CN-122005538-A - Application of flavonoid compounds in treating cerebral small vessel diseases

Abstract

The invention discloses application of flavonoid compounds in preparing medicaments for treating cerebral small vascular diseases, application of the flavonoid compounds in preparing medicaments for improving or relieving white matter damage, cerebral small vascular disease related cell damage, cerebral white matter damage related to cerebral small vascular diseases and/or cognitive dysfunction, and application potential of the flavonoid compounds in cerebral small vascular disease related white matter protection is verified, wherein the flavonoid compounds 5,6, 7-trimethoxy flavone and 2-hydroxy chalcone can obviously inhibit oligodendrocyte iron death related phenotype in an in vitro model, and improve the cerebral white matter damage and the cognitive dysfunction in an ovariectomy mouse model.

Inventors

• XING LINGYAN
• CAI XINYI
• LU XIAOJUAN
• ZHANG GUANGQI

Assignees

• 南通大学

Dates

Publication Date

20260512

Application Date

20260324

Claims (10)

1. 1. Application of flavonoids in preparing medicine for treating cerebral small vessel diseases is provided.
2. 2. The use according to claim 1, wherein the flavonoid comprises one or both of 5,6, 7-trimethoxyflavone or 2-hydroxy chalcone.
3. 3. The use according to claim 1 or 2, wherein the concentration of flavonoids is 1-20 μm.
4. 4. The use according to claim 1 or 2, characterized in that it comprises the use of said flavonoids for the preparation of a medicament for restoring oligodendrocyte viability.
5. 5. The use according to claim 4, wherein the use comprises the use of the flavonoid for a medicament for increasing oligodendrocyte cell viability in an iron death model, preferably induced by an iron death inducer.
6. 6. The use of claim 5, wherein the iron death inducer is present at a working concentration of about 0.1 μm to about 1 μm.
7. 7. The use according to any one of claims 3 to 6, wherein the medicament further comprises an iron death inhibitor Fer-1.
8. 8. The use according to claim 7, wherein the iron death inhibitor concentration is 1-2 μm.
9. 9. Use of flavonoids in the preparation of a medicament for improving or alleviating white matter damage, cell damage associated with cerebral small vessel disease, white matter damage associated with cerebral small vessel disease and/or cognitive dysfunction.
10. 10. The use according to claim 9, wherein the flavonoid comprises one or both of 5,6, 7-trimethoxyflavone or 2-hydroxy chalcone.

Description

Application of flavonoid compounds in treating cerebral small vessel diseases Technical Field The invention belongs to the technical field of crossing of cell pharmacology and natural drug development, and particularly relates to application of flavonoid compounds in treating cerebral small vessel diseases. Background Cerebral small vascular disease (Cerebral SMALL VESSEL DISEASE, CSVD) is a chronic cerebrovascular disease which involves micro arteries, micro veins and capillaries in the brain, and is one of important pathological bases of cognitive decline and vascular cognitive impairment in the elderly population. Clinical imaging studies show that cerebral small vascular diseases are mainly represented in the brain by changes such as high white matter signals, lacunar infarction, damaged brain microstructure integrity and the like, wherein the cerebral white matter diseases are pathological features which occur at the earliest and have the highest incidence and the most close relationship with cognitive function damage. At present, clinical intervention of cerebral small vascular diseases mainly takes dangerous factors such as blood pressure control and the like as cores, and measures such as blood pressure reduction, lipid regulation, vascular endothelial function improvement and the like are taken, and the intervention mode can delay the disease progression to a certain extent. However, such therapeutic strategies are mainly directed to systemic vascular risk factors, and there is no drug that acts directly on structural brain lesions, especially for the efficient intervention of the core intra-brain pathology, white matter lesions. Epidemiological studies have shown that postmenopausal women are a high risk group of cerebral small vessel disease. After menopause, due to the sudden drop of estrogen level, cerebrovascular endothelial dysfunction, declining cerebral microvascular perfusion and rising of oxidative stress level can be caused, thereby obviously increasing the occurrence risk of cerebral arteriolar diseases and leukoencephalopathy. Thus, postmenopausal status is considered to be an important physiologically susceptible background for the development of cerebral small vessel disease, whereas white matter damage is its prominent early pathological manifestation. From the pathological mechanism perspective, the white matter damage related to the cerebral small vessel disease is closely related to factors such as chronic low perfusion, oxidative stress enhancement, iron steady state disturbance and the like. Oligodendrocytes, which are key cells in the central nervous system responsible for myelination and maintenance, are highly sensitive to the above pathological changes. In the pathological microenvironment of cerebral small vessel disease formation, oligodendrocytes are easily damaged, thereby causing myelin sheath structure destruction and white matter microstructure abnormality. Early studies found that in the relevant model mimicking menopausal status, significant leukoencephalopathy was observed, whose cytopathological basis was mainly manifested as oligodendrocyte damage. Further studies suggest that this damage process is closely related to iron-dependent lipid peroxidation, consistent with the characteristics of iron death. However, the existing research related to cerebral small vascular diseases is mainly focused on vascular structures and hemodynamic levels, and oligodendrocyte iron death has not been used as a key pathological target of cerebral small vascular disease white matter injury for drug screening and intervention. The existing CSVD treatment mainly focuses on antiplatelet, depressurization and blood flow improvement, but does not relate to a cell death mechanism related to brain white matter injury, and is difficult to directly protect white matter structures. The flavonoid compounds are a large class of natural polyphenol compounds widely existing in plants, and comprise a plurality of structural subclasses such as isoflavone, flavonol, flavanone, chalcone and the like, and have good safety foundation and research accumulation in the field of natural product research. Studies have shown that some flavonoids have the effects of resisting oxidation, regulating redox homeostasis in cells and inhibiting lipid peroxidation, and have certain cytoprotective effects in various oxidative stress related cell injury models. Development and progression of brain white matter lesions associated with cerebrovascular disease are closely related to increased oxidative stress and imbalance in iron homeostasis, with oligodendrocyte iron death being considered an important cytopathological basis leading to myelin destruction and abnormal white matter architecture. Iron death is characterized by iron-dependent lipid peroxidation as a core and has an intrinsic relevance in terms of pathological mechanisms to the known antioxidant and anti-lipid peroxidation biological properties of flavonoi