 AU, p = 0.001). Although the between-group difference was not statistically significant (p = 0.191), the results indicated a clear trend favouring the hydrating potential of the K. elatine extract (Table 2).
The group treated with a cream with K. elatine extract showed a significant reduction in TEWL, suggesting an improvement in skin barrier function. In contrast, the placebo group experienced a slight, non-significant increase in TEWL, indicating no measurable benefit. Although the between-group difference after treatment was not statistically significant (p = 0.289), the results pointed toward a favourable effect of K. elatine on epidermal integrity (Table 2). The Cohen’s d effect size for the TEWL between the placebo and treated groups was 0.17, which meant that the mean differences between both groups were a relatively small effect.
The slight but significant decrease in luminance observed in the K. elatine-treated group may suggest improved skin tone uniformity or reduced surface shine compared to the placebo (Table 2).
The erythema index remained stable in the K. elatine-treated group, with no significant change observed (114.83 → 113.68 AU, p = 0.812), whereas the placebo group experienced a significant increase in redness (255.22 → 286.30 AU, p = 0.002). However, the between-group difference after treatment approached statistical significance (p = 0.051). Furthermore, the relative change (%) between the placebo and the K. elatine-treated group was 1.59%. The results suggest that K. elatine may help reduce or stabilise skin redness, indicating a potential anti-inflammatory effect (Table 2).
The skin of volunteers applying a cream with K. elatine extract showed a slight increase in melanin index from 276.58 to 295.40 AU (p = 0.210), while no change was observed in the placebo group (127.43 → 127.33 AU, p = 0.667), indicating a non-significant effect that requires further study to evaluate its impact on pigmentation (Table 2).
The K. elatine-treated skin showed a significant increase in sebum level from 12.40 to 35.85 (p < 0.001), while the placebo group exhibited no meaningful change (25.15 → 26.50, p = 0.823). Although the between-group difference was not statistically significant (p = 0.449), the results suggest that K. elatine cell extract may stimulate sebum production, which could be advantageous for individuals with dry or mature skin (Table 2).
In the K. elatine-treated group, skin pH remained relatively stable, showing only a slight, non-significant change from 5.53 to 5.44 (p = 0.522). In contrast, the placebo group experienced a significant decrease in pH from 5.45 to 5.07 (p = 0.001). The between-group difference after treatment was statistically significant (p = 0.019), indicating that K. elatine may help maintain the skin’s natural pH balance, which is essential for preserving barrier integrity and overall skin health (Table 2).
Table 3 and Figure 3 present skin parameter changes after six weeks of applying either a placebo or a cream containing Kickxia elatine cell extract, as assessed using the Nati Skin Analyzer. After six weeks of treatment, the skin treated with the K. elatine cream demonstrated a significant reduction in structure values (9.23 → 8.50, p = 0.028), indicating enhanced surface smoothness and improved texture. In contrast, the placebo group showed a significant increase (8.67 → 9.42, p = 0.023), suggesting a deterioration in skin uniformity. The difference between the two groups was statistically significant (p = 0.040), highlighting the beneficial effect of K. elatine on skin structure (Table 3).
Although the changes were not statistically significant, the K. elatine-treated group showed only a slight increase in wrinkle depth from 0.07 to 0.08 mm (p = 0.520), whereas the placebo group exhibited a greater increase from 0.09 to 0.14 mm (p = 0.178). The between-group difference (p = 0.516) was not significant; however, the smaller change observed in the group applying the cream with the extract may have indicated a mild protective or anti-ageing effect (Table 3).
The group treated with K. elatine cream showed a significant reduction in vascular lesions, decreasing from 2.72 to 1.54 mm2 (p = 0.011), suggesting a calming effect on the skin. In contrast, the placebo group experienced a significant increase in vascular changes from 1.78 to 2.83 mm2 (p = 0.002), indicating a deterioration. The statistically significant difference between groups (p = 0.005) supports the potential soothing and anti-inflammatory properties of K. elatine (Table 3).
The K. elatine-treated group demonstrated a significant reduction in skin discolouration, decreasing from 20.98% to 14.84% (p < 0.001), indicating an improvement in skin tone uniformity. In contrast, the placebo group showed a significant increase in discolouration from 18.06% to 22.71% (p < 0.001), reflecting a deterioration in pigmentation. The highly significant difference between the groups (p < 0.001) highlights the skin-brightening and tone-evening potential of the K. elatine extract (Table 3).
We conducted a comparison of the evaluation between the placebo and cream containing K. elatine cell extract based on nine attributes: colour, consistency, fragrance intensity, fragrant note, spreadability, absorption, effectiveness, and general assessment (Figure 4). The test was important to understand the receptiveness of participants to the studied product for formulation improvement [34]. In general, the participants gave positive reviews (general assessment average score of 16.8 for both creams). Furthermore, the addition of the K. elatine cell extract retained the same efficiency (15.8) and spreadability (18.2) as the placebo (15.6 and 18.2, respectively). Notably, slightly higher marks for absorption suggest a positive performance of the K. elatine cell extract cream from the participants (average score of 18.2). Participants perceived the cream as having a more intense sweet fragrance than the placebo (20 and 19, respectively). Yet, it was still received positively by the participants, shown by similar scores to the placebo of 14.4 and 14.6, respectively.
Table 4 below lists the identified compounds from our previous study [24] and their cosmetological benefits based on the CosIng (Cosmetics Ingredients) database and the scientific literature.

4. Discussion

The identification of the compounds in K. elatine cell culture has been performed using UPLC/HRMS-MS previously. Major compound classes identified were amino acids and derivatives (such as ferulic and p-coumaric acid), benzoic acids (e.g., protocatechuic acid), phenolic glycosides, hydroxycinnamic acids, linoleic acids, peptides, and fatty acids. Several phenylpropanoids were also identified, including echinacoside, lavandulifolioside, isoacteoside, and, notably, acteoside [24]. Acteoside, syn. Verbascoside is known for its antioxidant, anti-inflammatory, antineoplastic, and photoprotective activities [54,55]. Vertuani et al. (2011) suggested that acteoside and its derivatives could retain their antioxidant activity in a water-free formula, making it a potential cosmeceutical product [54]. Phenolic glycosides and tyrosol derivatives, including salidroside, were also present, suggesting possible moisturising and soothing effects beneficial for skincare applications [47,48]. The results from this study indicate that the cell extract of Kickxia elatine significantly enhances skin hydration and decreases transepidermal water loss, which suggest its moisturising and protective potential. Additionally, the extract may exhibit anti-inflammatory properties by stabilising erythema levels and may play a role in maintaining a balanced skin pH, which is crucial for barrier function. These promising effects support the potential of K. elatine as an active ingredient in future dermocosmetic formulations, particularly for skin types that are mature, dry, or sensitive.
The cream containing Kickxia elatine cell extract produced notable improvements in skin structure, vascular condition, and pigmentation, with statistically significant differences compared to the placebo. Although wrinkle depth remained relatively stable in both groups, the K. elatine group showed less deterioration, hinting at a mild anti-ageing effect. These findings support the potential of K. elatine as a valuable ingredient in functional skincare, particularly for improving texture, tone, and visible vascular concerns.
The present study demonstrated that the topical application of a facial cream containing Kickxia elatine cell suspension culture extract elicited favourable changes in multiple biophysical parameters of the skin. These outcomes align with a growing body of literature supporting the efficacy of botanical and cell culture-derived extracts in cosmetic dermatology. The current body of literature increasingly confirms that plant extracts—particularly those derived from calli and cell suspension cultures—have a measurable and beneficial impact on facial skin biophysical properties. Hydration of the stratum corneum is among the most commonly assessed parameters. Multiple studies have reported statistically significant increases in skin moisture after applying plant-based formulations. For example, the study by Milani & Sparavigna (2017) demonstrated that a formulation containing Centella asiatica extract, glycerine, and hyaluronic acid significantly improved skin hydration within 24 h and reduced TEWL by over 48%, indicating the enhancement of the skin’s barrier function [71]. Similarly, the application of Calendula officinalis extract over eight weeks resulted in statistically significant increases in skin moisture, while TEWL decreased modestly, though not significantly [72]. The erythema and melanin indices, typically assessed by Mexameter, were also modulated in several interventions. For instance, Calendula officinalis cream reduced both erythema and melanin indices significantly over the 8-week study period, indicating its potential anti-inflammatory and skin-brightening properties [72]. In addition, Glycyrrhiza glabra (liquorice root) extract was reported to reduce erythema, pigmentation, and pH imbalances in skin, though the methodology was less instrumentally robust than others. The normalisation of skin pH toward slightly acidic levels is beneficial for maintaining enzymatic activity and microbiome homeostasis [73]. Anti-ageing properties of plant extracts have been substantiated by improvements in structural parameters such as wrinkle depth and elasticity. A study using olive leaf extract cream (SuperHeal™ OLIVE) revealed a significant reduction in wrinkle depth and TEWL, along with improvements in surface texture, as confirmed by Visioscan® imaging [74]. Likewise, extracts from Pyrus pyrifolia callus culture—formulated in nanoliposomes—exhibited strong antioxidant and antiglycation activities, which are known to indirectly reduce wrinkle formation and structural degeneration in the dermis [75,76]. Callus- and suspension culture-derived extracts, such as those from Citrus junos, Lavandula angustifolia, Cirsium eriophorum, and Leontopodium alpinum, are gaining traction due to their reproducibility, scalability, and standardisation. They contain high levels of phenolics, flavonoids, and phytohormones like kinetin, which stimulate fibroblast activity and collagen synthesis. The study by Adhikari et al. (2017) emphasised the antioxidant and wound-healing potential of C. junos callus extract, reinforcing its dermal applications [77]. C. eriophorum cell culture extract, which is abundant in phenol compounds, plays a role in regulating the essential markers for regulating sebum production and refining pore size [78]. Through in vitro and in vivo assays, Cho et al. (2020) suggested that L. alpinum callus culture extract could regulate genes for keratinisation and cornification, which could then induce skin barrier formation, making it a promising anti-ageing agent [79].
Plant stem cell technology used in cosmetics begins with the selection of a suitable plant species that exhibits unique longevity or regenerative properties [15]. For example, Malus domestica (Swiss apple), Vitis vinifera (grape), Argania spinosa (argan tree), Centella asiatica, Leontopodium alpinum (edelweiss), Lycium barbarum (Goi), and Symphytum officinale (comfrey) are chosen for their high content of antioxidants, polyphenols, and protective secondary metabolites. All selected plant species demonstrate exceptional resistance to environmental stress factors such as UV radiation, extreme temperatures, dehydration, or oxidative damage. This natural resilience makes them ideal candidates for cosmetic applications aimed at protecting and revitalising human skin cells. The production of plant stem cell extracts for cosmetic use begins with the isolation and sterilisation of young plant tissue, which is cultured on nutrient media to induce the formation of the callus—a mass of pluripotent, undifferentiated cells. These are then transferred to a liquid culture system, allowing the cells to proliferate uniformly under sterile and controlled conditions. This biotechnological system allows for the continuous and scalable production of biomass rich in intracellular bioactivities, independent of environmental conditions, pesticides, or harvest variability. To ensure stability and efficacy, the extract is often encapsulated in liposomes or nanocarriers, facilitating deeper skin penetration and controlled release. Finally, the stabilised ingredient is incorporated into cosmetic emulsions—typically at concentrations of 0.4–1%—to create formulations with scientifically validated effects on skin hydration, elasticity, and barrier function. Although originating from different ecological backgrounds, these species all contribute to improved skin hydration, protection against oxidative stress, barrier function support, wrinkle reduction, and skin tone balance when formulated into skincare products [9,24,80].
Altogether, this study provides early evidence for the benefits of K. elatine cell biomass extract on various skin biophysical parameters. Further improvement could be made through conducting mid-checkpoint and follow-up post-treatment assessments, including additional surveys on organoleptic properties and subjective perceptions of the cream and its applications from the participants. This feedback would provide an in-depth understanding of the stability and progression of skin improvements. Further research involving a larger number of participants, a longer duration study, and varying extract concentrations is recommended to validate and expand on these findings. Moreover, the integration of molecular studies, such as collagen production or inflammatory marker measurement, would benefit our understanding of the mechanism of K. elatine cell extracts on skin. Additionally, research focusing on the optimisation and scaling up of the in vitro production is necessary to support the feasibility of commercial applications. These improvements would help with a more thorough examination and with facilitating the further growth of K. elatine-based products for use in dermocosmetics.

5. Conclusions

The results of this placebo-controlled study demonstrate that the cream containing Kickxia elatine cell suspension culture extract exerts beneficial effects on several key skin parameters. The extract significantly improved skin hydration, reduced transepidermal water loss, and increased sebum production, suggesting strong moisturising and barrier-supportive properties. Additionally, it contributed to the stabilisation of skin pH and showed a positive impact on skin structure, vascular alterations, and pigmentation, indicating potential soothing, anti-inflammatory, and brightening effects. These findings support the promising role of K. elatine as a multifunctional active ingredient in dermocosmetic formulations, particularly suited for dry, sensitive, and mature skin. Further studies are recommended to explore its long-term efficacy and underlying mechanisms of action.

Author Contributions

Conceptualization, A.K.-S. and M.U.; methodology, A.K.-S., M.U. and J.G.-P.; software, A.A.H. and A.K.-S.; formal analysis, A.A.H.; investigation, A.K.-S. and M.U.; resources, A.K.-S., M.U. and J.G.-P.; writing—original draft preparation, M.K. and A.A.H.; writing—review and editing, A.A.H., A.B., A.K.-S., J.G.-P., M.K. and M.U.; visualisation, A.A.H. and A.K.-S.; supervision, M.K.; project administration, J.G.-P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study was approved by the Ethics Committee of Poznan University of Medical Sciences (decision number 698/24, date of approval 5 December 2024).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.

Acknowledgments

Anastasia Hermosaningtyas participates in the Poznan University of Medical Science STER Internationalisation of Doctoral Schools Programs of the NAWA Polish National Agency for Academic Exchange No. PPI/STE/2020/1/0014/DEC/02. The selected artwork (Caucasian young woman) shown in Figure 2 was used from or adapted from pictures provided by ServierMedical Art (Servier; https://smart.servier.com/, accessed on 23 June 2025; licensed under a Creative Commons Attribution 4.0 Unported License).

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
2,4-D2,4-dichlorophenoxyacetic acid
CASChemical Abstract Service
CIDCompound ID
EIErythema index
MIMelanin index
TEWLTransepidermal water loss
UVUltraviolet

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Figure 1. Schematic process from in vitro culture to product formulation containing K. elatine cell extract.
Figure 1. Schematic process from in vitro culture to product formulation containing K. elatine cell extract.
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Figure 2. Designated area for measurement (A) and a graphical interpretation of the results (B) obtained after skin analysis with the Nati Skin Analyzer.
Figure 2. Designated area for measurement (A) and a graphical interpretation of the results (B) obtained after skin analysis with the Nati Skin Analyzer.
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Figure 3. Skin parameter changes were assessed using the Nati Skin Analyzer after six weeks of applying the cream containing K. elatine cell extract.
Figure 3. Skin parameter changes were assessed using the Nati Skin Analyzer after six weeks of applying the cream containing K. elatine cell extract.
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Figure 4. Radar chart analysis of the sensory characteristics of the placebo (purple) and cream containing K. elatine cell extract (green) based on participants’ assessments.
Figure 4. Radar chart analysis of the sensory characteristics of the placebo (purple) and cream containing K. elatine cell extract (green) based on participants’ assessments.
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Table 1. Colour grading and its numerical values for skin texture and wrinkle depth measured using the Nati Skin Analyzer.
Table 1. Colour grading and its numerical values for skin texture and wrinkle depth measured using the Nati Skin Analyzer.
Colour SpectrumSkin
Texture		Wrinkle Depth (mm)Vascular
Lesions (mm2)		Skin
Discolorations (%)
Green0–8
excellent		0–0.05
small, shallow		0–2
well-vascularised skin		0–10
Within the correct amount and distribution of melanin in the skin
Yellow8–10
good 		0.06–0.1
medium		2.01–10
poorly vascularised skin		11–55
Epidermal hyperpigmentation (yellow, yellow-brown)
Red>10
incorrect 		0.11–2.7
deep		>10
very poorly vascularised skin		56–100
Skin discolouration—greyish brown colour
Table 2. Skin parameter values before and after six weeks of application of placebo or cream containing K. elatine cell extract, measured using Courage & Khazaka MPA-9.
Table 2. Skin parameter values before and after six weeks of application of placebo or cream containing K. elatine cell extract, measured using Courage & Khazaka MPA-9.
Skin ParameterPlacebo
(n = 20)		Cream Containing K. elatine Cell Extract
(n = 20)		p-Value Between Groups
BeforeAfterBeforeAfterBeforeAfter
Skin hydration [AU]47.81 ± 13.5757.68 ± 14.6040.36 ± 10.1663.00± 10.270.057 c0.191 c
p-value0.001 *,a<0.001 *,a
Transepidermal water loss [g/h/m2]11.09 ± 3.1212.12 ± 7.3214.82 ± 3.6211.76 ± 2.420.001 *,c0.289 b
p-value0.927 b<0.001 *,a
Luminosity 8.19 ± 1.478.32 ± 2.318.32 ± 1.437.63 ± 1.210.773 c0.295 c
p-value0.830 a0.009 *,a
Erythema index [AU]255.22 ± 58.83286.30 ± 50.92114.83 ± 19.62113.68 ± 26.120.042 *,c0.051 b
p-value0.002 *,a0.812 b
Melanin index [AU]127.43 ± 18.27127.33 ± 20.73276.58 ± 77.12295.40 ± 99.010.331 c0.947 b
p-value0.667 b0.210 a
Sebum level25.15 ± 14.5826.50 ± 28.8112.40 ± 12.65 35.85 ± 31.190.004 *,b0.449 b
p-value0.823 b<0.001 *,b
Skin surface pH5.45 ± 0.335.07 ± 0.515.53 ± 0.465.44 ± 0.420.281 c0.019 *,b
p-value0.001 *,a0.522 b
* p-value is considered significant if < 0.05; a paired t-test was used to calculate the normally distributed data; b Wilcoxon signed-rank test was used to calculate the non-normally distributed data; c independent t-test was used to calculate the normally distributed data.
Table 3. Skin parameter values before and after six weeks of application of placebo or cream containing K. elatine cell extract, measured using Nati Skin Analyzer.
Table 3. Skin parameter values before and after six weeks of application of placebo or cream containing K. elatine cell extract, measured using Nati Skin Analyzer.
Skin ParameterPlacebo
(n = 20)		Cream Containing K. elatine Cell Extract
(n = 20)		p-Value Between Groups
BeforeAfterBeforeAfterBeforeAfter
Skin structure8.67 ± 1.439.42 ± 1.649.23 ± 1.248.50 ± 1.020.191 c0.040 *,c
p-value0.023 *,a0.028 *,a
Wrinkle depth [mm]0.09 ± 0.020.14 ± 0.210.07 ± 0.030.08 ± 0.030.011 *,b0.516 b
p-value0.178 b0.520 b
Vascular lesions [mm2]1.78 ± 1.502.83 ± 0.932.72 ± 0.931.54 ± 1.730.019 *,b0.005 *,b
p-value0.002 *,b0.011 *,b
Skin discolouration [%]18.06 ± 7.4622.71 ± 6.5920.98 ± 3.3014.84 ± 3.540.029 *,b<0.001 *,b
p-value<0.001 *,b<0.001 *,b
* p-value is considered significant if < 0.05; a paired t-test was used to calculate the normally distributed data; b Wilcoxon signed-rank test was used to calculate the non-normally distributed data; c independent t-test was used to calculate the normally distributed data.
Table 4. Selected identified compounds in K. elatine cell cultures based on the previous study [24] with known cosmetological uses/benefits according to the scientific literature and the CosIng database.
Table 4. Selected identified compounds in K. elatine cell cultures based on the previous study [24] with known cosmetological uses/benefits according to the scientific literature and the CosIng database.
NrIdentified CompoundMolecular
Formula		PubChem CIDCASInformationRef.
1Octanedioic acid
(Suberic acid)		C8H14O410457505-48-6It has not yet been registered in CosIng, but it has been discovered that suberic acid inhibits morphological changes in the skin caused by UV-B radiation (dry skin, wrinkle formation, and epidermal thickness) and induces the expression of genes responsible for the production of collagen and hyaluronic acid.[35,36,37]
2Pantothenate
(Pantothenic acid)		C9H17NO5663179-83-4Antistatic, conditioning for hair and skin (CosIng).[37,38]
3Diethyl-phthalateC12H14O4678184-66-2Denaturant, film formation, hair conditioning, fragrance, plasticiser, solvent (CosIng).
No significant toxicity after exposure to the compound. 		[37,39,40]
4N-Acetyl-L-phenylalanine
(Phenylalanine)		C9H11NO27483963-91-2/150-30-1Hair care, fragrance, skin care (CosIng).
Precursor of melanin.		[37,41]
5Citric acidC6H8O731177-92-9/
5949-29-1		Buffering, chelating, scent (CosIng).
No significant toxicity upon skin contact.
It increases the thickness of the viable epidermis and dermal glycosaminoglycans in sun-damaged skin.		[37,42,43]
6N-Acetyl-DL-methionine
(allantonin acetyl methionine)		C7H13NO3S61804207-40-3Antistatic, moisturising, skin-protecting, soothing (CosIng).[37]
7D-TryptophanC11H12N2O2 906054-12-6/73-22-3Antistatic, skin-conditioning, fragrance (CosIng).[37]
8XylitolC5H12O5691287-99-0Moisturises the skin and improves barrier function. Antiseborrhoeic, deodorant, humectant, fragrance, skin conditioning (humectant) (CosIng). [37,44]
92-Isopropylmalic acid C7H12O5 773237-44-3It has not been registered in CosIng, but studies have shown that this compound improves skin elasticity and reduces wrinkles.[45]
10N-AcetylglucosamineC8H15NO6241397512-17-6It has not yet been registered in CosIng, but clinical studies have shown that it may reduce facial hyperpigmentation.[46]
11Salidroside (Rhodioloside)C14H20O7159278 10338-51-9Skin protection (CosIng).
It inhibits inflammation and melanin production in the skin. Speeds up wound healing.		[37,47,48]
12Meglutol
(3-hydroxy-3-methylglutaric acid)		C6H10O51662503-49-1Known for its cholesterol-lowering effects, glutaric acid is available in its basic form in CosIng.[37]
13Azelaic acidC9H16O4 2266123-99-9Buffering, scent (CosIng). Its application to treat rosacea and the management of inflammatory conditions in acne vulgaris was previously studied. [37,49,50]
14N-Acetyl-L-tyrosineC11H13NO468310537-55-3Moisturising the skin, tanning, styling, and hair care (CosIng).[37]
15PG 34:2
(1-Palmitoyl-2-linoleoyl-sn-glycero-3-phosphoglycerol)		C40H75O10P5292724692347-24-5Emulsion stabilisation, skin condition, skin protection, surfactant—emulsifying (CosIng).
A report from a clinical patient with molecular test results showed that phosphatidylglycerol may improve psoriatic lesions. 		[37,51]
166-GingerolC17H26O444279323513-14-It has not yet been registered in CosIng, but clinical studies have shown that beverages containing 6-gingerol may affect skin temperature. The possibility of local anti-inflammatory action was shown in an ex vivo study using human skin.[52,53]
17Sodium gluconateC6H12O7.Na23672301527-07-1/14906-97-9Moisturising the skin, chelation (CosIng).[37]
18RaffinoseC18H32O16439242512-69-6Moisturising the skin (CosIng), [37]
20Acteoside
syn. Verbascoside		C29H36O15528180061276-17-3antioxidant, anti-inflammatory, antineoplastic, and photoprotective activities. Chelation, whitening, skin protection (CosIng).[37,54,55]
24Riboflavin C17H20N4O6493570201-507-1/204-988-6Dye, skin conditioning (CosIng).[37]
22Flavin mononucleotide (riboflavin 5′-phosphate)C17H21N4O9P643976146-17-8There is no data on the use of flavin mononucleotide as a cosmetic ingredient; however, this compound has been used as a food additive.[56]
23
Traumatic AcidC12H20O452830286402-36-4There are no records regarding the use of traumatic acid as a cosmetic ingredient. Nevertheless, the results show the potential of traumatic acid as a means to support collagen biosynthesis and wound healing.[57,58]
24D-TuranoseC12H22O115460935547-25-1There is no information on the use of Turanose in cosmetics, but this compound has been used in several applications, such as acting as a protein stabiliser in medicines, an anti-inflammatory agent, and a sweetener in beverages.[59]
25ManginferinC19H18O1152816474773-96-0Skin protection (CosIng).[37]
26MaltitolC12H24O11 493591 585-88-6Humectant, fragrance, moisturising, skin conditioning (CosIng).[37]
27MelezitoseC18H32O1692817597-12-6It is not listed in CosIng, but it is mentioned as the preferred oligosaccharide for the polymer in the cleaning composition (patent).[60,61]
28Ginsenoside F2C42H72O13991869262025-49-4The specific Ginsenoside F2 is not listed in the CosIng database. However, the Ginsenoside library is available and contains notes on skin conditioning. Moreover, in cell and animal studies, Ginsenoside F2 has shown anti-ageing, hair anagen-inducing, and anti-inflammatory properties.[62,63,64,65]
29NADHC21H29N7O14P2439153606-68-8Moisturising the skin, emollient moisturising the skin (CosIng).[37]
30TrehaloseC12H22O11742799-20-7Humectant and moisturising (CosIng).[37]
31Uridine 5′-monophosphateC9H13N2O9P603058-97-9/27416-86-0Not listed in the CosIng database, but the in vivo assay suggested the benefits of UMP as a wound healing agent.[66]
30Plantainoside CC30H38O1545359577-Not listed in the CosIng database, but the compound was previously identified in Plantago asiatica. The extract from this species showed positive results for its anti-wrinkle and anti-ageing effects (in vitro).[67,68]
31Ala-PheC12H16N2O3968143061-90-3Not listed in the CosIng database, but antioxidant and anti-inflammatory properties make this dipeptide a potential candidate for cosmetical formulation. Moreover, it has shown a moisturising effect to help skin hydration. [69]
32Gly-LeuC8H16N2O392843869-19-2Not listed in the CosIng database, but in vitro and in vivo studies suggested that oral administration of Gly-Leu improves skin hydration and elasticity in UVB-irradiated hairless mice.[70]
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Hermosaningtyas, A.A.; Kroma-Szal, A.; Gornowicz-Porowska, J.; Urbanska, M.; Budzianowska, A.; Kikowska, M. Impact of Kickxia elatine In Vitro-Derived Stem Cells on the Biophysical Properties of Facial Skin: A Placebo-Controlled Trial. Appl. Sci. 2025, 15, 8625. https://doi.org/10.3390/app15158625

AMA Style

Hermosaningtyas AA, Kroma-Szal A, Gornowicz-Porowska J, Urbanska M, Budzianowska A, Kikowska M. Impact of Kickxia elatine In Vitro-Derived Stem Cells on the Biophysical Properties of Facial Skin: A Placebo-Controlled Trial. Applied Sciences. 2025; 15(15):8625. https://doi.org/10.3390/app15158625

Chicago/Turabian Style

Hermosaningtyas, Anastasia Aliesa, Anna Kroma-Szal, Justyna Gornowicz-Porowska, Maria Urbanska, Anna Budzianowska, and Małgorzata Kikowska. 2025. "Impact of Kickxia elatine In Vitro-Derived Stem Cells on the Biophysical Properties of Facial Skin: A Placebo-Controlled Trial" Applied Sciences 15, no. 15: 8625. https://doi.org/10.3390/app15158625

APA Style

Hermosaningtyas, A. A., Kroma-Szal, A., Gornowicz-Porowska, J., Urbanska, M., Budzianowska, A., & Kikowska, M. (2025). Impact of Kickxia elatine In Vitro-Derived Stem Cells on the Biophysical Properties of Facial Skin: A Placebo-Controlled Trial. Applied Sciences, 15(15), 8625. https://doi.org/10.3390/app15158625

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