Abstract
Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine formula, is mainly used to clear away heat and detoxify and to promote blood circulation and relieve pain. Diabetic retinopathy (DR) is the most common type of microvascular complication caused by diabetes. This study is designed to examine the protective effect of SMYAD against DR and further to reveal the engaged mechanism via integrating network pharmacology and in vivo experimental evidence. Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetes. The dysfunction of the blood retina barrier (BRB) was observed by conducting Evan’s blue leakage assay, detecting tight junction (TJ) protein expression and counting the number of acellular capillaries in retinas. Our results showed that SMYAD alleviated BRB breakdown in vivo. Network pharmacology results demonstrated that regulating inflammation, immune responses, and angiogenesis might be associated with the efficacy of SMYAD in alleviating DR, in which the tumor necrosis factor (TNF) and hypoxia inducible factor 1 (HIF1) signal pathways were involved. Next, immunofluorescence staining results showed that SMYAD decreased microglia activation in retinas and reduced the enhanced adhesion of leukocytes into retinal vessels. SMYAD reduced the elevated serum TNFα content and retinal TNFα expression. SMYAD abrogated the activation of nuclear factor κB (NFκB) and HIF1α and consequently decreased the enhanced expression of some pro-inflammatory molecules and vascular endothelial growth factor (VEGF) in retinas. These results indicate that SMYAD attenuated DR development through suppressing retinal inflammation and angiogenesis via abrogating NFκB-TNFα and HIF1α-VEGF signal pathways.
Highlights
Diabetic retinopathy (DR), a common microvascular complication caused by diabetes, has become the most serious eye disease leading to the adult blindness in the world (Antonetti et al, 2012; Gardlik and Fusekova, 2015)
blood retina barrier (BRB) dysfunction is a crucial indicator for reflecting retinal microvascular injury in diabetic patients, which eventually causes severe visual impairment when no prompt intervention is applied (Rudraraju et al, 2020)
Si-Miao-Yong-An decoction (SMYAD) restored the decreased retinal claudin1 and claudin19 expression in vivo. These above results indicate that SMYAD ameliorated BRB dysfunction in vivo
Summary
Diabetic retinopathy (DR), a common microvascular complication caused by diabetes, has become the most serious eye disease leading to the adult blindness in the world (Antonetti et al, 2012; Gardlik and Fusekova, 2015). Laser photocoagulation is an invasive treatment, which can cause postoperative visual field defects, decreased contrast sensitivity, and some other adverse reactions including central dark spots or para-central dark spots (Oellers and Mahmoud, 2016). These side effects greatly limited the clinical application of laser photocoagulation. The application of the VEGF antagonist only is incapable of curing DR completely It has some side effects such as causing fibrovascular constriction and the sustained elevation of intraocular pressure (Singh and Kim, 2012; Bandello et al, 2013). More drugs with better efficacy and fewer side effects need to be found in the future
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