Suppressive Effect of Tetrahydrocurcumin on Pseudomonas aeruginosa Lipopolysaccharide-Induced Inflammation by Suppressing JAK/STAT and Nrf2/HO-1 Pathways in Microglial Cells

• Published in: Oxidative medicine and cellular longevity Vol. 2022; no. 1; p. 4978556
• Main Authors: Lin, Hui-Wen, Chen, Tzu-Chun, Yeh, Jui-Hsuan, Tsou, Shang-Chun, Wang, Inga, Shen, Ting-Jing, Chuang, Chen-Ju, Chang, Yuan-Yen
• Format: Journal Article
• Language: English
• Published: United States Hindawi 2022; John Wiley & Sons, Inc
• Subjects: Alzheimer's disease; Animals; Antibodies; Antioxidants; Curcumin - analogs & derivatives; Curcumin - metabolism; Curcumin - pharmacology; Cytokines; Cytotoxicity; Heme Oxygenase-1 - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - metabolism; Janus Kinase 1; Kinases; Lipopolysaccharides - pharmacology; Mice; Microglia - metabolism; NF-E2-Related Factor 2 - metabolism; Nitric Oxide - metabolism; Proteins; Pseudomonas aeruginosa; Vantaa Finland; United States > US; Finland
• ISSN: 1942-0900; 1942-0994; 1942-0994
• DOI: 10.1155/2022/4978556

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti-inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat Pseudomonas aeruginosa (P.a.) lipopolysaccharide- (LPS-) stimulated BV2 microglial cells. THC reduced P.a. LPS–induced mortality and the production of inflammatory mediators IL-6, TNF-α, MIP-2, IP-10, and nitrite. A further investigation revealed that THC decreased these inflammatory cytokines synergistically with JAK/STAT signaling inhibitors. THC also increased Nrf2/HO-1 signaling transduction which inhibits iNOS/COX-2/pNFκB cascades. Additionally, the presence of the HO-1 inhibitor Snpp increased the levels of IP-10, IL-6, and nitrite while THC treatment reduced those inflammatory factors in P.a. LPS–stimulated BV2 cells. In summary, we demonstrated that THC exhibits anti-inflammatory activities in P.a. LPS-induced inflammation in brain microglial cells by inhibiting STAT1/3-dependent NF-κB activation and inducing Nrf2-mediated HO-1 expression.