PMID- 33779055
OWN - NLM
STAT- MEDLINE
DCOM- 20210810
LR  - 20210810
IS  - 1612-1880 (Electronic)
IS  - 1612-1872 (Linking)
VI  - 18
IP  - 5
DP  - 2021 May
TI  - Natural Triterpenoids Isolated from Akebia trifoliata Stem Explants Exert a 
      Hypoglycemic Effect via alpha-Glucosidase Inhibition and Glucose Uptake Stimulation 
      in Insulin-Resistant HepG2 Cells.
PG  - e2001030
LID - 10.1002/cbdv.202001030 [doi]
AB  - The inhibition of alpha-glucosidase activity is a prospective approach to attenuate 
      postprandial hyperglycemia in the treatment of type 2 diabetes mellitus (T2DM). 
      Herein, the inhibition of alpha-glucosidase by three compounds T(1) -T(3) of Akebia 
      trifoliata stem, namely hederagenin (T(1) ), 3-epiakebonoic acid (T(2) ), and 
      arjunolic acid (T(3) ) were investigated using enzyme kinetics and molecular 
      docking analysis. The three triterpenoids exhibited excellent inhibitory 
      activities against alpha-glucosidase. T(1) -T(3) showed the strongest inhibition with 
      IC(50) values of 42.1+/-5.4, 19.6+/-3.2, and 11.2+/-2.3 muM, respectively, compared to 
      the acarbose positive control (IC(50) =106.3+/-8.2). Enzyme inhibition kinetics 
      showed that triterpenoids T(1) -T(3) demonstrated competitive, mixed, and 
      noncompetitive-type inhibition against alpha-glucosidase, respectively. The 
      inhibition constant (K(i) ) values were 21.21, 7.70, and 3.18 muM, respectively. 
      Docking analysis determined that the interaction of ligands T(1) -T(3) and 
      alpha-glucosidase was mainly forced by hydrogen bonds and hydrophobic interactions, 
      which could result in improved binding to the active site of the target enzyme. 
      The insulin resistant (IR)-HepG2 cell model used in this study (HepG2 cells 
      exposed to 10(-7)  M insulin for 24 h) and glucose uptake assays showed that 
      compounds T(1) -T(3) had no cytotoxicity with concentrations ranging from 6.25 to 
      25 muM and displayed significant stimulation of glucose uptake in IR-HepG2 cells. 
      Thus, triterpenoids T(1) -T(3) showed dual therapeutic effects of alpha-glucosidase 
      inhibition and glucose uptake stimulation and could be used as potential 
      medicinal resources to investigate new antidiabetic agents for the prevention or 
      treatment of diabetes.
CI  - (c) 2021 Wiley-VHCA AG, Zurich, Switzerland.
FAU - Bian, Guoyong
AU  - Bian G
AD  - Department of Marine Bio-Pharmacology, College of Food Science and Technology, 
      Shanghai Ocean University, Shanghai, 201306, P. R. China.
FAU - Yang, Jinbo
AU  - Yang J
AD  - Department of Marine Bio-Pharmacology, College of Food Science and Technology, 
      Shanghai Ocean University, Shanghai, 201306, P. R. China.
FAU - Elango, Jeevithan
AU  - Elango J
AD  - Department of Marine Bio-Pharmacology, College of Food Science and Technology, 
      Shanghai Ocean University, Shanghai, 201306, P. R. China.
FAU - Wu, Wenhui
AU  - Wu W
AUID- ORCID: 0000-0002-7283-8131
AD  - Department of Marine Bio-Pharmacology, College of Food Science and Technology, 
      Shanghai Ocean University, Shanghai, 201306, P. R. China.
AD  - National R&D Branch Center for Freshwater Aquatic Products Processing Technology, 
      Shanghai, 201306, P. R. China.
FAU - Bao, Bin
AU  - Bao B
AD  - National R&D Branch Center for Freshwater Aquatic Products Processing Technology, 
      Shanghai, 201306, P. R. China.
FAU - Bao, Chunling
AU  - Bao C
AD  - Shanghai Sixth People's Hospital East Campus, Shanghai, 201306, P. R. China.
LA  - eng
GR  - 81750110548/National Natural Science Foundation of China/
GR  - 81341082/National Natural Science Foundation of China/
GR  - International Young Scientist Research Fellowship/
GR  - 15410722500/Plan of Innovation Action in Shanghai/
GR  - 17490742500/Plan of Innovation Action in Shanghai/
PT  - Journal Article
DEP - 20210503
PL  - Switzerland
TA  - Chem Biodivers
JT  - Chemistry & biodiversity
JID - 101197449
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Biological Products)
RN  - 0 (Glycoside Hydrolase Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Plant Extracts)
RN  - 0 (Triterpenes)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
RN  - IY9XDZ35W2 (Glucose)
RN  - Lardizabalaceae
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/chemistry/isolation & 
      purification/*pharmacology
MH  - Biological Products/chemistry/isolation & purification/*pharmacology
MH  - Cell Survival/drug effects
MH  - Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Drug Screening Assays, Antitumor
MH  - Glucose/metabolism
MH  - Glycoside Hydrolase Inhibitors/chemistry/isolation & purification/*pharmacology
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoglycemic Agents/chemistry/isolation & purification/*pharmacology
MH  - Insulin Resistance
MH  - Molecular Conformation
MH  - Plant Extracts/chemistry/isolation & purification/*pharmacology
MH  - Ranunculales/*chemistry
MH  - Triterpenes/chemistry/isolation & purification/*pharmacology
MH  - alpha-Glucosidases/metabolism
OTO - NOTNLM
OT  - Akebia trifoliate
OT  - glucose uptake
OT  - inhibition kinetics
OT  - molecular docking
OT  - triterpenoids
OT  - alpha-glucosidase
EDAT- 2021/03/30 06:00
MHDA- 2021/08/11 06:00
CRDT- 2021/03/29 07:01
PHST- 2020/12/14 00:00 [received]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/03/30 06:00 [pubmed]
PHST- 2021/08/11 06:00 [medline]
PHST- 2021/03/29 07:01 [entrez]
AID - 10.1002/cbdv.202001030 [doi]
PST - ppublish
SO  - Chem Biodivers. 2021 May;18(5):e2001030. doi: 10.1002/cbdv.202001030. Epub 2021 
      May 3.