Benefits of Lemon: Bioactive Components and Functional Properties
Lemon (Citrus limon) is widely valued for its diverse range of bioactive compounds that contribute to its antioxidant, anti-inflammatory, antimicrobial, and metabolic regulatory effects in experimental models. These components act through multiple biochemical pathways, supporting cellular resilience, modulating oxidative stress, and influencing microbial dynamics. Below are the major classes of bioactives found in lemon and their associated functions based on published scientific studies:
- Flavonoids (e.g. Hesperidin, Limocitrin): Key phenolic compounds in lemon that reduce oxidative stress and inflammatory markers via modulation of COX-2, TNF-α, and IL-6, support vascular tone, and inhibit tyrosinase activity to help regulate pigmentation and skin homeostasis.
- Phenolic Acids (e.g. Ferulic Acid, p-Hydroxybenzoic Acid): Strong radical scavengers that work synergistically with vitamin C to enhance photoprotection, reduce UV-induced skin damage, and prevent lipid peroxidation in cell membranes.
- Monoterpenes (e.g. D-Limonene, β-Pinene, γ-Terpinene): Dominant components of lemon essential oil, shown to exert antimicrobial, anti-inflammatory, and skin-penetration-enhancing effects, as well as modulate tumor cell viability in vitro via apoptosis-related signaling.
- Limonoids (e.g. Limonin): Citrus-specific triterpenoids with reported neuroprotective and metabolic regulatory effects, including modulation of fat accumulation, insulin sensitivity, and neuronal apoptosis, though requiring dose attention due to potential mitochondrial stress.
- Ascorbic Acid (Vitamin C): A potent antioxidant that suppresses NF-κB-driven inflammation, supports immune defense mechanisms, and contributes to collagen biosynthesis and barrier function.
- Organic Acids (e.g. Citric Acid): Naturally occurring acids that support mineral absorption by adjusting gut pH, and aid in the dissolution of urinary calcium crystals, thus promoting renal and digestive health.
What are Lemon-Derived Exosomes?
Lemon exosome-like nanoparticles (LELNs) are naturally occurring nanosized (approximately 100 nm) extracellular vesicles derived from Citrus limon. These advanced vesicles are generated by plant cells through a coordinated process of endocytosis, vesicle fusion, and exocytosis, and they encapsulate a variety of biomolecules, including proteins, lipids, and nucleic acids.
The appeal of lemon-derived exosomes in research stems from several key advantages:
- Natural Origin: Sourced directly from lemons, they represent a natural platform for exploring biological interactions.
- Biocompatibility: Their plant origin often suggests favorable compatibility with biological systems, making them promising for various research applications.
- Bioactive Cargo Delivery: These exosomes naturally carry a diverse array of bioactive molecules, allowing for their exploration as delivery vehicles for specific compounds.
- Inherent Properties: Research indicates that plant-derived exosomes, including those from lemons, may possess inherent antioxidant, anti-inflammatory, and anti-aging properties, contributing to their broad research potential.
Physical and morphological analysis of nanovesicles derived from Citrus limon L. (A) Citrus lemon before and after juice extraction. (B) Transmission electron microscopy (TEM) image showing nanovesicles at 50,000× magnification. Scale bar = 100 nm. (C) Nanoparticle tracking analysis (NTA) showing size distribution and concentration profile of the nanovesicles. (Takakura H, et al., 2022)
Potential Applications of Lemon-Derived Exosomes
Antioxidant and Cellular Protection
Lemon exosome-like nanoparticles (LELNs) activate key cytoprotective pathways, including AhR and Nrf2, enhancing the expression of antioxidant enzymes and reducing intracellular ROS accumulation. These effects contribute to the maintenance of redox homeostasis and cellular integrity under oxidative stress, particularly in liver cells and inflamed tissues. Their ability to stabilize redox balance supports their use as natural antioxidants in experimental oxidative damage models.
Anti-inflammatory and Immunomodulatory Effects
Studies have shown that lemon-derived exosomes suppress pro-inflammatory signaling pathways such as ERK and NF-κB, while promoting anti-inflammatory responses through macrophage polarization. In animal models, they have been observed to alleviate tissue inflammation, reduce cytokine production, and aid in rebalancing immune responses, highlighting their potential as natural immunomodulators.
Microbiome and Gut Health Support
LELNs enhance the survival and function of beneficial gut bacteria by improving their resistance to bile salts and promoting stress adaptation. Additionally, these vesicles can modulate the gut microbial environment, indirectly inhibiting pathogenic species by supporting probiotic growth and metabolic function. Such findings underscore their potential as prebiotic enhancers in microbiota-related research.
Targeted Cellular Regulation
Lemon nanovesicles exhibit selective activity against cancer cells by triggering apoptosis pathways, particularly via TRAIL signaling. They have been shown to inhibit proliferation in various tumor cell lines and reduce tumor burden in vivo. Furthermore, their structural compatibility enables functionalization for drug encapsulation and targeted delivery, expanding their utility in therapeutic delivery system design.
Regenerative and Wound Healing Research
In tissue engineering studies, LELNs have been incorporated into biomaterials such as hydrogels to promote wound healing, especially in chronic or diabetic contexts. By modulating immune cell behavior and stimulating tissue repair mechanisms, they demonstrate promising potential for regenerative medicine applications.
References
- Raimondo S, Naselli F, Fontana S, et al. Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death. Oncotarget. 2015, 6(23): 19514.
- Lei C, Mu J, Teng Y, et al. Lemon exosome-like nanoparticles-manipulated probiotics protect mice from C. diff infection. Iscience. 2020, 23(10).
- Lei C, Teng Y, He L, et al. Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay. Iscience. 2021, 24(6).
- Takakura H, Nakao T, Narita T, et al. Citrus limon L.-derived nanovesicles show an inhibitory effect on cell growth in p53-inactivated colorectal cancer cells via the macropinocytosis pathway. Biomedicines. 2022, 10(6): 1352.
- Raimondo S, Urzì O, Meraviglia S, et al. Anti-inflammatory properties of lemon-derived extracellular vesicles are achieved through the inhibition of ERK/NF-κB signalling pathways. Journal of Cellular and Molecular Medicine. 2022, 26(15): 4195-4209.
- Urzì O, Cafora M, Ganji N R, et al. Lemon-derived nanovesicles achieve antioxidant and anti-inflammatory effects activating the AhR/Nrf2 signaling pathway. Iscience. 2023, 26(7).
- Tinnirello V, Zizzo M G, Conigliaro A, et al. Industrial-produced lemon nanovesicles ameliorate experimental colitis-associated damages in rats via the activation of anti-inflammatory and antioxidant responses and microbiota modification. Biomedicine & Pharmacotherapy. 2024, 174: 116514.
- Gasparro R, Gambino G, Duca G, et al. Protective effects of lemon nanovesicles: evidence of the Nrf2/HO-1 pathway contribution from in vitro hepatocytes and in vivo high-fat diet-fed rats. Biomedicine & Pharmacotherapy. 2024, 180: 117532.
- Jamshidi Z, Dehghani S, Nameghi M A, et al. Engineering extracellular vesicles derived from lemons for delivering chemotherapeutic drug employing periostin targeting. Journal of Drug Delivery Science and Technology. 2024, 99: 106011.
- Jin E, Yang Y, Cong S, et al. Lemon-derived nanoparticle-functionalized hydrogels regulate macrophage reprogramming to promote diabetic wound healing. Journal of Nanobiotechnology. 2025, 23(1): 68.