Application of alpha linolenic acid in preparation of medicine for improving schizophrenia

Abstract

The invention discloses application of alpha-linolenic acid in preparation of a medicine for improving schizophrenia. The alpha-linolenic acid has a remarkable curative effect after oral administration. Animal experiment results show that oral administration of the alpha-linolenic acid has the effect of improving cognitive impairment of the schizophrenia mice, the learning and memory ability of the schizophrenia mice can be remarkably improved, and anxiety symptoms and depression behaviors are improved.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to application of alpha-linolenic acid in the preparation of a drug for improving schizophrenia. Background Art

[0002] Schizophrenia (SCZ) is a chronic, severe mental illness characterized by heterogeneous neurodevelopmental disorders. Most patients develop the disease in late adolescence or young adulthood, and clinical symptoms mainly include positive symptoms, negative symptoms, and cognitive dysfunction. The lifetime prevalence of schizophrenia is about 1%, with recurrent episodes and poor prognosis. Therefore, seeking long-term effective drugs and treatment plans with few side effects is a problem that needs to be solved urgently.

[0003] Alpha linolenic acid (ALA) belongs to omega-3 polyunsaturated fatty acids (PUFAs), which mainly exists in the form of glycerides in plant seeds such as flaxseed. It is an essential fatty acid required by the body. In addition, alpha linolenic acid is the basic substance for cell membranes and biological enzymes, accounting for about 10% of the human brain organs. It is known as the "plant brain gold". α-linolenic acid deficiency will cause reduced brain function efficiency. However, whether alpha linolenic acid can improve the neuroinflammation of schizophrenia and its molecular mechanism have not yet been elucidated. At present, there are no reports at home and abroad on the benefits of alpha linolenic acid in improving schizophrenia and explaining its molecular mechanism for improving schizophrenia. Summary of the invention

[0004] The purpose of the present application is to provide an application of α-linolenic acid in the preparation of a drug for improving schizophrenia, to explore the potential role of α-linolenic acid in improving schizophrenia, and to help screen safer and more effective drugs and preventive and therapeutic methods for the treatment of schizophrenia.

[0005] To solve the above technical problems:

[0006] In a first aspect, the present application provides a use of α-linolenic acid in the preparation of a drug for improving schizophrenia.

[0007] In a second aspect, the present application provides a use of α-linolenic acid in the preparation of a drug for improving cognitive dysfunction caused by schizophrenia.

[0008] As a preferred embodiment, in the above application, the α-linolenic acid improves the learning and memory ability of schizophrenia mice and improves anxiety and depression symptoms.

[0009] Based on the above embodiments, as a preferred implementation mode, the drug is an oral preparation, including capsules and oral liquids.

[0010] Based on the above examples, as a preferred implementation mode, the α-linolenic acid is in liquid form with a purity greater than 99%, the intervention dose is 500 mg / kg / d, and the intervention time is 6 weeks.

[0011] Based on the above embodiments, as a preferred embodiment, the preparation method of the capsule is:

[0012] Use a vacuum oven to heat gelatin to its melting point, add glycerin after it becomes liquid, and continue heating and stirring to make the gelatin and glycerin evenly mixed;

[0013] Adding deionized water to the mixed solution to form a mixed material with viscosity and fluidity;

[0014] The mixed material is added into a gelatin making machine to form a shell, and the shell is filled with α-linolenic acid and then sealed by a sealing machine to form a capsule;

[0015] The shell weighs 550 mg, and one shell contains 500 mg of α-linolenic acid.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. The present invention is the first to discover a new application of α-linolenic acid in the preparation of medicines for improving schizophrenia, and its therapeutic effect is significant after oral administration.

[0018] 2. The experimental results show that oral administration of α-linolenic acid has the effect of improving schizophrenia. It can improve the learning and memory ability of schizophrenia mice, improve anxiety and depression symptoms, and thus improve the cognitive dysfunction of schizophrenia mice. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solution of the present application, the following briefly introduces the drawings required for use in the embodiments. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without inventiveness.

[0020] Figure 1 This is a schematic diagram of the effect of α-linolenic acid intervention on behavioral changes in schizophrenia mice provided in an example of the present application. DETAILED DESCRIPTION

[0021] In order to enable those skilled in the art to better understand the technical solutions in the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the accompanying drawings.

[0022] The core of this application is to provide an application of α-linolenic acid in the preparation of drugs for improving schizophrenia, explore the potential role of α-linolenic acid in improving schizophrenia, and help screen safer and more effective drugs and preventive and therapeutic methods for the treatment of schizophrenia.

[0023] Figure 1 This is a schematic diagram of the effect of α-linolenic acid intervention on behavioral changes in schizophrenia mice provided in the examples of this application, see Figure 1 shown.

[0024] The pharmaceutical dosage form of the present invention is preferably an oral dosage form, including capsules and oral liquids. α-linolenic acid can improve the cognitive dysfunction of schizophrenia mice by improving the learning and memory ability of schizophrenia mice, improving anxiety and depression symptoms. The present invention helps to deeply understand the pathogenesis of schizophrenia and deeply explore the potential application of α-linolenic acid in the prevention and treatment of the disease.

[0025] The α-linolenic acid used in the present invention is in liquid form with a purity greater than 99%, the intervention dose is 500 mg / kg / d, and the intervention time is 6 weeks.

[0026] The preparation method of the capsule is as follows:

[0027] Use a vacuum oven to heat gelatin to its melting point, add glycerin after it becomes liquid, and continue heating and stirring to make the gelatin and glycerin evenly mixed;

[0028] Adding deionized water to the mixed solution to form a mixed material with viscosity and fluidity;

[0029] The mixed material is added into a gelatin making machine to form a shell, and the shell is filled with α-linolenic acid and then sealed by a sealing machine to form a capsule;

[0030] The shell weighs 550 mg, and one shell contains 500 mg of α-linolenic acid.

[0031] The treatment plan for mice can be applied to humans, and the effective doses of all drugs for humans can be converted by the effective doses of the drugs for mice, which is also easy to achieve for ordinary technicians in this field.

[0032] In order to better understand the technical solution of the present invention, the new application of α-linolenic acid in improving schizophrenia is described and demonstrated in detail with specific experiments and conclusions below.

[0033] The present invention is further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention. If no specific techniques or conditions are specified in the embodiments, the techniques or conditions described in the literature in this field or the product instructions are used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased through regular channels. The test materials used in the following embodiments are all commercially available products unless otherwise specified.

[0034] The present invention selects 6-week-old male C57 / BL6 mice to be intraperitoneally injected with dizocilpine / dizocilpine (MK-801) to construct a schizophrenia mouse model, and after the model is successfully established, α-linolenic acid is given by gavage for 6 weeks. The effect of α-linolenic acid on the cognitive function of schizophrenia mice is evaluated by detecting the behavior of each group of mice. Behavioral studies have confirmed that dietary α-linolenic acid intervention can improve the learning and memory ability of schizophrenia mice and relieve anxiety and depression.

[0035] Conclusion: This study confirms that dietary α-linolenic acid can improve the cognitive dysfunction of schizophrenia mice by improving their learning and memory abilities, anxiety and depression symptoms. This invention helps to deeply understand the pathogenesis of schizophrenia and deeply explore the potential application of α-linolenic acid in the prevention and treatment of this disease.

[0036] Experimental Results

[0037] (1) Dietary α-linolenic acid intervention alleviates cognitive dysfunction in schizophrenia mice

[0038] Water maze test (eg Figure 1 AE in Figure 4 showed that compared with the CON group, the mice in the MOD group showed impaired spatial memory ability, significantly increased escape latency, and significantly decreased times of crossing the target platform and the time spent on the target platform (P<0.05, e.g. Figure 1 However, compared with the MOD group, the α-linolenic acid intervention model group significantly reduced the escape latency of schizophrenia mice from day 2 to day 5 (P < 0.05, as Figure 1 C), the risperidone intervention model group only significantly reduced the escape latency on the 4th and 5th days (P < 0.05, as Figure 1 In addition, compared with the MOD group, the number of crossing the target platform and the time spent on the target platform after α-linolenic acid or risperidone intervention were significantly increased (P<0.05, e.g. Figure 1 DE), indicating that dietary α-linolenic acid significantly improved the learning and memory ability of mice induced by MK-801. Figure 1 The FI in the middle showed that during the exploration phase, there was no significant difference in the time that mice in different groups spent exploring the same two objects (P>0.05, e.g. Figure 1 In the test phase, compared with the CON group, the mice in the MOD group spent significantly more time studying the old objects than the new objects, indicating that the recognition memory of schizophrenia mice was severely impaired (P < 0.05, e.g. Figure 1 Surprisingly, compared with the MOD group, intervention with α-linolenic acid or risperidone significantly improved the recognition index (P < 0.05, as Figure 1 Figure I), indicating that α-linolenic acid intervention can improve the recognition memory ability of schizophrenia mice.

[0039] In addition, the open field test and elevated plus maze test were used to assess anxiety-like behaviors. Figure 1 Compared with the CON group, the total walking distance, walking distance in the central area and staying time of the mice in the model group were significantly reduced (P<0.05, as shown in Figure 5). Figure 1 Fortunately, risperidone intervention significantly improved these abnormal behaviors (P<0.05, such as Figure 1 It is worth noting that α-linolenic acid intervention increased the walking distance and residence time of mice in the central area (P<0.05, e.g. Figure 1 The total walking distance (P = 0.05) and the number of paw lifting (P = 0.06) showed only an increasing trend (e.g. Figure 1 These results suggest that α-linolenic acid partially alleviates anxiety. The results of the elevated plus maze test (e.g. Figure 1 Compared with the CON group, the MOD group spent significantly less time in the open arm (P < 0.05, e.g. Figure 1 There was no significant difference between the MOD group and the risperidone or α-linolenic acid group (P>0.05, such as Figure 1 Medium PQ).

[0040] In addition, the tail suspension results showed that the immobility time of mice in the MOD group was increased compared with that in the CON group (P < 0.05, e.g. Figure 1 However, compared with the MOD group, α-linolenic acid or risperidone intervention significantly reduced the immobility time (P < 0.05, as Figure 1 R), indicating that α-linolenic acid has an antidepressant effect in schizophrenia mice.

[0041] In summary, behavioral results consistently show that schizophrenia mice exhibit severe learning and memory dysfunction, anxiety disorders, and depressive behaviors. Fortunately, these abnormal behaviors can be alleviated by taking α-linolenic acid, which is comparable to the positive control risperidone, a first-line clinical drug for schizophrenia, but is safer as a drug-food homologous agent, which provides a potential treatment strategy for schizophrenia.

[0042] Figure 1 The meanings of the letters in the figure are as follows: A: Typical trajectory of the positioning cruise experiment; B: Typical trajectory of the spatial probe test; C: Escape latency; D: Number of times the target platform was crossed; E: Time on the target platform; F: Typical trajectory of the exploration phase; G: Typical trajectory of the test phase; H: Exploration time; I: Recognition index; J: Typical trajectory of the mine test; K: Total distance traveled by mice in each group in the mine; L: Distance traveled in the central area; M: Time spent in the central area; N: Number of paw lifts; O: Typical trajectory of the elevated plus maze test; P: Total number of arm entries of mice in each group; Q: Percentage of time that mice in each group stayed in the open arm; R: Immobility time. *P<0.05, **P<0.01, ***P<0.001, ns: P>0.05.

Claims

1. An application of α-linolenic acid in the preparation of a drug for improving schizophrenia.

2. Use of α-linolenic acid in the preparation of a drug for improving cognitive dysfunction, characterized in that: The cognitive dysfunction is caused by schizophrenia.

3. The use according to claim 1 or 2, characterized in that: The α-linolenic acid improves learning and memory abilities, and improves anxiety and depression symptoms.

4. The use according to claim 1 or 2, characterized in that: The medicine is an oral preparation, including capsules and oral liquids.

5. The use according to claim 4, characterized in that: The α-linolenic acid is in liquid form with a purity greater than 99%, the intervention dose is 500 mg / kg / d, and the intervention time is 6 weeks.

6. The use according to claim 5, characterized in that: The preparation method of the capsule is as follows: Use a vacuum oven to heat gelatin to its melting point, add glycerin after it becomes liquid, and continue heating and stirring to make the gelatin and glycerin evenly mixed; Adding deionized water to the mixed solution to form a mixed material with viscosity and fluidity; The mixed material is added into a gelatin making machine to form a shell, and the shell is filled with α-linolenic acid and then sealed by a sealing machine to form a capsule; The shell weighs 550 mg, and one shell contains 500 mg of α-linolenic acid.

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