Skip to main content
NCBI home page
Journal of Ginseng Research logoLink to Journal of Ginseng Research
. 2026 Feb 28;50(3):101018. doi: 10.1016/j.jgr.2026.101018

Red ginseng-derived components attenuate UVB-induced keratinocyte senescence via senomorphic mechanisms

Sung Ha Lim 1, Hee-Seok Seo 1, Hyun Kang 1, Seung-Phil Hong 1,⁎
PMCID: PMC13149889  PMID: 42112114

Abstract

Background

Senescent cells progressively accumulate within tissues and induce further senescence in neighboring cells through the senescence-associated secretory phenotype (SASP), thereby contributing to tissue dysfunction and aging. While senolytics selectively eliminate senescent cells, senomorphics modulate SASP without inducing cell death. Although red ginseng has been studied for anti-photoaging properties, its role in directly modulating SASP-driven keratinocyte senescence and paracrine aging signaling remains insufficiently defined. This study aimed to investigate whether Korean red ginseng-derived components (RGCs) exert senolytic or senomorphic activity in ultraviolet B (UVB)-induced senescent primary human keratinocytes.

Methods

Cellular senescence was induced by repeated UVB irradiation in primary human keratinocytes. A transwell co-culture system was employed to evaluate SASP-mediated paracrine effects on neighboring keratinocytes. Three RGC fractions were examined. Senescence markers (p16 and p21), SASP factors (IL-6, IL-8, IL-1β, and TNF-α), and differentiation/proliferation markers were analyzed. Representative major ginsenosides (Rb1, Rg1, Rg3, Rc) and stress signaling pathways (MAPK/JNK and AKT) were also evaluated.

Results

RGCs did not exhibit significant senolytic activity or apoptosis induction. Instead, they demonstrated pronounced senomorphic effects by attenuating UVB-induced upregulation of p16, p21, IL-6, IL-8, and IL-1β. RGCs enhanced keratinocyte proliferation and partially restored early-to-intermediate differentiation markers. In the co-culture model, RGCs mitigated SASP-mediated paracrine effects, reducing senescence and inflammatory signaling in adjacent keratinocytes. These effects were associated with modulation of stress-responsive MAPK/JNK pathways and were partially recapitulated by ginsenosides.

Conclusion

Our findings demonstrate that RGCs function predominantly as senomorphic modulators in UVB-induced keratinocyte senescence, attenuating SASP propagation and stress signaling without inducing cell death.

Keywords: Anti-aging, Keratinocytes, Red ginseng extract, Saponin, Senescence, Senomorphics

Graphical abstract

Image 1

Open in a new tab

1. Introduction

Skin aging is a multifactorial process that leads to progressive changes in the epidermis and dermis, resulting in atrophy, wrinkles, loss of elasticity, dryness, and irregular pigmentation [1]. Both intrinsic (chronological aging, genetics, hormonal changes) and extrinsic factors contribute to skin aging. Ultraviolet (UV) radiation, especially UVB, is one of the major extrinsic contributors to cutaneous photoaging [2]. Chronic UVB exposure induces direct DNA damage and oxidative stress in skin cells, leading to epidermal thinning, collagen breakdown, and wrinkle formation [3,4]. Essentially, such stress accelerates cellular senescence, a state of irreversible growth arrest triggered by diverse stimuli including telomere shortening, and genotoxic stress [[5], [6], [7]].

The chronic accumulation of senescent cells contributes to tissue dysfunction and aging-related pathologies. A key feature of senescent cells is the senescence-associated secretory phenotype (SASP), which involves the secretion of pro-inflammatory cytokines and chemokines [8,9]. SASP amplifies local inflammation, degrades extracellular matrix components, and propagates senescence to neighboring healthy cells, thereby disrupting skin homeostasis.

In recent years, senotherapeutics have emerged as promising interventions to counteract aging phenotypes by targeting senescent cells [10]. These agents include senolytics, which selectively eliminate senescent cells, and senomorphics, which modulate the harmful effects of the SASP without inducing cell death. Although some plant-derived flavonoids such as quercetin and fisetin have shown senolytic activity in preclinical models, their clinical applicability remains limited due to potential off-target toxicity, leading to increased interest in safer, natural compounds with senotherapeutic properties [[11], [12], [13], [14]].

Panax ginseng, particularly red ginseng, is rich in bioactive components including ginsenosides, which have antioxidant, anti-inflammatory, and photoprotective effects. Red ginseng has been shown to improve skin hydration, elasticity, and reducing UV-induced damage in both in vitro and in vivo models [[15], [16], [17], [18]]. Moreover, emerging evidence suggests that red ginseng may regulate cellular senescence. Specifically, ginsenoside Rb1 and Rc were reported to protect cells from oxidative stress-induced senescence [19,20], and red ginseng extract downregulated expression of p16INK4A, a key senescence marker, in keratinocytes exposed to environmental stress, potentially delaying the onset of senescence [21]. However, most previous studies have primarily focused on dermal fibroblast–focused extracellular matrix remodeling [[22], [23], [24]] or general photoprotective effects [25], and have not clearly distinguished between senolytic and senomorphic mechanisms in primary human keratinocytes. In addition, the impact of red ginseng-derived components on SASP-mediated paracrine propagation of senescence within keratinocyte populations has not been directly examined. A clearer understanding of these aspects is essential for defining the senotherapeutic potential of red ginseng in epidermal aging.

In this study, we investigated the senotherapeutic effects of red ginseng-derived components (RGCs) in primary human keratinocytes subjected to UVB-induced senescence. Using a transwell co-culture system, we further evaluated the impact of RGCs on SASP-mediated paracrine propagation of senescence between keratinocytes. We assessed senescence and SASP markers, epidermal differentiation and barrier-related factors, as well as stress-associated signaling pathways and apoptotic activity to determine whether RGCs function as senolytics or senomorphics and to explore their potential in preventing skin aging at the cellular level.

2. Materials and methods

2.1. Red ginseng-derived components and senolytics

Red ginseng-derived components were provided by the Korea Ginseng Corporation (Daejeon, Republic of Korea). The red ginseng extract was fractionated into three preparations: total red ginseng extract (TE), saponin fraction (Sp), and non-saponin fraction (Non-Sp). The total extract was dissolved in distilled water to prepare a stock solution at a concentration of 300 mg/mL. The saponin and non-saponin fractions were each dissolved in dimethyl sulfoxide (DMSO; Sigma-Aldrich, USA) to a final concentration of 10 mg/mL. Quercetin (Q4951, Sigma-Aldrich, St. Louis, MO, USA) and fisetin (PHL82542, Sigma-Aldrich) were used as senolytics (positive controls) in this study. Both compounds were dissolved in DMSO to prepare stock solutions at a concentration of 100 mM and stored at −20 °C until use. All stock solutions were diluted in culture medium to the desired concentrations immediately prior to use. The final concentration of DMSO in the culture medium did not exceed 0.1% (v/v), and the same concentration of DMSO was used in the vehicle-treated control group. In addition, representative major ginsenosides of Korean red ginseng, Rb1 (Sigma-Aldrich, G0777), Rg1 (SML4075), Rg3 (SML0184), and Rc (G0902), were used for mechanistic validation experiments. Each ginsenoside was dissolved in DMSO and used at a final concentration of 0.5 μM.

All treatments with red ginseng-derived components were performed 24 h after the final UVB exposure to evaluate their protective and anti-photoaging effects in human epidermal keratinocytes.

2.2. Cell culture

Primary normal human epidermal keratinocytes (HEK), isolated from adult skin, were obtained from Gibco™ (Life Technologies, Grand Island, NY, USA) and cultured in EpiLife® medium (Gibco™) containing 0.06 mM calcium and supplemented with EpiLife™ Defined Growth Supplement (EDGS; Gibco™). Cells were maintained at 37 °C in a humidified atmosphere with 5% CO2. All experiments were conducted using HEKs at passage 3.

2.3. UVB irradiation for photoaging induction

To induce photoaging, HEKs were repeatedly exposed to subcytotoxic doses of UVB radiation using a UVB lamp (Sankyo Denki, Japan). Cells were irradiated with UVB at a dose of 5 mJ/cm2, administered every 30 min, for a total of 6 exposures (cumulative dose: 30 mJ/cm2). After each irradiation, the culture medium was replaced with fresh complete medium, and cells were returned to standard incubation conditions (37 °C, 5% CO2). The control group was treated identically, excluding UVB exposure.

2.4. Co-culture system

To investigate the effects of UVB-irradiated keratinocytes on non-irradiated keratinocytes, a co-culture system was established using Transwell® inserts (0.4 μm pore size; Corning Inc., NY, USA). HEKs were seeded at the same density (2 × 105 cells/well) into both the lower chamber (6-well plate) and the upper insert. After stabilization for 24 h, only the cells in the upper insert were exposed to UVB with dose of 5 mJ/cm2 for 6 times at 30-min intervals (cumulative dose: 30 mJ/cm2) using a UVB lamp (Sankyo Denki, Japan). After 24 h of UVB irradiation, the inserts were transferred to the corresponding lower chambers containing non-irradiated keratinocytes to initiate the co-culture. Cells were cultured in EpiLife® medium (Gibco™) supplemented with EDGS (Gibco™) under standard culture conditions (37 °C, 5% CO2) for the indicated experimental periods.

2.5. Cell viability assay

Cell viability was evaluated using the EZ-Cytox assay kit (DoGenBio, Seoul, Republic of Korea) according to the manufacturer’s instructions. For monoculture experiments, cells were seeded into 96-well plates at a density of 2 × 103 cells per well and cultured for 24 h prior to treatment. Following treatment under each experimental condition, the culture medium was replaced with fresh medium containing EZ-Cytox reagent at 10% of the total volume.

For co-culture experiments, a 24-well Transwell® system (Corning Inc., Corning, NY, USA) was used. Keratinocytes were seeded into the upper insert and the lower chamber, at a density of 5 × 103 cells per well. After the treatments, the insert was carefully separated from the lower chamber, and the medium in both compartments was replaced with fresh medium containing EZ-Cytox reagent. The plates were incubated for 1–2 h at 37 °C in a humidified atmosphere containing 5% CO2. Absorbance was measured at 450 nm using a microplate reader (Victor™ X3, PerkinElmer, Waltham, MA, USA). Cell viability was expressed as percentage relative to untreated control cells.

2.6. Quantitative real-time PCR (qRT-PCR)

Total RNA was extracted using TRIzol® reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s protocol. Complementary DNA (cDNA) was synthesized from 1 μg of total RNA using Moloney murine leukemia virus reverse transcriptase (Promega, Madison, WI, USA) following the manufacturer’s instructions. qRT-PCR was carried out using SYBR Green PCR Master Mix (Applied Biosystems, Foster City, CA, USA) on a QuantStudio 3 Real-Time PCR System (Thermo Fisher Scientific, Waltham, MA, USA). Gene expression levels were normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a housekeeping gene, and relative expression levels were calculated using the comparative threshold cycle (2^−ΔΔCT) method. Primer sequences used for quantitative PCR are listed in Supplementary Table 1.

2.7. Western blotting

Cells were harvested and lysed in RIPA (radioimmunoprecipitation) buffer supplemented with protease and phosphatase inhibitors. Lysates were centrifuged at 12,000 g for 15 min at 4 °C, and the supernatants were collected. Protein concentrations were determined using the bicinchoninic acid (BCA) protein assay (Thermo Fisher Scientific, Waltham, MA, USA), and equal amounts of total protein were loaded for each sample. Proteins were separated by sodium dodecyl sulfate -polyacrylamide gel electrophoresis (SDS-PAGE) and transferred onto nitrocellulose membranes (Bio-Rad, Hercules, CA, USA). Membranes were blocked with 3% bovine serum albumin (BSA) in Tris-buffered saline containing 0.1% Tris-buffered saline with Tween-20 (TBST) for 1 h at room temperature and incubated overnight at 4 °C with the following primary antibodies: anti-p16 (Proteintech 10883-1-AP, 1:1000, 16 kDa), anti-phospho-Histone H2A.X (Ser139; γH2A.X; CST #9718, 1:1000, 15 kDa), anti-IL-6 (CST #12153, 1:1000, 21 kDa), and anti-β-actin (Santa Cruz Biotechnology SC-47778, 1:4000, 43 kDa), which was used as a loading control. For pathway analysis, additional primary antibodies were used as follows: anti-phospho-AKT (CST #4060), anti-AKT (CST #9272), anti-phospho-p38 (CST #4511), anti-p38 (CST #8690), anti-phospho-ERK1/2 (CST #4370), anti-ERK1/2 (CST #4695), anti-phospho-JNK (CST #9251), anti-JNK (CST #9252), anti-COL1A1 (CST #72026), and anti-COL3A1 (CST #66887). Antibodies were used at dilutions ranging from 1:1000 to 1:4000 as recommended by the manufacturers. After washing, the membranes were incubated with appropriate horseradish peroxidase -conjugated secondary antibodies. Protein bands were visualized using an enhanced chemiluminescence (ECL) detection reagent, and signals were detected by exposure to X-ray film.

2.8. Immunofluorescence

Cells were fixed with 4% paraformaldehyde for 10 min at room temperature and permeabilized with 0.25% Triton™ X-100. After washing with phosphate-buffered saline (PBS), nonspecific binding sites were blocked by incubating the cells in 1% BSA in PBS for 1 h at room temperature. Subsequently, the cells were incubated with primary antibodies against ceramide (Enzo Life Sciences, ALX-804-196, 1:10) and Na+/H+ exchanger 1 (NHE-1; Abcam, ab67314, 1:100) incubated overnight at 4 °C. After thorough washing, cells were incubated with Alexa Fluor® 488-conjugated goat anti-rabbit or anti-mouse IgG (H + L) secondary antibodies (Invitrogen, A-11008 or A-11001, 1:200) diluted in PBS containing 0.2% BSA for 1 h at room temperature. The nuclei were counterstained with DAPI (Invitrogen, D1306), and filamentous actin (F-actin) was stained using Rhodamine Phalloidin (Invitrogen, R415, 1:300).

2.9. Senescence-associated β-galactosidase (SA-β-gal) staining

Cellular senescence was assessed by detecting SA-β-gal activity using a Senescence β-Galactosidase Staining Kit (Sigma-Aldrich, CS0030), according to the manufacturer’s instructions. Briefly, cells were washed twice with PBS and fixed with the provided fixative solution for 15 min at room temperature. After fixation, cells were rinsed with PBS and incubated with SA-β-gal staining solution (pH 6.0) at 37 °C in a dry incubator (without CO2) for 16 h.

Stained cells exhibiting blue coloration in the cytoplasm were considered SA-β-gal–positive. Images were captured using a bright-field microscope at 100 × magnification. The percentage of senescent cells was determined by counting SA-β-gal–positive cells relative to the total number of cells in randomly selected fields.

2.10. Caspase-3/7 activity assay

Caspase-3/7 activity was measured using the Caspase-Glo® 3/7 Assay Kit (Promega, Madison, WI, USA) according to the manufacturer’s protocol. HEKs were seeded in white 96-well plates at a density of 5 × 103 cells per well. Following UVB irradiation, cells were treated with red ginseng fractions (TE 100 μg/mL; Sp 10 μg/mL; Non-Sp 10 μg/mL) or individual ginsenosides (Rb1, Rg1, Rg3, Rc; 0.5 μM) for the indicated time points (1, 3, 6, 12, 24, or 48 h). An equal volume (100 μL) of Caspase-Glo® reagent was added to each well containing 100 μL of culture medium, followed by gentle shaking for 30 s at 300 rpm and incubation at room temperature for 1 h. Luminescence was measured using a plate-reading luminometer according to the manufacturer’s instructions. Caspase activity was normalized to untreated controls.

2.11. Statistics

All experiments were performed in triplicate, and all statistical analyses were performed using GraphPad Prism (ver. 10.4.0). Data are presented as mean ± standard error. The unpaired Student’s t-test was used for comparisons. Statistical significance was set at p < 0.05.

3. Results

3.1. Modulation of senescence by RGCs

To assess the senolytic potential of RGCs, we examined cell viability in UVB-induced senescent primary keratinocytes treated with total extract (TE), Sp, and Non-Sp fractions (Fig. 1A–D). Quercetin, previously identified as a senolytic [26], was included as positive control. As expected, quercetin significantly reduced cell viability at 48 and 72 h, particularly in UVB-treated senescent cells, confirming its senolytic activity under stress conditions (Fig. 1A).

Fig. 1.

Fig. 1

Open in a new tab

Evaluation of the senomorphic effects of RGCs in primary human keratinocytes. Cell viability after treatment with UVB and quercetin (A), Rg (B), Sp (C), or Non-Sp (D) compared to the corresponding UVB-only controls. ∗∗p < 0.01, UVB vs. reagent + UVB; #p < 0.05, reagent vs. reagent + UVB. Relative mRNA expression of p21 (E), p16 (F), IL-6 (G), and IL-8 (H) after UVB irradiation and RGC treatment. (I) Western blot analysis following UVB with or without RGCs. (J) SIRT1 expression in keratinocytes treated with UVB and RGCs. RGCs, red ginseng-derived components; UVB, ultraviolet B; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction. ∗p < 0.05; ∗∗p < 0.01.

In contrast, treatment with RGCs did not result in a significant decrease in cell viability across the tested time points (Fig. 1B–D). Instead, TE and Non-Sp fractions significantly increased cell viability at specific time points (TE at 72 h; Non-Sp at 48 and 72 h) compared with the UVB-only group. These findings suggest a cytoprotective or proliferative effect rather than senescent cell elimination. Sp treatment did not significantly alter viability under UVB stress.

Importantly, under UVB-non-irradiated conditions, treatment with TE, Sp, or Non-Sp did not induce cytotoxicity compared with untreated controls. A modest increase in cell viability was observed at select time points in some fractions; however, these changes were not comparable in magnitude to the UVB-dependent effects and did not suggest aberrant hyperproliferation. These findings indicate that RGCs do not adversely affect basal keratinocyte viability and that their viability-enhancing effects are more evident under UVB-induced stress conditions, supporting a context-dependent modulatory role.

3.2. RGCs suppress senescence markers and SASP in UVB-induced senescent keratinocytes

We next examined the senomorphic effects of RGCs by analyzing the expression of senescence markers (p21, p16) and SASP-associated cytokines (IL-6, IL-8) in UVB-induced senescent and control cells (Fig. 1E–J). Repeated low-dose UVB irradiation markedly upregulated the expression of all four genes (Fig. 1E–H). Treatment with RGCs, particularly the saponin and non-saponin fractions, led to a significant reduction in p21 and p16 expression. Similarly, IL-6 and IL-8 levels were significantly attenuated following RGCs treatment, with more pronounced effects observed in UVB-irradiated cells than in non-irradiated controls.

Protein-level analysis corroborated the transcriptomic findings, showing reduced expression of p16 and IL-6, as well as a decrease in levels of γH2AX, a marker of DNA damage, in both UVB-exposed and control keratinocytes following RGC treatment (Fig. 1I).

To further explore the anti-senescent potential of RGCs, we assessed the expression of SIRT1, a longevity-associated gene known to antagonize senescence pathways [27] (Fig. 1J). UVB irradiation downregulated SIRT1 expression, whereas RGC treatment enhanced SIRT1 levels in both UVB-treated and untreated cells.

Collectively, these findings indicate that RGCs suppress senescence and SASP factors, supporting a senomorphic mode of action.

3.3. RGCs restore keratinocyte differentiation and promote proliferation

To further investigate the regenerative potential of RGCs, we examined the expression of keratinocyte differentiation markers (KRT5, TGM1, and FLG) and proliferation markers (Ki67 and PCNA) (Fig. 2). UVB treatment resulted in a general downregulation of differentiation marker expression, indicating impaired epidermal maturation. Among these markers, the expression of KRT5, an epidermal basal marker reflecting basal-layer identity and proliferative potential, was partially restored following RGC treatment (Fig. 2A). The expression of TGM1, which is associated with cornified envelope formation (a crucial constituent of skin barrier), also showed moderate recovery, especially with saponin fraction (Fig. 2B). FLG, which is typically expressed in more terminally differentiated granular cells, exhibited low expression levels after UVB exposure and was modestly increased by RGCs (Fig. 2C). These findings suggest that RGCs partially reverse UVB-induced impairment in epidermal differentiation, primarily restoring early-to-intermediate stages of keratinocyte maturation. Consistently, RGCs significantly enhanced the expression of proliferation markers not only in UVB-damaged keratinocytes but also in untreated controls (Fig. 2D and E). This effect was observed across all RGC fractions, indicating that RGCs directly promote keratinocyte proliferation beyond restoration.

Fig. 2.

Fig. 2

Open in a new tab

Effects of RGCs in epidermal differentiation and proliferation markers in UVB-treated keratinocytes. Relative mRNA expression of KRT5 (A), TGM1 (B), FLG (C), Ki67 (D), and PCNA (E). (F) Immunofluorescence staining for ceramide (GFP) in keratinocytes. RGCs, red ginseng-derived components; UVB, ultraviolet B; GFP, green fluorescent protein; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction. ∗p < 0.05; ∗∗p < 0.01.

Additionally, immunofluorescence staining for ceramide, a critical lipid component of the epidermal barrier, revealed increased intracellular ceramide in RGC-treated keratinocytes under normal conditions, with the most prominent effect observed in the saponin group (Fig. 2F). This suggests that RGCs may enhance skin barrier lipid synthesis by slightly promoting differentiation.

3.4. RGCs reduce the effects of SASP secreted by UVB-senescent keratinocytes

To investigate whether RGCs attenuate the paracrine effects of the SASP secreted by senescent keratinocytes, we employed a transwell co-culture system (Fig. 3A). UVB irradiation (5 mJ/cm2, 6 times) was applied to keratinocytes cultured in the upper chamber, while cells in the lower chamber were maintained without UVB exposure. Following senescence induction, the upper chamber insert was placed onto the lower chamber; the insert membrane (0.4 μm pore size) allowed soluble SASP factors to diffuse and affect the underlying normal keratinocytes.

Fig. 3.

Fig. 3

Open in a new tab

RGCs reduce damage to adjacent cells by attenuating SASP-mediated effects from UVB-induced senescent keratinocytes. (A) Schematic of the transwell co-culture system using UVB-induced senescent and normal keratinocytes. (B, C) Cell viability measurement after treatment with fisetin/quercetin (B) or RGCs (C) in upper and lower chambers. ∗∗p < 0.01, vs. normal control (100% viability); ##p < 0.01, vs. upper chamber control (UVB only); ++ p < 0.01, vs. lower chamber control. (D, E) SA-β galactosidase staining of lower chamber cells following UVB and RGCs. Relative mRNA expression of p16 (F), p21 (G), IL-6 (H), IL-8 (I), IL-1β (J), and TNF (K). (L) Western blot analysis of lower chamber keratinocytes following UVB irradiation with or without RGC treatment. ∗p < 0.05, ∗∗p < 0.01, vs. normal control; #p < 0.05, ##p < 0.01, vs. UVB. RGCs, red ginseng-derived components; SASP, senescence-associated secretory phenotype; UVB, ultraviolet B; SA-β, senescence-associated β-galactosidase; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction.

Treatment of UVB-exposed upper chamber cells with the senolytics fisetin [28] and quercetin significantly decreased the viability of senescent cells while increasing the viability of the normal lower chamber cells (Fig. 3B). RGC treatment of UVB-senescent cells modestly increased the viability of both upper and lower chamber keratinocytes (Fig. 3C).

In addition, SA-β-gal staining revealed a lower proportion of positively stained cells in RGC-treated lower chamber cells, indicating reduced secondary senescence compared to the untreated controls (Fig. 3D and E). Collectively, these results indicate that RGCs exert mild protective effects against SASP-mediated paracrine stress.

3.5. RGCs attenuate senescence and inflammatory mediators induced by UVB-senescent cells

To further investigate the anti-inflammatory effects of RGCs in keratinocytes affected by SASP, we examined the expression of SASP-related cytokines (IL-6, IL-8, IL-1β, and TNF-α) in the Transwell co-culture system (Fig. 3F–L). While p16 expression in lower chamber cells was not significantly altered by RGCs, TE treatment led to a reduction in p21 levels, suggesting partial mitigation of stress-induced senescence (Fig. 3F and G). RGC treatment led to a reduction in IL-6 and IL-1β mRNA levels in UVB-senescent cells (upper chamber), while IL-6, IL-1β, and TNF-α levels were also decreased in the adjacent normal keratinocytes (lower chamber). IL-8 did not show significant alteration (Fig. 3H–K). Western blot analysis further supported the findings, showing decreased levels of p16, γH2AX, and IL-6 following RGC treatment (Fig. 3L). The overall trend suggests that RGCs can modulate senescence signaling in UVB-treated keratinocytes and partially dampen SASP-driven inflammatory responses in neighboring normal cells.

3.6. RGCs restore differentiation and NHE1 expression in adjacent keratinocytes

We also assessed the impacts of RGCs on keratinocyte differentiation and epidermal barrier function under SASP-induced stress. Treatment with RGCs significantly upregulated the expression of differentiation markers KRT5, KRT14, FLG, and IVL (not TGM1), as well as proliferation markers Ki67 and PCNA, in both UVB-senescent cells and SASP-exposed keratinocytes (Fig. 4A–G). Notably, the expression of NHE1, a membrane protein critical for pH regulation in stratum corneum barrier formation and cell survival, was also restored by RGCs (Fig. 4H). Immunofluorescence staining further confirmed increased NHE1 localization in both senescent and adjacent normal keratinocytes following RGC treatment (Fig. 4I). These findings suggest that RGCs alleviate SASP-mediated paracrine effects by promoting keratinocyte regeneration and restoring epidermal pH-regulating NHE1 expression.

Fig. 4.

Fig. 4

Open in a new tab

Effects of RGCs on epidermal differentiation, proliferation, and NHE1 expression after SASP-induced stress in adjacent normal keratinocytes. Relative mRNA expression of KRT5 (A), KRT14 (B), FLG (C), INV (D), TGM1 (E), Ki67 (F), PCNA (G), and NHE1 (H). (I) Immunofluorescence staining of NHE1 (GFP-green) in keratinocytes. RGCs, red ginseng-derived components; SASP, senescence-associated secretory phenotype; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction. ∗p < 0.05; ∗∗p < 0.01.

3.7. Ginsenosides reproduce the senomorphic phenotype without inducing apoptosis

To further delineate whether the senomorphic effects observed with RGC fractions could be attributed to specific bioactive constituents, we evaluated representative major ginsenosides (Rb1, Rg1, Rg3, and Rc) using the same UVB-induced keratinocyte senescence model (Fig. 5A–D). None of the tested ginsenosides significantly reduced cell viability under UVB-induced stress conditions. Instead, Rg1, Rg3, and Rc modestly preserved or partially improved viability compared with the UVB-only group, consistent with a cytoprotective rather than cytotoxic effect.

Fig. 5.

Fig. 5

Open in a new tab

Effects of representative ginsenosides and RGC fractions on apoptosis under UVB-induced stress. (A–D) Cell viability of primary human keratinocytes treated with representative ginsenosides Rb1 (A), Rg1 (B), Rg3 (C), and Rc (D) in the presence or absence of UVB exposure. (E-F) Caspase-3/7 activity in keratinocytes treated with individual ginsenosides (Rb1, Rg1, Rg3, Rc) and RGC fractions (TE, Sp, Non-Sp) with or without UVB exposure. RGCs, red ginseng-derived components; UVB, ultraviolet B; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction; Veh, vehicle control; Gs, ginsenoside. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, vs. vehicle; ##p < 0.01, ###p < 0.001, vs. UVB.

To more clearly examine senomorphic modulation, we next assessed apoptosis by measuring caspase-3/7 activity (Fig. 5E and F). UVB exposure alone increased caspase activity relative to vehicle-treated controls, reflecting stress-induced apoptotic signaling. In contrast, treatment with individual ginsenosides (Rb1, Rg1, Rg3, and Rc) as well as RGC fractions (TE, Sp, and Non-Sp) markedly attenuated UVB-induced caspase-3/7 activation. Treatment with Rb1 and Rg1 under non-UVB conditions also resulted in a significant reduction in basal caspase activity compared with controls.

Collectively, these findings indicate that neither individual ginsenosides nor RGC fractions promote apoptotic clearance of UVB-stressed keratinocytes. Instead, their effects are characterized by preservation of cell viability and attenuation of stress-associated apoptotic signaling, further supporting a predominantly senomorphic mode of action.

3.8. RGCs and ginsenosides regulate UVB-induced senescence-related signaling pathways

To further investigate whether ginsenosides reproduce the molecular effects observed with RGC fractions, we examined the expression of senescence markers, SASP factors, differentiation markers, and SIRT1 in UVB-induced keratinocytes (Fig. 6A–K). UVB irradiation significantly upregulated p16, p21, IL6, and IL8 expression at both 24 and 48 h (Fig. 6A–D). Treatment with ginsenosides (Rb1, Rg1, Rg3, and Rc) attenuated the UVB-induced upregulation of these senescence- and SASP-related genes to varying degrees, with more consistent reductions observed for IL6 and p16. In parallel, ginsenoside treatment partially restored early-to-intermediate differentiation markers, particularly KRT5 and INV, while effects on late differentiation markers such as FLG were more modest. Proliferation-associated genes (Ki67 and PCNA) were also preserved or modestly increased following ginsenoside treatment under UVB stress conditions (Fig. 6I and J). In addition, SIRT1 expression, was also restored following treatment with all ginsenosides (Fig. 6K), supporting a shift toward an anti-senescent transcriptional profile.

Fig. 6.

Fig. 6

Open in a new tab

RGCs and ginsenosides modulate senescence markers and UVB-activated MAPK/AKT signaling pathways. Relative mRNA expression of p16 (A), p21 (B), IL6 (C), IL8 (D), KRT5 (E), FLG (F), INV (G), TGM1 (H), Ki67 (I), PCNA (J), and SIRT1 (K) in keratinocytes treated with representative ginsenosides under UVB exposure. (L) Western blot analysis of p16, IL-6, and phosphorylated and total forms of AKT, ERK, JNK, and p38 in keratinocytes treated with individual ginsenosides under UVB conditions. (M) Western blot analysis of phosphorylated and total AKT, ERK, JNK, and p38 in keratinocytes treated with RGC fractions (TE, Sp, Non-Sp) under UVB exposure. RGCs, red ginseng-derived components; UVB, ultraviolet B; TE, total extract; Sp, saponin fraction; Non-Sp, non-saponin fraction. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, vs. control; #p < 0.05, ##p < 0.01, ###p < 0.001, vs. UVB.

To explore upstream signaling mechanisms underlying these transcriptional changes, we next examined key stress-responsive pathways implicated in UVB-induced senescence, including AKT and MAPK signaling cascades (ERK, JNK, and p38) (Fig. 6L and M). UVB irradiation markedly increased phosphorylation of JNK and p38, along with alterations in ERK and AKT signaling, consistent with activation of stress- and inflammation-associated pathways. Treatment with individual ginsenosides (Rb1, Rg1, Rg3, and Rc) partially attenuated UVB-induced phosphorylation of JNK and p38, while maintaining or modestly normalizing AKT and ERK phosphorylation patterns. Similar trends were observed with RGC fractions (TE, Sp, and Non-Sp), which reduced UVB-induced activation of JNK and p38 and moderately modulated AKT signaling. Concomitantly, both ginsenoside and RGC treatments reduced protein expression of p16 and IL-6, consistent with suppression of stress-activated inflammatory pathways rather than induction of apoptotic cell death.

Collectively, these findings suggest that RGCs and their representative ginsenosides may exert senomorphic effects, at least in part, through modulation of UVB-activated MAPK (particularly JNK and p38) and AKT signaling pathways, thereby attenuating stress-driven senescence and SASP expression in keratinocytes.

4. Discussion

This study demonstrates that RGCs exert predominantly senomorphic rather than senolytic effects in UVB-induced senescent human keratinocytes. Unlike classical senolytics, which eliminate senescent cells via cell death induction (apoptosis), RGCs did not reduce cell viability under UVB stress. Instead, TE, Non-sp fractions, and representative ginsenosides significantly enhanced cell viability, suggesting cytoprotective or pro-survival effects rather than senescent cell clearance. Importantly, additional caspase-3/7 activity assays supported that neither RGC fractions nor individual ginsenosides induced apoptotic activation under UVB conditions, further distinguishing their actions from senolytic mechanisms. Collectively, these findings position RGCs as phenotype-modulating senomorphics rather than apoptosis-inducing senolytics. At the molecular level, RGC treatment consistently downregulated canonical senescence markers (p16 and p21) and key SASP cytokines (IL-6 and IL-8), while upregulating SIRT1 expression, which is a longevity-associated regulator known to antagonize stress-induced senescence pathways and promotes differentiation of human keratinocytes [29,30]. These coordinated changes suggest that RGCs attenuate the senescence-associated inflammatory phenotype and promote a more homeostatic cellular state rather than eliminating damaged cells.

Beyond senescence suppression, RGCs enhanced keratinocyte regenerative capacity by upregulating proliferation markers (Ki67 and PCNA) and basal epidermal markers such as KRT5, and KRT14. Increased ceramide content in normal keratinocytes further suggests that RGCs may contribute to barrier lipid synthesis. In contrast, late differentiation markers such as FLG, INV, and TGM exhibited only modest recovery, indicating that RGCs primarily restore early-to-intermediate differentiation stages while preserving proliferative competence. These findings collectively suggest functional recovery of stressed keratinocytes but induction of terminal differentiation.

A key strength of this study lies in the transwell model designed to mimic SASP-mediated paracrine stress. In this system, RGCs mitigated secondary senescence and inflammatory responses in adjacent normal keratinocytes exposed to factors secreted by UVB-senescent cells. Reduced p21 expression, decreased SA-β-gal positivity, partial suppression of IL6, IL1B, and TNF, and attenuation of γH2AX levels in neighboring cells indicate that RGCs can limit the propagation of senescence signals. Restoration of NHE1 expression, a membrane transporter essential for maintaining the acidic pH of the stratum corneum and epidermal barrier integrity, further supports a role for RGCs in functional epidermal recovery under paracrine stress conditions.

Moreover, the additional experiments using representative major ginsenosides (Rb1, Rg1, Rg3, and Rc) revealed that individual components recapitulate key aspects of the senomorphic phenotype. These compounds attenuated senescence- and SASP-related markers without inducing cytotoxicity or apoptosis, supporting the biological relevance of defined ginsenosides within the RGC fractions. Mechanistic analyses further demonstrated that both RGC fractions and individual ginsenosides modulate UVB-activated stress signaling pathways, particularly by attenuating phosphorylation of JNK and p38 MAPK, while partially normalizing ERK and AKT signaling. Given the established role of JNK and p38 in stress-induced senescence and SASP amplification, their modulation provides a plausible mechanistic basis for the observed reduction in inflammatory mediators and senescence markers.

These findings align with and extend prior research on the dermatological effects of red ginseng, including its antiaging, anti-inflammatory, and regenerative properties. Several studies have demonstrated that red ginseng-treated mice exhibit decreased wrinkles and minimal epidermal hyperplasia, suggestive of delayed aging [31,32]. Ginsenosides such as compound K improve skin barrier function by normalizing UVB-induced reduction in SPINK5 in murine models [33], and have been reported to confer protection against UVB-induced damage in mouse fibroblasts by inhibiting MMP-1 and COX-2 while enhancing the expression of FLG, TGM, and hyaluronic acid synthases, promoting skin hydration [34]. Ginsenoside Rg3 has been implicated in partial reversal of senescence in human fibroblast through the modulation of PRDX3, an antioxidant mitochondrial enzyme [35]. Furthermore, protopanaxatriol, a secondary metabolite of ginsenosides, has been shown to stimulate epidermal differentiation markers and hyaluronic acid synthases via Src/AKT/NF-kB and MAPK pathways [36]. Moreover, red ginseng extract and saponin extractions inhibit UV-induced inflammasome activation by downregulating TLR-mediated pro-IL1B and NLRP3 expression [37]. Ginseng root-derived exosome-like nanoparticles also protect keratinocytes from UV-mediated oxidative stress by suppressing pro-apoptotic genes such as BAX and caspases, and proinflammatory genes including COX-2 and IL-6 [38]. In addition, red ginseng also promoted wound healing, possibly through induction of transforming growth factor-β and vascular endothelial growth factor. Collectively, these findings support the concept that ginseng and its metabolites modulate inflammation and stress pathways during skin aging. However, many of these prior studies have primarily focused on dermal fibroblasts or murine models [39], and have emphasized antioxidant capacity or extracellular matrix remodeling. In contrast, our study highlights primary human keratinocytes and directly evaluates senomorphic modulation of SASP-driven bystander senescence using a transwell paracrine model. Given that keratinocytes constitute the majority of the epidermis and play a central role in orchestrating cutaneous inflammatory responses, targeting keratinocyte senescence and SASP propagation may represent a biologically essential strategy for mitigating photoaging at the epidermal level.

From a therapeutic perspective, senomorphic modulation may offer a safer and more physiologically compatible alternative to senolytic strategies in the context of skin aging. While senolytics aim to eliminate senescent cells through apoptosis, their clinical applicability in the skin remains uncertain due to potential cytotoxicity and disruption of tissue integrity. In contrast, our findings suggest that RGCs attenuate senescence-associated inflammatory signaling and restore functional markers without inducing apoptotic cell death. Such phenotype modulation may be particularly advantageous in tissues such as the epidermis, where maintaining barrier continuity and regenerative capacity is essential.

The mechanistic analyses presented here further suggest that modulation of stress-responsive signaling pathways, particularly JNK and p38 MAPK, along with partial normalization of AKT signaling, may underlie the observed senomorphic effects. These pathways are commonly implicated in UV-induced damage and SASP amplification and are also targeted by various anti-inflammatory and antioxidant agents. Future studies directly comparing RGCs with established anti-photoaging compounds (e.g., retinoids, polyphenols, or flavonoids) at the level of MAPK/AKT signaling and SASP modulation would provide further insight into their relative efficacy and mechanism of action.

Several limitations should also be acknowledged. Although representative ginsenosides reproduced key phenotypes, the specific components primarily responsible for senomorphic modulation remain to be fully delineated, and synergistic interactions among constituents are likely. Additionally, the present findings are derived from in vitro models. In vivo validation using photoaging animal models will be necessary to confirm physiological relevance, tissue-level barrier recovery, and long-term safety. Ultimately, well-designed preclinical and clinical studies will be required to determine optimal dosing, formulation stability, and translational potential for dermatological or cosmeceutical applications.

In conclusion, our results indicate that RGCs function as senomorphic modulators in UVB-induced keratinocyte senescence. By attenuating SASP signaling, modulating stress-responsive pathways, and promoting epidermal regeneration without inducing apoptosis, RGCs may represent promising candidates for therapeutic or cosmeceutical strategies aimed at preventing or ameliorating UV-induced skin aging.

Disclaimers

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (# RS-2022-NR075682) and a 2022 grant from the Korean Society of Ginseng.

Conflict of interest

None.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.jgr.2026.101018.

Appendix A. Supplementary data

The following is the Supplementary data to this article:

Multimedia component 1
mmc1.docx (16.8KB, docx)

References

  • 1.Chin T., Lee X.E., Ng P.Y., Lee Y., Dreesen O. The role of cellular senescence in skin aging and age-related skin pathologies. Front Physiol. 2023;14 doi: 10.3389/fphys.2023.1297637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Fisher G.J., Wang Z.Q., Datta S.C., Varani J., Kang S., Voorhees J.J. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med. 1997;337(20):1419–1428. doi: 10.1056/NEJM199711133372003. [DOI] [PubMed] [Google Scholar]
  • 3.Kambayashi H., Yamashita M., Odake Y., Takada K., Funasaka Y., Ichihashi M. Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle formation in hairless mouse. J Dermatol Sci. 2001;27(Suppl 1):S19–S25. doi: 10.1016/s0923-1811(01)00113-x. [DOI] [PubMed] [Google Scholar]
  • 4.Panich U., Sittithumcharee G., Rathviboon N., Jirawatnotai S. Ultraviolet radiation-induced skin aging: the role of DNA damage and oxidative stress in epidermal stem cell damage mediated skin aging. Stem Cell Int. 2016;2016 doi: 10.1155/2016/7370642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Shmulevich R., Krizhanovsky V. Cell senescence, DNA damage, and metabolism. Antioxidants Redox Signal. 2021;34(4):324–334. doi: 10.1089/ars.2020.8043. [DOI] [PubMed] [Google Scholar]
  • 6.Hernandez-Segura A., Nehme J., Demaria M. Hallmarks of cellular senescence. Trends Cell Biol. 2018;28(6):436–453. doi: 10.1016/j.tcb.2018.02.001. [DOI] [PubMed] [Google Scholar]
  • 7.Kumari R., Jat P. Mechanisms of cellular senescence: cell cycle arrest and senescence associated secretory phenotype. Front Cell Dev Biol. 2021;9 doi: 10.3389/fcell.2021.645593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Acosta J.C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J.P., et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15(8):978–990. doi: 10.1038/ncb2784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Tchkonia T., Zhu Y., van Deursen J., Campisi J., Kirkland J.L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Investig. 2013;123(3):966–972. doi: 10.1172/JCI64098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Yoon J.H., Han H.J. Senotherapeutics: different approaches of discovery and development. Mol Cells. 2024;47(1) doi: 10.1016/j.mocell.2023.10.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Di Micco R., Krizhanovsky V., Baker D., d’Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021;22(2):75–95. doi: 10.1038/s41580-020-00314-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Li W., Qin L., Feng R., Hu G., Sun H., He Y., et al. Emerging senolytic agents derived from natural products. Mech Ageing Dev. 2019;181:1–6. doi: 10.1016/j.mad.2019.05.001. [DOI] [PubMed] [Google Scholar]
  • 13.Chen R., Lin J., Hong J., Han D., Zhang A.D., Lan R., et al. Potential toxicity of quercetin: the repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow. Toxicol Rep. 2014;1:450–458. doi: 10.1016/j.toxrep.2014.07.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Eguchi H., Kimura R., Matsunaga H., Matsunaga T., Yoshino Y., Endo S., et al. Increase in anticancer drug-induced toxicity by Fisetin in lung adenocarcinoma A549 spheroid cells mediated by the reduction of Claudin-2 expression. Int J Mol Sci. 2022;23(14) doi: 10.3390/ijms23147536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Saba E., Kim S.H., Lee Y.Y., Park C.K., Oh J.W., Kim T.H., et al. Korean Red Ginseng extract ameliorates melanogenesis in humans and induces antiphotoaging effects in ultraviolet B-irradiated hairless mice. J Ginseng Res. 2020;44(3):496–505. doi: 10.1016/j.jgr.2019.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Cai B.X., Jin S.L., Luo D., Lin X.F., Gao J. Ginsenoside Rb1 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair. Biol Pharm Bull. 2009;32(5):837–841. doi: 10.1248/bpb.32.837. [DOI] [PubMed] [Google Scholar]
  • 17.Oh S.J., Kim K., Lim C.J. Suppressive properties of ginsenoside Rb2, a protopanaxadiol-type ginseng saponin, on reactive oxygen species and matrix metalloproteinase-2 in UV-B-irradiated human dermal keratinocytes. Biosci Biotechnol Biochem. 2015;79(7):1075–1081. doi: 10.1080/09168451.2015.1020752. [DOI] [PubMed] [Google Scholar]
  • 18.Cong L., Ma J., Zhang Y., Zhou Y., Cong X., Hao M. Effect of anti-skin disorders of ginsenosides- A Systematic Review. J Ginseng Res. 2023;47(5):605–614. doi: 10.1016/j.jgr.2023.04.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Liu D.H., Chen Y.M., Liu Y., Hao B.S., Zhou B., Wu L., et al. Rb1 protects endothelial cells from hydrogen peroxide-induced cell senescence by modulating redox status. Biol Pharm Bull. 2011;34(7):1072–1077. doi: 10.1248/bpb.34.1072. [DOI] [PubMed] [Google Scholar]
  • 20.Oh Y., Lim H.W., Park K.H., Huang Y.H., Yoon J.Y., Kim K., et al. Ginsenoside Rc protects against UVB-induced photooxidative damage in epidermal keratinocytes. Mol Med Rep. 2017;16(3):2907–2914. doi: 10.3892/mmr.2017.6943. [DOI] [PubMed] [Google Scholar]
  • 21.Kang K.A., Piao M.J., Fernando P., Herath H., Yi J.M., Hyun J.W. Korean red ginseng attenuates particulate matter-induced senescence of skin keratinocytes. Antioxidants. 2023;12(8) doi: 10.3390/antiox12081516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Ngo H.T.T., Hwang E., Seo S.A., Yang J.E., Nguyen Q.T.N., Do N.Q., et al. Mixture of enzyme-processed Panax ginseng and Gastrodia elata extract prevents UVB-induced decrease of procollagen type 1 and increase of MMP-1 and IL-6 in human dermal fibroblasts. Biosci Biotechnol Biochem. 2020;84(11):2327–2336. doi: 10.1080/09168451.2020.1793657. [DOI] [PubMed] [Google Scholar]
  • 23.Park M.Y., Han S.J., Moon D., Kwon S., Lee J.W., Kim K.S. Effects of red ginseng on the elastic properties of human skin. J Ginseng Res. 2020;44(5):738–746. doi: 10.1016/j.jgr.2019.08.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Lee G.Y., Park K.G., Namgoong S., Han S.K., Jeong S.H., Dhong E.S., et al. Effects of Panax ginseng extract on human dermal fibroblast proliferation and collagen synthesis. Int Wound J. 2016;13(Suppl 1):42–46. doi: 10.1111/iwj.12530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Bauwens E., Parée T., Meurant S., Bouriez I., Hannart C., Wéra A.C., et al. Senescence induced by UVB in keratinocytes impairs amino acids balance. J Invest Dermatol. 2023;143(4):554–565.e9. doi: 10.1016/j.jid.2022.11.017. [DOI] [PubMed] [Google Scholar]
  • 26.Zoico E., Nori N., Darra E., Tebon M., Rizzatti V., Policastro G., et al. Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Sci Rep. 2021;11(1) doi: 10.1038/s41598-021-02544-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Lee S.H., Yang J.H., Park U.H., Choi H., Kim Y.S., Yoon B.E., et al. SIRT1 ubiquitination is regulated by opposing activities of APC/C-Cdh1 and AROS during stress-induced premature senescence. Exp Mol Med. 2023;55(6):1232–1246. doi: 10.1038/s12276-023-01012-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Hambright W.S., Mu X., Gao X., Guo P., Kawakami Y., Mitchell J., et al. The senolytic drug fisetin attenuates bone degeneration in the Zmpste24 (-/-) progeria mouse model. J Osteoporos. 2023;2023 doi: 10.1155/2023/5572754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Blander G., Bhimavarapu A., Mammone T., Maes D., Elliston K., Reich C., et al. SIRT1 promotes differentiation of normal human keratinocytes. J Invest Dermatol. 2009;129(1):41–49. doi: 10.1038/jid.2008.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Herranz D., Muñoz-Martin M., Cañamero M., Mulero F., Martinez-Pastor B., Fernandez-Capetillo O., et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun. 2010;1:3. doi: 10.1038/ncomms1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Lee H.J., Kim J.S., Song M.S., Seo H.S., Moon C., Kim J.C., et al. Photoprotective effect of red ginseng against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Phytother Res. 2009;23(3):399–403. doi: 10.1002/ptr.2640. [DOI] [PubMed] [Google Scholar]
  • 32.Hwang E., Sun Z.W., Lee T.H., Shin H.S., Park S.Y., Lee D.G., et al. Enzyme-processed Korean red ginseng extracts protects against skin damage induced by UVB irradiation in hairless mice. J Ginseng Res. 2013;37(4):425–434. doi: 10.5142/jgr.2013.37.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Park N.J., Bong S.K., Lee S., Jung Y., Jegal H., Kim J., et al. Compound K improves skin barrier function by increasing SPINK5 expression. J Ginseng Res. 2020;44(6):799–807. doi: 10.1016/j.jgr.2019.11.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Kim E., Kim D., Yoo S., Hong Y.H., Han S.Y., Jeong S., et al. The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng. J Ginseng Res. 2018;42(2):218–224. doi: 10.1016/j.jgr.2017.03.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Jang I.S., Jo E., Park S.J., Baek S.J., Hwang I.H., Kang H.M., et al. Proteomic analyses reveal that ginsenoside Rg3(S) partially reverses cellular senescence in human dermal fibroblasts by inducing peroxiredoxin. J Ginseng Res. 2020;44(1):50–57. doi: 10.1016/j.jgr.2018.07.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Lee J.O., Hwang S.H., Shen T., Kim J.H., You L., Hu W., et al. Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes. J Ginseng Res. 2021;45(2):354–360. doi: 10.1016/j.jgr.2020.12.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Ahn H., Han B.C., Hong E.J., An B.S., Lee E., Lee S.H., et al. Korean red Ginseng attenuates ultraviolet-mediated inflammasome activation in keratinocytes. J Ginseng Res. 2021;45(3):456–463. doi: 10.1016/j.jgr.2021.02.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Choi W., Cho J.H., Park S.H., Kim D.S., Lee H.P., Kim D., et al. Ginseng root-derived exosome-like nanoparticles protect skin from UV irradiation and oxidative stress by suppressing activator protein-1 signaling and limiting the generation of reactive oxygen species. J Ginseng Res. 2024;48(2):211–219. doi: 10.1016/j.jgr.2024.01.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Li Z., Jiang R., Wang M., Zhai L., Liu J., Xu X., et al. Ginsenosides repair UVB-induced skin barrier damage in BALB/c hairless mice and HaCaT keratinocytes. J Ginseng Res. 2022;46(1):115–125. doi: 10.1016/j.jgr.2021.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Multimedia component 1
mmc1.docx (16.8KB, docx)

Articles from Journal of Ginseng Research are provided here courtesy of Elsevier

RESOURCES