Shikonin shows retinoprotective effects in diabetic rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways

Abstract

Objective: To examine the effect of shikonin against streptozotocin (STZ)-induced diabetic retinopathy in rats and elucidate the underlying mechanisms.

Methods: Intraperitoneal administration of STZ (65 mg/kg) was used for the induction of diabetic retinopathy in rats. Rats received oral administration of shikonin (10, 20, and 30 mg/kg). The blood glucose level, insulin, body weight, and organ weight were estimated. Advanced glycation end products (AGEs) levels in serum and lens as well as protein carbonyl content of the lens were determined. The parameters related to oxidative stress and inflammation, and the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were also measured. In addition, quantitative RT-PCR was performed to determine the mRNA expressions.

Results: Shikonin treatment decreased glucose level and boosted insulin level, along with an increase in body weight and improved organ weight. It also lowered O2•-, ONOO-, serum and lens AGEs, and protein carbonyl content. Furthermore, shikonin treatment significantly alleviated oxidative stress and inflammation, as evidenced by reduced malonaldehyde, nitric oxide, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, cyclooxygenase-2, prostaglandin E2, protein carbonyl content, and nuclear factor kappa-B, and increased superoxide dismutase, glutathione, catalase, and glutathione peroxidase. Markedly decreased levels of ICAM-1 and VCAM-1, as well as heightened levels of Nrf2 and HO-1, were noticed after treatment with shikonin. Furthermore, the mRNA expressions of TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, RAGE, collagen IV, and fibronectin were significantly downregulated.

Conclusions: Shikonin exhibits protective effects against STZ-induced diabetic retinopathy in rats via modulating the Nrf2/HO-1 and NF-κB signaling pathways.

Keywords

Diabetic retinopathy / Shikonin / Serum AGEs / Nrf2/HO-1 / NF-κB signaling pathway

Conflict of interest statement

The authors declare no competing interests.

Funding

The study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

XR and JD designed the experimental study. MMZ interpreted the experimental data. XR and MMZ drafted the manuscript and JD approved the proof reading.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

We thank the Xi’an Children’s Hospital for providing the necessary facility for conducting the study.

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