PMID- 37124719
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230502
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues 
      Guided by Transcriptome Analysis.
PG  - 881182
LID - 10.3389/fphar.2022.881182 [doi]
LID - 881182
AB  - Background: Excessive inflammation results in severe tissue damage as well as 
      serious acute or chronic disorders, and extensive research has focused on finding 
      new anti-inflammatory hit compounds with safety and efficacy profiles from 
      natural products. As promising therapeutic entities for the treatment of 
      inflammation-related diseases, fusaproliferin and its analogs have attracted 
      great interest. However, the underlying anti-inflammatory mechanism is still 
      poorly understood and deserves to be further investigated. Methods: For the 
      estimation of the anti-inflammatory activity of fusaproliferin (1) and its 
      analogs (2-4) in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 
      macrophages and zebrafish embryos were employed. Then, transcriptome analysis was 
      applied to guide subsequent western blot analysis of critical proteins in related 
      signaling pathways. Surface plasmon resonance assays (SPR) combined with 
      molecular docking analyses were finally applied to evaluate the affinity 
      interactions between 1-4 and TLR4 and provide a possible interpretation of the 
      downregulation of related signaling pathways. Results: 1-4 significantly 
      attenuated the production of inflammatory messengers, including nitric oxide 
      (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis 
      factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta), as well as nitric oxide synthase 
      (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. 
      Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to 
      reverse LPS stimulation and the nuclear factor kappa-B (NF-kappaB) and 
      mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the 
      anti-inflammatory process. Experimental verification at the protein level 
      revealed that 1 can inhibit the activation of inhibitor of NF-kappaB kinase (IKK), 
      degradation of inhibitor of NF-kappaB (IkappaB), and phosphorylation of NF-kappaB and reduce 
      nuclear translocation of NF-kappaB. 1 also decreased the phosphorylation of MAPKs, 
      including p38, extracellular regulated protein kinases (ERK), and c-Jun 
      N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 
      1-4 exhibited affinity for the TLR4 protein with KD values of 23.5-29.3 muM. 
      Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment 
      of inflammation-associated diseases.
CI  - Copyright (c) 2022 Kuang, Lei, Li, Peng, Wang, Dai, Wang, Gu, Deng and Guo.
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, 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, China.
FAU - Li, Qing-Zhou
AU  - Li QZ
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu, China.
FAU - Peng, Wan
AU  - Peng W
AD  - Institute of Rare Diseases, West China Hospital of Sichuan University, Chengdu, 
      China.
FAU - Wang, Yu-Mei
AU  - Wang YM
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu, China.
FAU - Dai, Yi-Fei
AU  - Dai YF
AD  - Department of Basic Medical Sciences, School of Medicine, Tsinghua University, 
      Beijing, China.
FAU - Wang, Dong
AU  - Wang D
AD  - School of Basic Medical Sciences, Chengdu University of Traditional Chinese 
      Medicine, Chengdu, China.
FAU - Gu, Yu-Cheng
AU  - Gu YC
AD  - Syngenta Jealott's Hill International Research Centre, Berkshire, United Kingdom.
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, China.
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, China.
LA  - eng
PT  - Journal Article
DEP - 20220505
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10136769
OTO - NOTNLM
OT  - Fusarium proliferatum
OT  - anti-inflammatory activity
OT  - fusaproliferin analogues
OT  - surface plasmon resonance assays
OT  - transcriptome analysis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/01 06:42
MHDA- 2023/05/01 06:43
PMCR- 2022/05/05
CRDT- 2023/05/01 03:48
PHST- 2022/02/22 00:00 [received]
PHST- 2022/04/21 00:00 [accepted]
PHST- 2023/05/01 06:43 [medline]
PHST- 2023/05/01 06:42 [pubmed]
PHST- 2023/05/01 03:48 [entrez]
PHST- 2022/05/05 00:00 [pmc-release]
AID - 881182 [pii]
AID - 10.3389/fphar.2022.881182 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 May 5;13:881182. doi: 10.3389/fphar.2022.881182. 
      eCollection 2022.