期刊
AMERICAN JOURNAL OF CHINESE MEDICINE
卷 43, 期 6, 页码 1137-1158出版社
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X15500652
关键词
Phyllanthus acidus (Phyllanthaceae); MAPK; AP-1; TNF-alpha; IL-1 beta; IL-6; Hepatitis
资金
- Cooperative Research Program for Agriculture Science & Technology Development, Rural Development Administration, Korea [PJ009241]
Traditionally, Phyllanthus acidus (Phyllanthaceae) has been used for the treatment of rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Recently, we showed that a methanol extract of Phyllanthaceae (Pa-ME) has a potent anti-inflammatory activity in RAW264.7 cells and strongly ameliorates HCl/EtOH-induced gastric ulcers in mice by targeting the Src/Syk of NF-kappa B. In the present study, we explored the molecular mechanism of Pa-ME on the AP-1 activation pathway and evaluated its potential hepatoprotective effects. To do this, we employed lipopolysaccharide (LPS)-stimulated RAW264.7 cells and U937 cells and an LPS/D-galactosamine (D-GaIN)-induced acute hepatitis mouse model. We utilized a multitude of assays, including immunoblotting analysis, reporter gene assays, and mRNA expression analysis, to determine the effect of Pa-ME on the AP-1 pathway. Pa-ME strikingly suppressed the production of LPS-induced pro-inflammatory cytokines including interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). Furthermore, Pa-ME also strongly inhibited activator protein-1 (AP-1) activation and mitogen-activated protein kinase (MAPK) phosphorylation in LPS-stimulated RAW264.7 macrophages cells and the U937 monocyte like human cell line. Moreover, pre-treatment with Pa-ME exhibited strong hepatoprotective and curative effects in an LPS/D-Gal-induced mouse hepatitis model as evidenced by a decrease in elevated serum AST and ALT levels and the amelioration of histological damage. Taken together, our data suggest that Pa-ME might play a crucial ethnopharmacological role as a hepatoprotective herbal remedy by suppressing MAPK signaling and the activity of the downstream transcription factor AP-1.
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