PMID- 36352450 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221116 IS - 1749-8546 (Print) IS - 1749-8546 (Electronic) IS - 1749-8546 (Linking) VI - 17 IP - 1 DP - 2022 Nov 10 TI - Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver. PG - 128 LID - 10.1186/s13020-022-00683-8 [doi] LID - 128 AB - 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. CI - (c) 2022. The Author(s). FAU - Wu, You AU - Wu Y AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - School of Life Science, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Sun, Boju AU - Sun B AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Guo, Xiaoyuan AU - Guo X AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China. FAU - Wu, Lili AU - Wu L AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Hu, Yaomu AU - Hu Y AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Qin, Lingling AU - Qin L AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Department of Science and Technology, Beijing University of Chinese Medicine, Beijing, 100029, China. FAU - Yang, Tao AU - Yang T AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Li, Mei AU - Li M AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Qin, Tianyu AU - Qin T AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. FAU - Jiang, Miao AU - Jiang M AD - School of Life Science, Beijing University of Chinese Medicine, Beijing, 102488, China. doctorjiang@139.com. FAU - Liu, Tonghua AU - Liu T AUID- ORCID: 0000-0001-7015-5348 AD - Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China. thliu@vip.163.com. AD - Key Laboratory of Health Cultivation of Beijing, Beijing University of Chinese Medicine, Beijing, 102488, China. thliu@vip.163.com. LA - eng GR - B20055/Creation and Talent Introduction Base of Prevention and Treatment of Diabetes and Its Complications with Traditional Chinese Medicine/ GR - 2015B01022/International Cooperation Research Center for the Prevention and Treatment of Diabetes by Traditional Chinese Medicine/ PT - Journal Article DEP - 20221110 PL - England TA - Chin Med JT - Chinese medicine JID - 101265109 PMC - PMC9647929 OTO - NOTNLM OT - Diabetes OT - Glucolipid metabolism OT - Insulin resistance OT - Transcriptomics OT - ZiShen Pill COIS- The authors declare no conflict of interest. EDAT- 2022/11/11 06:00 MHDA- 2022/11/11 06:01 PMCR- 2022/11/10 CRDT- 2022/11/10 00:09 PHST- 2022/09/09 00:00 [received] PHST- 2022/10/26 00:00 [accepted] PHST- 2022/11/10 00:09 [entrez] PHST- 2022/11/11 06:00 [pubmed] PHST- 2022/11/11 06:01 [medline] PHST- 2022/11/10 00:00 [pmc-release] AID - 10.1186/s13020-022-00683-8 [pii] AID - 683 [pii] AID - 10.1186/s13020-022-00683-8 [doi] PST - epublish SO - Chin Med. 2022 Nov 10;17(1):128. doi: 10.1186/s13020-022-00683-8.