Application of methionine in preparation of medicine or composition for improving social disorder of schizophrenia

Abstract

The invention relates to the field of biomedicine, and discloses application of methionine in preparation of a medicine or a composition for improving social dysfunction caused by schizophrenia. Animal experiment results show that methionine can significantly improve the social novelty recognition ability of schizophrenia model mice by adjusting methylation. The medicine is preferably an oral preparation and can also be combined with vitamin B12, folic acid and other related auxiliary factors for use. According to the invention, the potential treatment value of methionine on the negative symptoms of schizophrenia is disclosed for the first time, and a new direction is provided for developing novel mental disorder intervention medicines or nutritional compositions.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a novel use of a natural amino acid—methionine—in the preparation of medicaments or compositions for improving social dysfunction caused by schizophrenia. Background Technology

[0002] Schizophrenia is a severe neuropsychiatric disorder characterized by hallucinations, delusions, thought disorders, and significant social dysfunction. Approximately 20%–50% of first-episode schizophrenia patients develop treatment-resistant schizophrenia, which is typically accompanied by more pronounced changes in brain structure (such as increased precordial cortex and decreased gray matter) and a more significant reduction in metabolomics synthesis (such as dopamine). Currently, clinical treatment primarily utilizes antipsychotic drugs such as dopamine receptor antagonists, which are effective for positive symptoms (such as hallucinations) but have limited efficacy for negative symptoms (such as social withdrawal). Methionine is an essential sulfur-containing amino acid and, as an important participant in one-carbon metabolism, its metabolite S-adenosylmethionine (SAM) plays a crucial role in neurotransmitter synthesis and DNA methylation. Previous studies have suggested that methionine possesses certain neuromodulatory potential in animal models of autism and depression. However, no literature reports its therapeutic effect on social impairment in schizophrenia. Summary of the Invention

[0003] The purpose of this invention is to provide a new use of methionine in the preparation of medicaments or compositions for improving social impairment caused by schizophrenia, filling the gap in existing treatments that do not adequately address negative symptoms.

[0004] To achieve the above objectives, the present invention proposes the following technical solution:

[0005] 1. Use of methionine in the preparation of drugs for improving social dysfunction caused by schizophrenia;

[0006] 2. The drug is an oral preparation, preferably a solid or liquid dosage form with methionine as the main active ingredient;

[0007] 3. In animal experiments, adding methionine at a dose of 19.6 g / kg to the regular diet of mice for two consecutive weeks significantly improved the social novelty recognition ability of MK-801-induced schizophrenia model mice.

[0008] Compared with the prior art, the present invention has the following beneficial effects:

[0009] 1. First discovery of the potential therapeutic role of methionine in social impairment caused by schizophrenia;

[0010] 2. It is administered orally, which ensures high safety and good patient compliance;

[0011] 3. It has the potential to be developed into an adjunct treatment drug or functional food for schizophrenia. Attached Figure Description

[0012] The attached figures show the results of the three-box social interaction experiment in normal mice (Vehicle group), schizophrenic mice (MK-801 group), and methionine-interventioned mice (MK-801+LM group). Figure A: Comparison of sniffing time between the tested mice and familiar mice (S1) and unfamiliar mice (S2) in the three-box social interaction experiment; Figure B: Social novelty preference index. In the three-box social interaction experiment, the sniffing time between normal mice (Vehicle group) and familiar mice (S1) was less than that between normal mice and unfamiliar mice (S2), suggesting that normal mice have a novelty-seeking social characteristic. There was no difference in sniffing time between schizophrenic mice (MK-801 group) and familiar mice (S1) and unfamiliar mice (S2), suggesting that schizophrenic mice cannot distinguish between familiar and unfamiliar mice and have impaired social novelty-seeking ability. Methionine intervention (MK-801+LM group) significantly improved these abnormal behaviors (Figure A). The social novelty index (SDI) = (sniffing time with unfamiliar mice – sniffing time with familiar mice) / total sniffing time. Schizophrenic mice (MK-801 group) showed a decreased SDI, suggesting impaired social novelty-seeking ability. However, methionine intervention (MK-801+LM group) significantly improved these abnormal behaviors (Figure B). These results indicate that methionine improves social impairments in schizophrenic mice.

[0013] In summary, the behavioral results indicate that schizophrenic mice exhibit severe social impairment, and this abnormal behavior can be alleviated by methionine intake. Methionine is a safer food-medicine alternative in clinical practice for schizophrenia, providing a potential treatment strategy for the disease.

[0014] *P<0.05, **P<0.01,***P<0.001, ns: P>0.05 Detailed Implementation

[0015] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0016] 1. Experimental Animals and Modeling Methods: Three-week-old male C57BL / 6J mice were used to establish an animal model of schizophrenia by intraperitoneal injection of MK-801. The intervention group was fed a diet containing 19.6 g / kg methionine during the modeling process, and the intervention period was 2 weeks.

[0017] 2. Behavioral evaluation employed a three-box social experiment to assess social novelty behavior:

[0018] Normal mice exhibited significant novelty-seeking behavior, with a significantly longer sniffing time with unfamiliar mice (S2) compared to familiar mice (S1). Model mice lost their social novelty preference. After methionine intervention, MK-801 model mice recovered this behavioral characteristic, and their social novelty preference index increased significantly.

[0019] 3. Conclusions show that methionine can effectively alleviate social novelty impairment in a mouse model of schizophrenia, and its mechanism of action may be related to methylation modification and neural circuit plasticity. This invention reveals the potential application of methionine as a nutritional intervention factor in the negative symptoms of schizophrenia.

[0020] Recommendations for application in the population

[0021] 1. Population Indications: The methionine intervention strategy proposed in this invention can be applied to schizophrenia patients with social dysfunction, especially those presenting primarily with negative symptoms (such as social withdrawal and emotional blunting). These patients often respond poorly to traditional antipsychotic drugs and experience slow recovery of social function, thus requiring adjunctive interventions.

[0022] 2. Recommended audience

[0023] Patients with social dysfunction who are experiencing first-episode or relapse-stage schizophrenia;

[0024] Patients whose predominant presentation is negative symptoms;

[0025] Young and middle-aged patients with a high need for functional recovery;

[0026] The recovery phase of schizophrenia patients, those undergoing maintenance treatment or medication tapering;

[0027] 3. Human Dosage Conversion Reference: The methionine dosage used in animal experiments was 19.6 g / kg (based on feed), corresponding to a daily intake of approximately 1.5–2 g / kg body weight for mice. Based on the standard conversion formula (human-mouse conversion factor = 12.3), the equivalent human dose is:

[0028] Human equivalent dose ≈ Mouse dose (mg / kg) ÷ 12.3 ≈ 2000 mg / kg ÷ 12.3 ≈ 162 mg / kg

[0029] For a 60kg adult, this is equivalent to a daily intake of approximately 9.7g of methionine.

[0030] The recommended initial dose is 2–6 g daily, adjusted according to patient tolerance and efficacy. It can also be supplemented in combination with one-carbon metabolism regulators such as vitamin B12 and folic acid.

[0031] 4. Dosage Form Recommendations: We recommend oral formulations, including granules, tablets, capsules, and functional drinks, to facilitate long-term adherence management.

[0032] 5. Safety Note: Although methionine is a safe amino acid, high doses may lead to a risk of hyperhomocysteinemia. It is recommended to use it in combination with B vitamins to aid metabolism, and to monitor plasma homocysteine ​​levels if necessary.

Claims

1. Use of methionine in the preparation of medicines for improving social dysfunction caused by schizophrenia.

2. The use according to claim 1, wherein the drug is an oral formulation comprising compounds capable of increasing methylation as pharmaceutical additives such as vitamin B12 and folic acid.

3. The use according to claim 2, wherein in animal experiments using mice as a model, the dose of methionine is 19.6 g / kg, and the administration time is 2 weeks or more.

4. The use according to any one of claims 1 to 3, wherein the improvement effect is manifested in enhancing the ability to identify social novelty.

5. A pharmaceutical composition comprising methionine and one or more methylation-promoting additives, said additives being selected from vitamin B12, folic acid, or pharmaceutically acceptable salts thereof.

6. The pharmaceutical composition according to claim 5, wherein the dose of methionine is equivalent to 2–6 g per day for human use, and the composition is in the form of tablets, granules, capsules or beverages.

7. Use of the composition according to claim 5 or 6 in the preparation of a medicament for improving social dysfunction caused by schizophrenia.

8. The use according to claim 7, wherein the social dysfunction is a decline in the ability to recognize social novelty.

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