PMID- 29047459
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20220409
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 39
IP  - 1
DP  - 2018 Jan
TI  - Protostemonine effectively attenuates lipopolysaccharide-induced acute lung 
      injury in mice.
PG  - 85-96
LID - 10.1038/aps.2017.131 [doi]
AB  - Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the 
      roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine). 
      Here, we reported the inhibitory effects of PSN on lipopolysaccharide 
      (LPS)-induced macrophage activation in vitro and LPS-induced acute lung injury in 
      mice. Macrophage cell line RAW264.7 cells and mouse bone marrow-derived 
      macrophages (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 mumol/L) for 0.5 h 
      and then challenged with LPS (0.1 mug/mL) for 24 h. Pretreatment with PSN 
      significantly inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS 
      expression and NO production in the macrophages. C57BL/6 mice were 
      intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI). 
      The mice were subsequently treated with PSN (10 mg/kg, ip) at 4 and 24 h after 
      LPS challenge. PSN administration significantly attenuated LPS-induced 
      inflammatory cell infiltration, reduced pro-inflammatory cytokine (TNF-alpha, IL-1beta 
      and IL-6) production and eliminated LPS-mediated lung edema. Furthermore, PSN 
      administration significantly inhibited LPS-induced pulmonary MPO activity. 
      Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO 
      production in the lungs were also suppressed. The results demonstrate that PSN 
      effectively attenuates LPS-induced inflammatory responses in vitro and in vivo; 
      the beneficial effects are associated with the decreased phosphorylation of MAPK 
      and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS, 
      NO and cytokines. These data suggest that PSN may be a potential therapeutic 
      agent in the treatment of ALI.
FAU - Wu, Ya-Xian
AU  - Wu YX
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, 
      China.
FAU - He, Hui-Qiong
AU  - He HQ
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, 
      China.
FAU - Nie, Yun-Juan
AU  - Nie YJ
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, 
      China.
FAU - Ding, Yun-He
AU  - Ding YH
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, 
      China.
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.
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.
AD  - Research Center for Cancer Precision Medicine, Bengbu Medical College, Bengbu 
      233030, China.
AD  - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer 
      Institute, Xuzhou Medical University, Xuzhou 221004, China.
LA  - eng
PT  - Journal Article
DEP - 20171019
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Alkaloids)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Lung Injury/chemically induced/*prevention & control
MH  - Alkaloids/administration & dosage/*therapeutic use
MH  - Animals
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/pathology
MH  - Macrophage Activation
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Peroxidase/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pulmonary Edema/prevention & control
MH  - RAW 264.7 Cells
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC5758663
EDAT- 2017/10/20 06:00
MHDA- 2018/09/25 06:00
PMCR- 2019/01/01
CRDT- 2017/10/20 06:00
PHST- 2017/02/13 00:00 [received]
PHST- 2017/06/02 00:00 [accepted]
PHST- 2017/10/20 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2017/10/20 06:00 [entrez]
PHST- 2019/01/01 00:00 [pmc-release]
AID - aps2017131 [pii]
AID - 10.1038/aps.2017.131 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2018 Jan;39(1):85-96. doi: 10.1038/aps.2017.131. Epub 2017 
      Oct 19.