RRC ID 56113
Author Tanaka M, Kishimoto Y, Sasaki M, Sato A, Kamiya T, Kondo K, Iida K.
Title Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS-Induced Inflammation and Oxidative Stress via MAPK/NF-κB and Akt/AMPK/Nrf2 Pathways.
Journal Oxid Med Cell Longev
Abstract Excessive oxidative stress plays a critical role in the progression of various diseases. Recently, we showed that Terminalia bellirica (Gaertn.) Roxb. extract (TBE) inhibits inflammatory response and reactive oxygen species (ROS) production in THP-1 macrophages. However, molecular mechanisms underlying anti-inflammatory and antioxidant activities of TBE and its major polyphenolic compounds gallic acid (GA) and ellagic acid (EA) remain unclear. We found that TBE and GA attenuated LPS-induced inflammatory mediator expression, ROS production, and activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) in RAW 264 macrophages. Furthermore, TBE and GA increased antioxidant enzyme expression along with upstream mediators nuclear factor erythroid-2-related factor 2 (Nrf2), Akt, and AMP-activated protein kinase (AMPK). Importantly, knockdown of Nrf2 by siRNA and specific inhibition of Akt and AMPK significantly reduced antioxidant enzyme expression induced by TBE and GA. Finally, in vivo effects on histopathology and gene expression were assessed in tissues collected after intraperitoneal injection of LPS with or without TBE treatment. TBE enhanced antioxidant enzyme expression and improved acute kidney injury in LPS-shock model mice. In conclusion, TBE and GA exert protective effects against inflammation and oxidative stress by suppressing MAPK/NF-κB pathway and by activating Akt/AMPK/Nrf2 pathway. These results suggest that TBE and GA might be effective for the treatment of inflammation-related diseases.
Volume 2018
Pages 9364364
Published 2018-11-8
DOI 10.1155/2018/9364364
PMID 30533177
PMC PMC6250009
MeSH Adenylate Kinase / drug effects Adenylate Kinase / metabolism Animals Anti-Inflammatory Agents / pharmacology* Gallic Acid / pharmacology* Inflammation / chemically induced Inflammation / metabolism Lipopolysaccharides / toxicity MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology Male Mice Mice, Inbred ICR NF-E2-Related Factor 2 / drug effects NF-E2-Related Factor 2 / metabolism NF-kappa B / drug effects NF-kappa B / metabolism Oxidative Stress / drug effects* Plant Extracts / pharmacology* Proto-Oncogene Proteins c-akt / drug effects Proto-Oncogene Proteins c-akt / metabolism RAW 264.7 Cells Signal Transduction / drug effects* Terminalia
IF 4.868
Times Cited 15
Human and Animal Cells RAW 264(RCB0535)