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Drug Res (Stuttg) 2025; 75(02): 76-83
DOI: 10.1055/a-2507-5528
Original Article

Thymoquinone Mediates Müller Cell Apoptosis via miR-29b/SP1 Pathway: A Potential Therapeutic Approach in Diabetic Retinopathy

Khalid M. Alkharfy
1   Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
,
Ajaz Ahmad
1   Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
,
Mohammad Raish
2   Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
,
Maha F. Alenazy
3   Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
› Author Affiliations Funding Information King Saud University Diabetes Research
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Abstract

Purpose

This study aims to explore the therapeutic potential of thymoquinone (TQ) in DR by assessing its effects on Müller cell apoptosis through modulation of the miR-29b/SP1 pathway in a diabetic animal model.

Methods

Healthy C57BL/6 mice (25 g) were used in the study. Retinal samples were collected from both normal and diabetic mice subjected to various treatments: TQ (1 mg/kg/day), glibenclamide (GLB, 250 mg/kg/day), sitagliptin (STG, 10 mg/kg/day), and metformin (MET, 5 mg/kg/day) over a period of 28 days. The study measured miR-29b and SP1 mRNA levels using qRT-PCR. Protein expressions of SP1, Bax, and bcl-2 were analyzed through western blotting, while Caspase-3 activity using an ELISA assay kit, and apoptosis levels by annexin V.

Results

TQ administration resulted in a 52% reduction in blood glucose levels. Similarly, GLB, STG, and MET treatments reduced blood glucose by 60%, 57%, and 61%, respectively (p<0.05). In addition, TQ upregulated miR-29b by 51.28% and downregulated SP1 mRNA by 32.52% (p<0.05). Bax protein expression levels were decreased by 64.99%, while Bcl-2 protein expression increased by 62.92% in the TQ treatment group as compared to the untreated diabetic controls. Furthermore, Caspase-3 activity was downregulated by 40.03% with TQ treatment (p<0.05). Interestingly, the effect TQ on SP1 mRNA expression was inhibited by a miR-29b blocker (p<0.05), while an miR-29b mimic enhanced this effect; this was associated with a mitigation of apoptosis of retinal Müller cells as measured by flow cytometry (p<0.05).

Conclusion

These results indicate that TQ might be a possible option for DR via its effect on the miR-29b/SP1 pathway; and therefore, playing a significant role in the mechanism against cell death.

Keywords

antidiabetic drugs - apoptosis - drug research


Publication History

Received: 09 December 2024

Accepted: 16 December 2024

Article published online:
15 January 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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