Astaxanthin Promotes the Survival of Adipose-Derived Stem Cells by Alleviating Oxidative Stress via Activating the Nrf2 Signaling Pathway

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3850
• Main Authors: Yang, Chang-Sheng, Guo, Xiao-Shuang, Yue, Ying-Ying, Wang, Yu, Jin, Xiao-Lei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Apoptosis; Astaxanthin; BAX protein; Bcl-2 protein; Bcl-x protein; Caspase 3 - metabolism; Caspase-3; Collagen (type I); Collagen (type II); Cyclin D1; Extracellular matrix; fat grafting; Grafting; Grafts; Health aspects; Humans; Interleukin 6; Membrane potential; mesenchymal stem cell; Mesenchymal Stem Cells - metabolism; Microenvironments; Mitochondria; NF-E2-Related Factor 2 - metabolism; Nrf2 signaling pathway; Oxidative stress; Oxidative Stress - drug effects; Proteins; Reconstructive surgery; Signal Transduction; Stem cells; Surgery; Survival; Transplantation; Tumor necrosis factor-α; Xanthophylls; Xanthophylls - pharmacology; United Kingdom; Illinois; China; fat grafting; mesenchymal stem cell; apoptosis; Nrf2 signaling pathway; oxidative stress; astaxanthin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043850

The survival of free fat grafts is dependent primarily on adipose-derived stem cells (ADSCs); however, ADSCs are susceptible to oxidative stress in the recipient area. Astaxanthin (Axt) is a natural xanthophyll carotenoid with potent antioxidant properties and numerous clinical applications. To date, the therapeutic potential of Axt in fat grafting has not been explored. The purpose of this study is to investigate the effects of Axt on oxidatively stressed ADSCs. An oxidative model of ADSCs was developed to simulate the host's microenvironment. Oxidative insult decreased the protein levels of Cyclin D1, type I collagen alpha 1 (COL1A1), and type II collagen alpha 1 (COL2A1), while increasing the expression of cleaved Caspase 3 and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ADSCs. Axt pre-treatment significantly reduced oxidative stress, increased the synthesis of an adipose extracellular matrix, alleviated inflammation, and restored the impaired adipogenic potential in the present model. Furthermore, Axt immensely activated the NF-E2-related factor 2 (Nrf2) pathway, and ML385, an inhibitor of Nrf2, could negate Axt's protective effects. Additionally, Axt alleviated apoptosis by inhibiting bcl-2-associated X protein (BAX)/Caspase 3 signaling and improving the mitochondrial membrane potential (MMP), which could also be abolished by ML385. Our results suggest that Axt may exert its cytoprotective effect on ADSCs through the Nrf2 signaling pathway and could be therapeutic in fat grafting.