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Applied Biological Chemistry
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Chikusetsusaponin IVa from Dolichos lablab Linne attenuates UVB-induced skin photoaging in mice by suppressing MAPK/AP-1 signaling

Applied Biological Chemistry volume 67, Article number: 79 (2024) Cite this article

Abstract

Ultraviolet-B (UVB) radiation-induced photoaging of the skin is characterized by amplified expression of matrix metalloproteinase-1 (MMP-1) and reduced collagen fibers, both of which contribute to skin wrinkle formation. Edible natural products can protect against skin photoaging. Here, we investigate the protective effect of Dolichos lablab Linne (DLL) water extract against UVB radiation-prompted skin damage and attempt to uncover its fundamental mechanisms in human keratinocytes (HaCaT) and HR-1 hairless mouse. We found DLL extract rescued the reduction in cell viability associated with UVB exposure without any associated cytotoxic effects. It also protected against skin photoaging by inhibiting mitogen-activating protein kinase (MAPK) signaling, thereby preventing the UVB-associated increase in MMP-1 and -9 expression. DLL extract also increased the expression of both superoxide dismutase 1 (SOD1) and catalase (CAT). We identified chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A as bioactive components of DLL. Although we have not yet identified the mechanisms by which these compounds reduce the effects of photoaging, we have demonstrated that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce MMP-1, MMP-9, p–c-Fos, and p–c-Jun expression, while also avoiding any cytotoxicity. We found oral administration of DLL extract effectively alleviated dorsal epidermal thickening and skin dehydration in HR-1 hairless mouse visible to UVB. DLL extract also prevents UVB-induced activation of the MAPK/AP-1 signaling pathway, thereby reducing the expression of MMPs in dorsal mouse skin. Our results indicate that chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A are bioavailable components of DLL extract that can reduce UVB-induced skin damage via MMPs by deactivating the MAPK/AP-1 signaling pathway. These findings suggest DLL extract can be used as a skin anti-photoaging agent.

Introduction

The skin is the main tissue of the human body and acts as an essential barrier against chemical damage, infection, and ultraviolet radiation. Skin aging occurs via both substantial and external mechanisms. Substantial aging, which occurs inevitably over time is affection by genetic issues. Extrinsic aging, in contrast, is triggered by harmful environmental factors like ultraviolet (UV) radiation exposure, air pollution, and smoking [1]. Especially skin aging induced by ultraviolet B (UV-B) radiation leads to wrinkling, pigmentation changes, and increased roughness secondary to changes in keratinocytes and fibroblasts [2]. UV-B radiation penetrates the skin and promotes the formation of reactive oxygen species (ROS), generating skin inflammation. In ref. [3] via hyperactivation of the mitogen-activated protein kinase (MAPK) pathway in cooperate with activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB) [4]. The increase in UV-B-induced ROS also induces matrix metalloproteinase (MMP) expression. The increased MMP levels associated with photo-damage cause degeneration of several extracellular matrix (ECM) components, for example elastin, hyaluronic acid (HA), and collagen, leading to wrinkle formation [5,6,7]. In addition, UV-B induced ROS elevates the basal expression of MMPs released for increase of ECM degradation, as well as the obliteration of collagen fibers, and subsequently resulting in wrinkle formation. Amplified of MMPs demolish ECM apparatuses such as elastin, and hyaluronic acid (HA), resulting in considerable appearances of photo impairment of skin. Since various study have showed that nutritional supplementation can advance or detain skin aging [8], there is considerable attention in the development of safe and effective compounds of botanical origin that can restrain skin damage. Dolichos lablab L. (DLL), is a recognized as hyacinth bean part of the family Fabaceae, largely cultivate in southern Asia, and India. DLL seeds are used as food, but they are also reportedly effective against hypercholesterolemia and hepatoprotective in a mouse model [9, 10]. Besides DLL dried seeds and flowers can alleviated excessive dampness, enhanced the spleen, reduces diarrhea. These ingredients can be administered separately or combined with other herbal formulas to effectively treated and prohibit condition such as dysentery, diarrhea, and other connected diseases [11]. Some studies have described the chemical investigation on lablabosides derivatives and chikusetsusaponin IVa [12]. Also, luteolin-4ʹ-o-β-d-glucopyranoside, and rhoifolin from DLL flowers has been isolated [13]. Several medicines or chemical suggest to improve skin aging have difficulties, elevated prices, and side effects [14]. Increasing concern in the evolution of secure and available material from natural sources to restrain skin injury. In a current phytochemical investigation, we showed that a diversity of compounds isolated from DLL extracts act to reduce obesity in a high-fat diet (HFD) mouse model [15]. Among these compounds, chikusetsusaponin IVa reduced lipid accumulation and affected differentiation-related transcriptional factors in 3T3-L1 adipocytes [16]. The additional reported that chikusetsusaponin IVa, a component of DLL extract, enhanced lipopolysaccharide-induced amplified liver injury in mice [17]. Oral dosage of soyasaponin Bb, has been founds to remarkably reduce the inflammatory markers myeloperoxidase, lipid peroxide, pro-inflammatory cytokines and nuclear transcription factor kappa B (NF-κB) activation in the 3,4,5-trinitrobenzenosulfonic acid (TNBS)-induced colitic mice [18]. However, the role anti-photoaging mechanisms activity of DLL extract or active compounds chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A were skin has not yet been elucidated. In our work, for evaluating the molecular action for the beneficial effect of DLL extract or chikusetsusaponin IVa on HR-1 hairless mice model as well as HaCaT human keratinocytes cells under UV-B irradiation. We assessed the several factors photoaging to evaluate the DLL extract in epidermis thickness, HA, and skin hydration. In addition, we analyzed MMP-1, MMP-9, p38 and JNK but not ERKs, and AP-1 expression levels after treated to DLL extract and chikusetsusaponin IVa, soyasaponin Bb, sandosaponin A in skin cells. These finding suggest DLL extract and chikusetsusaponin IVa can be utilities as a skin anti-aging agent.

Material and methods

Preparation of Dolichos lablab L. (DLL) extract powder

Dolichos lablab L. (DLL) extract powder was obtained from a health food manufacturing company (NOVAponin; Lablab bean hot water extract power from NOVAWells Co. Ltd. Cheongju-si Korea) after being produced in a GMP facility. To prepare DLL extract powder, dried Dolichos lablab seeds were purchased from Ci One TRADING Co. Ltd (Myanmar) in 2019. Aried D. lablab (total 3312 kg) was extracted with distilled water (33,120 mL) for 3 ± 1 h at 95 ± 5 ℃. The unformed extract solution was filtered, concentrated under reduced pressure at 55 ℃, and then mixed with dextrin. The final product was pulverized by spray drying to yield 460 kg (dry weight) of DLL extract powder (13.8% w/w yield). This DLL extract powder was packed in vacuum-sealed aluminum foil pouches (15 kg/pouch) and stored at room temperature until use. The final DLL extract powder comprised 70% DLL extract and 30% dextrin.

Chromatographic system and parameters for profiling the DLL extract powder

Quantitative decision of chikusetsusaponin IVa, soyasaponin Bb, sandosaponin A in DLL extract was performed while using a high-performance liquid chromatography system (Agilent Technologies, Palo Alto, CA, USA) by using a C18 column (4.6 × 250 mm, 5 μm pore size; Phenomenex) in an Agilent 1290 HPLC equipped with an evaporative light scattering detector (ELSD) The mobile phase comprised of solvent A (0.1% trifluoroacetic acid in water) and solvent B (trifluoroacetic acid in acetonitrile). The gradient conditions appear in Table 1. The column temperature was maintained at 40 °C with a flow rate of 1.0 mL/min. The injection volume was 10 μL. The ELSD was utilized at a drift tube temperature and of 80 °C, and pressure nitrogen 50 psi, a gain setting of 10, and a gas flow rate of 1.20 SLM. Data were collected and analyzed using the OpenLab CDS 3.6 chromatography data software (Agilent Technologies, Palo Alto, CA, USA).

Table 1 Gradient conditions
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Cell culture and ultraviolet B (UVB) irradiation

Human epidermal keratinocytes (HaCaT), were purchased from Lonza (Walkersville, MD, USA). The cells were cultured in Dulbecco’s modified eagle’s medium (DMEM, Hyclone, Logan, UT, USA), added with 10% fetal bovine serum, streptomycin and penicillin in (1% antibiotics) in an atmosphere of 5% CO2 at 37 ℃ humidified incubator. After incubation, the cells were seeded and allowed to adhere for overnights and then cells were treated with DLL extract, chikusetsusaponin IVa, soyasaponin Bb, or sandosaponin A. Subsequently, the medium containing samples were removed by Dulbecco’s phosphate-buffered saline (DPBS) washing. The cells were reveals for 20 s to a 302 nm UVB light source (20 mJ/cm2) with a UVP cross linker (Ultra-Violet Products Ltd., Cambridge, UK). After PBS washing, the cells were replaced with fresh growth medium and incubation for another 24 h.

Determination cell viability

HaCaT cells (1 × 105) were seeded into 96-well plates and treated with differing consistency of DLL extract, chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A for 24 h. Cell viability was prepared as described previously [9]. The visual density was sustained by a microplate fluorimeter (Molecular Devices, Sunnyvale, CA) at 490 nm.

MMP-1 and MMP-9 secretion measured by ELISA

HaCaT cells were treated with DLL extract and washed with PBS. Then, they were exposed to a 302 nm UVB light source (20 mJ/cm2) for 20 s in the presence of a UVP cross linker. The quantification of MMP-9 and MMP-1 secreted in the culture media were measured via complete MMP-9, MMP-1 ELISA kits (R&D System, Minneapolis, MN, USA) respectively.

Western blotting

Total protein extracted from UV-B treated or UV-B plus DLL extract treated cells were arranged as described previously [15]. Also, mouse skin lysates were arranged as described previously [9]. Proteins were subjected to SDS-PAGE (4–20% gradient gel). After electro-transferred to polyvinylidene fluoride (PVDF) membranes. The resulting membranes were blocked solution (5% BSA) and then with the first antibodies against: anti-MMP-9, anti-MMP-1, anti-Catalase, anti-Superoxide dismutase-1 (SOD-1), anti-phospho c-Fos, anti-phospho c-Jun, anti-phospho-ERK, anti-phospho-MEK, anti-phospho-p38, anti-phospho-JNK, total form c-Fos, c-Jun, MEK, ERK, p38, JNK, and β-actin (Cell Signaling Technology, Danvers, MA, USA) for overnight at 4 ℃. The membranes were incubated with horseradish peroxidase-conjugated secondary antibodies for 45 min (Cell Signaling Technology) washed again for three times with TBST, and developed. The protein expression levels were visualized by LAS 4000 analyzer (GE Healthcare Life Sciences, BKM, England).

Animals

All proceeding including mouse were permitted by the Korea Institute of Oriental Medicine Institutional Animal Care and Use Committee (17–109). Six-weeks old male HR-1 hairless mice were obtained in Japan SLC, Inc. (Shizuoka, Japan) and housed in environment maintained at 23 ± 1 °C and humidity 50% under a light/dark 12: 12-h cycle. After the adjusted for (1 week), mice before the experiments with ad libitum access to food and water. Following the mouse were randomly separated into control, UVB-exposure and vehicle-treated, and UVB-exposure DLL extract-treated groups (n = 6 per group). The UVB-exposure DLL extract-treated group was given 0.1 ml of water containing (100 mg/kg per mouse) DLL extract by mouth (5 days a week for 12 weeks).

Mouse UVB irradiation

UVB irradiation was applied to the back of mice skin, the effect of oral DLL extract on the dorsal skin of UV-irradiated mouse. And then mice were reveals at 48-h intervals for 12 weeks using a UVM-225D Mineralight UV Display Lamp (UVP, Phoenix, AZ, USA). The weekly radiation dose per exposure was amplified progressively from 60 mJ/cm2 (one minimal erythematous dose = 60 mJ/cm2) in week 1 to 120 mJ/cm2 in week 9.

Measuring transepidermal water loss (TEWL) and capacitance

After UVB radiation, TEWL and capacitance was quantify using a Tewameter TM 300 and Corneometer (Courage and Khazaka Electronics, Cologne, Germany) instrument furnished with a probe placed on the back of mice surface.

Histology

The dorsal skin specimens were collected, fixed in 10% neutral buffered formalin, embedded in paraffin, sectioned at 5 μm, and the sections were stained with hematoxylin and eosin (H&E) for skin layers and Masson’s trichrome staining was utilized to visualize collagen fibers. Epidermal thickness was evaluated via light microscopy using an eyepiece micrometer (Olympus, Tokyo, Japan).

Statistical analysis

All data are presented in triplicate, and the data are attending as the means ± standard error of the mean (SEM). Statistical analysis was accomplished of variance (ANOVA), followed by Tukey’s tests for multiple comparisons to identify any significant differences between groups. A significance level of P < 0.05 was applied.

Results

Identification of active compounds in DLL extract

To empathize with the anti-photoaging activity of DLL extract, we first performed a chromatographic analysis using an HPLC/ELSD system with chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A standards. As shown in Fig. 1, we identified a sandosaponin A peak at 11.08 min, a chikusetsusaponin IVa peak at 12.8 min, and a soyasaponin Bb peak at 14.2 min. The DLL extract contained 0.44 ± 0.05% chikusetsusaponin IVa.

Fig. 1
figure 1

Identification of active compounds in DLL extracts. A High-performance liquid chromatography of chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A in DLL extract identified using an evaporative light-scattering detector (HPLC-ELSD). ↑, compared to the retention time and reference standards. B The chemical structures of chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A

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DLL extract on cell viability and UVB-induced secretion of MMP-1 and MMP-9

We next examined the cytotoxic effects of DLL on UVB-induced HaCaT cell damage using the MTS assay. After treating HaCaT cells for 24 h with DLL extract, they showed no cytotoxic effects, even at concentrations of up to 1000 μg/ml. In addition, UVB radiation exposure reduced cell viability to 59.25% in control cells but only to 90.50% in the presence of DLL extract (Fig. 2A and B). We also found that UVB irradiation increased the expression of MMP-1 and MMP-9 in HaCaT cells, but DLL extract counteracted this increase (Fig. 2C and D). These results indicate that DLL extract can protect against UVB-induced photo-aging.

Fig. 2
figure 2

The effects of DLL extract on the viability of UVB-induced HaCaT cells, as well their secretion of MMP-1 and MMP-9. A HaCaT cells pretreated with various concentrations of DLL extract for 24 h with and B without UVB radiation. C and D HaCaT cells were pretreated with various concentrations of DLL extract for 24 h prior to UVB irradiation. ELISA analysis of MMP-1 and MMP-9 levels in the culture media following UVB irradiation. ***P < 0.001, **P < 0.01, *P < 0.05 for comparisons with controls

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DLL extract on UVB-induced secretion of MMPs, antioxidant enzymes, and MAPK signaling in HaCaT cells

MMPs are endopeptidases that degrade collagen, and MMP overexpression is a crucial representative of photo-damaged skin [12, 13]. We found that DLL treatment reduced the increase in MMP-1 and -9 expression induced by UVB radiation (Fig. 3A). We also found that DLL increased the expression of catalase and SOD-1 in a dose-dependent manner, indicating that the radical scavenging activity induced by DLL is mediated by antioxidant enzymes (Fig. 3B). Next, we examined the ability of DLL extract to modify the effects of UVB radiation on MAPK signaling. We found that while UVB radiation induced ERK1/2, p38, and JNK phosphorylation, DLL treatment suppressed the activation of p38 and JNK, but not ERK (Fig. 3C). These data suggest DLL prevents UVB-induced skin damage by reducing activation of p38 and JNK signaling.

Fig. 3
figure 3

The effects of DLL extract on MMP-1, MMP-9, CAT, and SOD-1 protein levels and MAPK phosphorylation in UVB-induced HaCaT cells. A MMP-1 and MMP-9 levels. B Catalase and superoxide dismutase-1 levels. C MAPK phosphorylation levels. HaCaT cells were pretreated with various concentrations of DLL extract for 24 h prior to UVB irradiation. MMP-1, MMP-9, CAT, and SOD-1 protein levels and MAPK phosphorylation levels were determined by western blot analysis. **P < 0.01, *P < 0.05 for comparisons with controls

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Active compounds in DLL extracts inhibit the activation of AP-1 and MAPK signaling in HaCaT cells exposed to UVB light

UVB radiation activates AP-1 and the MAPKs that act upstream of AP-1 to accelerate MMP transcription [14]. To confirm the mechanism of UVB-induced skin damage inhibition through active compounds. We examined that the active compounds in DLL extracts lacked any cytotoxic effects at concentrations of up to 20 μg/ml (Fig. 4A). We also found UVB light stimulated MAPK signaling, and the active compounds chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A suppressed the phosphorylation of p38 and JNK, but not ERK (Fig. 4B). Moreover, chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A inhibited phosphorylation of the AP-1 subunits c-Fos and c-Jun and reduced MMP-1 and -9 levels more than treatment with retinoic acid (Fig. 4C and D).

Fig. 4
figure 4

The effects of chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A on UVB-induced HaCaT cell viability, MAPK and AP-1 signaling, and MMP-1 and MMP-9 production. A HaCaT cells were pretreated with various concentrations of chikusetsusaponin IVa, soyasaponin Bb, or sandosaponin A for 24 h. Cell viability was measured via MTS assay. B MAPK phosphorylation. C AP-1 signaling. HaCaT cells were pretreated with the indicated concentrations of chikusetsusaponin IVa, soyasaponin Bb, sandosaponin A, or retinoic acid (positive control) for 24 h. Then, they were exposed for 20 s to a 302 nm UVB light source (20 mJ/cm2). The cells were then washed with PBS and incubated in fresh growth medium for either 4 h or D 12 h. MMP-1 and MMP-9 protein levels were determined by western blot analysis. **P < 0.01 for comparisons with controls

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The effects of DLL extract on epidermal thickness and skin hydration in hairless UVB-irradiated mouse

To determine whether DLL protects skin from photoaging in vivo, we administered oral DLL extract to hairless mice and assessed the effects of a course of UVB radiation. We found evidence in H&E-stained skin sections that DLL protected the skin from UVB-induced epidermal changes. Using Masson’s trichrome staining, we found that DLL-treated skin showed higher collagen fiber density than vehicle-treated skin (Fig. 5A). DLL even reduced the effects of UVB on epidermal thickness, with the DLL-treated group averaging 42.9 μm compared to vehicle-treated group’s 52.6 μm (Fig. 5B). DLL extract also reduced TEWL induced by UVB, while also increasing the levels of stratum corneum and HA (Fig. 5C). These results indicate DLL extract increased skin hydration and reduced the damage normally correlated with increased TEWL.

Fig. 5
figure 5

The effects of DLL extract on UVB-induced skin thickening and hydration in hairless mice. A Hematoxylin and eosin staining and Masson’s trichrome staining of UVB-irradiated hairless mouse skin. Scale bar: 50 μm. Collagen fibers are blue. Images were obtained at a magnification of 400 ×. B Dorsal skin epidermal thickness, 400 × magnification C Trans-epidermal water loss, capacitance, and hyaluronan levels. #P < 0.05 for the comparisons with controls and *P < 0.05 for the comparisons with vehicle + UVB

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DLL extract prevents MAPK and AP-1 activation and MMP-1, -9 production in hairless UVB-treated mice

We next examined whether the effects of DLL extract on the MAPK signaling pathway in mice skin. We found UVB light induced the phosphorylation of ERK, MEK, p38, and JNK. DLL extract suppressed this effect, also effectively reducing the expression of the AP-1 subunits c-Fos and c-Jun (Fig. 6A and B). Consistent with these results, we found that DLL extract also reduced the production of MMP-1 and MMP-9 (Fig. 6C). Together, these results indicate DLL significantly reduces the UVB-induced expression of MMP-1 and -9 through the MAPK/AP-1 signaling pathway.

Fig. 6
figure 6

The inhibitory effects of DLL extract on MAPK and AP-1 protein levels, as well as MMP-1 and MMP-9 levels in UVB-irradiated hairless mice. A Phosphorylation of MAPK and B the AP-1 subunits c-Jun and c-Fos was measured via western blot analysis. C MMP-1 and MMP-9 protein levels in UVB-irradiated hairless mouse skin. #P < 0.05 for the comparisons with controls and *P < 0.05 for the comparisons with vehicle + UVB

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Discussion

Extrinsic aging refers to aging caused by extrinsic stimuli, such as environmental pollutants, UVB, or infectious agents [19, 20]. Photoaging, a form of extrinsic aging induced by repetitive exposure to UV radiation, is characterized by accelerated skin wrinkling [21]. In the dermis, reduced levels of collagen, elastic fibers, and HA disrupt the structure of the ECM, leading to the formation of fine wrinkles [22]. UVB exposure induces ROS generation, which provokes the skin damage progression [23]. Here, we examined the effects of an extract of DLL, a plant widely used for food and medicines in India and China, on UVB radiation-induced photoaging of the skin. This is the first study to evaluate the effects of water extracts of DLL. The active chemical components were glycosides, flavonoids, organic acid; Among them, Chikusetsusaponin IVa, rutin have significantly anti-inflammatory effects [24, 25]. Therefore, we suggested that the anti-photoaging effects of DLL extract on UVB-treated mice may be due to the multiple active compounds. In our results, we establish that DLL extract not only cytoprotective the UVB-induced cytotoxicity, but also inhibits the production of MMP-1 and MMP-9 in human epidermal keratinocytes (HaCaTs). DLL extract also enhances the activity of antioxidant enzymes (i.e., SOD and CAT) in scavenging free radicals, thereby inhibiting UVB-induced oxidative stress. UVB-induced ROS triggers many signaling cascades involving activate intracellular transcription factors such NF-κB, AP-1, and STATs, contributing to skin aging [7]. In addition, the collagen degradation associated with skin photoaging occurs downstream of the activation of several transcriptional factors, including NF-κB and AP-1 [26]. The AP-1 subunits c-Fos and c-Jun are triggered by various stimuli, contained UV radiation. Numerous studies that the transcription and activation of c-Fos and c-Jun depends largely on MAPK activation. This pathway also regulates the transcription of MMPs, which degrade collagen [27]. p38 and JNK respond strongly to inflammation and stress [28]. ERK signaling, in contrast, helps transmit growth signals, promoting cell growth and survival [29]. Thus, our results suggest that DLL extract seems to inhibit the UVB radiation-induced production of MMP-1 and MMP-9 in hairless mice by inhibiting p38 and JNK/AP-1 signaling pathway. Also, its potently diminished epidermis thickness, skin dryness and TEWL in mice’s dorsal skin. Natural byproduct extracts are a rich source of bioactive compounds that can affect physiological or cellular activities [1].

Several compounds in DLL extracts have been identified and associated with antioxidative and anti-obesity effects [9, 16]. Chikusetsusaponin IVa has anti-inflammatory activity [30] and antioxidant activity that can prevent UV-induced skin damage [31]. Also, Chikusetsusaponin V and Chikusetsusaponin IVa demonstrated that cardioprotective effects on myocardial ischemia injury model animals through reduced oxidative stress-triggered damage and cardiac cell death [32, 33]. In addition to Chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A were also showed to exhibits these anti-inflammation properties via NF-κB and MAPK signaling [34, 35]. Our studies found that active components chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A suppressed the phosphorylation of p38 and JNK signaling, the exact underlying mechanism by which chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A reduce inflammation awaits further studies. Several constitutes AHE were known and proved tis anti-photoaging effect [23]. For instance, β-sitosterol increased the expression of keratinocytes' loricrin, involucrin, and filaggrin, which are skin barrier proteins [36]. In present study, we newly described the effects of the DLL extract components chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A on skin photoaging. When chikusetsusaponin IVa, soyasaponin Bb, and sandosaponin A were treated UVB-irradiated human epidermal keratinocytes cells, its reduction in MMP-1 and MMP-9 expression achieved via the inhibition of the AP-1, JNK, and p38 pathways.

Recent studies have reported anti-aging, antioxidant, and antimicrobial effects following oral supplementation with natural molecules [31]. Eight weeks of oral supplementation with vitamin E increased its concentration in the skin and reduced the effects of UV radiation-induced skin damage [37]. Finally, our in vivo and in vitro experiments showed that oral administration of DLL extract blocked the aging effects of UVB radiation on skin, reducing epidermal thickness, increasing HA levels, and reducing TEWL in the dorsal skin of mice. In addition, DLL extract inhibited p38 and JNK/AP-1 signaling to reduce MMP-1 and MMP-9 expression in UVB-damaged skin. Together, our results suggest DLL extract as a promising candidate for use in preventing and alleviating skin photoaging.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by the Korea Ministry of SMEs and Startups (RS-2023-00223362) in the form of funding for a collaborative R&D project uniting industry and academia. And Korea Institute of Oriental Medicine (NVN2213090).

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Authors and Affiliations

  1. KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea

    Ki Mo Kim, A.-Rang Im, Ki-Shuk Shim & Sungwook Chae

  2. KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea

    Chang-Seob Seo

  3. REX PHARM TECH CO., LTD., 120 Heungdeokjugang-ro, Giheung-gu, Yongin-si, Gyeonggi-do, 16950, Republic of Korea

    Yongnam Lee, Jonghun Lee & Ji Seok Yoo

  4. Department of Bioinformatics and Biosystems, Seongnam Campus of Korea Polytechnics, Seongnam, Gyeonggi-do, Republic of Korea

    Sunga Choi

  5. Korean Convergence Medicine, University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea

    Ki Mo Kim & Sungwook Chae

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Contributions

Conceptualization, ARI; formal analysis, JL; investigation, KMK, ARI and JSY; writing—original draft preparation: KSS, CSS and YL; writing—review and editing: KMK and SC; funding acquisition: SC. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Ki Mo Kim or Sungwook Chae.

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All proceeding including mouse were reviewed and approved by the Korea Institute of Oriental Medicine Institutional Animal Care and Use Committee (approval number: 17-109).

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Kim, K.M., Im, AR., Shim, KS. et al. Chikusetsusaponin IVa from Dolichos lablab Linne attenuates UVB-induced skin photoaging in mice by suppressing MAPK/AP-1 signaling. Appl Biol Chem 67, 79 (2024). https://doi.org/10.1186/s13765-024-00934-2

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