PMID- 27618898
OWN - NLM
STAT- MEDLINE
DCOM- 20170501
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 9
DP  - 2016 Aug 27
TI  - Cleome rutidosperma and Euphorbia thymifolia Suppress Inflammatory Response via 
      Upregulation of Phase II Enzymes and Modulation of NF-kappaB and JNK Activation in 
      LPS-Stimulated BV2 Microglia.
LID - 10.3390/ijms17091420 [doi]
LID - 1420
AB  - Cleome rutidosperma DC. and Euphorbia thymifolia L. are herbal medicines used in 
      traditional Indian and Chinese medicine to treat various illnesses. Reports 
      document that they have antioxidant and anti-inflammatory activities; 
      nonetheless, the molecular mechanisms involved in their anti-inflammatory actions 
      have not yet been elucidated. The anti-neuroinflammatory activities and 
      underlying mechanisms of ethanol extracts of Cleome rutidosperma (CR) and 
      Euphorbia thymifolia (ET) were studied using lipopolysaccharide (LPS)-stimulated 
      microglial cell line BV2. The morphology changes and production of 
      pro-inflammatory mediators were assayed. Gene expression of inflammatory genes 
      such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, 
      interleukin (IL)-1beta, and CC chemokine ligand (CCL)-2, as well as phase II enzymes 
      such as heme oxygenase (HO)-1, the modifier subunit of glutamate cysteine ligase 
      (GCLM) and NAD(P)H quinone dehydrogenase 1 (NQO1), were further investigated 
      using reverse transcription quantitative-PCR (RT-Q-PCR) and Western blotting. The 
      effects of CR and ET on mitogen activated protein kinases (MAPKs) and nuclear 
      factor (NF)-kappaB signaling pathways were examined using Western blotting and 
      specific inhibitors. CR and ET suppressed BV2 activation, down-regulated iNOS and 
      COX-2 expression and inhibited nitric oxide (NO) overproduction without affecting 
      cell viability. They reduced LPS-mediated tumor necrosis factor (TNF) and IL-6 
      production, attenuated IL-1beta and CCL2 expression, but upregulated HO-1, GCLM and 
      NQO1 expression. They also inhibited p65 NF-kappaB phosphorylation and modulated 
      Jun-N terminal kinase (JNK) activation in BV2 cells. SP600125, the JNK inhibitor, 
      significantly augmented the anti-IL-6 activity of ET. NF-kappaB inhibitor, Bay 
      11-7082, enhanced the anti-IL-6 effects of both CR and ET. Znpp, a competitive 
      inhibitor of HO-1, attenuated the anti-NO effects of CR and ET. Our results show 
      that CR and ET exhibit anti-neuroinflammatory activities by inhibiting 
      pro-inflammatory mediator expression and production, upregulating HO-1, GCLM and 
      NQO1, blocking NF-kappaB and modulating JNK signaling pathways. They may offer 
      therapeutic potential for suppressing overactivated microglia and alleviating 
      neurodegeneration.
FAU - Ding, Hsiou-Yu
AU  - Ding HY
AD  - Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, 
      Tainan 717, Taiwan. hsiou221@yahoo.com.tw.
FAU - Wu, Pei-Shan
AU  - Wu PS
AD  - Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 
      717, Taiwan. dc7575@gmail.com.
FAU - Wu, Ming-Jiuan
AU  - Wu MJ
AD  - Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 
      717, Taiwan. imwu@mail.cnu.edu.tw.
LA  - eng
PT  - Journal Article
DEP - 20160827
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrites)
RN  - 0 (Plant Extracts)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/chemistry/*pharmacology
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cleome/*chemistry
MH  - Euphorbia/*chemistry
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Microglia/drug effects/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Nitrites/metabolism
MH  - Plant Extracts/chemistry/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC5037699
OTO - NOTNLM
OT  - Cleome rutidosperma
OT  - Euphorbia thymifolia
OT  - HO-1
OT  - JNK
OT  - NF-kappaB
OT  - microglial cells
COIS- The founding sponsors had no role in the design of the study; in the collection, 
      analyses, or interpretation of data; in the writing of the manuscript, and in the 
      decision to publish the results.
EDAT- 2016/09/14 06:00
MHDA- 2017/05/02 06:00
PMCR- 2016/09/01
CRDT- 2016/09/14 06:00
PHST- 2016/06/29 00:00 [received]
PHST- 2016/08/07 00:00 [revised]
PHST- 2016/08/22 00:00 [accepted]
PHST- 2016/09/14 06:00 [entrez]
PHST- 2016/09/14 06:00 [pubmed]
PHST- 2017/05/02 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - ijms17091420 [pii]
AID - ijms-17-01420 [pii]
AID - 10.3390/ijms17091420 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 Aug 27;17(9):1420. doi: 10.3390/ijms17091420.