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Application of Withaferin A in preparing drug for treating fundus ischemic disease

A technology for ischemic diseases and drugs, applied in the field of pharmacy, can solve the problems of ignorance of WithaferinA's anti-oxidative stress cell death effect and targeted anti-VEGF dual effect, and no one has reported it, so that the mechanism of action is clear, Clear effect and stable chemical structure

Active Publication Date: 2019-08-23
闫喆一
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Previous molecular docking analysis found that Withaferin A may prevent NF-κB activation by inhibiting the activation of IKKβ; it is considered to have anti-inflammatory and anti-tumor effects, but it is not yet known that Withaferin A has anti-oxidation effects in fundus ischemic diseases The dual effects of stress cell death and targeted anti-VEGF, therefore, its application in the drug of fundus ischemic disease has not been reported

Method used

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  • Application of Withaferin A in preparing drug for treating fundus ischemic disease
  • Application of Withaferin A in preparing drug for treating fundus ischemic disease
  • Application of Withaferin A in preparing drug for treating fundus ischemic disease

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Effect test

Embodiment 1

[0030] Withaferin A (WFA) inhibits ischemia-reperfusion (I / R) and H in human retinal microvascular endothelial cells (HRMECs) 2 o 2 Induced oxidative stress cell death.

[0031] Due to the homology with the blood supply of the retina and choroid, primary human retinal microvascular endothelial cells (HRMECs) were used in this project; the administration of ischemia-reperfusion (I / R) to the cells can simulate the acute ischemia state of the fundus, and the administration of H 2 o 2 Treatment can mimic oxidatively stressed cellular damage resulting from acute and chronic ischemia. The primary cells of HRMECs were purchased from Angio-Proteomie. The cells were routinely revived with endothelial growth medium (EGM) containing 5% FBS, 1% penicillin and streptomycin, and 1% EGF. Subculture when the bottom surface is 70% full, centrifuge the cell suspension at 1,000rpm for 5 minutes, the general subculture ratio is 1:3, and evenly plant in the culture dish, and take the cells with...

Embodiment 2

[0033] Withaferin A inhibits H in HRMECs 2 o 2 Induced oxidative stress apoptosis.

[0034] In this experiment, H 2 o 2 Treatment mimics oxidatively stressed cellular damage resulting from acute and chronic ischemia. HRMECs were routinely cultured, and the inner cells of passage 7 were taken, pretreated with WFA (50nmol / ml) for a total of 15 minutes, H 2 o 2 (100 μmol / ml) treated for 2 hours in vitro to simulate oxidative stress injury, stain with Annexin V-FITC apoptosis detection kit to evaluate cell apoptosis, and count early apoptotic cells (Annexin V + / PI -) and late apoptotic cells (Annexin V + / PI - ), the result can be seen: H 2 o 2 Both early apoptotic cells and late apoptotic cells increased in the induced oxidative stress, while the apoptotic cells were significantly reduced after pretreatment with WFA. The histogram shows the number of HRMECs apoptosis in each group ( figure 2 A). This result indicates that Withaferin A inhibits H 2 o 2 Induced oxid...

Embodiment 3

[0036] Withaferin A protects the posterior vision function of fundus in mice with acute ischemia-reperfusion injury (I / R)

[0037] In this experiment, the mouse model of ischemia-reperfusion injury (I / R) was selected to simulate the acute ischemia-hypoxic injury of the fundus. Since the clinical manifestation of acute fundus ischemic disease is acute visual function damage, this experiment detects the visual function changes of mice in each group. Healthy wild-type male C57 mice, aged 6-8 weeks. All the mice had bright hair, no depilation, no abnormalities in eye examination, clear refractive media, and normal fundus. They were randomly divided into: 1. Control group; 2. I / R injury group; 3. I / R injury + WFA (10nmol / g / d) intraperitoneal injection group; 4. I / R injury + WFA (5nmol / g / d) peribulbar (peripheral) injection group. 20 in each group. The corresponding drug pretreatment was given 2 hours before the injury model. Using 2% isoflurane for stable anesthesia, put the ne...

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Abstract

The invention discloses application of Withaferin A in preparing a drug for treating a fundus ischemic disease. Experiments show that the Withaferin A can inhibit the fundus ischemic disease from theperspective of pathogenesis through two mechanisms that 1, oxidative stress cell necrosis and apoptosis caused by ischemia are significantly reduced; 2, targeted inhibition of a vascular endothelial growth factor and a signaling pathway of a receptor (VEGF-VEGFR2) of the vascular endothelial growth factor is achieved, and the pathological microvascular hemorrhage leakage, abnormal blood vessel growth and other symptoms are ameliorated. The Withaferin A significantly relieves the symptoms of the fundus ischemic disease and inhibits the generation and development of the disease through the dualeffects of the two mechanisms. The Withaferin A as a small molecule targeting compound has a stable and safe chemical structure and can penetrate through a blood-eye barrier, therefore the WithaferinA has a broad application prospect in the fundus ischemic disease.

Description

[0001] Technical field: [0002] The invention belongs to the technical field of pharmacy, and specifically relates to the application of Withaferin A in the preparation of medicines for treating fundus ischemic diseases. Background technique [0003] Retinal and choroidal ischemia and hypoxia are collectively referred to as ischemic fundus diseases, which are important causes of vision loss and loss, including: 1. Acute ischemia: ophthalmic artery occlusion, central retinal artery occlusion, branch retinal artery occlusion, ciliary Retinal artery occlusion, distant retinopathy, Purtscher-like retinopathy, etc.; 2. Chronic ischemia: central retinal vein occlusion, branch vein occlusion, diabetic retinopathy, ocular ischemic syndrome, Takayasu arteritis fundus lesions, premature infant retina lesions, age-related macular degeneration, etc. Chronic fundus ischemic disease can also lead to complications such as neovascular glaucoma and corneal neovascularization. [0004] Retin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/58A61P27/02A61P9/10A61P3/10
CPCA61K31/58A61P3/10A61P9/10A61P27/02
Inventor 闫喆一曹晓明王春芳
Owner 闫喆一
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