PNExo™ Exosome-Blueberry(PNE-FB34)

Blueberry Extract Benefits

Blueberries are recognized for their dense concentration of bioactive compounds, including anthocyanins, flavonoids, phenolic acids, and essential vitamins such as C and E. These phytochemicals exhibit notable antioxidant properties, effectively neutralizing reactive oxygen species (ROS) and mitigating oxidative stress at the cellular level.

• Anthocyanins (e.g. Delphinidin, Cyanidin): The primary flavonoids in blueberries, anthocyanins exhibit strong antioxidant capacity by scavenging ROS, inhibiting lipid peroxidation, and modulating signaling pathways such as JAK/STAT-3, PI3K/AKT/NF-κB, and ERK/CREB/BDNF, contributing to cellular protection, neuroplasticity, and inflammation control.
• Polyphenols (e.g. Proanthocyanidins, Chlorogenic Acid): These compounds act synergistically with anthocyanins to enhance antioxidant defense, improve vascular reactivity, and reduce cardiovascular risk markers.
• Ascorbic Acid (Vitamin C): A well-known antioxidant that directly neutralizes free radicals, supports collagen synthesis, and protects cells against oxidative injury.
• Vitamin E (Tocopherols): Though in lower concentration than in seeds or oils, blueberries contain tocopherols that help stabilize cellular membranes and reduce lipid oxidation.
• Dietary Fiber (Soluble and Insoluble): Contributes to improved glycemic control, lipid metabolism, and supports gut microbiota balance, which may have downstream effects on inflammation and metabolic health.
• Micronutrients (e.g. Manganese, Vitamin K1): Essential for enzymatic antioxidant defense and metabolic processes including glucose regulation and bone metabolism.

What Are Blueberry-Derived Exosomes?

Blueberry-derived exosomes-like nanoparticles (BELNs) are nanoscale, lipid bilayer vesicles (30-200 nm) extracted from blueberries, structurally similar to mammalian exosomes. They carry bioactive molecules such as proteins, lipids, miRNAs, and anthocyanins, and are believed to mediate intercellular and cross-kingdom communication. Isolated via differential centrifugation and characterized by TEM, AFM, and FTIR, BELNs show high purity, abundant malvidin content, and unique protein markers like class I chitinase, making them promising candidates for natural nanocarrier research and plant-derived extracellular vesicle studies.

Transmission electron microscopy (TEM) image of blueberry-derived extracellular nanovesicles isolated at 40,000×g. The vesicles were negatively stained with phosphotungstic acid to visualize their morphology. (Nguyen T N G, et al., 2023)

Advantages of Blueberry-derived Exosomes-like Nanoparticles (BELNs)

• Enhanced Stability: The lipid bilayer structure protects anthocyanins and miRNAs from degradation, preserving bioactivity.
• Efficient Delivery: Their nanoscale size (~100 nm) and high cellular uptake promote effective transintestinal transport of active molecules.
• Excellent Biocompatibility and Safety: BELNs exhibit low immunogenicity, no cytotoxicity, and avoid ethical issues linked to mammalian exosomes.
• Enriched Content: They contain higher protein levels than milk- or cell-derived exosomes, including distinct pathogen-related proteins like PR-2 and PR-3.

Potential Applications of Blueberry-Derived Exosomes

Therapeutic Potential in Metabolic and Neurological Disorders

Blueberry-derived exosomes (BELNs) have demonstrated the ability to alleviate non-alcoholic fatty liver disease (NAFLD) by reducing mitochondrial oxidative stress, and may deliver anthocyanins to the brain to support neuroprotection in degenerative conditions such as Alzheimer's disease.

Blueberry Exosomes as Targeted Drug Delivery Carriers

With engineering modifications, BELNs can serve as biocompatible nanocarriers for chemotherapeutic agents, enhancing tumor targeting and therapeutic precision, similar to the mechanisms observed in mesenchymal stem cell-derived exosome models.

Cosmetic Applications for Anti-Aging and Skin Barrier Support

BELNs contribute to UV-induced skin damage repair by upregulating metallothioneins and inhibiting MMP-9 activity, while polyphenolic components support hydration, barrier integrity, and inflammation relief.

Functional Food Applications for Oral Delivery of Bioactives

Encapsulating anthocyanins into BELN-based oral formulations improves their gastrointestinal stability and bioavailability, paving the way for next-generation functional food supplements.

Emerging Roles in Diagnostics and Gene Modulation

Surface proteins like PR-3 may serve as plant-derived exosome biomarkers for diagnostic research, while BELN-loaded plant miRNAs hold promise for cross-species gene regulation and novel gene therapy strategies.

References

1. De Robertis M, Sarra A, D’Oria V, et al. Blueberry-derived exosome-like nanoparticles counter the response to TNF-α-induced change on gene expression in EA. hy926 cells. Biomolecules. 2020, 10(5): 742.
2. Zhao W, Bian Y, Wang Q, et al. Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress. Acta Pharmacologica Sinica. 2022, 43(3): 645-658.
3. Nguyen T N G, Pham C V, Chowdhury R, et al. Development of blueberry-derived extracellular nanovesicles for immunomodulatory therapy. Pharmaceutics. 2023, 15(8): 2115.
4. Leng Y, Yang L, Zhu H, et al. Stability of blueberry extracellular vesicles and their gene regulation effects in intestinal Caco-2 cells. Biomolecules. 2023, 13(9): 1412.
5. Leng Y, Yang L, Pan S, et al. Characterization of blueberry exosome-like nanoparticles and miRNAs with potential cross-kingdom human gene targets. Food Science and Human Wellness. 2024, 13(2): 869-878.
6. Cox S N, Porcelli V, Romano S, et al. Blueberry-derived exosome like nanovesicles carry RNA cargo into HIEC-6 cells and down-regulate LPS-induced inflammatory gene expression: A proof-of-concept study. Archives of Biochemistry and Biophysics. 2025, 764: 110266.

Case Study 1: Blueberry Exosomes Alleviate Liver Oxidative Stress in NAFLD Models (Zhao W, 2022)

A study demonstrated that blueberry-derived exosome-like nanoparticles (BELNs) can significantly mitigate mitochondrial oxidative stress associated with nonalcoholic fatty liver disease (NAFLD). In vitro, BELNs reduced ROS production and preserved mitochondrial membrane potential in rotenone-treated HepG2 cells. Pre-treatment with 200 µg/mL BELNs increased cell viability from 69% to 88% and decreased apoptosis by modulating Bcl-2, Bax, and HO-1 expression.

In vivo, C57BL/6 mice fed a high-fat diet showed improved insulin sensitivity and reduced hepatic lipid accumulation after 4 weeks of oral BELN supplementation. BELNs also downregulated fatty acid synthesis genes (FAS, ACC1) and activated the Nrf2 antioxidant pathway in liver tissue. These results highlight the potential of BELNs as natural bioactive nanocarriers with antioxidant and metabolic regulatory functions relevant to NAFLD research.

Figure 1. Effect of BELNs on mitochondrial content and ROS production in HepG2 cells. (a) HepG2 cells were pretreated with BELNs (50, 100, or 200 µg/mL) or BHT (20 µM) for 4 h, followed by rotenone (2 µM) treatment for 24 h. Mitochondria were labeled with MitoTracker (red), and nuclei were stained with Hoechst 33342 (blue). Images were acquired using an E-C2 confocal microscope. Scale bar = 10 µm. (b-c) ROS levels were assessed after the same treatment by CM-H2DCFDA staining. Fluorescence images were captured with a fluorescence microscope, and signal intensity was measured with a microplate reader (excitation 485 nm, emission 530 nm).

Figure 2. Effect of BELNs on hepatic lipid accumulation and lipogenic gene expression in HFD-fed mice. (a) H&E and Oil Red O staining of liver sections show reduced vacuolation and lipid droplet accumulation after BELN treatment (25, 50, or 100 mg/mouse for 4 weeks). Scale bar = 50 µm. (b) Liver weight comparison across groups. (c, d) mRNA expression levels of fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver tissues measured by qRT-PCR.

Case Study 2: Blueberry Exosomes as Oral Nanocarriers for Immunomodulation and Drug Delivery (Nguyen T N G, 2023)

This study developed a 3D-filter-based method to isolate blueberry-derived nanovesicles (BENVs) with high protein yield and anthocyanin enrichment. BENVs achieved a curcumin encapsulation efficiency of over 90% and demonstrated sustained release under simulated gastrointestinal conditions. In vitro, BENVs suppressed IL-8 secretion by over 94% and elevated glutathione levels by 61.6% in oxidatively stressed Caco-2 cells, indicating strong immunomodulatory and antioxidant activity. The study also identified PR-3 as a potential universal marker for plant-derived EVs, supporting BENVs' use as scalable, edible nanocarriers for oral therapeutic applications.

Figure 1. Evaluation of curcumin delivery efficiency and biocompatibility using BENVs. (A) Encapsulation efficiency of curcumin and aspirin in BENVs at various incubation durations. (B) In vitro release profiles of free curcumin (Free CUR), BENV-CUR 15, and BENV-CUR 30 in simulated gastric (pH 1.2) and intestinal (pH 6.8) conditions over 24 hours. (C, D) Cell viability of Caco-2 cells after 48 h (C) and 72 h (D) exposure to BENVs, free curcumin, and BENV-CUR measured via MTT assay. PC: untreated control cells.

Figure 2. Assessment of anti-inflammatory and antioxidant responses in Caco-2 cells treated with anthocyanin-rich extracts. (A) IL-8 levels in the culture supernatant after extract pre-treatment (500 μg/mL for 1, 5, and 8 h) followed by oxidative stress induction with 2 mM H₂O₂ for 6 h. (B) Total glutathione (GSH) production in Caco-2 cells under the same treatment conditions. MJ: minced juice; AF: apoplastic fluid; BENV: blueberry-derived extracellular vesicles; NC: negative control; PC: positive control (H₂O₂ only).

References

1. Zhao W, Bian Y, Wang Q, et al. Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress. Acta Pharmacologica Sinica. 2022, 43(3): 645-658.
2. Nguyen T N G, Pham C V, Chowdhury R, et al. Development of blueberry-derived extracellular nanovesicles for immunomodulatory therapy. Pharmaceutics. 2023, 15(8): 2115.

• How are blueberry exosomes different from regular blueberry extracts?

  Blueberry exosomes are nano-sized vesicles naturally secreted by blueberry cells, containing concentrated bioactive molecules such as microRNAs, proteins, and anthocyanins. Unlike standard blueberry extracts, which contain freely dissolved compounds, exosomes are encapsulated in a lipid bilayer, providing enhanced stability, targeted delivery potential, and improved bioavailability of their contents.

• Are blueberry exosomes naturally found in blueberry extract?

  No. Traditional extracts may contain soluble compounds, but exosomes require specialized isolation methods and are not preserved in standard blueberry extracts.

• Can blueberry-derived exosomes be fluorescently labeled for tracking?

  Yes, we offer fluorescent labeling (e.g., DiD or FITC) for visualization in cellular uptake and biodistribution studies.

• What quality control methods are used for blueberry-derived exosomes?

  Each batch is validated using techniques such as nanoparticle tracking analysis (NTA), TEM, and protein marker analysis to ensure consistency and purity.

• Can PNExo™ Exosome-Blueberry be used in homemade products?

  No. It is strictly intended for research and industrial purposes. It is not formulated or authorized for use in DIY applications.

More Questions