PMID- 36995149
OWN - NLM
STAT- MEDLINE
DCOM- 20230922
LR  - 20230922
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 45
IP  - 5
DP  - 2023 Oct
TI  - Imperatorin inhibits LPS-induced bone marrow-derived macrophages activation by 
      decreased NF-kappaB p65 phosphorylation.
PG  - 581-588
LID - 10.1080/08923973.2023.2196603 [doi]
AB  - BACKGROUND: Imperatorin (IMP) is a secondary metabolite of plants and is the most 
      abundant in Angelica dahurica. Previous studies showed that IMP exhibited 
      anti-inflammatory activity in RAW264.7 cell line. Here, we aim to investigate the 
      roles and mechanisms of IMP in bone marrow-derived macrophages (BMDMs), in view 
      of the difference between primary macrophages and cell lines. METHODS: BMDMs were 
      stimulated with LPS for the inflammation model. Flow cytometry was performed with 
      BMDMs treated with different doses of IMP (0-20mg/L) within staining Annexin 
      V-APC for 5 min. The cytokines and inflammatory mediators were detected by RT-PCR 
      or ELISA. RNA-seq was performed in IMP-treated BMDMs or control, stimulated with 
      LPS for 6h. Western blotting is carried out to determine the phosphorylation of 
      p65, ERK1/2, JNK1, p38, and Akt. RESULTS: Our results showed that IMP inhibited 
      IL-12p40, IL-6, TNF-alpha and IL-1beta in LPS-stimulated BMDMs. RNA-seq analysis 
      suggested that IMP inhibits Toll-like receptor signaling pathway (KEGG), TNF 
      signaling pathway (KEGG), NF-kappaB signaling pathway (KEGG), Inflammatory Response 
      (GO). In addition, IMP inhibited myd88, tpl2, cxcl1, ptgs2(COX-2) expression in 
      mRNA level. Finally, we found decreased phosphorylation of NF-kappaB p65 in 
      IMP-treated BMDMs, after stimulated with LPS. CONCLUSION: IMP inhibits IL-12p40, 
      IL-6, TNF-alpha, and IL-1beta expression in LPS-stimulated BMDMs. IMP inhibits 
      macrophage activation, which maybe resulted in decreased phosphorylation of NF-kappaB 
      p65. Furthermore, IMP may protect against the progress of inflammatory-related 
      diseases.
FAU - Jiang, Yuan
AU  - Jiang Y
AD  - Department of Pulmonology, Children's Hospital, Zhejiang University School of 
      Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 
      China.
FAU - Fang, Hui
AU  - Fang H
AD  - Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang 
      University, School of Medicine, Hangzhou, China.
FAU - Lin, Siqi
AU  - Lin S
AD  - Department of Pulmonology, Children's Hospital, Zhejiang University School of 
      Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 
      China.
FAU - Chen, Yunyun
AU  - Chen Y
AD  - Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang 
      University, School of Medicine, Hangzhou, China.
FAU - Fu, Yuanzheng
AU  - Fu Y
AD  - Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang 
      University, School of Medicine, Hangzhou, China.
FAU - Tu, Yifan
AU  - Tu Y
AD  - Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang 
      University, School of Medicine, Hangzhou, China.
FAU - Li, Qiang
AU  - Li Q
AD  - The Emergency Department, The Second Affiliated Hospital of Zhejiang University 
      School of Medicine, Hangzhou, Zhejiang, China.
FAU - Hui, Zhaoyuan
AU  - Hui Z
AD  - Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang 
      University, School of Medicine, Hangzhou, China.
AD  - Department of Pathogenic Biology and Medical Immunology, School of Basic Medical 
      Sciences, Ningxia Medical University, Yinchuan, China.
AD  - Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, 
      Yinchuan, China.
LA  - eng
PT  - Journal Article
DEP - 20230411
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (NF-kappa B)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K713N25C78 (imperatorin)
SB  - IM
MH  - Humans
MH  - *NF-kappa B/metabolism
MH  - *Lipopolysaccharides/toxicity
MH  - Interleukin-12 Subunit p40/adverse effects/metabolism
MH  - Interleukin-6/metabolism
MH  - Phosphorylation
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Macrophages/metabolism
MH  - Inflammation/chemically induced/drug therapy/metabolism
OTO - NOTNLM
OT  - Imperatorin
OT  - LPS
OT  - NF-kappaB
OT  - activation
OT  - bone marrow-derived macrophages
EDAT- 2023/03/31 06:00
MHDA- 2023/09/22 06:42
CRDT- 2023/03/30 09:33
PHST- 2023/09/22 06:42 [medline]
PHST- 2023/03/31 06:00 [pubmed]
PHST- 2023/03/30 09:33 [entrez]
AID - 10.1080/08923973.2023.2196603 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2023 Oct;45(5):581-588. doi: 
      10.1080/08923973.2023.2196603. Epub 2023 Apr 11.