Open AccessInhibition of Inflammatory Responses byCentella asiaticavia Suppression of IRAK1-TAK1 in Mouse Macrophages
Author(s) -
Young-Chang Cho,
Huong Lan Vuong,
Jain Ha,
Sewoong Lee,
Jiyoung Park,
Agung Eru Wibow,
Sayeon Cho
Publication year - 2020
Publication title -
the american journal of chinese medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 63
eISSN - 1793-6853
pISSN - 0192-415X
DOI - 10.1142/s0192415x20500548
Subject(s) - centella , downregulation and upregulation , inflammation , phosphorylation , kinase , tumor necrosis factor alpha , pharmacology , medicine , microbiology and biotechnology , immunology , chemistry , biology , biochemistry , traditional medicine , gene
Centella asiatica (L.) Urb. (C. asiatica) has been widely treated for inflammation-related diseases in China for thousands of years. While C. asiatica showed relevant effects as traditional medicine, the mechanism of C. asiatica suppressing inflammation has not been thoroughly investigated. Therefore, this study was conducted to reveal the anti-inflammatory mechanism of methanol fraction from C. asiatica (MCA) at the molecular level in murine macrophages. Levels of inflammation-related mediators were observed with treatment of MCA. MCA significantly suppressed nitric oxide production and iNOS expression in RAW 264.7 macrophages. Prostaglandin E 2 production was alleviated by MCA via the downregulation of cyclooxygenase-2. MCA treatment also reduced pro-inflammatory tumor necrosis factor-[Formula: see text] and interleukin (IL)-6 levels. LPS/D-GalN-induced acute hepatitis in mouse was alleviated by MCA treatment. In addition, MCA decreased the phosphorylation of inhibitory [Formula: see text]B[Formula: see text] (I[Formula: see text]B[Formula: see text]) at Ser32/36 and thereby blocked I[Formula: see text]B[Formula: see text] degradation. TXY motif phosphorylation in the activation loops of mitogen-activated protein kinases (MAPKs) was also suppressed by MCA treatment. Further investigation revealed that MCA inhibited transforming growth factor-[Formula: see text]-activated kinase 1 (TAK1) phosphorylation and IL-1 receptor-associated kinase (IRAK1) degradation, the upstream kinases activating nuclear factor [Formula: see text]B and MAPKs. Taken together, MCA exhibited anti-inflammatory properties via the downregulation of IRAK1-TAK1 signaling pathways.