Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells. (15th May 2017)

• Record Type: Journal Article
• Authors: Chen, Xin; Ding, Hai-Wen; Li, Hai-Di; Huang, Hui-Min; Li, Xiao-Feng; Yang, Yang; Zhang, Yi-Long; Pan, Xue-Yin; Huang, Cheng; Meng, Xiao-Ming; Li, Jun
• Is Part Of: Toxicology letters. Volume 274(2017)
• Page Start: 51
• Page End: 63
• Publication Date: 2017-05-15
• Subjects: ALI acute liver injury -- KCs Kupffer cells -- HD-14 hesperidin derivative-14 -- PPAR-γ peroxisome proliferator-activated receptor-γ -- TNF-α tumor necrosis factor-α -- IL-6 interleukin-6 -- IL-1β interleukin-1β -- LPS lipopolysaccharide -- MTT methyl thiazolyl tetrazolium -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- AST aspartate aminotransferase; Acute liver injury -- Hesperetin derivative-14 -- Inflammation -- PPAR-γ; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.04.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Anti-inflammatory effects of hesperetin derivative-14 in vivo and in vitro . Hesperetin derivative-14 activates PPAR-γ expression in mice with ALI and LPS-induced RAW264.7 cells. The expression of p-JAK1 and p-STAT1 is attenuated by up-regulating PPAR-γ. Abstract: Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L . ( Rutaceae ). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2 μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100 mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl4 -induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury.