PNExo™ Exosome-Ginger(PNE-VG33)

What Are Ginger-Derived Exosomes?

• The Nano-Dimension of Ginger-Derived Exosomes

  Ginger-derived exosomes are typically sized between 50 and 200 nanometers, aligning with the dimensions of exosomes from various origins. This nano-scale dimension facilitates their interaction with cell membranes and the delivery of their cargo to target cells effectively.

• Bioactive Richness of Ginger-Derived Exosomes

  Ginger-derived exosomes are rich in a variety of bioactive molecules. They contain lipids, proteins, and nucleic acids that are common to plant exosomes, as well as proprietary active components unique to ginger, such as gingerols and shogaols. These compounds contribute to the exosomes' therapeutic potential. Additionally, the small RNAs encapsulated in ginger-derived exosomes play a crucial role in modulating the composition of gut microbes and their metabolites, inhibiting colitis in animal models, and maintaining a balance between immunity and gut microbes.

• Stability of Ginger-Derived Exosomes

  Ginger-derived exosomes are characterized by exceptional stability, rendering them ideal for a wide range of applications. Research indicates that these exosomes maintain their integrity when stored at 4°C for up to 25 days, preserving their initial characteristics. Their resilience in conditions that simulate gastric and intestinal fluids is crucial for their potential use in oral therapies and other biomedical applications. This enduring stability ensures the longevity and effectiveness of the bioactive components within, thereby amplifying their therapeutic efficacy.

Illustration of ginger-derived exosome bioactive components. (Zhu H, et al., 2023)

Applications of Ginger-Derived Exosomes

• Therapeutic Potential of Ginger-Derived Exosomes

  Ginger-derived exosomes have shown promise in several therapeutic areas due to their bioactive components and natural origin.
  1. Anti-Inflammatory Therapy
  The anti-inflammatory properties of ginger-derived exosomes are attributed to their bioactive lipid and protein content. These exosomes can modulate immune responses and reduce inflammation, making them potential candidates for treating inflammatory diseases such as arthritis, colitis, and cardiovascular diseases.
  2. Cancer Therapy
  Ginger-derived exosomes exhibit anticancer activities through the delivery of bioactive molecules that induce apoptosis and inhibit the proliferation of cancer cells. The presence of gingerols and shogaols in these exosomes enhances their ability to target and kill cancer cells while minimizing the side effects associated with conventional chemotherapy.

• Skin Care Applications of Ginger-Derived Exosomes

  The natural origin and bioactive properties of ginger-derived exosomes make them suitable for skin care products. They can enhance skin health by promoting collagen synthesis, reducing inflammation, and protecting against oxidative stress.
  1. Anti-Aging Effects
  Ginger-derived exosomes can stimulate the production of collagen and elastin, which are essential for maintaining skin elasticity and firmness. Their antioxidant properties help combat free radicals, reducing the appearance of fine lines and wrinkles.
  2. Wound Healing
  The anti-inflammatory and antimicrobial effects of ginger-derived exosomes can accelerate the wound healing process. They promote tissue regeneration and reduce the risk of infections, making them beneficial for treating cuts, burns, and other skin injuries.
  3. Skin Protection
  Ginger-derived exosomes can protect the skin from environmental damage, such as UV radiation and pollution. Their bioactive components help strengthen the skin barrier and enhance its resilience against external stressors.

References

1. Yin L, Yan L, Yu Q, et al. Characterization of the microRNA profile of ginger exosome-like nanoparticles and their anti-inflammatory effects in intestinal Caco-2 cells. Journal of Agricultural and Food Chemistry. 2022. 70(15): 4725-4734.
2. Zhu H, He W. Ginger: a representative material of herb-derived exosome-like nanoparticles. Frontiers in Nutrition. 2023. 10: 1223349.

Case study 1: Li Z, 2018

A recent investigation harnessed the arrangement of RNA to adorn human exosomes with ligands that target specific cells, facilitating the delivery of siRNA directly to cancer cells. Building upon this concept, scientists have now employed ginger-derived exosomes (GDENs), adorned with arrowtail RNA nanoparticles, to facilitate the targeted delivery of siRNA and to suppress tumor growth following intravenous injection. Isolated through a combination of cushion and equilibrium density gradient ultracentrifugation techniques, these GDENs have shown properties akin to those of exosomes derived from human sources. By integrating folic acid (FA) onto the GDENs, they have been able to direct survivin siRNA specifically to KB cancer cells. The FA-3WJ/GDENs/siRNA complex has demonstrated equivalent in vitro gene silencing effectiveness to conventional transfection techniques and has notably curbed tumor progression in a transplanted tumor model. This underscores the potential of GDENs as an economical and potent system for the delivery of siRNA.

Figure 1. Confocal microscopy was utilized to assess the binding and internalization efficiency of FA-pRNA-3WJ arrowtail and arrowhead-modified GDENs in KB cells that exhibit an elevated expression of folate receptors. The cellular imaging captured distinct fluorescent signals representing the nucleus (colored blue), the cytoplasm (rendered in green), and the Alexa647-tagged RNA encapsulated within the GDENs (displayed in red).

Figure 2. Targeting and siRNA delivery to cancer cells by GDENs with specific ligands were assessed. (A) Flow cytometry was used to determine the targeting efficiency, which increased with the concentration of FA-modified RNA. (B) The delivery of survivin siRNA to KB cells was confirmed through qRT-PCR, with mRNA levels normalized to the PBS control set at 1. Data are expressed as mean ± S.D. and represent fold changes relative to the control. Statistical analysis was performed using one-way ANOVA with Tukey’s post-test. The comparison between FA-modified GDENs and the other groups showed p-values of >0.9999 for transfection, 0.9174 for unmodified GDENs, and <0.0001 for the scrambled control (indicating a significant difference, denoted by ****).

Case study 2: Chen X, 2019

A recent study has investigated the ability of food-derived nanoparticles, similar to exosomes, to reduce the activity of the NLRP3 inflammasome, which is crucial in diseases like Alzheimer's and type 2 diabetes. Researchers tested these nanoparticles from nine types of fruits and vegetables on primary immune cells, called macrophages. They found that nanoparticles from ginger root, known as ginger-derived exosomes, effectively decreased the activation of the NLRP3 inflammasome. These ginger exosomes, which are rich in lipids, proteins, and RNA, were well absorbed by macrophages and stopped several processes, including the activation of caspase-1, the release of inflammatory proteins like IL-1β and IL-18, and a type of cell death called pyroptosis. The lipids in ginger exosomes were identified as the main contributors to this effect. By preventing the formation of the NLRP3 inflammasome, ginger exosomes have shown promise as a treatment. The study suggests that ginger exosomes could be developed into treatments for diseases related to abnormal NLRP3 inflammasome activity, due to their ability to protect important molecules and keep them available in tissues.

Figure 1. Ginger-derived exosomes effectively suppressed the secretion of IL-1β and IL-18, which are mediated by the NLRP3 inflammasome, as well as the occurrence of pyroptosis. In part (A), the ginger-derived exosomes were found to prevent the release of both IL-1β and IL-18. However, as depicted in part (B), they did not exert a significant influence on the secretion of IL-6 and TNFα. Part (C) illustrates the inhibitory effect of ginger-derived exosomes on pyroptosis. Bone marrow-derived macrophages (BMDMs) were exposed to ginger-derived exosomes for a duration of 16 hours prior to the induction of the NLRP3 inflammasome via LPS and ATP. Subsequently, the supernatant from the cell culture, devoid of cells, was harvested for the quantification of IL-1β, IL-18, IL-6, TNFα, and LDH. The LDH release assay was conducted using a medium that contained 5% FBS. A comparison was made against a control group of BMDMs that were only treated with LPS, which was indicative of the absence of inflammasome activation. Statistical significance is denoted by * for p values less than 0.05 and ** for p values less than 0.01, with reference to the BMDMs that were subjected to both LPS and ATP (represented by the black bar).

Figure 2. Ginger-derived exosomes were found to suppress the activation of the NLRP3 inflammasome in response to various triggers, yet they did not impact the autocleavage of Casp1 during AIM2 inflammasome activation. Specifically, (A) the ginger-derived exosomes effectively curtailed the NLRP3 inflammasome's response to stimuli such as nigericin and alum. In contrast, (B) there was no discernible influence on the AIM2 inflammasome's ability to mediate Casp1 autocleavage. BMDMs were pre-treated with a concentration of 3 × 10^10/mL ginger-derived exosomes for a period of 16 hours, after which they were subjected to the activation of either the NLRP3 or AIM2 inflammasome. Statistical significance, indicated by * for p values below 0.05 and ** for p values below 0.01, was determined in comparison to macrophages that were primed with LPS and subsequently exposed to different stimuli (represented by the black bar).

References

1. Li Z, Wang H, Yin H, et al. Arrowtail RNA for ligand display on ginger exosome-like nanovesicles to systemic deliver siRNA for cancer suppression. Scientific Reports. 2018. 8(1): 14644.
2. Chen X, Zhou Y, Yu J. Exosome-like nanoparticles from ginger rhizomes inhibited NLRP3 inflammasome activation. Molecular Pharmaceutics. 2019. 16(6): 2690-2699.

• What are the main bioactive components present in ginger-derived exosomes?

  Ginger exosomes contain a variety of bioactive molecules such as gingerols, shogaols, lipids, proteins, and RNAs. These components contribute to their therapeutic properties, including anti-inflammatory, antioxidant, and potentially anticancer effects.

• What methods are used to isolate and purify ginger exosomes, ensuring their quality and bioactivity?

  We employ advanced techniques like ultracentrifugation and density gradient centrifugation to isolate and purify ginger exosomes. These methods ensure that the exosomes maintain their structural integrity and bioactivity, critical for their efficacy.

• Are there specific applications or therapeutic areas where ginger exosomes have shown particular promise?

  Ginger exosomes show promise in anti-inflammatory therapies, skin care, and potentially cancer treatment due to their ability to modulate immune responses and deliver bioactive compounds effectively.

• Can your ginger exosomes be used for in vivo studies?

  Yes, our ginger exosomes are suitable for in vivo studies. They exhibit excellent biocompatibility and low immunogenicity.

• Are your ginger exosomes customized for specific research applications?

  Yes, we offer customized ginger exosome products tailored to specific research applications. Whether you are interested in targeted drug delivery, immune modulation, or other therapeutic areas, our team can modify the exosomes to suit your specific needs, including surface modification and cargo loading.

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