PNExo™ Exosome-Olive oil (Leaf)(PNE-NOO01)

Bioactive Components and Actions of Olive Leaf

Olive leaf (Olea europaea L.), a traditional Mediterranean plant, has been extensively studied for its rich chemical composition and diverse biological properties, well-documented in numerous scientific literature. Olive leaf contains a variety of crucial bioactive compounds that synergistically contribute to its numerous potential health benefits:

• Oleuropein: This is one of the most abundant secoiridoid glycosides found in olive leaves, constituting 6% to 9% of its dry weight. Oleuropein and its hydrolysis products, hydroxytyrosol and tyrosol, are key active components. They are widely researched for their potent antioxidant capacity, effectively scavenging reactive oxygen species like superoxide anion and hydroxyl radicals, thereby inhibiting oxidative stress and helping protect cells from DNA damage. Furthermore, studies indicate that these compounds can modulate inflammatory pathways, for instance, by inhibiting the NF-κB signaling pathway, reducing the secretion of pro-inflammatory factors such as tumor necrosis factor-alpha (TNF-α), and activating the Nrf2 antioxidant pathway, thus exerting potential anti-inflammatory and immunomodulatory effects.
• Flavonoids: This group includes compounds like luteolin 7-O-glucoside, apigenin, and rutin, among others. These flavonoids significantly contribute to the overall antioxidant activity of olive leaf, accounting for 13% to 27% of its total antioxidant capacity. They also work synergistically with oleuropein and other components to combat oxidative stress.
• Triterpenes: Such as oleanolic acid, which makes up approximately 3% of the olive leaf's dry weight. Research suggests that oleanolic acid possesses a wide range of biological activities.
• Other Phenolic Compounds: These also include caffeic acid, p-coumaric acid, and others, which contribute to the overall biological functions of olive leaf.

What Are Olea europaea Leaf Exosomes?

Olive leaf exosomes belong to a class of naturally occurring nanoparticles known as Plant Exosome-like Nanoparticles (PELNs). These nanoscale vesicles, typically 30–150 nm in diameter, are secreted by plant cells and encapsulated by a lipid bilayer. Functioning as biological messengers, they carry a diverse range of bioactive cargo—such as RNAs, proteins, and lipids—to facilitate intercellular communication. Specifically, olive leaf exosomes are isolated from fresh olive leaves through gentle physical methods like ultracentrifugation and ultrafiltration. Unlike traditional plant extracts, these nanovesicles offer a concentrated form of the leaf’s bioactive compounds. Their membrane structure, rich in phospholipids such as phosphatidylcholine and monogalactosyl diglycerides, closely resembles that of natural cell membranes, contributing to excellent biocompatibility and stability. What sets olive leaf exosomes apart is their ability to encapsulate functional molecules—such as miRNAs that may regulate inflammation-related pathways, oleuropein derivatives, and natural antioxidant enzymes. Thanks to their inherent structural integrity and the use of stabilization methods like freeze-drying, these exosomes are well-suited for applications that benefit from sustained bioactivity, including transdermal and functional delivery systems.

Preparation and Characterization of Olive Leaf-Derived Exosome-Like Nanovesicles (OLELNVs) (Wang Z, et al., 2024)

Potential Applications of Olive Leaf Exosomes

With their biocompatible structure and rich molecular cargo, olive leaf-derived exosomes are attracting increasing interest across multiple research fields. Below are several areas where their unique properties are being actively explored:

• Olive Leaf Exosomes as Natural Nanocarriers

  Olive leaf exosomes have shown promise as carriers for therapeutic agents. Their natural targeting properties make them suitable for delivering small molecules or gene-editing tools such as CRISPR/Cas9, with enhanced delivery efficiency and specificity. The phospholipid bilayer of these vesicles also helps protect sensitive compounds like oleuropein from degradation, potentially improving their stability and circulation time in biological systems.

• OLELNVs for Skin Health Applications

  Research has indicated that olive leaf exosomes may support skin health by modulating the skin microbiota. They have been shown to suppress harmful bacteria while promoting beneficial microbial growth, contributing to skin barrier repair. When integrated into topical delivery systems such as hyaluronic acid-based hydrogels, they may assist in UV protection and facilitate skin regeneration following photo-damage.

• Olive Leaf-Derived Nanovesicles in Metabolic Research

  In the context of metabolic disorders, olive leaf exosomes are being studied for their ability to influence gene expression related to glucose and lipid metabolism, including GLUT1 and AMPK pathways. These regulatory effects could be relevant for research into insulin resistance and hepatic lipid accumulation.

• Antitumor Potential of Olive Leaf Exosomes

  Studies have begun to explore the role of plant-derived exosomes in modulating tumor microenvironments. Olive leaf exosomes may inhibit the expression of glycolytic enzymes such as PKM2 and MCT4, which are associated with cancer cell proliferation and metastasis. Additionally, their potential to present antigens may help activate dendritic cells, offering insights into immune system modulation in oncology.

• OLELNVs in Food and Agricultural Applications

  Thanks to their natural antimicrobial activity, olive leaf exosomes are being considered as bio-based preservatives to extend the shelf life of food products. In agriculture, they may act as signaling molecules that activate plant defense mechanisms, enhancing resistance to environmental stress and disease.

References

1. Umeno A, Takashima M, Murotomi K, et al. Radical-scavenging activity and antioxidative effects of olive leaf components oleuropein and hydroxytyrosol in comparison with homovanillic alcohol. Journal of Oleo Science. 2015, 64(7): 793-800. https://doi.org/10.5650/jos.ess15042
2. Abaza L, Taamalli A, Nsir H, et al. Olive tree (Olea europeae L.) leaves: Importance and advances in the analysis of phenolic compounds. Antioxidants. 2015, 4(4): 682-698. https://doi.org/10.3390/antiox4040682
3. Boss A, Bishop K S, Marlow G, et al. Evidence to support the anti-cancer effect of olive leaf extract and future directions. Nutrients. 2016, 8(8): 513. https://doi.org/10.3390/nu8080513
4. Borjan D, Leitgeb M, Knez Ž, et al. Microbiological and antioxidant activity of phenolic compounds in olive leaf extract. Molecules. 2020, 25(24): 5946. https://doi.org/10.3390/molecules25245946
5. Ruzzolini J, Peppicelli S, Bianchini F, et al. Cancer glycolytic dependence as a new target of olive leaf extract. Cancers. 2020, 12(2): 317. https://doi.org/10.3390/cancers12020317
6. Allegretta C, Difonzo G, Caponio F, et al. Olive leaf extract (OLE) as a novel antioxidant that ameliorates the inflammatory response in cystic fibrosis. Cells. 2023, 12(13): 1764. https://doi.org/10.3390/cells12131764
7. Wang Z, Yuan J, Xu Y, et al. Olea europaea leaf exosome-like nanovesicles encapsulated in a hyaluronic acid/tannic acid hydrogel dressing with dual “defense-repair” effects for treating skin photoaging. Materials Today Bio. 2024, 26: 101103. https://doi.org/10.1016/j.mtbio.2024.101103

Case Study 1: Olive Leaf Exosome-like Nanovesicles for Skin Photoaging Protection (Wang Z, 2024)

A recent study demonstrated that exosome-like nanovesicles derived from Olea europaea leaves (OLELNVs), when encapsulated in a hyaluronic acid–tannic acid (HA/TA) hydrogel, provide dual protection against UV-induced skin photoaging. Compared to olive leaf extract, OLELNVs showed higher biocompatibility, enhanced cell migration, and superior antioxidant activity—achieving 82.2% ABTS radical scavenging at 0.1 mg/mL and maintaining over 90% cell viability. In mouse models, the OLELNVs@HA/TA hydrogel reduced epidermal thickening by 45%, restored collagen, and downregulated inflammation-related NF-κB signaling via miR168a-5p, offering a stable, bioactive platform for advanced skin protection research.

Figure 1. Improved safety and efficacy of exosome-like nanovesicles derived from Olea europaea leaves (OLELNVs) compared to Olea europaea leaf extract (OLEX). (a) HaCaT cell proliferation assessed by CCK-8 assay after treatment with OLELNVs or OLEX. (b, c) Wound healing assay showing enhanced closure with OLELNVs at 12 and 24 h. (d, e) Antioxidant activity measured by ABTS radical scavenging.

Figure 2. OLELNVs inhibit UVB-induced cellular aging in HaCaT and HDF-α cells. (a, b) Morphological improvement in UVB-treated HaCaT and HDF-α cells after OLELNV treatment. (c, d) Enhanced cell proliferation assessed by CCK-8 assay. (e) Increased SOD activity, (f) reduced IL-6 expression, and (g, h) decreased ROS levels in UVB-treated HaCaT cells.

References

1. Wang Z, Yuan J, Xu Y, et al. Olea europaea leaf exosome-like nanovesicles encapsulated in a hyaluronic acid/tannic acid hydrogel dressing with dual “defense-repair” effects for treating skin photoaging. Materials Today Bio. 2024, 26: 101103. https://doi.org/10.1016/j.mtbio.2024.101103

• What are the advantages of olive leaf-derived exosomes over traditional olive leaf extracts?

  Olive leaf-derived exosomes (OLELNVs) provide a concentrated and bioavailable form of key actives such as hydroxytyrosol, oleuropein, and antioxidant enzymes. Unlike conventional extracts, which may have low transdermal efficiency and potential cytotoxicity at high doses, OLELNVs demonstrate excellent skin penetration, high biocompatibility, and sustained bioactivity, making them ideal for research on targeted delivery and anti-photoaging mechanisms.

• How are olive leaf exosomes isolated and ensured to be of high purity?

  OLELNVs are extracted using a multi-step process involving low-speed centrifugation, ultrafiltration, and size-exclusion chromatography. The resulting nanovesicles undergo thorough characterization by NTA, TEM, and zeta potential analysis to ensure consistent size, high particle concentration, and high purity.

• What types of biomolecules are encapsulated in olive leaf exosomes?

  Exosomes derived from Olea europaea leaves carry a rich cargo of naturally occurring bioactive compounds, including phenolic antioxidants (e.g., hydroxytyrosol), trace levels of oleuropein, antioxidant enzymes such as SOD, and plant-derived microRNAs like miR168a-5p, which have been shown to modulate inflammatory signaling pathways.

• What are the recommended storage and handling conditions for this product?

  OLELNVs are available in lyophilized or frozen formats. Lyophilized powder should be stored at 4°C and reconstituted with deionized water prior to use. Frozen formulations should be kept at -20°C to -80°C. To preserve vesicle integrity, avoid repeated freeze–thaw cycles and gently resuspend by pipetting without generating bubbles.

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