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....

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, You, Sun, Boju, Guo, Xiaoyuan, Wu, Lili, Hu, Yaomu, Qin, Lingling, Yang, Tao, Li, Mei, Qin, Tianyu, Jiang, Miao, Liu, Tonghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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
_version_ 1784827474295652352
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
work_keys_str_mv AT wuyou zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT sunboju zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT guoxiaoyuan zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT wulili zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT huyaomu zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT qinlingling zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT yangtao zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT limei zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT qintianyu zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT jiangmiao zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver
AT liutonghua zishenpillalleviatesdiabetesindbdbmiceviaactivationofpi3kaktpathwayintheliver