PMID- 36469428
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240122
IS  - 1612-1880 (Electronic)
IS  - 1612-1872 (Linking)
VI  - 20
IP  - 1
DP  - 2023 Jan
TI  - Anti-Diabetic Effects and Molecular Mechanisms of Amide Alkaloids from Piper 
      longum Based on Network Pharmacology Integrated with Cellular Assays.
PG  - e202200904
LID - 10.1002/cbdv.202200904 [doi]
AB  - Piper longum is a well-known spice and traditional medicine. It was revealed to 
      possess anti-diabetic activity, but few information about its active component 
      and underlying mechanism could be available. In this study, retrofractamides A 
      (1) and C (2) isolated from P. longum showed potent inhibitory activity against 
      PTP1B. Therefore, the potential mechanism was predicted by network pharmacology 
      and molecular docking. PI3K/AKT was obtained as the most remarkable pathway 
      against type 2 diabetes mellitus (T2DM), and AKT1 and GSK3beta were yielded as the 
      top two core targets of retrofractamides A (1) and C (2). Molecular docking of 
      compounds with AKT1 and GSK3beta showed strong binding affinity between them. 
      Additionally, cellular experiments with a L6 cell model was conducted to further 
      verify the above predictions. Results indicated that retrofractamides A (1) and C 
      (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they 
      promoted glucose consumption, glucose uptake, glycogen synthesis and glycolysis.
CI  - (c) 2022 Wiley-VHCA AG, Zurich, Switzerland.
FAU - Gou, Guang-Hui
AU  - Gou GH
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
AD  - University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
FAU - Liu, Liu
AU  - Liu L
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
FAU - Abdubakiev, Sardorbek
AU  - Abdubakiev S
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
FAU - Xin, Xue-Lei
AU  - Xin XL
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
AD  - University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
FAU - Akber Aisa, Haji
AU  - Akber Aisa H
AUID- ORCID: 0000-0003-4652-6879
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
AD  - University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
FAU - Li, Jun
AU  - Li J
AUID- ORCID: 0000-0002-7990-1295
AD  - State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource 
      Utilization and Key Laboratory of Plants Resources and Chemistry of Arid Zone, 
      Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of 
      Sciences, South Beijing Road 40-1, Urumqi 830011, Xinjiang, P. R. China.
AD  - University of Chinese Academy of Sciences, Beijing, 100039, P. R. China.
LA  - eng
GR  - 31500273/National Natural Science Foundation of China/
GR  - 2020YFE0205600/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20221215
PL  - Switzerland
TA  - Chem Biodivers
JT  - Chemistry & biodiversity
JID - 101197449
RN  - 0 (Alkaloids)
RN  - 0 (Amides)
RN  - 0 (Drugs, Chinese Herbal)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (retrofractamide C)
SB  - IM
MH  - *Alkaloids
MH  - Amides
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - *Drugs, Chinese Herbal
MH  - Glycogen Synthase Kinase 3 beta
MH  - Molecular Docking Simulation
MH  - Network Pharmacology
MH  - Phosphatidylinositol 3-Kinases
MH  - *Piper
MH  - Proto-Oncogene Proteins c-akt
OTO - NOTNLM
OT  - Piper longum
OT  - anti-diabetic
OT  - molecular docking
OT  - network pharmacology
OT  - retrofractamides A and C
EDAT- 2022/12/06 06:00
MHDA- 2023/01/25 06:00
CRDT- 2022/12/05 12:03
PHST- 2022/09/24 00:00 [received]
PHST- 2022/12/05 00:00 [accepted]
PHST- 2022/12/06 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2022/12/05 12:03 [entrez]
AID - 10.1002/cbdv.202200904 [doi]
PST - ppublish
SO  - Chem Biodivers. 2023 Jan;20(1):e202200904. doi: 10.1002/cbdv.202200904. Epub 2022 
      Dec 15.