PNExo™ Exosome-Ginseng(PNE-VG63)

Benefits of Ginseng

Ginseng (Panax ginseng C.A. Meyer) is a well-known medicinal plant highly valued for its diverse pharmacological effects, supported by a wide array of bioactive constituents. The major functional components of ginseng include ginsenosides, polysaccharides, gintonin, peptides, and essential oils. These compounds have been extensively studied for their roles in modulating oxidative stress, immune responses, and cellular signaling pathways.

• Ginsenosides: These triterpenoid saponins, especially types like Rb1, Rg1, and Re, regulate inflammation by inhibiting NF-κB/MAPK signaling and enhance antioxidant defenses via Nrf2 activation. Some also support vascular function and cellular protection in oxidative models.
• Polysaccharides: Ginseng polysaccharides stimulate macrophages, promote lymphocyte proliferation, and modulate immune responses, making them valuable in immunological research.
• Gintonin: A lysophosphatidic acid-containing complex, gintonin activates LPA receptors and influences calcium signaling, with reported effects on neural activity and memory-related pathways.
• Peptides and Oils: Minor components like peptides and essential oils contribute to antioxidant effects and cellular energy balance, supporting ginseng’s broad-spectrum bioactivity.

What Are Ginseng-Derived Exosomes?

Ginseng-derived exosomes (GDEs) are nano-sized extracellular vesicles (typically 60-200 nm) isolated from ginseng roots or cultured ginseng cells. Structurally enclosed by a lipid bilayer, these vesicles carry a cargo of proteins, RNAs, and other bioactive molecules. GDEs exhibit spherical morphology, a negatively charged surface, and high structural stability, maintaining integrity for up to 90 days under appropriate conditions.

Isolation of GDEs is commonly achieved through ultracentrifugation combined with sucrose gradient purification or polymer-based precipitation methods such as the ExoQuick system, which improves purity significantly. Characterization techniques including dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA) are used to assess their size distribution, morphology, and particle concentration.

Enhanced Ginseng Exosome Purity via Combined Ultracentrifugation and ExoQuick Isolation. (A) Ginseng exosomes were isolated using a hybrid ultracentrifugation (UC) and ExoQuick (EQ) approach. The arrow marks the exosome-rich layer, and the arrowhead marks the final pellet. (B) Cryo-TEM images confirm morphology of exosomes isolated by the UC+EQ method. (C) NTA shows vesicle distribution predominantly in the 50-150 nm range. (D) Quantitative results show improved exosome yield and purity via UC+EQ. (E-G) Comparison of UC, EQ, and UC+EQ methods demonstrates that the combination method yields significantly higher purity. (Jang J, et al., 2023)

Advantages of Panax Ginseng Exosomes

• Excellent biocompatibility: Composed primarily of sphingolipids and phosphatidic acids, GDEs exhibit lower cytotoxicity compared to crude ginseng extracts.
• Enhanced stability: Resistant to enzymatic degradation, making them suitable for oral administration and long-term storage.
• Targeted delivery potential: Naturally capable of delivering cargo to specific cell types, including intestinal stem cells, and crossing biological barriers such as the skin and blood-brain barrier.
• Efficient bioactive compound loading: Able to encapsulate ginsenosides (e.g., Rg1), prolonging their half-life and improving bioavailability in cellular models.

Potential Applications of Ginseng Exosomes

Ginseng-derived exosomes (GDEs) have gained increasing attention for their potential roles in diverse biomedical research areas due to their natural origin, biocompatibility, and efficient delivery capabilities. Current studies have explored their applications in the following areas:

Ginseng Exosomes for Skin Health and Anti-Aging

GDEs have shown potential in mitigating UVB-induced inflammation by downregulating pro-inflammatory cytokines such as IL-1β and TNF-α. They also help restore epidermal differentiation and reduce markers of cellular senescence (e.g., β-galactosidase) in dermal fibroblasts, contributing to anti-aging and skin-brightening effects.

Ginseng Exosomes in Inflammatory Disease Modulation

In models of inflammatory bowel disease (IBD), GDEs enhance intestinal barrier function and reduce mucosal inflammation by suppressing cytokines like TNF-α. Additionally, ginsenoside Rg6-loaded exosomes have been shown to inhibit NF-κB/MAPK signaling pathways, demonstrating promise in experimental arthritis models.

Ginseng Exosomes for Neuroregeneration and Cancer Research

Exosomes carrying ginsenoside Rg1 have been reported to support neuronal survival and reduce oxidative stress following spinal cord injury. As drug delivery vehicles, GDEs can also encapsulate natural compounds such as curcumin or paclitaxel, improving tumor penetration and minimizing systemic toxicity.

Emerging Uses of Ginseng Exosomes in Oral Delivery and Fibrosis

Due to their resistance to enzymatic degradation in the gastrointestinal tract, GDEs are being investigated as oral delivery platforms. Moreover, preliminary studies suggest anti-fibrotic potential through the inhibition of hepatic stellate cell activation in liver fibrosis models.

References

1. Chen H, Yang H, Fan D, et al. The anticancer activity and mechanisms of ginsenosides: an updated review. eFood. 2020, 1(3): 226-241.
2. Cho E G, Choi S Y, Kim H, et al. Panax ginseng-derived extracellular vesicles facilitate anti-senescence effects in human skin cells: an eco-friendly and sustainable way to use ginseng substances. Cells. 2021, 10(3): 486.
3. Jang J, Jeong H, Jang E, et al. Isolation of high-purity and high-stability exosomes from ginseng. Frontiers in Plant Science. 2023, 13: 1064412.
4. Seo K, Yoo J H, Kim J, et al. Ginseng-derived exosome-like nanovesicles extracted by sucrose gradient ultracentrifugation to inhibit osteoclast differentiation. Nanoscale. 2023, 15(12): 5798-5808.
5. Kim J, Zhang S, Zhu Y, et al. Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of inflammatory cytokines. Journal of Ginseng Research. 2023, 47(5): 627-637.
6. Choi W, Cho J H, Park S H, et al. Ginseng root-derived exosome-like nanoparticles protect skin from UV irradiation and oxidative stress by suppressing activator protein-1 signaling and limiting the generation of reactive oxygen species. Journal of Ginseng Research. 2024, 48(2): 211-219.
7. Kim J, Zhu Y, Chen S, et al. Anti-glioma effect of ginseng-derived exosomes-like nanoparticles by active blood–brain-barrier penetration and tumor microenvironment modulation. Journal of Nanobiotechnology. 2023, 21(1): 253.
8. Yang S, Lu S, Ren L, et al. Ginseng-derived nanoparticles induce skin cell proliferation and promote wound healing. Journal of Ginseng Research. 2023, 47(1): 133-143.
9. Yang S, Fan L, Yin L, et al. Ginseng exosomes modulate M1/M2 polarisation by activating autophagy and target IKK/IкB/NF-кB to alleviate inflammatory bowel disease. Journal of Nanobiotechnology. 2025, 23(1): 1-20.

Case Study 1: Ginseng-Derived Nanoparticles Promote Skin Regeneration (Yang S, 2023)

A recent study demonstrated that ginseng-derived nanoparticles (GDNPs), isolated from Panax ginseng roots and enriched with ginsenosides (15.8 mg/mg total), significantly enhanced skin cell activity. GDNPs were readily internalized by keratinocytes, fibroblasts, and endothelial cells, where they promoted proliferation, migration, and ECM secretion—including MMP-1, fibronectin-1, elastin-1, and COL1A1.

Mechanistic analysis revealed that GDNPs activated ERK and AKT/mTOR signaling, upregulating cyclins and downstream effectors like S6K and eIF4G. In a mouse wound model, topical GDNPs accelerated wound closure within 15 days, reduced inflammatory markers (e.g., NF-κB, iNOS), and increased expression of Ki-67 and TGF-β, supporting their potential as natural bio-nanocarriers for skin repair research.

Figure 1. GDNPs promote wound healing and angiogenesis. Representative scratch assay images show increased migration in HaCaT and HUVEC cells after 0, 24, and 48 hours of GDNP treatment at various concentrations. (C) Tube formation assay reveals enhanced capillary-like structure formation by HUVECs after 12 hours on Matrigel with 20 μg/mL GDNPs. Quantified data confirm a significant increase in tube formation compared to the control.

Figure 2. Therapeutic effect of GDNPs on skin wound healing in a mouse model. (A) Full-thickness excisional wounds on ICR mice treated daily with 10 mg/mL GDNPs or vehicle control. (B) H&E-stained skin sections show improved tissue morphology with GDNPs. (C) Western blot analysis reveals increased TGF-β and Ki-67 expression, and decreased NF-κB, iNOS, and COX-2 levels. (D) Quantitative analysis confirms accelerated wound closure.

Case Study 2: Ginseng-Derived Exosome-like Nanoparticles in Neurological Research (Kim J, 2023)

A recent study revealed the potential of ginseng-derived exosome-like nanoparticles (GENs) as bio-nanocarriers in neurological research. These vesicles, rich in phospholipids and bioactive molecules, demonstrated an ability to cross the blood-brain barrier (BBB) and accumulate in glioma tissue.

In both in vitro and in vivo glioma models, GENs significantly inhibited tumor progression and modulated the tumor microenvironment. Notably, they promoted the recruitment of M1-type macrophages and influenced tumor-associated immune cells, including T cells and regulatory T cells. These findings suggest that GENs may serve as effective tools for investigating immune regulation and targeted delivery within the central nervous system.

Figure 1. Apoptosis in C6 glioma cells and cellular uptake following treatment with GENs. (a) Annexin V/PI staining indicates dose-dependent apoptosis after 24 h of GEN exposure. (b) Cell viability significantly decreases with increasing GEN concentration. (c) Confocal images confirm internalization of DiD-labeled GENs (red) into C6 cells, with nuclei stained by Hoechst (blue). (d-e) Uptake of GENs increases over time, assessed by fluorescence imaging and efficiency quantification. (f) qPCR shows time-dependent upregulation of apoptosis-related genes at 24 and 48 h.

Figure 2. Brain-targeting efficiency of GENs in glioma models. (a) In vivo fluorescence imaging reveals time-dependent accumulation of DiD-labeled GENs, with conventional liposomes as controls. (b) Ex vivo imaging of major organs 24 h post-injection shows higher GEN fluorescence in the brain versus controls. (c) Quantitative ROI analysis indicates ~2.26-fold increase in brain fluorescence intensity with GENs. (d) GENs demonstrate significantly enhanced penetration into 3D tumor spheroids compared to conventional liposomes.

Case Study 3: Ginseng Exosomes Mitigate Intestinal Inflammation via Autophagy and Immune Modulation (Yang S, 2025)

A study demonstrated that ginseng-derived exosomes (GEs) alleviate inflammatory bowel disease (IBD) by promoting autophagy and modulating immune responses. Isolated GEs contained miRNAs targeting key inflammatory genes such as NF-κB and TNF-α. In vitro, GEs shifted macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype, increased IL-10 secretion, and reduced TNF-α and nitric oxide levels in co-cultured intestinal epithelial cells. These effects were autophagy-dependent and linked to suppression of the AKT/mTOR and IKK/IκB/NF-κB pathways. In vivo, orally administered GEs improved DSS-induced colitis in mice by reducing intestinal permeability, restoring tight junction proteins (ZO-1, occludin), and lowering inflammatory cytokine levels.

Figure 1. Histological and physiological evidence of the therapeutic effects of GEs on DSS-induced colitis in mice. (A) H&E staining shows reduced inflammatory infiltration and preserved tissue structure following GE treatment. (B) Intestinal length measurement indicates reduced tissue damage. (C) Disease activity index (DAI) and survival curves demonstrate improved clinical outcomes. (D-E) GE treatment downregulated IL-1β and upregulated IL-10 levels in intestinal tissue, indicating anti-inflammatory activity.

Figure 2. GEs protect the intestinal mucosa and restore epithelial barrier function in IBD mice. (A) Serum FITC-dextran levels indicating reduced intestinal permeability. (B) D-lactate levels reflecting improved mucosal integrity. (C) DAO levels in colon tissue and serum showing reduced barrier damage. (D-E) ELISA detection of 5-HT and SP demonstrating reduced neurogenic inflammation. (F) Immunofluorescence showing ZO-1 expression in intestinal tissue. (G) Western blot of occludin indicating restored tight junction proteins.

References

1. Yang S, Lu S, Ren L, et al. Ginseng-derived nanoparticles induce skin cell proliferation and promote wound healing. Journal of Ginseng Research . 2023, 47(1): 133-143.
2. Kim J, Zhu Y, Chen S, et al. Anti-glioma effect of ginseng-derived exosomes-like nanoparticles by active blood–brain-barrier penetration and tumor microenvironment modulation. Journal of Nanobiotechnology. 2023, 21(1): 253.
3. Yang S, Fan L, Yin L, et al. Ginseng exosomes modulate M1/M2 polarisation by activating autophagy and target IKK/IкB/NF-кB to alleviate inflammatory bowel disease. Journal of Nanobiotechnology. 2025, 23(1): 1-20.

• What makes ginseng exosomes different from animal-derived exosomes?

  Unlike animal-derived exosomes, ginseng exosomes come from plant sources, making them more sustainable, less immunogenic, and easier to scale. They are suitable for plant-based research models and may be preferred in cosmetic or nutraceutical development.

• What are Panax ginseng exosomes and how do they differ from ginseng extracts?

  Panax ginseng exosomes are tiny vesicles naturally released from ginseng roots or cultured cells. Unlike regular ginseng extracts that mainly contain soluble compounds like ginsenosides, these exosomes carry bioactive molecules such as RNA and proteins within a protective lipid shell. Their structure allows them to deliver these molecules directly into cells, making them useful in research and targeted delivery applications.

• What makes Panax ginseng and Panax quinquefolius different, and does it affect their exosome content?

  Ginseng species exhibit notable variations in ginsenoside profiles, influencing their physiological effects; Panax ginseng is generally associated with energizing properties, whereas Panax quinquefolius is recognized for its calming effects. These distinctions may impact exosome composition, including the specific small RNAs and proteins contained within. Consequently, to promote consistency and reliability, the majority of research endeavors employ exosomes derived from standardized Panax ginseng.

• What is exosome enrichment, and how does it apply to ginseng exosome production?

  Exosome enrichment refers to the process of purifying and concentrating exosomes from a biological source to increase their purity, yield, and functional integrity. In ginseng, this typically involves ultracentrifugation, polymer-based precipitation, or sucrose gradient separation. High-quality ginseng exosomes should undergo enrichment protocols to ensure minimal contamination and optimal activity for downstream applications.

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