PMID- 35447407
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20220630
IS  - 1090-2120 (Electronic)
IS  - 0045-2068 (Linking)
VI  - 124
DP  - 2022 Jul
TI  - Proliferatins suppress lipopolysaccharide-induced inflammation via inhibition of 
      the NF-kappaB and MAPK signaling pathways.
PG  - 105810
LID - S0045-2068(22)00215-2 [pii]
LID - 10.1016/j.bioorg.2022.105810 [doi]
AB  - Three previously undescribed polyketides [proliferatin A-C (1-3)] with 
      anti-inflammatory activity were isolated from Fusarium proliferatum. 1-3 
      attenuated the production of inflammatory signal messengers including nitric 
      oxide (NO), reactive oxygen species, proinflammatory cytokines interleukin-6 
      (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta), as well as 
      the related proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in 
      lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Transcriptome analyses 
      based on RNA-seq indicated the potential anti-inflammatory mechanism of 1-3 
      involved in the nuclear factor kappa-B (NF-kappaB) and mitogen activated protein 
      kinases (MAPKs) signaling pathways. Experimental evaluation of the protein levels 
      revealed that 1-3 can inhibit the phosphorylation of IkappaB kinase (IKK), the 
      degradation of NF-kappaB Inhibitor-alpha (IkappaBalpha), the phosphorylation of nuclear factor-kappaB 
      (NF-kappaB) and can reduce NF-kappaB transportation to the nucleus. Interestingly, 1-3 
      decreased the phosphorylation of MAPKs including p-p38, p-ERK, and p-JNK. 
      Molecular docking models suggest that binding of 1-3 to TLR4-MD-2 complex may 
      lead to inhibition of NF-kappaB and MAPK signaling pathways, which was confirmed in 
      vitro by surface plasmon resonance (SPR) assays. 1-3 can thus constitute 
      potential therapeutic candidates for the treatment of inflammation-associated 
      diseases.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Kuang, Qi-Xuan
AU  - Kuang QX
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
      Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, 
      People's Republic of China.
FAU - Li, Qing-Zhou
AU  - Li QZ
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
      Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, 
      People's Republic of China.
FAU - Lei, Li-Rong
AU  - Lei LR
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
      Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, 
      People's Republic of China.
FAU - Wang, Yu-Mei
AU  - Wang YM
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, People's Republic of China.
FAU - Huang, Li-Jun
AU  - Huang LJ
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, People's Republic of China.
FAU - Dai, Yi-Fei
AU  - Dai YF
AD  - Department of Basic Medical Sciences, School of Medicine, Tsinghua University, 
      Beijing 100084, People's Republic of China.
FAU - Peng, Wan
AU  - Peng W
AD  - Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu 
      610065, People's Republic of China.
FAU - Zhang, Ming-Zhi
AU  - Zhang MZ
AD  - Jiangsu Key Laboratory of Pesticide Science, College of Sciences, Nanjing 
      Agricultural University, Nanjing 210095, People's Republic of China.
FAU - Wang, Dong
AU  - Wang D
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu 611137, People's Republic of China.
FAU - Gu, Yu-Cheng
AU  - Gu YC
AD  - Syngenta Jealott's Hill International Research Centre, Berkshire, UK.
FAU - Deng, Yun
AU  - Deng Y
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
      Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, 
      People's Republic of China. Electronic address: dengyun@cdutcm.edu.cn.
FAU - Guo, Da-le
AU  - Guo DL
AD  - State Key Laboratory of Southwestern Chinese Medicine Resources, School of 
      Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, 
      People's Republic of China. Electronic address: guodale@cdutcm.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220413
PL  - United States
TA  - Bioorg Chem
JT  - Bioorganic chemistry
JID - 1303703
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Cyclooxygenase 2/metabolism
MH  - Humans
MH  - Inflammation/chemically induced/drug therapy
MH  - *Lipopolysaccharides/metabolism/pharmacology
MH  - MAP Kinase Signaling System
MH  - Molecular Docking Simulation
MH  - *NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Anti-inflammatory activity
OT  - Fusarium proliferatum
OT  - MAPK
OT  - NF-kappaB
OT  - Proliferatin A-C
EDAT- 2022/04/22 06:00
MHDA- 2022/06/07 06:00
CRDT- 2022/04/21 20:13
PHST- 2021/11/22 00:00 [received]
PHST- 2022/04/07 00:00 [revised]
PHST- 2022/04/11 00:00 [accepted]
PHST- 2022/04/22 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/04/21 20:13 [entrez]
AID - S0045-2068(22)00215-2 [pii]
AID - 10.1016/j.bioorg.2022.105810 [doi]
PST - ppublish
SO  - Bioorg Chem. 2022 Jul;124:105810. doi: 10.1016/j.bioorg.2022.105810. Epub 2022 
      Apr 13.