PMID- 31151763
OWN - NLM
STAT- MEDLINE
DCOM- 20191213
LR  - 20231213
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 140
IP  - 1
DP  - 2019 May
TI  - Inhibitory effects of ursolic acid from Bushen Yijing Formula on TGF-beta1-induced 
      human umbilical vein endothelial cell fibrosis via AKT/mTOR signaling and Snail 
      gene.
PG  - 33-42
LID - S1347-8613(19)30037-4 [pii]
LID - 10.1016/j.jphs.2019.04.001 [doi]
AB  - The present study aimed to investigate the functional components from Bushen 
      Yijing Formula and their inhibition of endothelial-mesenchymal transition (EndMT) 
      and fibrosis in human umbilical vascular endothelial cells (HUVECs). HUVEC 
      fibrosis was induced by treatment of transforming growth factor beta (TGF-beta) as the 
      cellular model. Expression of EndMT biomarker gene and cofactors were determined 
      by quantitative real-time-PCR, western blotting, and immunofluorescence. 
      Angiogenesis capacity of vein endothelial cells was evaluated using tube 
      formation assay. Ursolic acid and drug-contained serum ameliorated EndMT 
      biomarker gene expression changes and angiogenesis capacity suppression induced 
      by TGF-beta treatment. Slug, Snail, and Twist gene expression and phosphorylation of 
      mammalian target of rapamycin (mTOR) and AKT altered by TGF-beta in HUVECs were 
      suppressed by ursolic acid and drug-contained serum. Treatment with the mTOR 
      signaling pathway inhibitor, rapamycin, inhibited the phosphorylation of mTOR and 
      AKT, decreased Snail and Vimentin protein levels, and increased VE-cad protein 
      levels. Overexpression of Snail gene promoted expression of EndMT-related genes 
      and suppressed angiogenesis in HUVECs, which were attenuated by application of 
      ursolic acid and drug-contained serum. Ursolic acid from Bushen Yijing Formula 
      inhibits human umbilical vein endothelial cell EndMT and fibrosis, mediated by 
      AKT/mTOR signaling and Snail gene expression.
CI  - Copyright (c) 2019 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Zhu, Ke
AU  - Zhu K
AD  - Department of Dermatology, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, Guangzhou, 510405, China.
FAU - Cao, Cuixiang
AU  - Cao C
AD  - Department of Dermatology, Guangzhou Red Cross Hospital, Medical College, Jinan 
      University, Guangzhou, 510220, China.
FAU - Huang, Jiaqi
AU  - Huang J
AD  - Department of Dermatology, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, Guangzhou, 510405, China.
FAU - Cheng, Zixuan
AU  - Cheng Z
AD  - Department of Dermatology, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, Guangzhou, 510405, China.
FAU - Li, Donghai
AU  - Li D
AD  - Department of Dermatology, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, Guangzhou, 510405, China.
FAU - Liu, Xiuting
AU  - Liu X
AD  - Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, 510120, China.
FAU - Mao, Yueping
AU  - Mao Y
AD  - Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, 510120, China. Electronic address: mao_yp@tom.com.
FAU - Qi, Qing
AU  - Qi Q
AD  - Department of Dermatology, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, Guangzhou, 510405, China; Department of Dermatology, Guangzhou 
      Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China; 
      Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 
      Guangzhou, 510120, China. Electronic address: qing_qi@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190415
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Bushen formula)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Triterpenes)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Drugs, Chinese Herbal/*chemistry
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Fibrosis
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/*drug effects/genetics
MH  - Snail Family Transcription Factors/*genetics
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Transforming Growth Factor beta1/*adverse effects
MH  - Triterpenes/isolation & purification/*pharmacology
MH  - Ursolic Acid
OTO - NOTNLM
OT  - Bushen Yijing Formula
OT  - Snail
OT  - Ursolic acid
OT  - mTOR signaling
EDAT- 2019/06/04 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/06/02 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2019/03/26 00:00 [revised]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/02 06:00 [entrez]
AID - S1347-8613(19)30037-4 [pii]
AID - 10.1016/j.jphs.2019.04.001 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2019 May;140(1):33-42. doi: 10.1016/j.jphs.2019.04.001. Epub 
      2019 Apr 15.