PMID- 36336221
OWN - NLM
STAT- MEDLINE
DCOM- 20221201
LR  - 20221201
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 302
IP  - Pt A
DP  - 2023 Feb 10
TI  - Huangqin Qingre Qubi Capsule inhibits RA pathology by binding FZD8 and further 
      inhibiting the activity of Wnt/beta-catenin signaling pathway.
PG  - 115886
LID - S0378-8741(22)00925-4 [pii]
LID - 10.1016/j.jep.2022.115886 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Qingre Qubi Capsule (HQC) is a Chinese 
      herbal compound for the treatment of rheumatoid arthritis (RA), which is made 
      from dry roots of Scutellaria baicalensis Georgi, dry mature seeds of Gardenia 
      jasminoides J.Ellis, dry and mature seeds of Coix lacryma-jobi var. stenocarpa 
      Oliv., dry mature seeds of Amygdalus persica L. and roots and rhizomes of 
      Clematis chinensis Osbeck in the proportion of 10:9:30:5:10. HQC has a 
      significant effect in clinical treatment of RA, which can inhibit RA 
      inflammation, improve oxidative stress state, and effectively relieve symptoms of 
      RA patients. AIM OF THE STUDY: The anti-arthritis effect of HQC and its 
      mechanism, especially whether it improves RA through FZD8-Wnt/beta-catenin signal 
      axis, were studied using adjuvant arthritis (AA) rats and FLS from RA patients. 
      MATERIALS AND METHODS: Real time qPCR (RT-qPCR), Western blot (WB), confocal 
      microscopy and other molecular biological methods were used to study the anti-RA 
      effect of HQC and its mechanism. RESULTS: The expression of FZD8 was 
      significantly up-regulated in synovium and FLS of AA rats and RA FLS. FZD8 
      significantly activated the Wnt/beta-catenin signaling pathway, promoted abnormal 
      proliferation of FLS, increased the levels of inflammatory factors IL-1beta, IL-6 
      and IL-8, and significantly increased the expression of matrix metalloproteinase 
      3 (MMP3) and fibronectin. HQC has significant therapeutic effect on AA rats. 
      Molecular docking and molecular dynamics showed that HQC had a good binding 
      ability with FZD8. We also confirmed that HQC inhibited Wnt/beta-catenin signaling 
      pathway by binding FZD8, and reduced the levels of the above inflammatory factors 
      and pathological genes of RA. CONCLUSIONS: The expression of FZD8 is 
      significantly increased in AA rats and FLS from RA patients. Clarify that HQC 
      improves RA through the FZD8-Wnt/beta-catenin signal axis, provide a clear 
      therapeutic mechanism for HQC to improve RA, and also provide a basis for 
      clinical promotion of HQC.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Zhou, Wanwan
AU  - Zhou W
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China.
FAU - Wang, Yuting
AU  - Wang Y
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China.
FAU - Huang, Yurong
AU  - Huang Y
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China.
FAU - Liu, Jian
AU  - Liu J
AD  - Department of Rheumatology, The First Affiliated Hospital, Anhui University of 
      Chinese Medicine, Hefei, China; Institute of Rheumatism, Anhui University of 
      Chinese Medicine, Hefei, China. Electronic address: liujianahzy@126.com.
FAU - Cheng, Chenglong
AU  - Cheng C
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China.
FAU - Xue, Qiuyun
AU  - Xue Q
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China.
FAU - Wang, Xiao
AU  - Wang X
AD  - Department of Clinical Nursing, School of Nursing, Anhui University of Chinese 
      Medicine, Hefei, China.
FAU - Chang, Jun
AU  - Chang J
AD  - Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China; Anhui Public Health Clinical Center, Hefei, China; 
      Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of 
      Life Sciences, Anhui Medical University, Hefei, China. Electronic address: 
      changjun_2008@hotmail.com.
FAU - Miao, Chenggui
AU  - Miao C
AD  - Department of Pharmacology, School of Integrated Chinese and Western Medicine, 
      Anhui University of Chinese Medicine, Hefei, China; Institute of Rheumatism, 
      Anhui University of Chinese Medicine, Hefei, China. Electronic address: 
      miaocg@ahtcm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221104
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (beta Catenin)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Wnt Signaling Pathway
MH  - Scutellaria baicalensis
MH  - beta Catenin/metabolism
MH  - Molecular Docking Simulation
MH  - *Arthritis, Rheumatoid/drug therapy/metabolism
MH  - *Arthritis, Experimental/metabolism
MH  - Synovial Membrane/metabolism
MH  - Fibroblasts/metabolism
OTO - NOTNLM
OT  - Adjuvant-induced arthritis
OT  - FZD8
OT  - Huangqin qingre chubi capsule
OT  - Rheumatoid arthritis
OT  - Wnt/beta-catenin signaling pathway
COIS- Conflicts of interest We confirm that there are no conflicts of interest in this 
      publication and no financial support that has an impact on this work.
EDAT- 2022/11/07 06:00
MHDA- 2022/12/02 06:00
CRDT- 2022/11/06 19:36
PHST- 2022/09/07 00:00 [received]
PHST- 2022/10/18 00:00 [revised]
PHST- 2022/10/26 00:00 [accepted]
PHST- 2022/11/07 06:00 [pubmed]
PHST- 2022/12/02 06:00 [medline]
PHST- 2022/11/06 19:36 [entrez]
AID - S0378-8741(22)00925-4 [pii]
AID - 10.1016/j.jep.2022.115886 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2023 Feb 10;302(Pt A):115886. doi: 10.1016/j.jep.2022.115886. 
      Epub 2022 Nov 4.