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CN-121971469-A - Bacopa monnieri glycoside 2 targeting post-stroke AQP1 target of mice and application of Bacopa monnieri glycoside 2 in stroke intervention

CN121971469ACN 121971469 ACN121971469 ACN 121971469ACN-121971469-A

Abstract

The invention discloses a Bacopa 2 targeting an AQP1 target after cerebral apoplexy of a mouse and application thereof in cerebral apoplexy intervention, relates to the technical field of biological medicines, and relates to an action mechanism of the medicine for targeted inhibition of the expression and/or the function of aquaporin 1, wherein the application of the Bacopa 2 is related to the specific inhibition of the AQP1 target which is highly expressed in astrocytes after cerebral apoplexy, and the application of the Bacopa 2 can further play a role in regulating pathogenic interaction of the AQP1 and downstream protein 4EBP 2. The dual action mechanism of the upstream target inhibition-downstream interaction interference provides a new thought and a clear intervention node for developing a cooperative therapeutic drug aiming at the ischemic brain injury complex pathological network, and surpasses the traditional strategy of single target inhibition.

Inventors

  • SONG YUANJIAN
  • ZHANG JINGYUAN
  • LIU YAN
  • HUANG MENGYAO
  • QI CHENGYU
  • ZHOU XUN
  • Hu Fuchan

Assignees

  • 徐州医科大学

Dates

Publication Date
20260505
Application Date
20260318

Claims (8)

  1. 1. Use of bacoside 2 in the manufacture of a medicament for the treatment or amelioration of neurobehavioral dysfunction following ischemic brain injury, characterised in that the mechanism of action of the medicament is targeted inhibition of aquaporin 1 expression and/or function.
  2. 2. The use according to claim 1, wherein the ischemic brain injury is ischemic stroke.
  3. 3. The use according to any one of claims 1, wherein the neuro-behavioral dysfunction comprises at least one of dyskinesia, hypomuscular strength, and anxiety-like behavior.
  4. 4. The use according to claim 1, wherein the bacoside 2 acts therapeutically by inhibiting the interaction of aquaporin 1 with 4E binding protein 2.
  5. 5. The use according to claim 1, wherein the medicament is for inhibiting the expression of aquaporin 1 in ischemic penumbra tissue, comprising astrocytes.
  6. 6. The use according to claim 1, wherein the medicament is in the form of an oral formulation.
  7. 7. A pharmaceutical composition for treating or ameliorating neurobehavioral dysfunction following ischemic brain injury, comprising the bacoside 2 of claim 4 as an active ingredient, and a pharmaceutically acceptable carrier or adjuvant.
  8. 8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is in the form of an oral formulation.

Description

Bacopa monnieri glycoside 2 targeting post-stroke AQP1 target of mice and application of Bacopa monnieri glycoside 2 in stroke intervention Technical Field The invention relates to the technical field of biological medicines, in particular to a Bacopa monnieri glycoside 2 targeting an AQP1 target point after cerebral apoplexy of mice and application thereof in cerebral apoplexy intervention. Background Ischemic cerebral apoplexy (IschemicStroke) is the most common clinical cerebrovascular disease, and accounts for more than 80% of the total cerebral vascular diseases, and the core pathological mechanism is cerebral tissue ischemia and hypoxia caused by cerebral local blood supply artery occlusion, which causes ischemia penumbra formation, nerve cell apoptosis, blood brain barrier destruction and cerebral edema cascade injury, and finally leads to permanent nerve dysfunction (such as motor coordination capacity reduction, anxiety-like behavior, muscular strength reduction and the like). At present, clinical treatment means mainly depend on intravenous thrombolysis (such as rtPA) and mechanical thrombolysis, but are limited by a strict time window (within 4.5-6 hours after onset), only a few patients can benefit, but the research and development of neuroprotective drugs aiming at ischemic brain injury are still in bottleneck, and lack of specific treatment means capable of effectively improving long-term behavioral prognosis of patients. Aquaporin 1 (AQP 1) is a key protein mediating the transmembrane transport of water molecules, and has been found to play an important regulatory role in cerebral ischemic injury in recent years. Existing researches suggest that the expression of AQP1 is up-regulated in ischemic brain tissues and is closely related to cerebral edema formation and blood brain barrier permeability increase, but the dynamic expression rule of AQP1 in specific cell types (such as astrocytes) of ischemic penumbra and the regulation mechanism of the AQP1 and downstream interaction proteins are not clear, and the application report of specific inhibitors of AQP1 in improving neurobehavioral after ischemic brain injury is lacking. In view of the above, the application provides a bacoside 2 targeting the post-stroke AQP1 target of mice and application thereof in cerebral stroke intervention, which are used for solving the problems. Disclosure of Invention The invention aims to provide a Bacopa 2 targeting an AQP1 target after cerebral apoplexy of a mouse and application thereof in cerebral apoplexy intervention, so as to solve the problems that the dynamic expression rule of the AQP1 in specific cell types (such as astrocytes) of ischemic penumbra and the regulation mechanism of the AQP1 and downstream interaction proteins are not clear, and the application report of specific inhibitors of the AQP1 in neurobehavioral improvement after ischemic brain injury is lacked in the prior art. In order to achieve the above object, the present invention provides the following technical solutions: Use of bacoside 2 in the manufacture of a medicament for the treatment or amelioration of neurobehavioral dysfunction following ischemic brain injury, the mechanism of action of the medicament being targeted inhibition of expression and/or function of aquaporin 1 (AQP 1). Further, the ischemic brain injury is ischemic stroke. Further, the neurobehavioral dysfunction includes at least one of dyskinesia, hypomuscular strength, and anxiety-like behavior. Further, the bacoside 2 exerts a therapeutic effect by inhibiting the interaction of AQP1 with 4E binding protein 2 (4 EBP 2). Further, the agents are useful for inhibiting up-regulation of AQP1 expression in ischemic penumbra tissue, particularly astrocytes. Further, the dosage form of the medicine is an oral preparation. A pharmaceutical composition for treating or ameliorating neurobehavioral dysfunction following ischemic brain injury, comprising a therapeutically effective amount of bacoside 2 as described above as an active ingredient, together with a pharmaceutically acceptable carrier or adjuvant. Further, the dosage form of the pharmaceutical composition is an oral preparation. Compared with the prior art, the Bacopa monnieri glycoside 2 targeted to the post-stroke AQP1 target of the mice and the application thereof in cerebral stroke intervention are provided, the application of the Bacopa monnieri glycoside 2 is related to the specific inhibition of the high-expression AQP1 target in the post-stroke astrocytes, and the application of the Bacopa monnieri glycoside 2 can further play a role by regulating pathogenic interaction of the AQP1 and downstream protein 4EBP 2. The dual action mechanism of the upstream target inhibition-downstream interaction interference provides a new thought and a clear intervention node for developing a cooperative therapeutic drug aiming at the ischemic brain injury complex pathological network, and surpasses the traditional strategy