PMID- 34798519
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20211214
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 94
DP  - 2022 Jan
TI  - Gegen Qinlian Decoction ameliorates type 2 diabetes osteoporosis via 
      IGFBP3/MAPK/NFATc1 signaling pathway based on cytokine antibody array.
PG  - 153810
LID - S0944-7113(21)00353-6 [pii]
LID - 10.1016/j.phymed.2021.153810 [doi]
AB  - BACKGROUND: Osteoporosis affects more than half the patients with type 2 diabetes 
      mellitus (T2DM). Up to data, there is no effective clinical practice in managing 
      type 2 diabetes osteoporosis (T2DOP) because of its complex pathogenesis. Gegen 
      Qinlian Decoction (GQD) has been used for the long-term management of T2DM. 
      However, the underlying mechanism of GQD in the treatment of T2DOP remains 
      unknown. PURPOSE: To reveal the role of GQD in T2DOP and its potential 
      therapeutic targets in the management of T2DOP. STUDY DESIGN: The effect of GQD 
      on T2DOP was observed in db/db mice in four groups: model group, GQD low-dose 
      group (GQD-L), GQD high-dose group (GQD-H), and metformin (positive control) 
      group. C57BL/6J mice were used as the negative control group. METHODS: 
      Quantitative phytochemical analysis of GQD was performed using high-performance 
      liquid chromatography (HPLC). Micro-CT and hematoxylin-eosin (H&E) staining were 
      used to evaluate bone histomorphometry. To screen for candidate targets of GQD, a 
      cytokine antibody array was used, followed by bioinformatics analysis. 
      Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to 
      determine expression levels. RESULTS: The major active components of GQD were 
      confirmed by HPLC. Micro-CT and H&E staining showed that bone mass was 
      significantly increased in the GQD-H group compared with the model group. 
      Antibody arrays revealed that the expression of insulin-like growth factor 
      binding protein 3 (IGFBP3) was elevated in the GQD-H group. The MAPK pathway was 
      identified using bioinformatics analysis. Additionally, the levels of 
      osteoclastogenesis-related genes, including cathepsin K (Ctsk), acid phosphatase 
      5 (Acp5), matrix metallopeptidase 9 (Mmp9), and ATPase H+ transporting V0 subunit 
      D2 (Atp6v0d2) were significantly decreased in the GQD-H group. Compared with the 
      model group, high-dosage GQD inhibited phosphorylation of extracellular 
      signal-regulated kinases (ERKs) and P38 mitogen-activated protein kinase (MAPK) 
      and the expression of c-Fos and nuclear factor of activated T cells 1 (NFATc1). 
      CONCLUSION: GQD plays a protective role in T2DOP by upregulating IGFBP3 
      expression and downregulating the IGFBP3/MAPK/NFATc1 signaling pathway. IGFBP3 in 
      serum may also be a novel biomarker in the treatment of T2DOP. Our current 
      findings not only expand the application of GQD, but also provide a theoretical 
      basis and guidance for T2DOP.
CI  - Copyright (c) 2021 Elsevier GmbH. All rights reserved.
FAU - Yang, Junzheng
AU  - Yang J
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - He, Qi
AU  - He Q
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Wang, Yunhan
AU  - Wang Y
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, PR China.
FAU - Pan, Zhaofeng
AU  - Pan Z
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Zhang, Gangyu
AU  - Zhang G
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Liang, Jianming
AU  - Liang J
AD  - Science and Technology Innovation Center, Guangzhou University of Chinese 
      Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, PR China.
FAU - Su, Lijun
AU  - Su L
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Wang, Ailin
AU  - Wang A
AD  - Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China.
FAU - Zeng, Chuning
AU  - Zeng C
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Luo, Haoran
AU  - Luo H
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Liu, Lingyun
AU  - Liu L
AD  - College of Basic Medicine, Guangzhou University of Chinese Medicine, 12 Jichang 
      Road, Baiyun District, Guangzhou 510405, PR China.
FAU - Li, Jianliang
AU  - Li J
AD  - First School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 
      Jichang Road, Baiyun District, Guangzhou 510405, PR China; The Laboratory of 
      Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou 
      University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 
      510405, PR China.
FAU - Rao, Qiuhong
AU  - Rao Q
AD  - Department of Pharmacy, The First Affiliated Hospital, Guangzhou University of 
      Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, PR China.
FAU - Wang, Baohua
AU  - Wang B
AD  - Department of Endocrinology, The First Affiliated Hospital, Guangzhou University 
      of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, PR 
      China. Electronic address: wangbaohua@gzhtcm.edu.cn.
FAU - Wang, Haibin
AU  - Wang H
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital, Guangzhou 
      University of Chinese Medicine, 16 Jichang Road, Baiyun District, Guangzhou, 
      Guangdon 510405, PR China. Electronic address: hipknee@163.com.
FAU - Chen, Peng
AU  - Chen P
AD  - Department of Orthopaedic Surgery, The First Affiliated Hospital, Guangzhou 
      University of Chinese Medicine, 16 Jichang Road, Baiyun District, Guangzhou, 
      Guangdon 510405, PR China. Electronic address: docchen777@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20211025
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Cytokines)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (IGFBP3 protein, human)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (NFATC1 protein, human)
RN  - 0 (Nfatc1 protein, mouse)
RN  - 0 (gegenqinlian)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cytokines
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Drugs, Chinese Herbal
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 3
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NFATC Transcription Factors
MH  - *Osteoporosis/drug therapy
MH  - Protein Kinases
MH  - Signal Transduction
OTO - NOTNLM
OT  - Cytokine antibody array
OT  - Gegen qinlian decoction
OT  - IGFBP3/MAPK/NFATc1 signaling pathway
OT  - Type 2 diabetes osteoporosis
EDAT- 2021/11/20 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/11/19 20:32
PHST- 2021/05/02 00:00 [received]
PHST- 2021/10/09 00:00 [revised]
PHST- 2021/10/17 00:00 [accepted]
PHST- 2021/11/20 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/11/19 20:32 [entrez]
AID - S0944-7113(21)00353-6 [pii]
AID - 10.1016/j.phymed.2021.153810 [doi]
PST - ppublish
SO  - Phytomedicine. 2022 Jan;94:153810. doi: 10.1016/j.phymed.2021.153810. Epub 2021 
      Oct 25.