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Lemon balm-derived nanovesicles restore mitochondrial function and reduce cytokine production in skin fibroblasts
Gabrielė Kulkovienė1, Martyna Uldukytė2, Sofiya Haluts3
1Department of Drug Chemistry, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas, 50166, Lithuania; Laboratory of Pharmaceutical Sciences, Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, Kaunas, 50166, Lithuania.
Abstract:
Mitochondrial dysfunction, particularly excessive fission, has been implicated in inflammatory signalling in skin diseases such as psoriasis and atopic dermatitis (AD). Current systemic treatments, while effective, are often associated with adverse effects, variable patient responses and high costs. Plant extracts have shown notable anti-inflammatory properties; however, their therapeutic potential is limited due to low penetration and poor bioavailability. Thus, plant-derived nanovesicles (PDNVs) have emerged as an alternative delivery platform, offering bioactive cargo with improved skin penetration and low immunogenic potential. Melissa officinalis L. (Lemon Balm, LB) extracts have demonstrated beneficial effects in inflammatory skin conditions; however, the potential of LB-NVs to modulate skin cell function and cellular energetics in inflammatory conditions remains unexplored. Thus, this study investigated the effects of LB-NVs on mitochondrial function and structure in human skin fibroblasts exposed to a cytokine cocktail (IL-22, IL-17A, TNF-α) to induce a pro-inflammatory state (PInfS). LB-NVs rescued cells from inflammatory metabolic reprogramming by restoring mitochondrial respiration and preventing elevated glycolysis induced by PinfS. Additionally, they reduced mitochondrial fragmentation by regulating the activation of Drp1 and lowered the total p38 MAPK level. Lastly, LB-NVs suppressed IL-4 and IL-13, which are central to AD pathogenesis, and reduced IL-18, a cytokine that commonly increases with disease activity. These findings, for the first time, demonstrate the ability of PDNVs to directly target mitochondrial functions and modulate inflammation, positioning LB-NVs as a highly promising strategy for treating chronic skin inflammation.
Insights
Plant-derived nanovesicles from Lemon Balm (LB-NVs) effectively target mitochondrial dysfunction and inflammation in skin cells. These novel nanovesicles restore cellular energetics and reduce inflammatory markers, offering a promising therapeutic approach for chronic skin conditions.
Area of Science:
- Dermatology
- Cell Biology
- Nanotechnology
Background:
- Mitochondrial dysfunction, specifically excessive fission, contributes to inflammatory skin diseases like psoriasis and atopic dermatitis (AD).
- Existing systemic treatments for inflammatory skin conditions have limitations including adverse effects, variable responses, and high costs.
- Plant extracts possess anti-inflammatory properties but suffer from poor skin penetration and bioavailability, necessitating advanced delivery systems.
Purpose of the Study:
- To investigate the effects of Melissa officinalis L. derived nanovesicles (LB-NVs) on mitochondrial function and structure in human skin fibroblasts under pro-inflammatory conditions.
- To explore the potential of LB-NVs in modulating cellular energetics and inflammatory signaling pathways relevant to skin diseases.
Main Methods:
- Human skin fibroblasts were exposed to a cytokine cocktail (IL-22, IL-17A, TNF-α) to simulate a pro-inflammatory state (PInfS).
- The impact of LB-NVs on mitochondrial respiration, glycolysis, mitochondrial morphology (fission/fusion dynamics), and key signaling molecules (Drp1, p38 MAPK) was assessed.
- The expression of inflammatory cytokines (IL-4, IL-13, IL-18) was measured following LB-NV treatment.
Main Results:
- LB-NVs restored mitochondrial respiration and prevented the increase in glycolysis induced by the pro-inflammatory state.
- LB-NVs reduced mitochondrial fragmentation by regulating Dynamin-related protein 1 (Drp1) activation and decreased p38 MAPK levels.
- LB-NVs suppressed the expression of IL-4, IL-13, and IL-18, cytokines implicated in AD pathogenesis and disease activity.
Conclusions:
- Plant-derived nanovesicles (PDNVs) can directly target and improve mitochondrial function in skin cells.
- LB-NVs demonstrate significant potential in modulating cellular energetics and reducing key inflammatory pathways relevant to chronic skin inflammation.
- LB-NVs represent a promising, novel therapeutic strategy for managing inflammatory skin conditions by addressing mitochondrial dysfunction and associated inflammation.
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