Naringenin Attenuates Diabetic Cardiac Injury via SIRT1 Activation in Streptozotocin-Induced Rats.

Authors

Baolan Wang, Dandan Zhang, Fudan Zhang, Xue Meng, Li Zhang, Zhenzuo Li, Amirabas Bostani

Published in

Cardiovascular therapeutics. Volume 2026. Issue 1. Pages e9581618.

Abstract

Diabetic cardiomyopathy (DCM) lacks targeted therapies. This study investigated naringenin (NAR), a citrus flavonoid, in a streptozotocin (STZ)-induced diabetic rat model with cardiac complications, focusing on SIRT1-mediated mechanisms.
Rats (n = 8/group) included control, NAR, DCM, DCM + NAR, and DCM + NAR + EX-527 (SIRT1 inhibitor). After 8 weeks, metabolic profiles, cardiac function, histopathology, oxidative stress (Nuclear Factor Erythroid-Related Factor 2 [Nrf2], MDA, SOD, and GSH), inflammation (nuclear factor kappa B [NF-κB], TNF-α, and IL-6), apoptosis (Bax/Bcl-2 and Caspase-3), fibrosis (transforming growth factor beta [TGF-β] and Smad2), and SIRT1 signaling were analyzed.
NAR exhibited hypoglycemic effects, stimulated the release of insulin, and enhanced the lipid profile, thus maintaining the structural integrity of cardiomyocytes and preventing an increase in heart weight, while also restoring the histomorphology in DCM rats. Moreover, NAR influenced both systolic and diastolic blood pressure; reduced serum levels of CK-MB, BNP, and troponin T; downregulated the activity of TGF-β, Smad2, and Caspase-3; and decreased the Bax/Bcl-2 ratio. Crucially, NAR upregulated SIRT1 and modulated the levels of Nrf2, NF-κB, Smad2, and Forkhead Box Protein O1 (FOXO1) in the cardiac tissues of the DCM group. These findings were associated with a significant reduction in oxidative stress and inflammation, alongside diminished NF-κB activity, while promoting Nrf2 activity and Bcl-2. Importantly, the effects of NAR were counteracted by EX-527.
NAR protects against DCM primarily through SIRT1 activation, integrating hypoglycemic, antioxidant, anti-inflammatory, antifibrotic, and antiapoptotic actions. SIRT1 represents a promising target for flavonoid-based DCM therapy.

PMID:
42852983
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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