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Gegen Qinlian Decoction ameliorates type 2 diabetes osteoporosis via IGFBP3/MAPK/NFATc1 signaling pathway based on cytokine antibody array

Gegen Qinlian Decoction ameliorates type 2 diabetes osteoporosis via IGFBP3/MAPK/NFATc1 signaling pathway based on cytokine antibody array

Authors :
Jianming Liang
Gangyu Zhang
Qi He
Junzheng Yang
Lijun Su
Zhaofeng Pan
Yunhan Wang
Haibin Wang
Jianliang Li
Haoran Luo
Qiuhong Rao
Peng Chen
Ailin Wang
Lingyun Liu
Chuning Zeng
Baohua Wang
Source :
Phytomedicine. 94:153810
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

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 GOD 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.

Details

ISSN :
09447113
Volume :
94
Database :
OpenAIRE
Journal :
Phytomedicine
Accession number :
edsair.doi.dedup.....88e20cb237b930b97d3172e25a1da3c0
Full Text :
https://doi.org/10.1016/j.phymed.2021.153810