Scutellarin Prevents Angiogenesis in Diabetic Retinopathy by Downregulating VEGF/ERK/FAK/Src Pathway Signaling

Abstract

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.

Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer

“…To support LHT effect in a mechanistic way, we identified the phosphorylation of the VEGFR, extracellular signal-regulated kinase (ERK), and focal adhesion kinase (FAK) protein. As shown in Figure 6 A [ 61 , 62 ] , the phosphorylation of VEGFR can stimulate the phosphorylation of ERK for cell migration and phosphorylation of FAK for cell migration. When LHT is added to HUVECs, it may attenuate the interaction between VEGF and VEGFR on the cellular membrane, thereby modulating the phosphorylation of ERK and FAK in the cytosol.…”

Scutellarin alleviates type 2 diabetes (HFD/low dose STZ)-induced cardiac injury through modulation of oxidative stress, inflammation, apoptosis and fibrosis in mice

“…In recent years, the focus has been shifted towards nding the e cacy and mechanism of action of Scutellarin (SCU). SCU is well known for its protective potential against neurotoxicity (Guo et al, 2013), diabetic nephropathy (Xu et al, 2013;Liu et al, 2019), diabetic retinopathy (Long et al, 2019;Mei et al, 2019), diabetes-induced testicular damage (Long et al, 2015) and diabetes-induced liver injury (Wang et al, 2020) through its antioxidant (Wu and Jia, 2019) and antiin ammatory actions. Previously, studies reported that SCU protects doxorubicininduced acute cardiotoxicity (Sun et al, 2017), isopranaline-induced myocardial infarction (Huang et al, 2018) and ischemia-reperfusion (I/R)-induced myocardial injury .…”

Scutellarin alleviates type 2 diabetes (HFD/low dose STZ)- induced cardiac injury through modulation of oxidative stress, inflammation, apoptosis and fibrosis in mice

“…In recent years, the focus has been shifted towards nding the e cacy and mechanism of action of Scutellarin (SCU). SCU is well known for its protective potential against neurotoxicity (Guo et al, 2013), diabetic nephropathy (Xu et al, 2013;Liu et al, 2019), diabetic retinopathy (Long et al, 2019;Mei et al, 2019), diabetes-induced testicular damage (Long et al, 2015) and diabetes-induced liver injury (Wang et al, 2020) through its antioxidant (Wu and Jia, 2019) and antiin ammatory actions. Previously, studies reported that SCU protects doxorubicininduced acute cardiotoxicity (Sun et al, 2017), isopranaline-induced myocardial infarction (Huang et al, 2018) and ischemia-reperfusion (I/R)-induced myocardial injury .…”