Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents.

The skin is a multilayered and primary defensive organ. Intimate intercellular communication in the skin is necessary to ensure effective surveillance. Extracellular vesicles (EVs) are being explored for their involvement in intercellular skin communication. The aim of this study was to evaluate how human dermal fibroblasts (HDFs) accelerate EV production during senescence and the effects of senescence-associated EVs on epidermal homeostasis. Replicative senescent HDFs were assessed with senescence-associated β-galactosidase staining and the expression of senescence-related markers. Isolated EVs were characterized by dynamic light scattering and EV marker expression. EVs secreted from untreated young or senescent HDFs, or from those treated with a nSMase inhibitor, antioxidant, and lysosomal activity regulators, were determined by sandwich ELISA for CD81. Human epidermal keratinocytes were treated with young- and senescent HDF-derived EVs. Compared to young HDFs, senescent HDFs produced relatively high levels of EVs due to the increased nSMase activity, oxidative stress, and altered lysosomal activity. The nSMase inhibitor, antioxidant, and agents that recovered lysosomal activity reduced EV secretion in senescent HDFs. Relative to young HDF-derived EVs, senescent HDF-derived EVs were less supportive in keratinocyte differentiation and barrier function but increased proinflammatory cytokine IL-6 levels. Our study suggests that dermis-derived EVs may regulate epidermal homeostasis by reflecting cellular status, which provides insight as to how the dermis communicates with the epidermis and influences skin senescence.

Post-inflammatory hyperpigmentation (PIH) results from inflammatory responses that leave persistent dark spots around pores after acne lesions are resolved. This pigmentation is caused by increased melanogenesis in melanocytes stimulated by acne-causing bacteria, followed by phagocytosis of excess melanin by macrophages that remain in the dermis. Therefore, to eliminate PIH caused by acne, it is essential not only to suppress excessive melanin synthesis by melanocytes but also to promote the degradation of melanin retained within macrophages. In this study, we investigated whether a culture extract of Bacillus velezensis AmoreLumina (AL), containing more than 80% moranoline (1-Deoxynojirimycin), could inhibit acne-induced pigmentation. Moranoline reduces melanin synthesis by inhibiting the glycosylation of tyrosinase, a key melanogenic enzyme, thereby suppressing its activity. The extract suppressed the upregulation of melanogenic enzymes (tyrosinase, TRP1, and TRP2) and melanin production in melanocytes exposed to acne bacteria, while promoting melanin degradation via macrophage lysosomal activity, as assessed by the relative protein expression level of p62 using Western blotting. Furthermore, in an ex vivo human skin model subjected to acne and ultraviolet radiation-induced pigmentation, treatment with the extract (0.2%) significantly reduced pigmentation (relative delta L 2.98, p value < 0.01). These findings suggest that cosmetic or pharmaceutical formulations incorporating AL extract or moranoline may potentially improve PIH caused by acne-related inflammation.