Ester of a Phospholipid With Conjugated Linoleic Acid for the Treatment of Psychiatric Disorders With Neuroinflammatory and Neurodegenerative Basis

Abstract

An ester of a phospholipid with conjugated linoleic acid for use in the therapeutic treatment of or as a food supplement for psychiatric disorders with neuroinflammatory and neurodegenerative basis, such as depression and schizophrenia.

Claims

1. An ester of a phospholipid with conjugated linoleic acid or conjugated linoleic acid and docosahexaenoic acid for use in the treatment of psychiatric disorders.

2. The ester according to claim 1, for use in the treatment of psychiatric disorders with neuroinflammatory and neurodegenerative basis.

3. The ester according to claim 1, for use in the treatment and the prevention of psychiatric disorders, preferably having neuroinflammatory and neurodegenerative basis.

4. The ester according to claim 1, wherein said phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine.

5. The ester according to claim 1, wherein the conjugated linoleic acid is the c9,t11 isomer.

6. The ester according to claim 1, wherein the psychiatric disorders with neuroinflammatory and neurodegenerative basis are selected from the group consisting of psychotic disorders such as schizophrenia, schizophreniform disorder, schizoaffective disorder, or mood disorders such as major depression, dysthymic disorder.

7. A pharmaceutical composition comprising of an ester of a phospholipid with conjugated linoleic acid or conjugated linoleic acid and docosahexaenoic acid as active ingredient, in association with one or more pharmaceutically acceptable excipients and/or adjuvants, for use in the treatment and the prevention of psychiatric disorders.

8. The pharmaceutical composition according to claim 7, wherein said phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine.

9. The pharmaceutical composition according to claim 7, wherein the conjugated linoleic acid is the c9,t11 isomer.

10. The pharmaceutical composition according to claim 7, further comprising antipsychotic and/or antidepressant drugs.

11. The pharmaceutical composition according to claim 7, wherein said pharmaceutical composition is a therapeutic composition or a food supplement.

12. The pharmaceutical composition as defined in claim 7, for use in the treatment and the prevention of psychiatric disorders having neuroinflammatory and neurodegenerative basis.

13. The pharmaceutical composition according to claim 12, wherein the psychiatric disorders with neuroinflammatory and neurodegenerative basis are selected from the group consisting of psychotic disorders such as schizophrenia, schizophreniform disorder, schizoaffective disorder, or mood disorders such as major depression, dysthymic disorder.

Description

[0033] A preferred embodiment of the present invention will now be described by way of non limiting example with particular reference to the annexed drawings, wherein:

[0034] FIG. 1 shows the value of PEA and OEA in rat brain slices incubated with CLA (80% c9,t11 isomer) (A) or WY (B) for 15, 30 or 60 min. The values, mean and DS, are expressed as molar % of the total fatty acids. Different letters indicate significant differences (p<0.05); the One-way ANOVA statistical analysis was used, with Tukey test for post-hoc analysis. Similar results were obtained by using pure (99%) c9,t11 isomer.

[0035] FIG. 2 shows the values of PEA and OEA in the frontal cortex of mice treated for 14 days with a diet containing 0.2% of fenofibrate or administration of CLA (80% c9,t11 isomer) 12 h prior to sacrifice. The values, mean and DS, are expressed as pmoles/g tissue. Different letters indicate significant differences (p<0.05); the One-way ANOVA statistical analysis was used, with Tukey test for post-hoc analysis.

[0036] FIG. 3 shows the values of TNF alpha in astrocytes after treatment with oleic acid (OA) or CLA (80% c9,t11 isomer) and subsequent treatment with LPS. The values, mean and DS, are expressed as % of the values obtained with oleic acid. * significantly different (p<0.05) with Student's t-test.

EXAMPLE 1: EX VIVO AND IN VIVO STUDY ON THE EFFECT OF CLA ON THE LEVELS OF PEA, OEA AND TNF ALPHA

[0037] The methods employed for the analysis of the levels of conjugated linoleic acid, PEA and OEA in vivo and in vitro are described in detail in (Melis et al. 2001) and in (Piscitelli et al. 2011), respectively.

Results

[0038] Studies conducted on brain slices have demonstrated how ex vivo incubation with CLA in free form, i.e. both with 80% c9,t11 isomer and with pure isomer, increases the levels of PEA and OEA (FIG. 1A) by about 5 times. On the contrary, WY14643 (WY), a synthetic agonist of PPAR alpha used as a comparison since it is an inductor of PPAR alpha, increases the levels of PEA and OEA by about 3-4 times (FIG. 1B).

[0039] In addition, acute in vivo administration of CLA (80% c9,t11 isomer), 12 hours prior to sacrifice and collection of brain sections, significantly increases the levels of OEA in the frontal cortex of mice, to a level comparable to that induced by a diet with fenofibrate, another known synthetic agonist of PPAR alpha (Puligheddu et al., 2013) (FIG. 2). Since astrocytes are involved in neuroinflammation, the action of CLA (80% c9,t11 isomer) was also verified in cultures of astrocytes after having induced neuroinflammation with LPS. Oleic acid was used as a control. The results clearly demonstrate a significant decrease of TNF alpha in cultured astrocytes (FIG. 3).

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