PMID- 34597905
OWN - NLM
STAT- MEDLINE
DCOM- 20211015
LR  - 20211015
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 92
DP  - 2021 Nov
TI  - Aqueous extract of Paeoniae Radix Rubra prevents deep vein thrombosis by 
      ameliorating inflammation through inhibiting GSK3beta activity.
PG  - 153767
LID - S0944-7113(21)00310-X [pii]
LID - 10.1016/j.phymed.2021.153767 [doi]
AB  - BACKGROUND: Deep vein thrombosis (DVT) is a kind of blood stasis syndrome. 
      Paeoniae Radix Rubra (PRR) has long been widely used for eliminating blood stasis 
      in China, but its effect on DVT has not yet been reported. PURPOSE: The present 
      study aimed to assess the potential inhibitory effect of the aqueous extract of 
      PRR (i.e.,PRR dispensing granule, PRRDG) on DVT and explore the underlying 
      mechanism. STUDY DESIGN/METHODS: The chemical profile of PRRDG was analyzed by 
      high-performance liquid chromatography. Sprague-Dawley rats were intragastrically 
      treated with PRRDG (0.625, 1.25 and 1.875 g crude drug/kg/d) once daily for 7 
      consecutive days. On the sixth day, a model of inferior vena cava (IVC) 
      stenosis-induced DVT was established. All rats were sacrificed on the seventh 
      day. Serum was collected for enzyme-linked immunosorbent assay. 
      Thrombus-containing IVC was weighed and further processed for histopathologic 
      examination, immunohistochemical analysis and western blotting. LiCl and LY294002 
      were adopted to block and increase the activity of glycogen synthase kinase 3beta 
      (GSK3beta), respectively. RESULTS: The chemical profile analysis showed that 
      paeoniflorin, benzoylpaeoniflorin, albiflorin, gallic acid and catechin were the 
      main constituents of PRRDG. LiCl decreased thrombus weight, reduced the number of 
      inflammatory cells in thrombus and vein wall, down-regulated phosphorylated NF-kappaB 
      p65 (p-p65) protein expression. Similarly, PRRDG decreased thrombus weight and 
      tissue factor (TF) protein expression. PRRDG reduced the protein expression 
      levels of P-selectin, monocyte chemoattractant protein-1 (MCP-1), intercellular 
      cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) 
      in venous endothelium, serum levels of tumor necrosis factor-alpha (TNF-alpha) and 
      interleukin-1beta (IL-1beta), and the number of inflammatory cells in thrombus and vein 
      wall. Moreover, PRRDG down-regulated p-p65 protein expression and up-regulated 
      phosphorylated GSK3beta (p-GSK3beta) protein expression. LY294002 abrogated the 
      inhibitory effects of PRRDG on thrombus weight, TF protein expression, TNF-alpha and 
      IL-1beta serum levels, inflammatory cells influxes, and p-p65 protein expression. 
      CONCLUSION: PRRDG prevents DVT by ameliorating inflammation through inhibiting 
      GSK3beta activity.
CI  - Copyright (c) 2021 Elsevier GmbH. All rights reserved.
FAU - Lu, Ziqi
AU  - Lu Z
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China; Guangzhou Hipower Pharmaceutical R&D Co., 
      Ltd., Medicine Department, Guangzhou 510006, Guangdong, China.
FAU - Ye, Yuxin
AU  - Ye Y
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Liu, Youchen
AU  - Liu Y
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Yang, Xinrong
AU  - Yang X
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Ding, Qi
AU  - Ding Q
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Wang, Yiting
AU  - Wang Y
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Wu, Zhongrui
AU  - Wu Z
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Zhan, Yaxian
AU  - Zhan Y
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Gui, Shuhua
AU  - Gui S
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China.
FAU - Lin, Bingqing
AU  - Lin B
AD  - College of Mathematics and Statistics, Shenzhen University, Shenzhen 518060, 
      Guangdong, China. Electronic address: bqlin@szu.edu.cn.
FAU - Lin, Baoqin
AU  - Lin B
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou 510006, Guangdong, China. Electronic address: linbaoqin@gzucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210920
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Pharmaceutical Preparations)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Glycogen Synthase Kinase 3
MH  - Inflammation/drug therapy
MH  - *Paeonia
MH  - *Pharmaceutical Preparations
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vena Cava, Inferior
MH  - *Venous Thrombosis/drug therapy/prevention & control
OTO - NOTNLM
OT  - Aqueous extract of Paeoniae Radix Rubra
OT  - Deep vein thrombosis
OT  - Dispensing granule
OT  - GSK3beta
OT  - Inflammation
EDAT- 2021/10/02 06:00
MHDA- 2021/10/16 06:00
CRDT- 2021/10/01 20:24
PHST- 2021/06/26 00:00 [received]
PHST- 2021/09/14 00:00 [revised]
PHST- 2021/09/16 00:00 [accepted]
PHST- 2021/10/02 06:00 [pubmed]
PHST- 2021/10/16 06:00 [medline]
PHST- 2021/10/01 20:24 [entrez]
AID - S0944-7113(21)00310-X [pii]
AID - 10.1016/j.phymed.2021.153767 [doi]
PST - ppublish
SO  - Phytomedicine. 2021 Nov;92:153767. doi: 10.1016/j.phymed.2021.153767. Epub 2021 
      Sep 20.