PNExo™ Exosome-Mushroom(PNE-VM18)

The Benefits of Mushrooms

• Polysaccharides: Key components include polysaccharides, particularly beta-glucans, which are known for their immune-modulating effects. Beta-glucans stimulate the immune system by enhancing the activity of macrophages and natural killer cells, providing a defense against infections and possibly even cancer.
• Ergothioneine: Another crucial component is ergothioneine, an antioxidant amino acid found abundantly in mushrooms. Ergothioneine helps reduce oxidative stress, protecting cells from damage and slowing down the aging process.
• Triterpenoids: Another class of bioactives found predominantly in Reishi and Chaga mushrooms, have demonstrated anti-inflammatory, anti-tumor, and antioxidant properties. These compounds can help reduce inflammation, combat oxidative stress, and even inhibit the growth of cancer cells.
• Phenolic Compounds: These compounds in mushrooms offer potent antioxidant effects. They neutralize harmful free radicals, reducing oxidative stress and thereby lowering the risk of chronic diseases such as heart disease and diabetes.
• Additionally, mushrooms are rich in vitamins such as B vitamins and vitamin D2, which support metabolic function and bone health, respectively. Mushrooms also contain a variety of minerals, including selenium, potassium, and copper, which are essential for maintaining overall health.

What Are Mushroom-Derived Exosomes?

Mushroom-derived exosomes share similar structural features with their mammalian counterparts. They consist of a lipid bilayer that encases a cargo of bioactive compounds. These include polysaccharides, proteins, enzymes, and nucleic acids such as mRNA and miRNA.
The bioactive cargo within mushroom-derived exosomes is what truly sets them apart. These vesicles carry a concentrated version of the mushroom’s beneficial compounds. For example, the exosomes from Reishi mushrooms might be loaded with triterpenoids, while those from Shiitake could be rich in beta-glucans.

Shiitake exosomes' protective effect on acute liver injury in mice induced by D-Galactosamine and lipopolysaccharide. (Liu B, et al., 2020)

Applications of Mushroom-Derived Exosomes

• Medical Applications of Mushroom-Derived Exosomes

  One of the most promising areas is in medical therapeutics. Mushroom-derived exosomes could serve as natural, non-toxic drug delivery systems. Their small size allows them to navigate through the human body with ease, making them effective carriers of therapeutic agents.
  For instance, these exosomes can be engineered to deliver anti-cancer drugs directly to tumor cells, thereby increasing the efficacy of the treatment while reducing side effects. Similarly, their immune-modulating properties make them potential candidates for treating autoimmune diseases and boosting overall immunity.

• Mushroom-Derived Exosomes in Skin Care and Cosmetic Industry

  In the realm of beauty and skincare, mushroom-derived exosomes are making waves. Their antioxidant and anti-inflammatory properties can contribute to healthier, more youthful skin. Skincare products infused with these exosomes could offer benefits such as enhanced skin hydration, reduced inflammation, and even skin regeneration.

• Nutritional Supplements

  Mushroom-derived exosomes can also be incorporated into dietary supplements. Given their ability to encapsulate and protect bioactive compounds, these exosomes can enhance the bioavailability of nutrients, ensuring that our bodies absorb them more efficiently.

• Agricultural Uses

  Lastly, mushroom-derived exosomes could have applications in agriculture. They can be used to deliver natural pesticides or fertilizers, promoting sustainable farming practices. Their biocompatibility and non-toxic nature make them safe for the environment, offering a green alternative to chemical treatments.

References

1. Liu B, Lu Y, Chen X, et al. Protective role of shiitake mushroom-derived exosome-like nanoparticles in D-galactosamine and lipopolysaccharide-induced acute liver injury in mice. Nutrients. 2020. 12(2): 477.
2. Ling Y, Li X, Gao H, et al. Biyang floral mushroom-derived exosome-like nanovesicles: characterization, absorption stability and ionizing radiation protection. Food & Function. 2024.

Case study 1: Lu Y, 2019

A recent study has unveiled the potential of shiitake-derived exosome-like nanoparticles (S-ELNs) as novel therapeutic agents that exhibit a significant inhibitory effect on NLRP3 inflammasome activation, a critical pathway implicated in various inflammatory diseases. Through meticulous experimentation and analysis, the study demonstrated that S-ELNs, containing a complex mixture of RNAs, proteins, and lipids, could suppress the NLRP3 inflammasome's response to diverse stimuli, thereby reducing the secretion of pro-inflammatory cytokines like IL-1β. The identification of bioactive lipids within S-ELNs as key players in this process presents a promising avenue for future research and the development of targeted treatments for chronic inflammatory conditions.

Figure 1. Mushroom-derived ELNs suppressed the NLRP3 inflammasome's caspase-1 cleavage and IL-1β release. Macrophages were pre-treated with ELNs from various mushrooms for 16 hours, followed by LPS for 3 hours, and then FFA for 12 hours. The levels of caspase-1 and IL-1β were assessed by western blot and ELISA. Tubulin served as a loading control, and statistical significance was indicated by * P < 0.05 and ** P < 0.01. The treated groups (ELNs+LPS+FFA, white bars) are contrasted with the untreated control (LPS+FFA, black bar). The mushrooms tested include: A. White beach mushroom, B. Brown beach mushroom, C. King mushroom, D. White common mushroom, E. Brown common mushroom, and F. Shiitake mushroom.

Figure 2. S-ELNs inhibited NLRP3 inflammasome activation by diverse stimuli. A. Alum-induced NLRP3 was suppressed by S-ELNs in LPS-primed BMDMs followed by 5h Alum exposure. B. Nigericin-induced NLRP3 was inhibited by S-ELNs in LPS-primed BMDMs after 30 min nigericin treatment. C. ATP-induced NLRP3 was mitigated by S-ELNs in LPS-primed BMDMs post 30 min ATP exposure. Tubulin served as a loading reference. Statistical significance indicated by * P < 0.05; ** P < 0.01, comparing treated (S-ELNs+LPS+stimuli, white bar) with control (LPS+stimuli, black bar).

Case study 2: Liu B, 2020

Researchers have discovered that exosome-like nanoparticles (ELNs) derived from shiitake mushrooms possess significant anti-inflammatory properties, offering a potential therapeutic strategy for fulminant hepatic failure (FHF). It was found that these nanoparticles, designated as S-ELNs, effectively inhibit the activation of the NLRP3 inflammasome, a critical component in the inflammatory response associated with FHF. The research involved the extraction and characterization of ELNs from seven common edible mushrooms, with shiitake-derived ELNs demonstrating the ability to suppress NLRP3 inflammasome activation and reduce the secretion of interleukin-6 (IL-6). In an experimental model, mice pre-treated with S-ELNs exhibited reduced liver damage when subjected to D-galactosamine and lipopolysaccharide-induced acute liver injury, indicative of the protective role of S-ELNs in liver pathology.

Figure 1. Characterization of mushroom-derived exosome-like nanoparticles (ELNs). (A) Comparative sizes of ELNs from various mushroom species. (B) Comparative yields of ELNs from different mushrooms. (C) SEM images of shiitake mushroom ELNs at two magnifications: 20,000× (main) and 50,000× (inset). (D) RNA size determination from ELNs using agarose gel electrophoresis, with and without RNase treatment. (E) Protein composition of ELNs visualized by Coomassie blue staining on Bis-Tris gels. (F) Lipid profile of ELNs revealed by TLC, with lipids detected using a CuSO4 solution.

Figure 2. S-ELNs inhibition of NLRP3 inflammasome and cytokine release. (A) IL-1β levels after S-ELNs pre-treatment and LPS+FFA activation. (B) IL-18 levels under the same conditions. (C) LDH release as a measure of cell damage. (D) IL-6 levels following S-ELNs and LPS+FFA exposure. (E) TNFα levels in response to the same stimuli. (F) Immunoblot detection of Casp1 p10 in lysates from cells activated by LPS+FFA or LPS+DNA.

References

1. Lu Y. Inhibitory effects of Shiitake-derived exosome-like nanoparticles on NLRP3 inflammasome activation. 2019.
2. Liu B, Lu Y, Chen X, et al. Protective role of shiitake mushroom-derived exosome-like nanoparticles in D-galactosamine and lipopolysaccharide-induced acute liver injury in mice. Nutrients. 2020. 12(2): 477.

• What types of mushrooms are used to derive the exosomes?

  We source our exosomes from a variety of medicinal mushrooms known for their health benefits, including but not limited to Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes), and Maitake (Grifola frondosa). Each type offers unique bioactive profiles.

• How do you ensure the consistency and quality of the mushroom exosome batches?

  We ensure consistency and quality through stringent quality control protocols, which include assessments of size, concentration, purity, and bioactivity. Each batch undergoes characterization using cutting-edge techniques like NTA (Nanoparticle Tracking Analysis) and Western Blot.

• Are there any specific storage conditions required for maintaining the stability of mushroom exosomes?

  Yes, to maintain the stability and functionality of our mushroom exosomes, it is recommended to store them at -80°C. Thawing should be done minimally to prevent degradation, and repeated freeze-thaw cycles should be avoided.

• Can I receive any technical documentation or data sheets along with the product?

  Yes. Each order of mushroom exosomes comes with detailed technical documentation, including data sheets that provide information on the isolation process, characterization data, and suggested usage protocols. Additional support documents can be provided upon request.

• Can you customize mushroom exosomes for specific research needs?

  Yes, we offer customization services where we can modify the cargo of the mushroom exosomes based on your specific research requirements. This can include incorporating particular proteins, nucleic acids, or other bioactive molecules.

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