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Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling
Lingli Long1,2, Yubin Li3, Shuang Yu1
1Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Background:
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. This study demonstrates the antiangiogenic effects of scutellarin (SCU) on high glucose- and hypoxia-stimulated human retinal endothelial cells (HRECs) and on a diabetic rat model by oral administration. The antiangiogenic mechanisms of SCU in vitro and in vivo were investigated.
Method:
HRECs were cultured in high glucose- (30 mM D-glucose) and hypoxia (cobalt chloride-treated)-stimulated diabetic condition to evaluate the antiangiogenic effects of SCU by CCK-8 test, cell migration experiment (wound healing and transwell), and tube formation experiment. A streptozotocin-induced type II diabetic rat model was established to measure the effects of oral administration of SCU on protecting retinal microvascular dysfunction by Doppler waveforms and HE staining. We further used western blot, luciferase reporter assay, and immunofluorescence staining to study the antiangiogenic mechanism of SCU. The protein levels of phospho-ERK, phospho-FAK, phospho-Src, VEGF, and PEDF were examined in HRECs and retina of diabetic rats.
Result:
Our results indicated that SCU attenuated diabetes-induced HREC proliferation, migration, and tube formation and decreased neovascularization and resistive index in the retina of diabetic rats by oral administration. SCU suppressed the crosstalk of phospho-ERK, phospho-FAK, phospho-Src, and VEGF in vivo and in vitro.
Conclusions:
These results suggested that SCU can be an oral drug to alleviate microvascular dysfunction of DR and exerts its antiangiogenic effects by inhibiting the expression of the crosstalk of VEGF, p-ERK, p-FAK, and p-Src.
Insights
Scutellarin (SCU) demonstrates antiangiogenic effects, alleviating diabetic retinopathy (DR) microvascular dysfunction. It inhibits key signaling pathways involved in abnormal blood vessel growth in both cells and diabetic rats.
Area of Science:
- Ophthalmology
- Endocrinology
- Pharmacology
Background:
- Diabetic retinopathy (DR) is a severe complication of diabetes affecting retinal microvasculature.
- Understanding DR's pathogenesis is crucial for developing effective treatments.
- Identifying novel therapeutic agents with antiangiogenic properties is a key research area.
Purpose of the Study:
- To investigate the antiangiogenic effects of scutellarin (SCU).
- To elucidate the mechanisms underlying SCU's action in diabetic retinopathy.
- To evaluate SCU's efficacy in both in vitro and in vivo models of DR.
Main Methods:
- Human retinal endothelial cells (HRECs) were stimulated with high glucose and hypoxia.
- SCU's effects on HREC proliferation, migration, and tube formation were assessed.
- A streptozotocin-induced diabetic rat model was used to evaluate SCU's in vivo efficacy and mechanisms via western blot, luciferase assays, and immunofluorescence.
Main Results:
- SCU significantly attenuated high glucose/hypoxia-induced HREC proliferation, migration, and tube formation.
- Oral administration of SCU reduced retinal neovascularization and improved vascular function in diabetic rats.
- SCU suppressed the signaling crosstalk involving VEGF, p-ERK, p-FAK, and p-Src in both cellular and animal models.
Conclusions:
- Scutellarin (SCU) exhibits significant antiangiogenic properties relevant to diabetic retinopathy.
- SCU effectively alleviates microvascular dysfunction in DR models.
- The antiangiogenic mechanism involves the inhibition of VEGF, p-ERK, p-FAK, and p-Src signaling pathways.
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