PMID- 31736758
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Safranal Alleviates Dextran Sulfate Sodium-Induced Colitis and Suppresses 
      Macrophage-Mediated Inflammation.
PG  - 1281
LID - 10.3389/fphar.2019.01281 [doi]
LID - 1281
AB  - Introduction: Crocus sativus (saffron) is widely used in China, Iran, and India 
      for dyeing and as a food additive and medicinal plant. Safranal, as one of the 
      main constituents of saffron, is responsible for its aroma and has been reported 
      to have anticancer, antioxidant, and anti-inflammation properties. Objective: In 
      this study, we investigated the anti-inflammatory effects of Safranal in RAW264.7 
      cells, bone marrow-derived macrophages (BMDMs), and dextran sulfate sodium 
      (DSS)-induced colitis mice. Methods: Safranal toxicity was determined using an 
      MTT assay. We evaluated the inhibitory effect of nitric oxide (NO) and levels of 
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 
      cells and BMDMs. We assessed the inhibitory effect of pro-inflammatory cytokines, 
      and the mRNA expressions of interleukin-6 (IL-6), tumor necrosis factor alpha 
      (TNF-alpha), classical inflammatory pathways (MAPK and NF-kappaB), and the nuclear 
      translocation factors AP-1 and NF-kappaB p65 were investigated. The in vivo 
      anti-inflammatory effects of Safranal were assessed in a DSS-induced colitis 
      model. DSS3.5% was used to induce colitis in mice with or without Safranal for 7 
      days; weight and disease activity index (DAI) were recorded daily. At the end of 
      the experiment, the colon, mesenteric lymph nodes (MLNs), and spleen were 
      collected for flow cytometry, ELISA, and Western blot analysis. Results: Safranal 
      suppressed NO production, iNOS, and COX-2 in lipopolysaccharide (LPS)-stimulated 
      RAW264.7 cells and BMDMs. Safranal decreased the production and mRNA expression 
      of IL-6 and TNF-alpha in the RAW264.7 cell line and inhibited the phosphorylation and 
      nuclear translocation of components of the MAPK and NF-kappaB pathways. Safranal 
      alleviated clinical symptoms in the DSS-induced colitis model, and colon 
      histology showed decreased severity of inflammation, depth of inflammatory 
      involvement, and crypt damage. Immunohistochemical staining and flow cytometry 
      showed reduced macrophage infiltration in colonic tissues and macrophage numbers 
      in MLNs and the spleen. The levels of colonic IL-6 and TNF-alpha also decreased in 
      Safranal-treated colitis mice. This study elucidates the anti-inflammation 
      activity of Safranal, which may be a candidate for inflammatory bowel syndrome 
      (IBD) therapy.
CI  - Copyright (c) 2019 Lertnimitphun, Jiang, Kim, Fu, Zheng, Tan, Zhou, Zhang, Pei, Lu 
      and Xu.
FAU - Lertnimitphun, Peeraphong
AU  - Lertnimitphun P
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Jiang, Yiwen
AU  - Jiang Y
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Kim, Nami
AU  - Kim N
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Fu, Wenwei
AU  - Fu W
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Zheng, Changwu
AU  - Zheng C
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Tan, Hongsheng
AU  - Tan H
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Zhou, Hua
AU  - Zhou H
AD  - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western 
      Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Zhang, Xue
AU  - Zhang X
AD  - Shanghai Traditional Chinese medicine Co., Ltd., Shanghai, China.
FAU - Pei, Weizhong
AU  - Pei W
AD  - Shanghai Traditional Chinese medicine Co., Ltd., Shanghai, China.
FAU - Lu, Yue
AU  - Lu Y
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
FAU - Xu, Hongxi
AU  - Xu H
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
AD  - Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western 
      Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20191101
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6838343
OTO - NOTNLM
OT  - Crocus sativus
OT  - MAPKs
OT  - NF-kappaB
OT  - colitis
OT  - macrophages
OT  - saffron
OT  - safranal
OT  - traditional Chinese medicine
EDAT- 2019/11/19 06:00
MHDA- 2019/11/19 06:01
PMCR- 2019/11/01
CRDT- 2019/11/19 06:00
PHST- 2019/06/28 00:00 [received]
PHST- 2019/10/07 00:00 [accepted]
PHST- 2019/11/19 06:00 [entrez]
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2019/11/19 06:01 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - 10.3389/fphar.2019.01281 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Nov 1;10:1281. doi: 10.3389/fphar.2019.01281. eCollection 
      2019.