Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver
Abstract 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 u...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-022-00683-8 |
| _version_ | 1817970301347037184 |
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| author | You Wu Boju Sun Xiaoyuan Guo Lili Wu Yaomu Hu Lingling Qin Tao Yang Mei Li Tianyu Qin Miao Jiang Tonghua Liu |
| author_facet | You Wu Boju Sun Xiaoyuan Guo Lili Wu Yaomu Hu Lingling Qin Tao Yang Mei Li Tianyu Qin Miao Jiang Tonghua Liu |
| author_sort | You Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T20:32:23Z |
| format | Article |
| id | doaj.art-798edf083b5b42d2a5ac39b6c8432047 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-04-13T20:32:23Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-798edf083b5b42d2a5ac39b6c84320472022-12-22T02:31:08ZengBMCChinese Medicine1749-85462022-11-0117111310.1186/s13020-022-00683-8Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liverYou Wu0Boju Sun1Xiaoyuan Guo2Lili Wu3Yaomu Hu4Lingling Qin5Tao Yang6Mei Li7Tianyu Qin8Miao Jiang9Tonghua Liu10Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineSchool of Life Science, Beijing University of Chinese MedicineKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese MedicineAbstract 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.https://doi.org/10.1186/s13020-022-00683-8ZiShen PillDiabetesInsulin resistanceTranscriptomicsGlucolipid metabolism |
| spellingShingle | You Wu Boju Sun Xiaoyuan Guo Lili Wu Yaomu Hu Lingling Qin Tao Yang Mei Li Tianyu Qin Miao Jiang Tonghua Liu Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver Chinese Medicine ZiShen Pill Diabetes Insulin resistance Transcriptomics Glucolipid metabolism |
| 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 | ZiShen Pill Diabetes Insulin resistance Transcriptomics Glucolipid metabolism |
| url | https://doi.org/10.1186/s13020-022-00683-8 |
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