Suppressive Effect of Tetrahydrocurcumin on <i>Pseudomonas aeruginosa</i> Lipopolysaccharide‐Induced Inflammation by Suppressing JAK/STAT and Nrf2/HO‐1 Pathways in Microglial Cells
Hui‐Wen Lin, Tzu‐Chun Chen, Jui‐Hsuan Yeh, Shang‐Chun Tsou, Inga Wang, Ting‐Jing Shen, Chen‐Ju Chuang, Yuan‐Yen Chang
Abstract
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/pNF κ B 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‐ κ B activation and inducing Nrf2‐mediated HO‐1 expression.