Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver
BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647929/ https://www.ncbi.nlm.nih.gov/pubmed/36352450 http://dx.doi.org/10.1186/s13020-022-00683-8 |
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author | Wu, You Sun, Boju Guo, Xiaoyuan Wu, Lili Hu, Yaomu Qin, Lingling Yang, Tao Li, Mei Qin, Tianyu Jiang, Miao Liu, Tonghua |
author_facet | Wu, You Sun, Boju Guo, Xiaoyuan Wu, Lili Hu, Yaomu Qin, Lingling Yang, Tao Li, Mei Qin, Tianyu Jiang, Miao Liu, Tonghua |
author_sort | Wu, You |
collection | PubMed |
description | BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP’s hypoglycemic effects using db/db mice. METHODS: Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques. RESULTS: ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group. CONCLUSION: ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-022-00683-8. |
format | Online Article Text |
id | pubmed-9647929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96479292022-11-15 Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver Wu, You Sun, Boju Guo, Xiaoyuan Wu, Lili Hu, Yaomu Qin, Lingling Yang, Tao Li, Mei Qin, Tianyu Jiang, Miao Liu, Tonghua Chin Med Research BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP’s hypoglycemic effects using db/db mice. METHODS: Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques. RESULTS: ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group. CONCLUSION: ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-022-00683-8. BioMed Central 2022-11-10 /pmc/articles/PMC9647929/ /pubmed/36352450 http://dx.doi.org/10.1186/s13020-022-00683-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wu, You Sun, Boju Guo, Xiaoyuan Wu, Lili Hu, Yaomu Qin, Lingling Yang, Tao Li, Mei Qin, Tianyu Jiang, Miao Liu, Tonghua Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title | Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title_full | Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title_fullStr | Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title_full_unstemmed | Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title_short | Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver |
title_sort | zishen pill alleviates diabetes in db/db mice via activation of pi3k/akt pathway in the liver |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647929/ https://www.ncbi.nlm.nih.gov/pubmed/36352450 http://dx.doi.org/10.1186/s13020-022-00683-8 |
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