Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing

AIM:To determine the effects of safranal on choroidal neovascularization(CNV)and oxidative stress damage of human choroidal microvascular endothelial cells(HCVECs)and its possible mechanisms.METHODS:Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal(0.5 mg/kg·d,intraperitoneally)on CNV.CNV leakage on fluorescein angiography(FA)and CNV thickness on histology was compared.HCVECs were used for a H_(2)O_(2)-induced oxidative stress model to test the effect of safranal in vitro.MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations.Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations.mRNA transcriptome sequencing was performed to find the possible signal pathway.The expressions of different molecules and their phosphorylation level were validated by Western blotting.RESULTS:On FA,the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm^(2)(P=0.012)in the control and safranal-treated group respectively.The average CNV thickness was 127.4±18.75 and 100.6±17.34μm(P=0.001)in control and safranal-treated group.Under the condition of oxidative stress,cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4%at the different concentrations.For tube formation study,the number of new branches was 364 in control group and 35,42,and 17 in 20,40,and 80μg/mL safranal groups respectively(P<0.01).From the KEGG pathway bubble graph,the PI3K-AKT signaling pathway showed a high gene ratio.The protein expression was elevated of insulin receptor substrate(IRS)and the phosphorylation level of PI3K,phosphoinositide-dependent protein kinase 1/2(PDK1/2),AKT and Bcl-2 associated death promoter(BAD)was also elevated under oxidative stress condition but inhibited by safranal.CONCLUSION:Safranal can inhibit CNV both in vivo and in vitro,and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV.

Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases

Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

SAFRAN系统—战场上应用的数字波束形成雷达

1 引言 1.1 计划目标 21世纪头10年的空中防御系统将需要使用新的探测和目标识别技术,以与变化的威胁环境相适应,特别是提供较好的抗干扰能力和较快的反应时间。 SAFRAN验证系统是法国国防部的探索研究系统,旨在证实用作未来战场监视系统的新的雷达技术。