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Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway

Podocyte lipid accumulation is a potential therapeutic target for diabetic nephropathy (DN). This study was aimed at clarifying the mechanism of Gandi capsule (GDC) ameliorating DN by regulating the lipid metabolism of podocytes. Network pharmacology methods were performed to screen the key molecule...

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Autores principales: Zhang, Ying, Yao, Huijuan, Li, Chao, Sun, Wei, Chen, Xiaofei, Cao, Yan, Liu, Yue, Liu, Yan, Chen, Jihui, Qi, Jia, Zhang, Qiqiang, Zhang, Hai, Xu, Ajing, Zhang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038418/
https://www.ncbi.nlm.nih.gov/pubmed/35480869
http://dx.doi.org/10.1155/2022/6275505
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author Zhang, Ying
Yao, Huijuan
Li, Chao
Sun, Wei
Chen, Xiaofei
Cao, Yan
Liu, Yue
Liu, Yan
Chen, Jihui
Qi, Jia
Zhang, Qiqiang
Zhang, Hai
Xu, Ajing
Zhang, Jian
author_facet Zhang, Ying
Yao, Huijuan
Li, Chao
Sun, Wei
Chen, Xiaofei
Cao, Yan
Liu, Yue
Liu, Yan
Chen, Jihui
Qi, Jia
Zhang, Qiqiang
Zhang, Hai
Xu, Ajing
Zhang, Jian
author_sort Zhang, Ying
collection PubMed
description Podocyte lipid accumulation is a potential therapeutic target for diabetic nephropathy (DN). This study was aimed at clarifying the mechanism of Gandi capsule (GDC) ameliorating DN by regulating the lipid metabolism of podocytes. Network pharmacology methods were performed to screen the key molecules and potential targets of GDC for constructing the molecular-protein interaction network of GDC and conducting signal pathway enrichment analysis. GDC was predicted to ameliorate DN through SIRT1/AMPK/HNF4A pathway. Our results showed that GDC improved renal function in db/db mice. Besides, GDC exhibited effectiveness in relieving kidney tissue damage and renal lipid accumulation in db/db mice, and same effects were present in GDC-active ingredient baicalin. We further proved the new role of HNF4A in the lipid metabolism of DN mediated by SIRT1 and AMPK signaling pathways. The results suggested decreased expression of SIRT1 and p-AMPKα in the kidney tissue and increased expression of HNF4A of db/db mice compared with the control group. GDC and baicalin could reverse these expression changes. Furthermore, similar expression changes were observed in the murine podocyte cell line (MPC-5) treated with different concentrations of GDC and baicalin. Our research suggested that GDC and its active ingredient baicalin could alleviate the abnormal lipid metabolism in the kidney of db/db mice and might exert renal protection through the SIRT1/AMPK/HNF4A pathway.
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spelling pubmed-90384182022-04-26 Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway Zhang, Ying Yao, Huijuan Li, Chao Sun, Wei Chen, Xiaofei Cao, Yan Liu, Yue Liu, Yan Chen, Jihui Qi, Jia Zhang, Qiqiang Zhang, Hai Xu, Ajing Zhang, Jian Oxid Med Cell Longev Research Article Podocyte lipid accumulation is a potential therapeutic target for diabetic nephropathy (DN). This study was aimed at clarifying the mechanism of Gandi capsule (GDC) ameliorating DN by regulating the lipid metabolism of podocytes. Network pharmacology methods were performed to screen the key molecules and potential targets of GDC for constructing the molecular-protein interaction network of GDC and conducting signal pathway enrichment analysis. GDC was predicted to ameliorate DN through SIRT1/AMPK/HNF4A pathway. Our results showed that GDC improved renal function in db/db mice. Besides, GDC exhibited effectiveness in relieving kidney tissue damage and renal lipid accumulation in db/db mice, and same effects were present in GDC-active ingredient baicalin. We further proved the new role of HNF4A in the lipid metabolism of DN mediated by SIRT1 and AMPK signaling pathways. The results suggested decreased expression of SIRT1 and p-AMPKα in the kidney tissue and increased expression of HNF4A of db/db mice compared with the control group. GDC and baicalin could reverse these expression changes. Furthermore, similar expression changes were observed in the murine podocyte cell line (MPC-5) treated with different concentrations of GDC and baicalin. Our research suggested that GDC and its active ingredient baicalin could alleviate the abnormal lipid metabolism in the kidney of db/db mice and might exert renal protection through the SIRT1/AMPK/HNF4A pathway. Hindawi 2022-04-18 /pmc/articles/PMC9038418/ /pubmed/35480869 http://dx.doi.org/10.1155/2022/6275505 Text en Copyright © 2022 Ying Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Ying
Yao, Huijuan
Li, Chao
Sun, Wei
Chen, Xiaofei
Cao, Yan
Liu, Yue
Liu, Yan
Chen, Jihui
Qi, Jia
Zhang, Qiqiang
Zhang, Hai
Xu, Ajing
Zhang, Jian
Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title_full Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title_fullStr Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title_full_unstemmed Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title_short Gandi Capsule Improved Podocyte Lipid Metabolism of Diabetic Nephropathy Mice through SIRT1/AMPK/HNF4A Pathway
title_sort gandi capsule improved podocyte lipid metabolism of diabetic nephropathy mice through sirt1/ampk/hnf4a pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038418/
https://www.ncbi.nlm.nih.gov/pubmed/35480869
http://dx.doi.org/10.1155/2022/6275505
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