TY - JOUR
T1 - Boerhavia diffusa L. ethanol extract suppresses inflammatory responses via inhibition of Src/Syk/TRAF6
AU - Van Thai, Ha
AU - Kim, Eunji
AU - Kim, Seung Cheol
AU - Jeong, Deok
AU - Yang, Sungjae
AU - Baek, Kwang Soo
AU - Kim, Yong
AU - Ratan, Zubair Ahmed
AU - Yoon, Kee Dong
AU - Kim, Jong Hoon
AU - Cho, Jae Youl
N1 - Funding Information:
We are grateful to Drs. Deok Hyo Yoon, Khin Myo Htwe, Young-Dong Kim, and Woo-Shin Lee for providing excellent technical assistance. A National Institute of Biological Resources (NIBR) grant funded by the Korean government (ME) and supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare , Republic of Korea ( HI12C0050 ), supported this work.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Boerhavia diffusa L. is a green vegetable used as an herbal medicine in several Asian countries for the treatment of hepatitis, kidney stones, liver disorders, nephritis, urinary disorders, and urinary retention. In this study, the anti-inflammatory activity and the molecular inhibitory mechanisms of B. diffusa L. ethanol extract (Bd-EE) in vitro and in vivo were evaluated. Lipopolysaccharide (LPS)-activated peritoneal macrophage RAW264.7 cells and a mouse gastritis model induced by HCl/EtOH treatment were chosen to determine the in vitro and in vivo anti-inflammatory activities of Bd-EE. This extract (100 and 200 μg/ml) significantly (P < 0.01) inhibited nitric oxide (NO) and tumour necrosis factor (TNF)-α production in peritoneal macrophages and in RAW264.7 cells during LPS exposure at both. The inducible nitric oxide synthase (iNOS) and TNF-α mRNA expression levels were decreased. In addition, nuclear levels of p65, p50, c-Fos, and c-Jun transcription factors were reduced by Bd-EE treatment; moreover, it inhibited NF-κB upstream signalling via IκBα, PI3K, Syk, and Src. Furthermore, analysis of AP-1 upstream signalling revealed that the AP-1 activation pathway consisting of TRAF6, TAK1, MKK4/7, and MKK3/6 was also predominantly inhibited by Bd-EE. By HPLC analysis, luteolin was identified as a major ingredient displaying NO inhibitory activity. The data provided here strongly suggest that the anti-inflammatory property of Bd-EE is linked to the suppression of Syk, Src, and TRAF6.
AB - Boerhavia diffusa L. is a green vegetable used as an herbal medicine in several Asian countries for the treatment of hepatitis, kidney stones, liver disorders, nephritis, urinary disorders, and urinary retention. In this study, the anti-inflammatory activity and the molecular inhibitory mechanisms of B. diffusa L. ethanol extract (Bd-EE) in vitro and in vivo were evaluated. Lipopolysaccharide (LPS)-activated peritoneal macrophage RAW264.7 cells and a mouse gastritis model induced by HCl/EtOH treatment were chosen to determine the in vitro and in vivo anti-inflammatory activities of Bd-EE. This extract (100 and 200 μg/ml) significantly (P < 0.01) inhibited nitric oxide (NO) and tumour necrosis factor (TNF)-α production in peritoneal macrophages and in RAW264.7 cells during LPS exposure at both. The inducible nitric oxide synthase (iNOS) and TNF-α mRNA expression levels were decreased. In addition, nuclear levels of p65, p50, c-Fos, and c-Jun transcription factors were reduced by Bd-EE treatment; moreover, it inhibited NF-κB upstream signalling via IκBα, PI3K, Syk, and Src. Furthermore, analysis of AP-1 upstream signalling revealed that the AP-1 activation pathway consisting of TRAF6, TAK1, MKK4/7, and MKK3/6 was also predominantly inhibited by Bd-EE. By HPLC analysis, luteolin was identified as a major ingredient displaying NO inhibitory activity. The data provided here strongly suggest that the anti-inflammatory property of Bd-EE is linked to the suppression of Syk, Src, and TRAF6.
KW - Anti-inflammatory effect
KW - Boerhavia diffusa L. (Phyllanthaceae)
KW - Luteolin
KW - Src
KW - Syk
KW - TRAF6
UR - http://www.scopus.com/inward/record.url?scp=84938853725&partnerID=8YFLogxK
U2 - 10.1016/j.jff.2015.06.004
DO - 10.1016/j.jff.2015.06.004
M3 - Article
AN - SCOPUS:84938853725
VL - 17
SP - 476
EP - 490
JO - Journal of Functional Foods
JF - Journal of Functional Foods
SN - 1756-4646
ER -