PMID- 33729688
OWN - NLM
STAT- MEDLINE
DCOM- 20210604
LR  - 20210604
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
VI  - 36
IP  - 7
DP  - 2021 Jul
TI  - Shenlian extract protects against ultrafine particulate matter-aggravated 
      myocardial ischemic injury by inhibiting inflammation response via the activation 
      of NLRP3 inflammasomes.
PG  - 1349-1361
LID - 10.1002/tox.23131 [doi]
AB  - Air pollution is a growing public health burden associated with several negative 
      health effects, especially cardiovascular disease. Shenlian extract (SL), a 
      traditional Chinese medicine, has the effects of clearing heat-toxin and 
      promoting blood circulation for removing blood stasis, and it has long been used 
      to treat cardiovascular diseases and atherosclerosis. This study explored the 
      underlying action mechanism of SL against ultrafine particle-induced myocardial 
      ischemic injury (UFP-MI) through network pharmacology prediction and experimental 
      verification. Male Sprague-Dawley rats with UFP-MI were pre-treated with SL 
      intragastrically for 7 days. All the rats were then euthanized. Inflammatory 
      cytokine detection and histopathological analysis were performed to assess the 
      protective effects of SL. For the mechanism study, differentially expressed genes 
      (DEGs) were identified in UFP-MI rats treated with SL through transcriptomic 
      analysis. Subsequently, in combination with network pharmacology, potential 
      pathways involved in the effects of SL treatment were identified using the 
      Internet-based Computation Platform (www.tcmip.cn) and Cytoscape 3.6.0. Further 
      validation experiments were performed to reveal the mechanism of the therapeutic 
      effects of SL on UFP-MI. The results show that SL significantly suppressed 
      inflammatory cell infiltration into myocardial tissue and exhibited significant 
      anti-inflammatory activity. Transcriptomic analysis revealed that the DEGs after 
      SL treatment had significant anti-inflammatory, immunomodulatory, and anti-viral 
      activities. Network pharmacology analysis illustrated that the targets of SL were 
      mainly involved in regulation of the inflammatory response, apoptotic process, 
      innate immune response, platelet activation, and coagulation process. By 
      combining transcriptomic and network pharmacology data, we found that SL may 
      exert anti-inflammatory effects by acting on the NOD-like signaling pathway to 
      regulate immune response activation and inhibit systemic inflammation. 
      Verification experiments revealed that SL can suppress the secretion of the 
      inflammatory cytokines Interleukin-1 (IL-1), Interleukin-18(IL-18) and 
      Interleukin-33(IL-33) and suppress NLRP3 inflammasome activity. The results 
      suggested that SL can directly inhibit the activation of NLRP3 inflammasomes and 
      reduce the release of cytokines to protect against ultrafine particulate 
      matter-aggravated myocardial ischemic injury.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Qu, Shuiqing
AU  - Qu S
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
AD  - School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 
      Guangzhou, China.
FAU - Li, Kai
AU  - Li K
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Yang, Ting
AU  - Yang T
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Yang, Yuanmin
AU  - Yang Y
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Zheng, Zhongyuzn
AU  - Zheng Z
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Liu, Hui
AU  - Liu H
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
AD  - School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 
      Guangzhou, China.
FAU - Wang, Xi
AU  - Wang X
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Deng, Shuoqiu
AU  - Deng S
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Zhu, Xiaoxin
AU  - Zhu X
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
FAU - Chen, Lina
AU  - Chen L
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Li, Yujie
AU  - Li Y
AUID- ORCID: 0000-0002-2359-2673
AD  - Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing, 
      China.
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
LA  - eng
GR  - 2017ZX09101002-001-001-3/Major National Science and Technology Program of China 
      for Innovative Drug/
GR  - 2017ZX09301012002/Major National Science and Technology Program of China for 
      Innovative Drug/
GR  - 81803814/Innovative Research Groups of the National Natural Science Foundation of 
      China/
GR  - 81841001/Innovative Research Groups of the National Natural Science Foundation of 
      China/
GR  - 81673640/Innovative Research Groups of the National Natural Science Foundation of 
      China/
PT  - Journal Article
DEP - 20210317
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, rat)
RN  - 0 (Particulate Matter)
SB  - IM
MH  - Animals
MH  - *Inflammasomes
MH  - Inflammation/chemically induced/prevention & control
MH  - Male
MH  - *NLR Family, Pyrin Domain-Containing 3 Protein/genetics
MH  - Particulate Matter/toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - NLRP3 inflammasomes
OT  - SL extract
OT  - mechanism of action
OT  - myocardial ischemic injury
OT  - network pharmacology
OT  - ultrafine particle
EDAT- 2021/03/18 06:00
MHDA- 2021/06/05 06:00
CRDT- 2021/03/17 12:52
PHST- 2021/03/05 00:00 [revised]
PHST- 2020/09/17 00:00 [received]
PHST- 2021/03/07 00:00 [accepted]
PHST- 2021/03/18 06:00 [pubmed]
PHST- 2021/06/05 06:00 [medline]
PHST- 2021/03/17 12:52 [entrez]
AID - 10.1002/tox.23131 [doi]
PST - ppublish
SO  - Environ Toxicol. 2021 Jul;36(7):1349-1361. doi: 10.1002/tox.23131. Epub 2021 Mar 
      17.