PMID- 34946711
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20240405
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 26
IP  - 24
DP  - 2021 Dec 16
TI  - Carpachromene Ameliorates Insulin Resistance in HepG2 Cells via Modulating 
      IR/IRS1/PI3k/Akt/GSK3/FoxO1 Pathway.
LID - 10.3390/molecules26247629 [doi]
LID - 7629
AB  - Insulin resistance contributes to several disorders including type 2 diabetes and 
      cardiovascular diseases. Carpachromene is a natural active compound that inhibits 
      alpha-glucosidase enzyme. The aim of the present study is to investigate the 
      potential activity of carpachromene on glucose consumption, metabolism and 
      insulin signalling in a HepG2 cells insulin resistant model. A HepG2 insulin 
      resistant cell model (HepG2/IRM) was established. Cell viability assay of 
      HepG2/IRM cells was performed after carpachromene/metformin treatment. Glucose 
      concentration and glycogen content were determined. Western blot analysis of 
      insulin receptor, IRS1, IRS2, PI3k, Akt, GSK3, FoxO1 proteins after carpachromene 
      treatment was performed. Phosphoenolpyruvate carboxykinase (PEPCK) and hexokinase 
      (HK) enzymes activity was also estimated. Viability of HepG2/IRM cells was over 
      90% after carpachromene treatment at concentrations 6.3, 10, and 20 microg/mL. 
      Treatment of HepG2/IRM cells with carpachromene decreased glucose concentration 
      in a concentration- and time-dependant manner. In addition, carpachromene 
      increased glycogen content of HepG2/IRM cells. Moreover, carpachromene treatment 
      of HepG2/IRM cells significantly increased the expression of phosphorylated/total 
      ratios of IR, IRS1, PI3K, Akt, GSK3, and FoxO1 proteins. Furthermore, PEPCK 
      enzyme activity was significantly decreased, and HK enzyme activity was 
      significantly increased after carpachromene treatment. The present study 
      examined, for the first time, the potential antidiabetic activity of 
      carpachromene on a biochemical and molecular basis. It increased the expression 
      ratio of insulin receptor and IRS1 which further phosphorylated/activated 
      PI3K/Akt pathway and phosphorylated/inhibited GSK3 and FoxO1 proteins. Our 
      findings revealed that carpachromene showed central molecular regulation of 
      glucose metabolism and insulin signalling via IR/IRS1/ PI3K/Akt/GSK3/FoxO1 
      pathway.
FAU - Alaaeldin, Rania
AU  - Alaaeldin R
AUID- ORCID: 0000-0002-1084-7323
AD  - Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, 
      Egypt.
FAU - Abdel-Rahman, Iman A M
AU  - Abdel-Rahman IAM
AUID- ORCID: 0000-0002-2586-9023
AD  - Department of Pharmacognosy, Faculty of Pharmacy, South Valley University, Qena 
      83523, Egypt.
FAU - Hassan, Heba Ali
AU  - Hassan HA
AUID- ORCID: 0000-0002-2631-5831
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Sohag University, Sohag 82524, 
      Egypt.
FAU - Youssef, Nancy
AU  - Youssef N
AD  - Department of Clinical Pathology, Faculty of Medicine, Minia University, Minia 
      61512, Egypt.
FAU - Allam, Ahmed E
AU  - Allam AE
AD  - Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut 
      71524, Egypt.
FAU - Abdelwahab, Sayed F
AU  - Abdelwahab SF
AUID- ORCID: 0000-0002-9636-7485
AD  - Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif 
      University, Taif 21944, Saudi Arabia.
FAU - Zhao, Qing-Li
AU  - Zhao QL
AD  - Department of Radiology, Graduate School of Medicine and Pharmaceutical Sciences, 
      University of Toyama, Toyama 930-0194, Japan.
FAU - Fathy, Moustafa
AU  - Fathy M
AUID- ORCID: 0000-0002-0734-5007
AD  - Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia 61519, 
      Egypt.
AD  - Department of Regenerative Medicine, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
LA  - eng
GR  - (JP21K07614)/JSPS KAKENHI Grant Number/
GR  - (TURSP-2020/51)/Taif University Researchers Supporting Project Number/
PT  - Journal Article
DEP - 20211216
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Benzopyrans)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Benzopyrans/*pharmacology
MH  - Forkhead Box Protein O1/*metabolism
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Hep G2 Cells
MH  - Humans
MH  - Insulin Receptor Substrate Proteins/*metabolism
MH  - *Insulin Resistance
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC8708443
OTO - NOTNLM
OT  - HepG2 cells
OT  - PI3K/Akt/GSK3/FoxO1 pathway
OT  - carpachromene
OT  - insulin receptor
OT  - insulin resistance
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/02/11 06:00
PMCR- 2021/12/16
CRDT- 2021/12/24 01:12
PHST- 2021/11/13 00:00 [received]
PHST- 2021/12/07 00:00 [revised]
PHST- 2021/12/14 00:00 [accepted]
PHST- 2021/12/24 01:12 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2021/12/16 00:00 [pmc-release]
AID - molecules26247629 [pii]
AID - molecules-26-07629 [pii]
AID - 10.3390/molecules26247629 [doi]
PST - epublish
SO  - Molecules. 2021 Dec 16;26(24):7629. doi: 10.3390/molecules26247629.