F. Ginseng (Panax ginseng) is planted in the forest to enhance the natural ginseng resources, which have an immense medicinal and economic value. The morphology of the cultivated plants becomes similar to that of wild growing ginseng (W. Ginseng) over the years. So far, there have been no studies highlighting the physiological or functional changes in F. Ginseng and its wild counterparts. In the present study, we used proteomic technologies (2DE and iTRAQ) coupled to mass spectrometry to compare W. Ginseng and F. Ginseng at various growth stages. Hierarchical cluster analysis based on protein abundance revealed that the protein expression profile of 25-year-old F. Ginseng was more like W. Ginseng than less 20-year-old F. Ginseng. We identified 192 differentially expressed protein spots in F. Ginseng. These protein spots increased with increase in growth years of F. Ginseng and were associated with proteins involved in energy metabolism, ginsenosides biosynthesis, and stress response. The mRNA, physiological, and metabolic analysis showed that the external morphology, protein expression profile, and ginsenoside synthesis ability of the F. Ginseng increased just like that of W. Ginseng with the increase in age. Our study represents the first characterization of the proteome of F. Ginseng during development and provides new insights into the metabolism and accumulation of ginsenosides.

The present study aimed to compare the relative abundance of proteins and amino acid metabolites to explore the mechanisms underlying the difference between wild and cultivated ginseng (Panax ginseng Meyer) at the amino acid level. Two-dimensional polyacrylamide gel electrophoresis and isobaric tags for relative and absolute quantitation were used to identify the differential abundance of proteins between wild and cultivated ginseng. Total amino acids in wild and cultivated ginseng were compared using an automated amino acid analyzer. The activities of amino acid metabolism-related enzymes and the contents of intermediate metabolites between wild and cultivated ginseng were measured using enzyme-linked immunosorbent assay and spectrophotometric methods. Our results showed that the contents of 14 types of amino acids were higher in wild ginseng compared with cultivated ginseng. The amino acid metabolism-related enzymes and their derivatives, such as glutamate decarboxylase and S-adenosylmethionine, all had high levels of accumulation in wild ginseng. The accumulation of sulfur amino acid synthesis-related proteins, such as methionine synthase, was also higher in wild ginseng. In addition, glycolysis and tricarboxylic acid cycle-related enzymes as well as their intermediates had high levels of accumulation in wild ginseng. This study elucidates the differences in amino acids between wild and cultivated ginseng. These results will provide a reference for further studies on the medicinal functions of wild ginseng.

Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

The tumor microenvironment (TME) plays a key role in promoting the initiation and progression of tumors, leading to chemoradiotherapy resistance and immunotherapy failure. Targeting of the TME is a novel anti-tumor therapeutic approach and is currently a focus of anti-tumor research. Panax ginseng C. A. Meyer (ginseng), an ingredient of well-known traditional Asia medicines, exerts beneficial anti-tumor effects and can regulate the TME. Here, we present a systematic review that describes the current status of research efforts to elucidate the functions and mechanisms of ginseng active components (including ginsenosides and ginseng polysaccharides) for achieving TME regulation. Ginsenosides have variety effects on TME, such as Rg3, Rd and Rk3 can inhibit tumor angiogenesis; Rg3, Rh2 and M4 can regulate the function of immune cells; Rg3, Rd and Rg5 can restrain the stemness of cancer stem cells. Ginseng polysaccharides (such as red ginseng acidic polysaccharides and polysaccharides extracted from ginseng berry and ginseng leaves) can regulate TME mainly by stimulating immune cells. In addition, we propose a potential mechanistic link between ginseng-associated restoration of gut microbiota and the tumor immune microenvironment. Finally, we describe recent advances for improving ginseng efficacy, including the development of a nano-drug delivery system. Taken together, this review provides novel perspectives on potential applications for ginseng active ingredients as anti-cancer adjuvants that achieve anti-cancer effects by reshaping the tumor microenvironment.