Astaxanthin alleviates inflammatory pain by regulating the p38 mitogen-activated protein kinase and nuclear factor-erythroid factor 2-related factor/heme oxygenase-1 pathways in mice

• Published in: Food & function 2021-12, Vol.12 (24), p.12381-12394
• Main Authors: Zhao, Lin, Tao, Xueshu, Wan, Chengfu, Dong, Daosong, Wang, Chenglong, Xi, Qi, Liu, Yan, Song, Tao
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants; Astaxanthin; Chemical compounds; Disease Models, Animal; Dorsal root ganglia; Freund's adjuvant; Ganglia; Heme; Heme oxygenase (decyclizing); Heme Oxygenase-1 - metabolism; Inflammation; Inflammation - drug therapy; Inflammatory response; Kinases; Lipids; Lobsters; Male; MAP kinase; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2 - metabolism; Oxygenase; p38 Mitogen-Activated Protein Kinases - metabolism; Pain; Pain Measurement - drug effects; Pain perception; Pharmacology; Phytotherapy; Protein kinase; Proteins; Quality of life; Xanthophylls - pharmacology; Xanthophylls - therapeutic use
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d1fo02326h

Inflammatory pain is a complex process that has a substantial negative impact on post-injury quality of life. Astaxanthin (AST), which is a lipid-soluble red-orange carotenoid that is found in lobsters, inhibits the development and maintenance of inflammation in mice via its antioxidant and anti-inflammatory activities. However, the specific mechanisms underlying these effects remain unclear. In this study, we aimed to elucidate the mechanism by which astaxanthin alleviated inflammation using a mouse model with Complete Freund's adjuvant (CFA)-induced inflammatory pain. Mechanical allodynia and thermal hyperalgesia were observed on days 1-14 post CFA injection. Expression of p38 mitogen-activated protein kinase (MAPK) in the left paw and L4-6 dorsal root ganglia (DRG) were upregulated in the CFA-induced mice. Expression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways were also increased. Astaxanthin relieved mechanical allodynia and thermal hyperalgesia induced by CFA and inhibited the inflammatory response ( e.g. , infiltration of inflammatory cells and production of inflammatory factors) in the ipsilateral paw and DRG. Additionally, AST inhibited p38 MAPK and enhanced Nrf2/HO-1 contents in the left paw and DRG, and reversed the pain induced by p38 MAPK agonist and Nrf2 inhibitors. These findings suggest that AST exerts anti-inflammatory effects and regulates p38 MAPK and Nrf2/HO-1 to alleviate inflammatory pain. AST may be a potential therapeutic agent for relieving inflammation. Astaxanthin suppressed the CFA-induced upregulation of p38 MAPK and enhanced Nrf2/HO-1 pathway. Additionally, AST reduced the inflammatory response ( e.g. , inflammatory cells and pro-inflammatory factors) to alleviate symptoms of inflammatory pain.