PMID- 38026992
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Linagliptin and secoisolariciresinol diglucoside attenuate hyperlipidemia and 
      cardiac hypertrophy induced by a high-methionine diet in rats via suppression of 
      hyperhomocysteinemia-induced endoplasmic reticulum stress.
PG  - 1275730
LID - 10.3389/fphar.2023.1275730 [doi]
LID - 1275730
AB  - Background: Cardiac hypertrophy (CH) is one of the contributing causes of 
      morbidity and mortality. Hyperhomocysteinemia (HHcy) is one of the diseases which 
      may predispose hyperlipidemia and CH. Linagliptin (Lina) and secoisolariciresinol 
      diglucoside (SDG) are known to alleviate a variety of illnesses by reducing 
      oxidative stress and inflammation. Aim: This study aimed to study the effect of 
      HHcy on cardiac tissues, with a special focus on endoplasmic reticulum (ER) 
      stress as a mainstay pathophysiological pathway. In addition, our study examined 
      the protective effect of Lina, SDG, and their combination against HHcy-induced 
      hyperlipidemia and CH in rats. Methods: Seventy-five male Sprague-Dawley rats 
      were randomly divided into five groups, and for 60 days, the following regimen 
      was administered: Group I: rats received distilled water; Group II: rats received 
      methionine (MET) (2 g/kg/day, p.o.); groups III and IV: rats received Lina 
      (3 mg/kg/day, p.o.) and SDG (20 mg/kg/day, p.o.), respectively, followed by MET 
      (2 g/kg/day, p.o.); Group V: rats received Lina and SDG, followed by MET 
      (2 g/kg/day, p.o.). Results: Pretreatment with Lina, SDG, and their combination 
      showed a significant decrease in serum levels of HHcy and an improved lipid 
      profile compared to the MET group. Moreover, both drugs improved cardiac injury, 
      as evidenced by the substantial improvement in ECG parameters, morphological 
      features of the cardiac muscle, and reduced serum levels of cardiac markers. 
      Additionally, Lina and SDG significantly attenuated cardiac oxidative stress, 
      inflammation, and apoptosis. Furthermore, Lina, SDG, and their combination 
      remarkably downregulated the enhanced expression of endoplasmic reticulum (ER) 
      stress markers, GRP78, PERK, ATF-4, CHOP, NF-kappaB, and SREBP1c compared to the 
      MET-group. Conclusion: Lina and SDG showed cardioprotective effects against 
      HHcy-induced heart hypertrophy and hyperlipidemia in rats.
CI  - Copyright (c) 2023 Jalal, Elkhoely, Mohamed and Ahmed.
FAU - Jalal, Israa A
AU  - Jalal IA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Cairo, Egypt.
FAU - Elkhoely, Abeer
AU  - Elkhoely A
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Cairo, Egypt.
FAU - Mohamed, Shimaa K
AU  - Mohamed SK
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Cairo, Egypt.
FAU - Ahmed, Amany A E
AU  - Ahmed AAE
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20231109
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10665493
OTO - NOTNLM
OT  - ATF-4
OT  - CHOP
OT  - GRP78
OT  - PERK
OT  - SREPB1c
OT  - hyperhomocysteinemia
OT  - linagliptin
OT  - secoisolariciresinol diglucoside
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/11/09
CRDT- 2023/11/29 17:00
PHST- 2023/08/10 00:00 [received]
PHST- 2023/10/16 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 17:00 [entrez]
PHST- 2023/11/09 00:00 [pmc-release]
AID - 1275730 [pii]
AID - 10.3389/fphar.2023.1275730 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Nov 9;14:1275730. doi: 10.3389/fphar.2023.1275730. 
      eCollection 2023.