Abstract
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.
Highlights
IntroductionExtracellular vesicles (EVs) are heterogeneous in terms of their origins, sizes, and molecular compositions, they are classified into two major populations according to their biogenesis [2,3,4]
The ginseng root-derived extracellular vesicles (GrEVs) were located between 0.8 M and 2 M sucrose fractions after sucrose cushion ultracentrifugation, and this fraction was used to validate their biological effects in human skin cells
GrEVs revealed a closed spherical structure with diameter below 100 nm according to the cryo-electron microscopy (cryo-EM) and the bio-EM image analyses (Figure 1b,c) and showed an average diameter of 92.04 ± 4.85 nm and an average polydispersity index of 0.2 ± 0.02 based on dynamic light scattering (DLS) analysis (Figure 1d)
Summary
EVs are heterogeneous in terms of their origins, sizes, and molecular compositions, they are classified into two major populations according to their biogenesis [2,3,4]. These populations include (i) exosomes (30–100 nm in diameter) formed by inward budding of endosomal membranes during the maturation of multivesicular bodies (MVBs) and secreted upon MVB fusion with the plasma membrane and (ii) microvesicles (50–1000 nm in diameter) generated by the outward budding and fission of the plasma membrane
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