PMID- 32428667
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20210603
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 158
DP  - 2020 Aug
TI  - Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 
      inflammasome activation and pyroptosis.
PG  - 104884
LID - S1043-6618(20)31192-0 [pii]
LID - 10.1016/j.phrs.2020.104884 [doi]
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease 
      with limited therapeutic strategies. Lycorine (LYC), an alkaloid isolated from 
      Amaryllidaceae family plants, exhibits effective anti-inflammatory, antiviral, 
      and anti-tumor activities. In this study, we attempted to determine the effect of 
      LYC on bleomycin (BLM)-induced IPF and NLRP3 inflammasome activation. Our results 
      demonstrated that the LYC treatment ameliorated BLM-induced pulmonary fibrosis 
      and inflammation in mice. LYC inhibited active Caspase-1 expression and lactate 
      dehydrogenase (LDH) release during BLM-induced acute lung injury (ALI) in mice. 
      Furthermore, our in vitro assay showed that LYC inhibited LPS/Nigericin- or 
      LPS/ATP-induced NACHT, LRP and PYD domains-containing protein 3 (NLRP3) 
      inflammasome activation, and pyroptosis in bone marrow-derived macrophages 
      (BMDMs). Mechanically, LYC could disturb the interaction of NLRP3 with 
      apoptosis-associated speck-like protein containing a CARD (ASC) by targeting the 
      pyrin domain (PYD) on Leu9, Leu50, and Thr53. Our findings indicate that LYC 
      ameliorated BLM-induced pulmonary fibrosis by inhibiting NLRP3 inflammasome 
      activation and pyroptosis through targeting the PYD domain of ASC. Thus, LYC 
      might be a potential therapeutic agent for pulmonary inflammation and fibrosis.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Liang, Qing
AU  - Liang Q
AD  - Department of Pharmacy, Shanghai Fifth People's Hospital, Fudan University, 
      Shanghai, 200240, China.
FAU - Cai, Wuyang
AU  - Cai W
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China.
FAU - Zhao, Yaxue
AU  - Zhao Y
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China.
FAU - Xu, Huanbai
AU  - Xu H
AD  - Department of Endocrinology and Metabolism, Shanghai General Hospital, School of 
      Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, China.
FAU - Tang, Huirong
AU  - Tang H
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China.
FAU - Chen, Daijie
AU  - Chen D
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China.
FAU - Qian, Feng
AU  - Qian F
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China; Anhui Province Key Laboratory of Translational Cancer Research, Bengbu 
      Medical College, Bengbu, Anhui Province, 233003, China. Electronic address: 
      fengqian@sjtu.edu.cn.
FAU - Sun, Lei
AU  - Sun L
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China. Electronic address: sunlei_vicky@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200516
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Amaryllidaceae Alkaloids)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Phenanthridines)
RN  - 11056-06-7 (Bleomycin)
RN  - I9Q105R5BU (lycorine)
SB  - IM
MH  - Amaryllidaceae Alkaloids/chemistry/pharmacology/*therapeutic use
MH  - Animals
MH  - Antibiotics, Antineoplastic/toxicity
MH  - Bleomycin/*toxicity
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - HEK293 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Docking Simulation/methods
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & 
      inhibitors/metabolism
MH  - Phenanthridines/chemistry/pharmacology/*therapeutic use
MH  - Protein Structure, Secondary
MH  - Pulmonary Fibrosis/*chemically induced/*drug therapy/metabolism
MH  - Pyroptosis/*drug effects/physiology
OTO - NOTNLM
OT  - Lycorine
OT  - NLRP3 inflammasome
OT  - Pulmonary fibrosis
OT  - Pyroptosis
COIS- Declaration of Competing Interest The authors declare that they have no competing 
      financial interests.
EDAT- 2020/05/20 06:00
MHDA- 2021/06/04 06:00
CRDT- 2020/05/20 06:00
PHST- 2019/12/25 00:00 [received]
PHST- 2020/04/10 00:00 [revised]
PHST- 2020/05/01 00:00 [accepted]
PHST- 2020/05/20 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2020/05/20 06:00 [entrez]
AID - S1043-6618(20)31192-0 [pii]
AID - 10.1016/j.phrs.2020.104884 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Aug;158:104884. doi: 10.1016/j.phrs.2020.104884. Epub 2020 
      May 16.