PMID- 29766401
OWN - NLM
STAT- MEDLINE
DCOM- 20190102
LR  - 20190102
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 41
IP  - 5
DP  - 2018 Oct
TI  - Penehyclidine Hydrochloride Decreases Pulmonary Microvascular Endothelial 
      Inflammatory Injury Through a Beta-Arrestin-1-Dependent Mechanism.
PG  - 1610-1620
LID - 10.1007/s10753-018-0804-9 [doi]
AB  - Penehyclidine hydrochloride (PHC), a type of hyoscyamus drug, has both 
      antimuscarinic and antinicotinic activities and retains potent central and 
      peripheral anticholinergic activities. Compared with other hyoscyamine, the 
      notable advantage of PHC is that it has few M(2) receptor-associated 
      cardiovascular side effects. Recent studies and clinical trials have suggested 
      that treatment with penehyclidine hydrochloride may also possess good effects in 
      the treatment of lung injury. The mechanism responsible for this effect has yet 
      to be determined; however, one possibility is that they might do so by a direct 
      effect on pulmonary vascular endothelium. Since inflammatory reactions of the 
      endothelium are signs of endothelial injury in the pathogenesis of lung injury, 
      we determined the effects of penehyclidine hydrochloride on endothelial 
      inflammatory injury in cultured human pulmonary microvascular endothelial cells 
      (HPMVEC). Furthermore, human pulmonary microvascular endothelial cells were 
      transfected with a shRNA-containing plasmid that specifically targets 
      beta-arrestin-1 mRNA, to test whether the effect of penehyclidine hydrochloride 
      on lipopolysaccharide (LPS)-induced endothelial cell injury is dependent on its 
      upregulation of beta-arrestin-1 or not. Penehyclidine hydrochloride reduced the 
      inflammatory responses to LPS stimulation, as evidenced by reduced lactate 
      dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-alpha), and interleukelin-6 
      (IL-6) levels, as well as vascular cell adhesion molecule 1 (VCAM-1) and 
      intercellular cell adhesion molecule-1 (ICAM-1) expressions. This was found to 
      result from increased beta-arrestin-1 expression and decreased nuclear 
      transcription factor-kappaB (NF-kappaB) activation. Expression of a shRNA-containing 
      plasmid that specifically targets beta-arrestin-1 mRNA nullified these effects of 
      penehyclidine hydrochloride. The results indicate that penehyclidine 
      hydrochloride exerts a protective effect on pulmonary microvascular endothelial 
      inflammatory injury induced by LPS. We also demonstrate that this is due to its 
      ability to increase beta-arrestin-1, which in turn inhibits NF-kappaB activation.
FAU - Zheng, Fei
AU  - Zheng F
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China.
FAU - Xiao, Fei
AU  - Xiao F
AD  - Department of Orthopedics, Wuhan Fourth Hospital; Puai Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, 430033, Hubei, 
      People's Republic of China.
FAU - Yuan, Qing-Hong
AU  - Yuan QH
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China.
FAU - Liu, Qiang-Sheng
AU  - Liu QS
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China.
FAU - Zhang, Zong-Ze
AU  - Zhang ZZ
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China.
FAU - Wang, Yan-Lin
AU  - Wang YL
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China.
FAU - Zhan, Jia
AU  - Zhan J
AD  - Department of Anesthesiology, Zhongnan Hospital of Wuhan University, East-Lake 
      Road 169, Wuhan, 430071, Hubei, People's Republic of China. 
      jia19811001@whu.edu.cn.
LA  - eng
GR  - 81101408/National Natural Science Foundation of China/
GR  - 2016070204010150/Youth Science Plan for Light of the Morning Sun of Wuhan City/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (ARRB1 protein, human)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Quinuclidines)
RN  - 0 (beta-Arrestin 1)
RN  - 353CX8CSHD (penehyclidine)
SB  - IM
MH  - Cells, Cultured
MH  - Endothelial Cells/*pathology
MH  - Humans
MH  - Inflammation/chemically induced/*drug therapy
MH  - Lipopolysaccharides
MH  - Lung Injury/chemically induced/*drug therapy
MH  - Microvessels/pathology
MH  - NF-kappa B/antagonists & inhibitors
MH  - Quinuclidines/*pharmacology/therapeutic use
MH  - Up-Regulation/drug effects
MH  - beta-Arrestin 1/*metabolism
OTO - NOTNLM
OT  - NF-kappaB
OT  - beta-arrestin-1
OT  - penehyclidine hydrochloride
OT  - shRNA
EDAT- 2018/05/17 06:00
MHDA- 2019/01/03 06:00
CRDT- 2018/05/17 06:00
PHST- 2018/05/17 06:00 [pubmed]
PHST- 2019/01/03 06:00 [medline]
PHST- 2018/05/17 06:00 [entrez]
AID - 10.1007/s10753-018-0804-9 [pii]
AID - 10.1007/s10753-018-0804-9 [doi]
PST - ppublish
SO  - Inflammation. 2018 Oct;41(5):1610-1620. doi: 10.1007/s10753-018-0804-9.