Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats : possible involvement of PDE-1/TGF-β/ Smad 2/3 signalling pathways

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OBJECTIVE: Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats.

METHODS: Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-β (TGF-β) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR.

KEY FINDING: Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-β and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril.

CONCLUSIONS: Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-β/Smad 2/3.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:75

Enthalten in:

The Journal of pharmacy and pharmacology - 75(2023), 9 vom: 01. Sept., Seite 1198-1211

Sprache:

Englisch

Beteiligte Personen:

Vishwakarma, Vishal Kumar [VerfasserIn]
Shah, Sadia [VerfasserIn]
Kaur, Tajpreet [VerfasserIn]
Singh, Amrit Pal [VerfasserIn]
Arava, Sudheer Kumar [VerfasserIn]
Kumar, Niraj [VerfasserIn]
Yadav, Raj Kanwar [VerfasserIn]
Yadav, Sushma [VerfasserIn]
Arora, Taruna [VerfasserIn]
Yadav, Harlokesh Narayan [VerfasserIn]

Links:

Volltext

Themen:

543512OBTC
69PN84IO1A
Diabetic cardiomyopathy
EC 3.1.4.-
Enalapril
Journal Article
Oxidative stress
Phosphodiesterase-1
Phosphoric Diester Hydrolases
TGF-β
Transforming Growth Factor beta
Vinpocetine

Anmerkungen:

Date Completed 05.09.2023

Date Revised 05.09.2023

published: Print

Citation Status MEDLINE

doi:

10.1093/jpp/rgad043

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM357319478