PMID- 34438030
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20230515
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 281
DP  - 2021 Dec 5
TI  - Hypoglycemic effect of astragaloside IV via modulating gut microbiota and 
      regulating AMPK/SIRT1 and PI3K/AKT pathway.
PG  - 114558
LID - S0378-8741(21)00787-X [pii]
LID - 10.1016/j.jep.2021.114558 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali, the dried root of Astragalus 
      mongholicus Bunge, has long been used in traditional Chinese Medicine to treat 
      diabetes. Astragaloside IV (AS-IV), one of the most active ingredients in the 
      root, has been shown to have anti-diabetes ability; however, its underlying 
      mechanism is still unclear. MATERIALS AND METHODS: In this study, we evaluated 
      the hypoglycemic effect and possible mechanisms of AS-IV in diabetic mice and 
      insulin resistance-HepG2 cells. The components of the intestinal microflora in 
      mice with type 2 diabetes mellitus (T2DM) were determined using high-throughput 
      16S rRNA gene sequencing. Moreover, the molecular mechanisms of specific members 
      of insulin signaling pathways were analyzed. RESULTS: AS-IV significantly 
      reversed the abnormalities in blood lipids, glucose, insulin resistance, as well 
      as oxidative stress levels in T2DM mice. Histological finding showed that AS-IV 
      could protect the cellular architecture of the liver and pancreas. AS-IV also 
      regulated the abundance and diversity of intestinal flora of T2DM mice in a 
      positive direction and increased butyric acid levels. The active role of AS-IV as 
      an anti-diabetic compound by regulating the AMPK/SIRT1 and PI3K/AKT signaling 
      pathways was revealed using a T2DM model and verified through the intervention of 
      inhibitors using insulin-resistance HepG2 cells. CONCLUSION: Our results 
      suggested that AS-IV may be used as an anti-diabetic drug candidate owing to its 
      effects of regulating gut microbiota and AMPK/SIRT1 and PI3K/AKT signaling 
      pathways.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Gong, Pin
AU  - Gong P
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: gongpin@sust.edu.cn.
FAU - Xiao, Xuyang
AU  - Xiao X
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: 739336702@qq.com.
FAU - Wang, Shuang
AU  - Wang S
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: 970736802@qq.com.
FAU - Shi, Fuxiong
AU  - Shi F
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: 1247812066@qq.com.
FAU - Liu, Ni
AU  - Liu N
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: liun@sust.edu.cn.
FAU - Chen, Xuefeng
AU  - Chen X
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: chenxf@sust.edu.cn.
FAU - Yang, Wenjuan
AU  - Yang W
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: yangwenjuan@sust.edu.cn.
FAU - Wang, Lan
AU  - Wang L
AD  - College of Food and Biotechnology, Shaanxi University of Science and Technology, 
      Xi'an, 710021, China. Electronic address: wangl@sust.edu.cn.
FAU - Chen, Fuxin
AU  - Chen F
AD  - School of Chemistry and Chemical Engineering, Xi'an University of Science and 
      Technology, Xi'an, 710054, China. Electronic address: chenfuxin1981@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210824
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (Blood Glucose)
RN  - 0 (Dietary Sucrose)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Saponins)
RN  - 0 (Triterpenes)
RN  - 3A592W8XKE (astragaloside A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.4.3 (Adenylate Kinase)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
EIN - J Ethnopharmacol. 2023 Sep 15;313:116629. PMID: 37188618
MH  - Adenylate Kinase/genetics/*metabolism
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Diabetes Mellitus, Experimental/drug therapy
MH  - Diet, High-Fat/adverse effects
MH  - Dietary Sucrose/adverse effects
MH  - Gastrointestinal Microbiome/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/metabolism
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoglycemic Agents/chemistry/pharmacology
MH  - Insulin/blood
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Saponins/*pharmacology
MH  - Sirtuin 1/genetics/*metabolism
MH  - Specific Pathogen-Free Organisms
MH  - Triterpenes/*pharmacology
OTO - NOTNLM
OT  - AMPK/SIRT1 and PI3K/AKT signaling pathways
OT  - Astragaloside IV
OT  - Gut microbiota
OT  - Insulin resistance
OT  - T2DM
EDAT- 2021/08/27 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/08/26 20:15
PHST- 2021/05/16 00:00 [received]
PHST- 2021/08/08 00:00 [revised]
PHST- 2021/08/21 00:00 [accepted]
PHST- 2021/08/27 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/08/26 20:15 [entrez]
AID - S0378-8741(21)00787-X [pii]
AID - 10.1016/j.jep.2021.114558 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2021 Dec 5;281:114558. doi: 10.1016/j.jep.2021.114558. Epub 
      2021 Aug 24.