PMID- 37142684
OWN - NLM
STAT- MEDLINE
DCOM- 20230831
LR  - 20230922
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 44
IP  - 9
DP  - 2023 Sep
TI  - Bergapten inhibits NLRP3 inflammasome activation and pyroptosis via promoting 
      mitophagy.
PG  - 1867-1878
LID - 10.1038/s41401-023-01094-7 [doi]
AB  - Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects 
      in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin 
      phytohormone present in many herbal medicines and fruits, exibits 
      anti-inflammatory activity. In this study we characterized the therapeutic 
      potential of BeG against bacterial infection and inflammation-related disorders, 
      and elucidated the underlying mechanisms. We showed that pre-treatment with BeG 
      (20 muM) effectively inhibited NLRP3 inflammasome activation in both 
      lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived 
      macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1beta 
      release, as well as reduced ASC speck formation and subsequent gasdermin D 
      (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated 
      the expression of genes involved in mitochondrial and reactive oxygen species 
      (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished 
      mitochondrial activity and ROS production after NLRP3 activation, and elevated 
      the expression of LC3-II and enhanced the co-localization of LC3 with 
      mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory 
      effects of BeG on IL-1beta, cleaved caspase-1 and LDH release, GSDMD-N formation as 
      well as ROS production. In mouse model of Escherichia coli-induced sepsis and 
      mouse model of Citrobacter rodentium-induced intestinal inflammation, 
      pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation 
      and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and 
      pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. 
      These results suggest BeG as a promising drug candidate for the treatment of 
      bacterial infection and inflammation-related disorders.
CI  - (c) 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia 
      Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.
FAU - Luo, Tong
AU  - Luo T
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Jia, Xin
AU  - Jia X
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, 100029, China.
FAU - Feng, Wan-di
AU  - Feng WD
AD  - Beijing Academy of Traditional Chinese Medicine, Beijing University of Chinese 
      Medicine, Beijing, 100029, China.
FAU - Wang, Jin-Yong
AU  - Wang JY
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, 100029, China.
FAU - Xie, Fang
AU  - Xie F
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Kong, Ling-Dong
AU  - Kong LD
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, 
      Beijing, 100029, China.
FAU - Wang, Xue-Jiao
AU  - Wang XJ
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Lian, Rui
AU  - Lian R
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Liu, Xia
AU  - Liu X
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Chu, Ying-Jie
AU  - Chu YJ
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China.
FAU - Wang, Yao
AU  - Wang Y
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China. yaowang@bucm.edu.cn.
FAU - Xu, An-Long
AU  - Xu AL
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, 
      China. xuanlong@bucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230504
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Reactive Oxygen Species)
RN  - 4FVK84C92X (5-Methoxypsoralen)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Inflammasomes/metabolism
MH  - *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Pyroptosis
MH  - Reactive Oxygen Species/metabolism
MH  - 5-Methoxypsoralen/pharmacology
MH  - Mitophagy
MH  - Inflammation/drug therapy/metabolism
MH  - Caspase 1/metabolism
MH  - Interleukin-1beta/metabolism
PMC - PMC10462717
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - bergapten
OT  - intestinal inflammation
OT  - mitophagy
OT  - pyroptosis
OT  - sepsis
COIS- The authors declare no competing interests.
EDAT- 2023/05/05 00:42
MHDA- 2023/08/31 06:41
PMCR- 2024/09/01
CRDT- 2023/05/04 23:22
PHST- 2022/12/12 00:00 [received]
PHST- 2023/04/17 00:00 [accepted]
PHST- 2024/09/01 00:00 [pmc-release]
PHST- 2023/08/31 06:41 [medline]
PHST- 2023/05/05 00:42 [pubmed]
PHST- 2023/05/04 23:22 [entrez]
AID - 10.1038/s41401-023-01094-7 [pii]
AID - 1094 [pii]
AID - 10.1038/s41401-023-01094-7 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2023 Sep;44(9):1867-1878. doi: 10.1038/s41401-023-01094-7. 
      Epub 2023 May 4.