PNExo™ Exosome-Garlic(PNE-VG07)

Garlic's Main Active Ingredients and Benefits

• Allicin: Exhibits broad-spectrum antimicrobial properties against bacteria, viruses, and fungi.
• Diallyl Disulfide and Trisulfide: Modulate immune responses and reduce inflammation.
• Organosulfur Compounds: Induce apoptosis in cancer cells and inhibit tumor growth.
• Selenium and Vitamin C: Enhance immune function and protect against infections.
• Various Compounds: Mitigate oxidative stress, contributing to cardioprotective effects. Improve blood pressure, cholesterol levels, and overall heart health.

What Are Garlic-Derived Exosomes?

Exosomes are nanosized vesicles (30-150 nm) secreted by cells that play crucial roles in cell communication. They carry proteins, lipids, and nucleic acids, facilitating the transfer of these molecules between cells. Garlic-derived exosomes are isolated from garlic. These exosomes encapsulate garlic's bioactive compounds, enhancing their stability and bioavailability. Garlic-derived exosomes can deliver their therapeutic payloads directly to target cells, making them an attractive tool for medical and cosmetic applications.

Garlic-derived exosomes ease acute liver failure by inhibiting CCR2/CCR5. (Zhao X, et al., 2023)

Applications of Garlic-Derived Exosomes

• Garlic-Derived Exosomes in Therapeutics

  1. Cancer Therapy
  One of the most promising applications of garlic-derived exosomes is in cancer treatment. Research has shown that garlic-derived exosomes can induce apoptosis in cancer cells by activating the caspase-mediated pathway. Caspases are enzymes that play essential roles in programmed cell death. By triggering these enzymes, garlic-derived exosomes help to selectively kill cancer cells without harming normal cells. Additionally, garlic-derived exosomes inhibit angiogenesis, and the formation of new blood vessels, which is crucial for tumor growth and metastasis.
  2. Neuroprotection
  Garlic-derived exosomes have shown potential in neuroprotection by interacting with brain acid soluble protein 1 (BASP1) in microglia through their phosphatidic acid content. This interaction inhibits the c-Myc/STING/IFNIDO1 inflammatory signaling cascade, reducing microglial inflammation and preventing nerve cell death. This mechanism suggests that garlic-derived exosomes could be valuable in treating neurodegenerative diseases and other conditions characterized by excessive inflammation and neuronal damage.
  3. Colitis Treatment
  Inflammatory bowel diseases (IBD), including colitis, may also benefit from GDE therapy. Studies in mice have demonstrated that garlic-derived exosomes ameliorate colitis via the TLR4/MyD88/NF-κB pathway and by modulating the intestinal microbiota. The ability of garlic-derived exosomes to regulate these pathways highlights their potential as a natural therapeutic option for managing IBD and maintaining gut health.
  4. Metabolic Health
  Garlic-derived exosomes contain a unique microRNA, miR-396e, which has been shown to modulate interactions between macrophages and adipocytes. This regulation of glycolytic enzyme genes reduces inflammation in adipocytes, highlighting a potential strategy for treating obesity-related inflammation. Furthermore, miR-396e also modulates interactions between macrophages and hepatocytes, alleviating high-fat diet-induced liver dysfunction and inflammation, indicating a role for garlic-derived exosomes in managing metabolic disorders.
  5. Anti-inflammatory Effects
  Garlic-derived exosomes have demonstrated the ability to inhibit the migration of monocytes to the liver and reduce macrophage infiltration, thus ameliorating inflammatory outbreaks. This anti-inflammatory effect is primarily achieved by inhibiting CCR2/CCR5 signaling pathways, offering a novel approach to managing chronic inflammatory conditions.

• The Diagnostic Applications of Garlic-Derived Exosomes

  Exosomes are increasingly being explored as diagnostic tools due to their ability to carry disease-specific biomarkers. Garlic-derived exosomes, enriched with garlic's bioactive compounds, could serve as a novel diagnostic platform. By isolating and analyzing garlic-derived exosomes from bodily fluids, it might be possible to detect specific biomarkers associated with various diseases, leading to early and accurate diagnosis.

• Garlic-Derived Exosomes in Skin Care and Cosmetic Industry

  1. Anti-aging and Skin Rejuvenation
  The anti-inflammatory and antioxidant properties of garlic-derived exosomes make them suitable for skincare applications. These exosomes can help reduce oxidative stress and inflammation in the skin, which are major contributors to aging. By promoting cellular repair and rejuvenation, garlic-derived exosomes can help maintain youthful and healthy skin.
  2. Hair Growth Promotion
  Garlic-derived exosomes have been found to promote hair growth by upregulating key growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1) through the Wnt/β-catenin signaling pathway. This property makes garlic-derived exosomes a potential treatment for hair loss and related conditions.
  3. Wound Healing
  The ability of garlic-derived exosomes to modulate inflammatory responses and promote cellular regeneration can also be harnessed for wound healing. By enhancing the skin's natural repair mechanisms, garlic-derived exosomes can accelerate wound healing and improve skin health.

References

1. Zhao X, Yin F, Fu L, et al. Garlic-derived exosome-like nanovesicles as a hepatoprotective agent alleviating acute liver failure by inhibiting CCR2/CCR5 signaling and inflammation. Biomaterials Advances. 2023. 154: 213592.

Case study 1: Özkan İ, 2021

In this research, nanoscale extracellular vesicles originating from garlic were meticulously isolated and characterized through nanoparticle tracking analysis, electron microscopy, and the use of antibodies specific to the vesicle surface. In assessing their potential to combat cancer, cell lines of A498 human kidney carcinoma and A549 human lung carcinoma were employed as experimental models, alongside normal human dermal fibroblasts. Utilizing Annexin V/PI staining, coupled with an in-depth analysis of the expression levels of both apoptotic mRNA and proteins, it was observed that the garlic-derived exosomes triggered the intrinsic apoptotic cascade. Furthermore, the application of these vesicles notably diminished the expression of the angiogenesis-promoting VEGF protein in cancer cells. Notably, the garlic-derived exosomes specifically induced apoptotic cell death in cancerous cells, leaving the normal cells unharmed. This pioneering study presents evidence that plant exosomes are capable of initiating caspase-mediated apoptosis, presenting a groundbreaking alternative for cancer therapy.

Figure 1. Garlic-derived exosomes have been shown to impact the cell cycle progression in A498 and A549 cancer cells, as demonstrated by flow cytometry. Treatment with these vesicles for 24 and 48 hours resulted in a significant increase in the proportion of cells in the S phase, while the number of cells in the G0/G1 phase notably decreased. This effect was less pronounced in HDF cells, suggesting that garlic exosomes selectively target the cell cycle of cancer cells, potentially contributing to their growth inhibition without significantly affecting normal dermal fibroblast cells.

Case study 2: Yuksel E I, 2023

This study explored the impact of garlic exosome (GE) on hair growth in rats, utilizing a controlled experimental design. The research involved the application of different concentrations of GE and measured various hair growth parameters and protein levels associated with hair follicle development. Results indicated that GE significantly increased the number of anagen follicles and follicle diameter, particularly in the higher concentration group. Furthermore, the study found that GE elevated the levels of proteins involved in hair growth pathways, such as Wnt-1, β-catenin, VEGF, PDGF, and TGF-β1, suggesting that GE promotes hair growth through these signaling mechanisms.

Figure 1. The influence of garlic exosome (GE) on the histological features of rat skin was assessed, with a focus on the quantity of anagen and telogen hair follicles, as well as the dimensions of hair follicles and the thickness of the epidermis, dermis, and subcutaneous layers. The dorsal skin samples from rats were examined under a microscope at 40x magnification after hematoxylin and eosin (H&E) staining.

Figure 2. The impact of garlic-derived exosomes on various proteins within the dorsal skin of rats was examined, specifically focusing on Wnt-1, β-catenin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor beta-1 (TGF-β1), and type I collagen, as depicted in the respective figure sections A through F. The optical densities from Western Blot analyses were quantified using densitometry. The results are presented as a ratio comparing the experimental group's values to those of the control group. Each Western Blot experiment was conducted a minimum of three times to ensure reliability, with β-actin serving as a reference protein. The graphical representation of the data displays the average values accompanied by their standard deviations. Statistically significant disparities between group averages are denoted by distinct alphabetical superscripts, signifying a p-value less than 0.05.

References

1. Özkan İ, Koçak P, Yıldırım M, et al. Garlic (Allium sativum)-derived SEVs inhibit cancer cell proliferation and induce caspase mediated apoptosis. Scientific Reports. 2021. 11(1): 14773.
2. Yuksel E I, Cicek D, Demir B, et al. Garlic exosomes promote hair growth through the Wnt/β-catenin pathway and growth factors. Cureus. 2023. 15(7).

• What is the typical yield of garlic-derived exosomes from a standard extraction process?

  The yield of garlic-derived exosomes can vary based on the extraction method and the starting material. Typically, our optimized protocols ensure a consistent yield suitable for research and development purposes.

• Can garlic-derived exosomes be tailored to target specific types of cancer cells?

  While garlic-derived exosomes naturally possess anti-cancer properties, we are exploring surface modifications and ligand attachments to enhance their specificity towards particular cancer cell types.

• How do you ensure the purity of the garlic-derived exosomes?

  We can use a combination of ultracentrifugation, size exclusion chromatography, and immunoaffinity capture techniques to ensure the high purity of garlic-derived exosomes, removing contaminants such as proteins and nucleic acids.

• What specific bioactive components are found within the garlic-derived exosomes?

  Garlic-derived exosomes contain a range of bioactive components, including various proteins, lipids, and nucleic acids. Notably, they carry microRNAs and proteins involved in apoptosis, angiogenesis inhibition, and immune modulation.

• How stable are garlic-derived exosomes during storage and transport?

  Garlic-derived exosomes are stable at -80°C for long-term storage. For transport, we recommend maintaining them at 4°C to -20°C to preserve their integrity and bioactivity.

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