Antioxidant Effect of a Plant-Derived Extracellular Vesicles' Mix on Human Skin Fibroblasts: Induction of a Reparative Process

Overview

Journal Antioxidants (Basel)

Date 2024 Nov 27

PMID 39594515

Authors

Rossella Di Raimo

Davide Mizzoni

Antonella Aloi

Giulia Pietrangelo

Vincenza Dolo

Giuseppina Poppa

Stefano Fais

Mariantonia Logozzi

Affiliations

Soon will be listed here.

Abstract

Plant-Derived Extracellular Vesicles extracellular vesicles (PDEVs) from organic agriculture (without the use of pesticides and microbicides) contain high levels of antioxidants. Organic PDEVs have shown an increased antioxidant power compared to PDEVs from single plants, suggesting a synergistic effect of the bioactives constitutively expressed in the PDEVs from single fruits. With this study, we wanted to investigate the beneficial effects of a mix of PDEVs on human skin cells. We found detectable levels of citric acid, ascorbic acid, glutathione, catalase, and SOD in a mix of PDEVs deriving from five different fruits (grape, red orange, papaya, pomegranate, and tangerine). We then treated HO-conditioned fibroblasts with the mix of PDEVs. The results showed that the PDEVs' mixture reverted the HO-induced redox imbalance, restoring mitochondrial homeostasis, with a strong reduction of mitochondrial anion superoxide and an increase in sirtuin levels. The antioxidant action was consistent with wound repair on a lesion produced in a fibroblast's monolayer. This result was consistent with an increased level of vimentin and matrix metalloproteinase-9, whose expression is directly related to the efficiency of the reparative processes. These data support a beneficial role of PDEVs in both preventing and treating skin injuries through their potent antioxidant and reparative activities.

References

Pullar J, Carr A, Vissers M . The Roles of Vitamin C in Skin Health. Nutrients. 2017; 9(8). PMC: 5579659. DOI: 10.3390/nu9080866. View

Ivaska J, Pallari H, Nevo J, Eriksson J . Novel functions of vimentin in cell adhesion, migration, and signaling. Exp Cell Res. 2007; 313(10):2050-62. DOI: 10.1016/j.yexcr.2007.03.040. View

Kim M, Jang H, Kim W, Kim D, Park J . Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases. Antioxidants (Basel). 2023; 12(6). PMC: 10295733. DOI: 10.3390/antiox12061286. View

Addis R, Cruciani S, Santaniello S, Bellu E, Sarais G, Ventura C . Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome. Int J Med Sci. 2020; 17(8):1030-1042. PMC: 7211158. DOI: 10.7150/ijms.43986. View

Dave J, Bayless K . Vimentin as an integral regulator of cell adhesion and endothelial sprouting. Microcirculation. 2014; 21(4):333-44. DOI: 10.1111/micc.12111. View

Warner R, Bhagavathula N, Nerusu K, Lateef H, Younkin E, Johnson K . Matrix metalloproteinases in acute inflammation: induction of MMP-3 and MMP-9 in fibroblasts and epithelial cells following exposure to pro-inflammatory mediators in vitro. Exp Mol Pathol. 2004; 76(3):189-95. DOI: 10.1016/j.yexmp.2004.01.003. View

Bruno S, Paolini A, DOria V, Sarra A, Sennato S, Bordi F . Extracellular Vesicles Derived From Modulate Inflammatory Genes and Tight Junctions in a Human Model of Intestinal Epithelium. Front Nutr. 2021; 8:778998. PMC: 8652296. DOI: 10.3389/fnut.2021.778998. View

Mendez M, Kojima S, Goldman R . Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J. 2010; 24(6):1838-51. PMC: 2874471. DOI: 10.1096/fj.09-151639. View

Varani J, Warner R, Gharaee-Kermani M, Phan S, Kang S, Chung J . Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000; 114(3):480-6. DOI: 10.1046/j.1523-1747.2000.00902.x. View

10.

Hahn H, Kim K, An I, Ahn K, Han H . Protective effects of rosmarinic acid against hydrogen peroxide‑induced cellular senescence and the inflammatory response in normal human dermal fibroblasts. Mol Med Rep. 2017; 16(6):9763-9769. DOI: 10.3892/mmr.2017.7804. View

11.

Morgan C, Nigam Y . Naturally derived factors and their role in the promotion of angiogenesis for the healing of chronic wounds. Angiogenesis. 2013; 16(3):493-502. DOI: 10.1007/s10456-013-9341-1. View

12.

Xu Z, Xu Y, Zhang K, Liu Y, Liang Q, Thakur A . Plant-derived extracellular vesicles (PDEVs) in nanomedicine for human disease and therapeutic modalities. J Nanobiotechnology. 2023; 21(1):114. PMC: 10049910. DOI: 10.1186/s12951-023-01858-7. View

13.

Yosipovitch G, Misery L, Proksch E, Metz M, Stander S, Schmelz M . Skin Barrier Damage and Itch: Review of Mechanisms, Topical Management and Future Directions. Acta Derm Venereol. 2019; 99(13):1201-1209. DOI: 10.2340/00015555-3296. View

14.

Perry S, Norman J, Barbieri J, Brown E, Gelbard H . Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011; 50(2):98-115. PMC: 3115691. DOI: 10.2144/000113610. View

15.

Spinelli J, Haigis M . The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018; 20(7):745-754. PMC: 6541229. DOI: 10.1038/s41556-018-0124-1. View

16.

Chiang B, Essick E, Ehringer W, Murphree S, Hauck M, Li M . Enhancing skin wound healing by direct delivery of intracellular adenosine triphosphate. Am J Surg. 2007; 193(2):213-8. PMC: 1850226. DOI: 10.1016/j.amjsurg.2006.08.069. View

17.

Izyumov D, Avetisyan A, Pletjushkina O, Sakharov D, Wirtz K, Chernyak B . "Wages of fear": transient threefold decrease in intracellular ATP level imposes apoptosis. Biochim Biophys Acta. 2004; 1658(1-2):141-7. DOI: 10.1016/j.bbabio.2004.05.007. View

18.

He B, Cai Q, Qiao L, Huang C, Wang S, Miao W . RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles. Nat Plants. 2021; 7(3):342-352. PMC: 7979528. DOI: 10.1038/s41477-021-00863-8. View

19.

Najafi M, Nikpayam O, Tavakoli-Rouzbehani O, Papi S, Amrollahi Bioky A, Ahmadiani E . A comprehensive insight into the potential effects of resveratrol supplementation on SIRT-1: A systematic review. Diabetes Metab Syndr. 2021; 15(5):102224. DOI: 10.1016/j.dsx.2021.102224. View

20.

Gilchrest B . Skin aging and photoaging: an overview. J Am Acad Dermatol. 1989; 21(3 Pt 2):610-3. DOI: 10.1016/s0190-9622(89)70227-9. View