PMID- 34875953
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220501
IS  - 1525-6065 (Electronic)
IS  - 1064-1955 (Linking)
VI  - 41
IP  - 1
DP  - 2022 Feb
TI  - Combined apocyanin and aspirin treatment activates the PI3K/Nrf2/HO-1 signaling 
      pathway and ameliorates preeclampsia symptoms in rats.
PG  - 39-50
LID - 10.1080/10641955.2021.2014518 [doi]
AB  - OBJECTIVE: Pre-eclampsia (PE) is a pregnancy-associated disease characterized by 
      placental dysfunction and increased oxidative stress. Apocyanin is a potent 
      antioxidant and anti-inflammatory which has shown beneficial effects on PE 
      pathogenesis. Aspirin is recognized as the recommendable drug in PE prevention 
      and therapy. Therefore, we aimed to investigate the effects of combining 
      apocyanin and aspirin to treat PE on rat models induced by N-nitro-L-arginine 
      methyl ester (L-NAME) from gestational day (GD) 6 to 16 and elucidate the 
      potential mechanisms. METHODS: First, female pregnant rats were divided into five 
      different groups: pregnant control, PE, PE + apocyanin, PE + aspirin, and PE + 
      apocyanin + aspirin. Animals received apocyanin (16 mg/kg/day) orally or aspirin 
      by gavage (1.5 mg/kg BM/day) from GD 4 to 16. Blood pressure and urine protein 
      content were monitored every 4 days. RESULTS: In the PE rat model, elevated 
      systolic blood pressure and proteinuria were ameliorated by the combination of 
      apocyanin and aspirin. Meanwhile, compared with single-dose apocyanin or aspirin, 
      the combined treatment significantly corrected abnormal pregnancy outcomes, 
      decreased sFlt-1 and PlGF, and alleviated oxidative stress both in blood and 
      placental tissues. Moreover, the combined treatment upregulated PI3K, Akt, Nrf2, 
      and HO-1 protein levels in the placental tissues from PE rats. CONCLUSION: 
      Overall, our results suggested that combined treatment of apocyanin and aspirin 
      ameliorates the PE symptoms compared with single-dose apocyanin or aspirin in a 
      PE rat model. Also, we demonstrated that activating the PI3K/Nrf2/HO-1 pathway 
      can be a valuable therapeutic target to improve the pregnancy outcomes of PE.
FAU - Ju, Yaru
AU  - Ju Y
AD  - Perinatal Center, the Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, 
      China.
FAU - Feng, Yan
AU  - Feng Y
AD  - Department of Neurosurgery, The Second Hospital of Hebei Medical University, 
      Hebei, China.
FAU - Hou, Xiaolin
AU  - Hou X
AD  - Prenatal Diagnostic, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, 
      China.
FAU - Wu, Lixia
AU  - Wu L
AD  - Department of Obstetrics, The Fourth Hospital of Shijiazhuang; Hebei, China.
FAU - Yang, Huixia
AU  - Yang H
AD  - Department of Obstetrics, Gaoyi County People's Hospital, Shijiazhuang, Hebei, 
      China.
FAU - Zhang, Hongjuan
AU  - Zhang H
AD  - Department of Obstetrics, Xiongxian Maternal and Child Health Care Hospital, 
      Baoding, Hebei China.
FAU - Ma, Yan'Na
AU  - Ma Y
AD  - Department of Obstetrics, Xiongxian Maternal and Child Health Care Hospital, 
      Baoding, Hebei China.
LA  - eng
PT  - Journal Article
DEP - 20211207
PL  - England
TA  - Hypertens Pregnancy
JT  - Hypertension in pregnancy
JID - 9421297
RN  - 0 (NF-E2-Related Factor 2)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Animals
MH  - Aspirin/adverse effects
MH  - Female
MH  - NF-E2-Related Factor 2/metabolism/pharmacology/therapeutic use
MH  - Phosphatidylinositol 3-Kinases/metabolism/pharmacology/therapeutic use
MH  - Placenta/metabolism
MH  - *Pre-Eclampsia
MH  - Pregnancy
MH  - Rats
MH  - Signal Transduction
OTO - NOTNLM
OT  - Preeclampsia
OT  - apocyanin
OT  - aspirin
OT  - oxidative stress
OT  - pi3k/nfr2/ho-1
EDAT- 2021/12/09 06:00
MHDA- 2022/02/25 06:00
CRDT- 2021/12/08 05:29
PHST- 2021/12/09 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2021/12/08 05:29 [entrez]
AID - 10.1080/10641955.2021.2014518 [doi]
PST - ppublish
SO  - Hypertens Pregnancy. 2022 Feb;41(1):39-50. doi: 10.1080/10641955.2021.2014518. 
      Epub 2021 Dec 7.