CN-121129861-B - Application of liver 20-HETE synthesis inhibitor in preparation of medicines for treating perimenopausal mood disorders

Abstract

The invention discloses application of a liver 20-HETE synthesis inhibitor in preparation of a medicine for treating perimenopausal mood disorder. According to the invention, a perimenopausal mouse model is constructed through ovariectomy, the behavior test shows that the perimenopausal mouse model shows obvious depression and anxiety-like behaviors, the expression of 20-HETE synthesizing enzyme Cyp4a12a in the liver of the ovariectomy mouse is obviously increased, the 20-HETE level in blood plasma is obviously increased, the 20-HETE content in the blood plasma of the ovariectomy mouse is obviously reduced through the intervention of liver 20-HETE synthesizing enzyme inhibitor TS-011, and the depression and anxiety-like behaviors of the mouse are obviously improved. The invention discovers that the liver 20-HETE synthesis inhibitor can be applied to the development or preparation of perimenopausal mood disorder treatment medicines with low side effects and high clinical acceptability, and has higher clinical conversion value.

Inventors

• WANG YUN
• JIA SIQI
• NI LIANGYU

Assignees

• 北京大学

Dates

Publication Date

20260512

Application Date

20250819

Claims (2)

1. Use of a 20-hydroxyeicosatetraenoic acid synthesis inhibitor in the manufacture of a medicament for the treatment of perimenopausal mood disorders, wherein the 20-hydroxyeicosatetraenoic acid synthesis inhibitor is N- (3-chloro-4-morpholinophenyl) -N' -hydroxyformamidine.
2. 2. The use according to claim 1, wherein the symptoms of perimenopausal mood disorders comprise at least one of the following: 1) Depression; 2) Anxiety disorder; 3) Dehairing; 4) The content of 20-hydroxyeicosatetraenoic acid in body fluid is increased.

Description

Application of liver 20-HETE synthesis inhibitor in preparation of medicines for treating perimenopausal mood disorders Technical Field The invention belongs to the technical field of biology, and particularly relates to application of a liver 20-HETE synthesis inhibitor in preparation of a medicine for treating perimenopausal mood disorder. Background Perimenopause is a transitional period in women from vigorous fertility to declining, and is also a high risk period for women to develop mood disorders. Significant depression symptoms were reported in 45-68% of perimenopausal women, and significant anxiety symptoms were reported in 20.2%. Currently, first-line antidepressants (such as 5-hydroxytryptamine and norepinephrine reuptake inhibitors and optionally 5-hydroxytryptamine reuptake inhibitors) are often used in the treatment of perimenopausal mood disorders, but long-term administration of such drugs can lead to significant increases in the incidence of nausea, headache, dizziness and appetite changes in patients, and can limit the efficacy of antidepressants into the brain due to the presence of the blood brain barrier, resulting in about 50% of patients not being effective with antidepressants. In addition, estrogen replacement therapy is widely used for improving perimenopausal symptoms and mood disorders in women, but long-term administration of estrogen increases the risk of occurrence of various diseases such as endometrial cancer and breast cancer in women, and mood disorders in patients after estrogen withdrawal are aggravated sharply, and withdrawal is occurred. It follows that perimenopausal mood disorders have become a clinical challenge to be addressed, and that it is important to find new treatments for perimenopausal mood disorders. The brain function steady state is regulated by other organs of the organism, especially the regulation mechanisms of liver-brain axis, intestine-brain axis, fat-brain axis and the like, and plays a vital role in regulating key physiological processes of cerebral inflammation, neuron survival, synaptic plasticity and the like, and advanced brain functions of emotion, learning, memory and the like. Among them, the liver serves as the core of the energy metabolism of the organism, and has important effects on the processes such as the prominent integrity of the central nervous system and neuroinflammation. Cyp4a12a is an important member of cytochrome P450 enzyme system in liver, belongs to Cyp4a subfamily, and is mainly responsible for catalyzing the metabolism of arachidonic acid to generate 20-hydroxy eicosatetraenoic acid (20-HETE). 20-HETE is a lipid mediator with a variety of biological activities and plays an important role in regulating cell proliferation, inflammatory response, sodium transport, oxidative stress and blood brain barrier integrity. In addition, 20HETE, a powerful vasoconstrictor, can activate protein kinase C and depolarize vascular smooth muscle by inhibiting Kca channels and increase Ca 2+ influx through L-type Ca 2+ channels. Disclosure of Invention The technical problem to be solved by the invention is how to develop or prepare a medicament for treating or assisting in treating perimenopausal mood disorder and/or how to develop and/or prepare a medicament for improving or assisting in improving perimenopausal mood disorder. In order to solve the technical problems, the invention firstly provides application of a 20-hydroxyeicosatetraenoic acid synthesis inhibitor in developing and/or preparing medicines for treating or/and preventing perimenopausal mood disorders. In the above applications, the term "prevention" generally refers to a method performed to prevent or delay the occurrence of a disease or disorder or symptom in a subject. The term "treatment" generally refers to a method that is performed in order to obtain beneficial or desired clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., no longer worsening) disease, delay or slowing of disease progression, amelioration or palliation or remission of the disease state (whether partial or complete), whether detectable or undetectable. Furthermore, treatment may also refer to an extended survival period compared to the expected survival period when the subject is not receiving treatment. In the above application, the medicament may be for animals, such as mammals, having ovaries. In the above application, the symptoms of perimenopausal mood disorders may include at least one of: 1) Depression of 2) Anxiety disorder; 3) Dehairing; 4) The content of 20-hydroxyeicosatetraenoic acid in body fluid is increased. In the above application, the inhibitor of 20-hydroxyeicosatetraenoic acid synthesis may be a substance that inhibits the expression of an enzyme that catalyzes the production of 20-hydroxyeicosatetraenoic acid. In one embodiment of the invention, the enzyme is Cyp4a12