PMID- 30864233
OWN - NLM
STAT- MEDLINE
DCOM- 20191231
LR  - 20191231
IS  - 1098-2299 (Electronic)
IS  - 0272-4391 (Linking)
VI  - 80
IP  - 3
DP  - 2019 May
TI  - The protective effect of kaempferol on heart via the regulation of Nrf2, NF-kappabeta, 
      and PI3K/Akt/GSK-3beta signaling pathways in isoproterenol-induced heart failure in 
      diabetic rats.
PG  - 294-309
LID - 10.1002/ddr.21495 [doi]
AB  - This study was designed to delineate the effect of kaempferol (KF) on heart 
      failure (HF) in diabetic rats. Streptozotocin-induced male diabetic rats received 
      KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the 
      experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to 
      induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and 
      histological investigations. Systolic blood pressure, diastolic blood pressure, 
      and mean arterial blood pressure were elevated in KF-treated HF-induced diabetic 
      rats. Moreover, KF treatment resulted in decreased fasting blood glucose and 
      glycosylated hemoglobin levels with increased serum insulin levels. Besides, 
      serum cardiac injury markers like troponin-I, creatine kinase-muscle/brain, 
      lactate dehydrogenase, and brain natriuretic peptide levels were significantly 
      reduced in KF treatment. KF treatment has shown decrease in cardiac heme 
      oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and 
      gamma-glutamylcysteine synthetase with increased Keap1 mRNA levels. The 
      cardioprotection of KF was improved by inhibition of apoptosis via blocking 
      phosphorylation of Akt/glycogen synthase kinase (GSK)-3beta and p38 
      mitogen-activated protein-kinase/extracellular signal-regulated kinases signaling 
      pathways in HF-induced diabetic rats. Moreover, reduced cardiac apoptosis in KF 
      treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP 
      nick-end labeling (TUNEL) positive cells, histopathological changes in HF-induced 
      diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the 
      regulation of Nrf2, nuclear factor kappa-light-chain-enhancer of activated B 
      cells, and Akt/GSK-3beta signaling pathways in HF-induced diabetic rats.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Zhang, Long
AU  - Zhang L
AD  - Cardiology Department, Xidian Group Hospital, Xi'an, People's Republic of China.
FAU - Guo, Zhaoxia
AU  - Guo Z
AD  - Department of Cardiovascular, Gansu Provincial Hospital, Lanzhou, People's 
      Republic of China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, People's Republic of China.
FAU - Geng, Jun
AU  - Geng J
AD  - Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, People's Republic of China.
FAU - Han, Shuyi
AU  - Han S
AUID- ORCID: 0000-0002-6520-7817
AD  - Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20190312
PL  - United States
TA  - Drug Dev Res
JT  - Drug development research
JID - 8204468
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Kaempferols)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 731P2LE49E (kaempferol)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology/therapeutic use
MH  - Diabetes Mellitus, Experimental/drug therapy/*metabolism
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Heart/drug effects
MH  - Heart Failure/chemically induced/drug therapy/*metabolism
MH  - Isoproterenol
MH  - Kaempferols/*pharmacology/therapeutic use
MH  - Male
MH  - Myocardial Infarction/drug therapy/*metabolism
MH  - Myocardium/*metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - apoptosis
OT  - diabetes
OT  - heart failure
OT  - inflammation
OT  - oxidative stress
EDAT- 2019/03/14 06:00
MHDA- 2020/01/01 06:00
CRDT- 2019/03/14 06:00
PHST- 2018/09/06 00:00 [received]
PHST- 2018/11/05 00:00 [revised]
PHST- 2018/11/07 00:00 [accepted]
PHST- 2019/03/14 06:00 [pubmed]
PHST- 2020/01/01 06:00 [medline]
PHST- 2019/03/14 06:00 [entrez]
AID - 10.1002/ddr.21495 [doi]
PST - ppublish
SO  - Drug Dev Res. 2019 May;80(3):294-309. doi: 10.1002/ddr.21495. Epub 2019 Mar 12.