Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0–2 × 10⁹ particles/mL), and followed by UVB irradiation or H₂O₂ exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C–O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H₂O₂, and the keratinocyte cells were treated with SYR (0–200 μg/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H₂O₂-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC₅₀ value of 10.77 and 10.35 μg/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H₂O₂-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. SYR showed antioxidant activity and up-regulated autophagy activity in H₂O₂-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

Ginseng is processed into several types such as white ginseng, red ginseng, and black ginseng, according to the processing methods such as drying, steaming, and heating. These processing conditions can change the portion of the useful ingredients. Recently, new processing method was established to develop ‘lymphanax’, an aged fresh white ginseng prepared under anaerobic condition. This aging process was revealed to increase the content of gypenoside 17 (Gyp17) as well as ginsenoside Re, known to have anti-inflammatory effects. As the next step, therefore, we aimed to investigate the anti-inflammatory activity of lymphanax using its ethanol extract of lymphanax (Lymphanax-EE). LC-MS/MS identified the ginsenoside content of lymphanax-EE. A nitric oxide (NO) assay revealed the anti-inflammatory activity of lymphanax-EE. Pro-inflammatory gene expression was analyzed by quantitative PCR. Finally, we identified the underlying mechanism for the anti-inflammatory activity of lymphanax-EE through luciferase analysis, Western blotting, and CETSA. The LC-MS/MS analysis revealed lymphanax-EE to contain more protopanaxatriol-type ginsenosides, and Gyp17 than fresh ginseng. Lymphanax-EE (0–200 μg/ml) suppressed NO release and mRNA levels of pro-inflammatory cytokines such as iNOS and COX-2 in LPS-treated RAW264.7 cells. Moreover, lymphanax-EE (200 μg/ml) reduced the activity of NF-κB and phosphorylation of NF-κB signal proteins such as p65, p50, IκBα, and IKKα/β. Finally, lymphanax-EE (200 μg/ml) decreased the phosphorylation of IKKα/β induced by AKT overexpression. Among the components of lymphanax-EE, ginsenoside Re and Gyp17 were found to suppress AKT1 activity. Lymphanax-EE-containing ginsenosides and Gyp17 with anti-inflammatory properties suppressed LPS-induced inflammation by reducing the NF-κB signal.

Grewia tomentosa Juss. is a deciduous shrub that mainly grows in Asia. Despite studies of other Grewia species for treatment of various diseases, Grewia tomentosa Juss. has not been studied as a medicinal herb. This study evaluates the anti-allergic and anti-topic dermatitis activity of Grewia tomentosa Juss. ethanol extract (Gt-EE). The results show that Gt-EE suppressed IgE–antigen-induced β-hexosaminidase release. The mRNA expression of IL-1β, IL-4, IL-5, IL-6, IL-13, TNF-α, MCP-1, and TSLP, which are involved in allergic responses, was inhibited by Gt-EE in IgE-stimulated RBL-2H3 cells. In addition, the phosphorylation of Syk, PLCγ1, PKCδ, PI3K, AKT, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2 was decreased by Gt-EE in these cells. Gt-EE also showed anti-inflammatory effects in in vivo mouse models. In passive cutaneous anaphylaxis (PCA), a commonly used mouse model, Gt-EE decreased the allergic response, infiltration of mast cells, and mRNA level of IL-4. Furthermore, Gt-EE ameliorated symptoms of DNCB-induced atopic dermatitis (AD). In DNCB-induced AD, Gt-EE suppressed the increase in mast cells, serum IgE level, expression of allergic mediators (IL-1β, IL-4, IL-5, IL-6, TNF-α), and phosphorylation of proteins (IκBα, NF-κB p65, NF-κB p50, p38, JNK, and ERK1/2) implicated in allergic reactions