PMID- 38495630
OWN - NLM
STAT- MEDLINE
DCOM- 20240319
LR  - 20240319
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 18
DP  - 2024
TI  - Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus 
      Based on Network Pharmacology and Experimental Verification in Drosophila.
PG  - 747-766
LID - 10.2147/DDDT.S439876 [doi]
AB  - PURPOSE: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin 
      uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been 
      used to treat T2DM; however, the fundamental biological mechanisms remain 
      unclear. This study aimed to understand the active ingredients, potential 
      targets, and underlying mechanisms through which PDB treats T2DM. METHODS: 
      Components and action targets were predicted using network pharmacology and 
      molecular docking analyses. PDB extracts were prepared and validated through 
      pharmacological intervention in a Cg>InR(K1409A) diabetes Drosophila model. 
      Network pharmacology and molecular docking analyses were used to identify the key 
      components and core targets of PDB in the treatment of T2DM, which were 
      subsequently verified in animal experiments. RESULTS: Network pharmacology 
      analysis revealed five effective compounds made up of 107 T2DM-related 
      therapeutic targets and seven protein-protein interaction network core molecules. 
      Molecular docking results showed that quercetin has a strong preference for 
      interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 
      (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to 
      tumor necrosis factor and AKT1; beta-sitosterol demonstrated pronounced binding to 
      Caspase-3 (CASP3). High-performance liquid chromatography data quantified 
      quercetin, kaempferol, and beta-sitosterol at proportions of 0.030%, 0.025%, and 
      0.076%, respectively. The animal experiments revealed that PDB had no effect on 
      the development, viability, or fertility of Drosophila and it ameliorated 
      glycolipid metabolism disorders in the diabetes Cg>InR(K1409A) fly. Furthermore, 
      PDB improved the body size and weight of Drosophila, suggesting its potential to 
      alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and 
      suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. 
      CONCLUSION: Our findings suggest that PDB ameliorates diabetes metabolism 
      disorders in the fly model by enhancing Akt activity and suppressing CASP3 
      expression. This will facilitate the development of key drug targets and a 
      potential therapeutic strategy for the clinical treatment of T2DM and related 
      metabolic diseases.
CI  - (c) 2024 Li et al.
FAU - Li, Yinghong
AU  - Li Y
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Wu, Fanwu
AU  - Wu F
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Zhang, Jianbo
AU  - Zhang J
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Xu, Ye
AU  - Xu Y
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Chang, Hong
AU  - Chang H
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Yu, Yueyue
AU  - Yu Y
AUID- ORCID: 0009-0006-7354-6321
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Jiang, Chunhua
AU  - Jiang C
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Gao, Xiujuan
AU  - Gao X
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Liu, Huijuan
AU  - Liu H
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Chen, Zhen
AU  - Chen Z
AD  - Oriental Herbs KFT, Budapest, Hungary.
FAU - Wu, Chenxi
AU  - Wu C
AUID- ORCID: 0000-0003-2712-4823
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
FAU - Li, Ji-An
AU  - Li JA
AD  - Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for 
      Diabetes and Its Complications, College of Traditional Chinese Medicine, North 
      China University of Science and Technology, Tangshan, People's Republic of China.
AD  - School of Public Health, North China University of Science and Technology, 
      Tangshan, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20240311
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (Kaempferols)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Caspase 3
MH  - Kaempferols
MH  - *Potentilla
MH  - Drosophila
MH  - *Insulin Resistance
MH  - Molecular Docking Simulation
MH  - Network Pharmacology
MH  - Proto-Oncogene Proteins c-akt
MH  - Quercetin
PMC - PMC10941989
OTO - NOTNLM
OT  - Drosophila
OT  - Potentilla discolor Bunge
OT  - T2DM
OT  - molecular docking
OT  - network pharmacology
COIS- The authors report no conflicts of interest in this work.
EDAT- 2024/03/18 06:43
MHDA- 2024/03/19 06:43
PMCR- 2024/03/11
CRDT- 2024/03/18 04:24
PHST- 2023/10/27 00:00 [received]
PHST- 2024/03/07 00:00 [accepted]
PHST- 2024/03/19 06:43 [medline]
PHST- 2024/03/18 06:43 [pubmed]
PHST- 2024/03/18 04:24 [entrez]
PHST- 2024/03/11 00:00 [pmc-release]
AID - 439876 [pii]
AID - 10.2147/DDDT.S439876 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2024 Mar 11;18:747-766. doi: 10.2147/DDDT.S439876. 
      eCollection 2024.