Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway

Abstract Purpose This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice. Methods Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg...

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Main Authors: Ying Chen, Rong Rui, Li Wang, Hao Wang, Bingbing Zhu, Aili Cao
Format: Article
Language:English
Published: BMC 2023-06-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-023-04029-1
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author Ying Chen
Rong Rui
Li Wang
Hao Wang
Bingbing Zhu
Aili Cao
author_facet Ying Chen
Rong Rui
Li Wang
Hao Wang
Bingbing Zhu
Aili Cao
author_sort Ying Chen
collection DOAJ
description Abstract Purpose This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice. Methods Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed. Results HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice. Conclusion HQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.
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spelling doaj.art-21813464e5894c4aaacc9c8d2dbe88322023-07-02T11:07:05ZengBMCBMC Complementary Medicine and Therapies2662-76712023-06-0123111310.1186/s12906-023-04029-1Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathwayYing Chen0Rong Rui1Li Wang2Hao Wang3Bingbing Zhu4Aili Cao5Department of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineAbstract Purpose This study aims to investigate the mechanism underlying the beneficial effects of Huangqi decoction (HQD) on Diabetic kidney disease (DKD) in diabetic db/db mice. Methods Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were served as the control group. These mice received HQD treatment for 8 weeks. After treatment, the kidney function, histopathology, micro-assay, and protein expression levels were assessed. Results HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin excretion, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the of mesangial matrix proliferation, foot process effacement, decreased nephrin expression and reduced number of podocytes. Expression profiling analysis revealed global transcriptional changes that predicted related functions, diseases and pathways. HQD treatment activated protein expressions of BMP2, BMP7, BMPR2, and active-Rap1, while inhibiting Smad1 and phospho-ERK. In addition, HQD was associated with improvements in lipid deposition in the kidneys of db/db mice. Conclusion HQD ameliorated the progression of DKD in db/db mice by regulating BMP transcription and downstream targets, inhibiting the phosphorylation of ERK and the expression of Smad1, promoting Rap1 binding to GTP, and regulating the lipid metabolism. These findings provide a potential therapeutic approach for treating DKD.https://doi.org/10.1186/s12906-023-04029-1Huangqi decoction (HQD)Diabetic kidney disease (DKD)Lipid metabolismDb/db mice
spellingShingle Ying Chen
Rong Rui
Li Wang
Hao Wang
Bingbing Zhu
Aili Cao
Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
BMC Complementary Medicine and Therapies
Huangqi decoction (HQD)
Diabetic kidney disease (DKD)
Lipid metabolism
Db/db mice
title Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
title_full Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
title_fullStr Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
title_full_unstemmed Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
title_short Huangqi decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway
title_sort huangqi decoction ameliorates kidney injury in db db mice by regulating the bmp smad signaling pathway
topic Huangqi decoction (HQD)
Diabetic kidney disease (DKD)
Lipid metabolism
Db/db mice
url https://doi.org/10.1186/s12906-023-04029-1
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