# Isorhamnetin as a promising agent for reducing diabetes-induced cardiac damage: insights into antioxidant and enzyme regulatory mechanisms

**Authors:** Esam Qnais, Abdelrahim Alqudah, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan, Badriyah S. Alotaibi, Alaa A. A. Aljabali, Taher Hatahet

PMC · DOI: 10.1007/s11033-025-10941-1 · Molecular Biology Reports · 2025-10-16

## TL;DR

This study shows that Isorhamnetin can protect the hearts of diabetic rats by reducing oxidative stress and inflammation.

## Contribution

The study demonstrates Isorhamnetin's multi-target cardioprotective effects in diabetes-induced heart damage.

## Key findings

- Isorhamnetin reduced oxidative stress markers and improved antioxidant enzyme activity in diabetic rats.
- Isorhamnetin restored ATPase enzyme activity and reduced inflammation and apoptosis in heart tissue.
- Histopathological analysis showed reduced heart muscle damage in Isorhamnetin-treated rats.

## Abstract

This study assessed the protective effect of Isorhamnetin in diabetic rats induced by streptozotocin (STZ).

Male Wistar rats were randomly divided into five groups. Normal control, Diabetic control, Low dose of Isorhamnetin – 50 mg/kg, High dose of Isorhamnetin – 150 mg/kg, and Metformin – 200 mg/kg. Diabetes was induced by a single intraperitoneal injection of STZ and treatment was given orally for a period of 21 days. The parameters that were observed in this study were oxidative markers, ATPase and phosphatase activities, p53 and VCAM-1gene expression, myocardial injury markers and histopathology.

Diabetic rats increased the level of MDA, decreased antioxidant enzyme catalase, SOD, GPx, and GST activity, decreased ATPase activities of Na+/ K+-ATPase, Ca2+/Mg2+- ATPase, and Mg2+-ATPase, increased the expression of p53 and VCAM-1 gene compared to normal control. Low and High dose of Isorhamnetin significantly decreased the MDA level, increased the antioxidant enzyme activity, ATPase, and Na+/K+-ATPase activity compared to diabetic rats and this activity was similar to metformin. Isorhamntenin decreased the p53 and VCAM gene concisely to the diabetic group, increased AST and ALTand reduced the CK-MB and cardiac troponins. Histopathological study showed that reduced the muscle fiber degeneration and congestion pattern of heart congestion.

Isorhamnetin plays a cardioprotective effect in diabetic rats by reducing oxidative stress, increased antioxidant defense, restored and enzyme activity of ATPase and reduced inflammation and apoptosis. Hence, Isorhamnetin can be used as a promising multi-target drug for diabetes-induced cardiac and injury.

## Linked entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157], VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412]
- **Chemicals:** Isorhamnetin (PubChem CID 5281654), streptozotocin (PubChem CID 29327), GPx (PubChem CID 135460989), GST (PubChem CID 5288476), ALT (PubChem CID 10219674)
- **Diseases:** diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 25361] {aka VCAM1B}
- **Diseases:** myocardial injury (MESH:D009202), inflammation (MESH:D007249), heart congestion (MESH:D006333), cardiac and injury (MESH:D006331), Diabetes (MESH:D003920)
- **Chemicals:** Isorhamnetin (MESH:C047368), STZ (MESH:D013311), Metformin (MESH:D008687), MDA (MESH:D015104), Na+/ (MESH:D012964), Isorhamntenin (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12532663/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12532663/full.md

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Source: https://tomesphere.com/paper/PMC12532663