PMID- 33607200
OWN - NLM
STAT- MEDLINE
DCOM- 20210914
LR  - 20240226
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 272
DP  - 2021 May 23
TI  - Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT/mTOR/NF-kappaB 
      signaling in pressure overload-induced rats.
PG  - 113920
LID - S0378-8741(21)00146-X [pii]
LID - 10.1016/j.jep.2021.113920 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pinoresinol diglucoside (PDG), the active 
      compound extracted from Eucommia ulmoides, Styrax sp. and Forsythia suspensa, 
      plays the roles in regulating hypertension, inflammation and oxidative stress. 
      AIMS: Considering that hypertension and inflammation has been proved to 
      contribute to cardiac remodeling, we tested the effects of PDG on cardiac 
      hypertrophy (CM). METHODS: Male Sprague Dawley (SD) rats were used to construct 
      hypertrophic rats by partial abdominal aortic constriction (AAC)-surgery. PDG 
      solution (2 mg/ml) was used to treat AAC-induced rats by intraperitoneal 
      injection at low dose (L-PDG, 2.5 mg/kg per day), medium dose (M-PDG, 5 mg/kg per 
      day), and high dose (H-PDG, 7.5 mg/kg per day) for 3 weeks post AAC-surgery. CM 
      was evaluated by the ratio of left ventricular weight to body weight ratio 
      (LVW/BW), left ventricular wall thickness by H&E staining, and collagen content 
      deposit by Masson's staining. Further, isoproterenol (ISO) and phenylephrine (PE) 
      were used to produce cellular models of CM in neonatal rat ventricular 
      cardiomyocytes (NRVMs). PDG pre-treated NRVMs 2 h at low dose (L-PDG, 2.5 mug/ml), 
      medium dose (M-PDG, 5 mug/ml), and high dose (H-PDG, 7.5 mug/ml) for 24 h with or 
      without PE- and ISO-stimulation. CM was evaluated by the expressions of 
      hypertrophic biomarkers. Next, the hypertrophic biomarkers and pro-inflammatory 
      cytokines were measured using quantitative real-time PCR (qRT-PCR), the 
      expressions of protein kinase B (AKT)/mammalian target of rapamycin 
      (mTOR)/transcription factor nuclear factor-kappa B (NF-kB) signaling pathway were 
      determined by Western blotting. RESULTS: PDG treatment prevented cardiac 
      histomorphology damages, decreased upregulations of hypertrophic biomarkers, and 
      prevented fibrosis and inflammation after pressure overload resulting from 
      AAC-surgery. Consistently, PDG remarkably inhibited the changes of cardiomyocyte 
      hypertrophic biomarkers and inflammatory responses in cellular models of CM. 
      Interestingly, PDG administration inhibited the activation of AKT/mTOR/NF-kB 
      signaling pathway both in vivo and in vitro. CONCLUSIONS: PDG prevents 
      AAC-induced CM in vivo, PE- and ISO-induced CM in vitro. The AKT/mTOR/NF-kB 
      signaling pathway could be the potential therapeutic target involved in the 
      protection of PDG. These findings provide novel evidence that PDG might be a 
      promising therapeutic strategy for CM.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Chen, Yusha
AU  - Chen Y
AD  - School of Nursing, PR China.
FAU - Pan, Ruiyan
AU  - Pan R
AD  - School of Pharmacy, PR China.
FAU - Zhang, Juanjuan
AU  - Zhang J
AD  - School of Stomatology, PR China.
FAU - Liang, Tianming
AU  - Liang T
AD  - School of Biological Science and Technology, PR China.
FAU - Guo, Juan
AU  - Guo J
AD  - School of Nursing, PR China.
FAU - Sun, Tai
AU  - Sun T
AD  - School of Basic Medicine, PR China.
FAU - Fu, Xiaoyan
AU  - Fu X
AD  - School of Basic Medicine, PR China.
FAU - Wang, Ling
AU  - Wang L
AD  - Medical Experiment and Training Center, Weifang Medical University, Weifang 
      261053, PR China.
FAU - Zhang, Lane
AU  - Zhang L
AD  - School of Nursing, PR China. Electronic address: zhangle@wfmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210216
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
RN  - 0 (Lignans)
RN  - 0 (NF-kappa B)
RN  - 1WS297W6MV (Phenylephrine)
RN  - 63902-38-5 (pinoresinol diglucoside)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Aorta, Abdominal/surgery
MH  - Cardiomegaly/*drug therapy/etiology/pathology
MH  - Constriction, Pathologic
MH  - Disease Models, Animal
MH  - Fibrosis/prevention & control
MH  - Inflammation/prevention & control
MH  - Isoproterenol/toxicity
MH  - Lignans/*pharmacokinetics/*therapeutic use
MH  - Male
MH  - Myocytes, Cardiac/drug effects
MH  - NF-kappa B/*metabolism
MH  - Phenylephrine/toxicity
MH  - Pressure
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Ventricular Remodeling/drug effects
MH  - Rats
OTO - NOTNLM
OT  - AKT/mTOR/NF-kappaB signaling
OT  - Cardiac inflammation and fibrosis
OT  - Pinoresinol diglucoside (PDG)
EDAT- 2021/02/20 06:00
MHDA- 2021/09/15 06:00
CRDT- 2021/02/19 20:11
PHST- 2020/12/08 00:00 [received]
PHST- 2021/02/01 00:00 [revised]
PHST- 2021/02/08 00:00 [accepted]
PHST- 2021/02/20 06:00 [pubmed]
PHST- 2021/09/15 06:00 [medline]
PHST- 2021/02/19 20:11 [entrez]
AID - S0378-8741(21)00146-X [pii]
AID - 10.1016/j.jep.2021.113920 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2021 May 23;272:113920. doi: 10.1016/j.jep.2021.113920. Epub 
      2021 Feb 16.