COMPOSITION COMPRISING O-CYCLIC PHYTOSPHINGOSINE-1-PHOSPHATE FOR PREVENTING OR TREATING PARKINSON'S DISEASE

Abstract

A pharmaceutical or health food composition for preventing or treating Parkinson's disease containing O-cyclic phytosphingosine-1-phosphate. The composition can prevent the death of SH-SY5Y nerve cells, which are dopaminergic nerve cells, and increase the expression of tyrosine hydroxylase, an enzyme required for dopamine formation. Accordingly, the composition can be effectively used for preventing or treating Parkinson's disease.

Claims

1. A composition comprising a compound of the following Chemical Formula I or a pharmaceutically acceptable salt thereof: ##STR00006##

2. The composition according to claim 1, wherein the compound of the Chemical Formula I or a pharmaceutically acceptable salt thereof increases expression of tyrosine hydroxylase.

3. The composition according to claim 1, wherein the pharmaceutically acceptable salt is hydrochloride salt.

4. The composition according to claim 1, which is a pharmaceutical composition, food composition, or a dietary supplement.

5. The composition according to claim 4, wherein the compound of the Chemical Formula I or a pharmaceutically acceptable salt thereof increases the expression of tyrosine hydroxylase.

6. The composition according to claim 4, wherein the pharmaceutically acceptable salt is hydrochloride salt.

7. A method for preventing or treating Parkinson's disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound of the following Chemical Formula I or a pharmaceutically acceptable salt thereof: ##STR00007##

8. (canceled)

9. The method according to claim 7, wherein administering the compound of the Chemical Formula I or a pharmaceutically acceptable salt thereof to the subject increases expression of tyrosine hydroxylase in the subject.

10. The method according to claim 7, wherein the pharmaceutically acceptable salt is hydrochloride salt.

11. A method for increasing expression of tyrosine hydroxylase in a subject in need thereof, comprising administering to the subject a compound of the following Chemical Formula I or a pharmaceutically acceptable salt thereof: ##STR00008##

12. The method according to claim 11, wherein the subject has Parksinson's disease.

13. The method according to claim 11, wherein the compound of Chemical Formula I or a pharmaceutically acceptable salt thereof is in a form of a pharmaceutical composition, food composition, or a dietary supplement.

Description

BRIEF DESCRIPTION OF FIGURES

[0023] FIG. 1 is a graph showing the effect of the concentration of the cP1P drug on the proliferation of the SH-SY5Y human nerve cell line.

[0024] FIG. 2 is a graph showing the efficacy of the cP1P drug to inhibit the death of SH-SY5Y nerve cells in the rotenone-treated Parkinson's disease cell model.

[0025] FIG. 3 is a graph showing the efficacy of the cP1P drug to inhibit the death of SH-SY5Y nerve cells in the MPP.sup.+-treated Parkinson's disease cell model.

[0026] FIG. 4 shows the results of measuring the effect of the cP1P drug on the expression of tyrosine hydroxylase (TH) in SH-SY5Y nerve cells by immunohistochemical method and Western blot method.

BEST MODE

[0027] Hereinafter, examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the present invention is not limited to the following examples.

Example 1: Effects of cP1P Drug on Proliferation of Dopaminergic Human Nerve Cells (SH-SY5Y)

[0028] The SH-SY5Y human nerve cell line purchased from ATCC was used as a nerve cell line to evaluate the effect of the cP1P drug on the proliferation of dopaminergic human nerve cells. Dulbeco's Modified Eagle's Media/high glucose (with 10% FBS, 0.5% P/S) was used as a medium for culturing nerve cells, and the nerve cells were cultured at 37° C. in 5% CO.sub.2 incubator.

[0029] In order to observe the effect of cP1P drug on the proliferation of the dopaminergic human nerve cells, SH-SY5Y cells were treated with cP1P drug at concentrations of 10 nM, 100 nM and 1000 nM, respectively, and cultured for 48 hours. MTT assay (Molecular Probes) was performed according to the manufacturer's method to measure the cell proliferation rate.

[0030] The results are shown in FIG. 1.

[0031] As shown in FIG. 1, the effect on the proliferation of SH-SY5Y cells appeared even at a low concentration of 10 nM of the cP1P drug. The effect on the nerve cell proliferation was highest when the concentration of the cP1P drug was 100 nM.

Example 2: Effects of cP1P Drug in Rotenone-Treated Parkinson's Disease Cell Model

[0032] Rotenone is a substance widely used in cell models to induce Parkinson's disease. It is well known that when a nerve cell is treated with rotenone, mitochondrial function is destroyed, and oxidative stress is induced to cause death of the nerve cell.

[0033] The SH-SY5Y nerve cell culture medium was treated with cP1P drug at concentrations of 100 nM and 1000 nM, respectively, and cultured for 24 hours. Then, rotenone (Sigma) was dissolved in DMSO, diluted to a final concentration of 2 μM, and added to the SH-SY5Y nerve cell culture medium. The SH-SY5Y nerve cells were cultured for an additional 24 hours. SH-SY5Y nerve cells were obtained and cultured in the same manner as in Example 1.

[0034] Necrotic cell death was measured for the cultured SH-SY5Y nerve cells using a lactate dehydrogenase (LDH) detection kit (BioVision).

[0035] For comparison, the necrotic cell death was also measured for the control group that was treated only with DMSO without cP1P drug and rotenone, and the control group that was treated only with diluted rotenone solution without cP1P drug. In addition, the necrotic cell death was measured for the treatment of the nerve cells with the cP1P drug at concentrations of 100 nM and 1000 nM, respectively.

[0036] The results are shown in FIG. 2.

[0037] As shown in FIG. 2, in the control group treated only with rotenone, the degree of nerve cell death was high enough to exceed 30%. However, when the cP1P drug was first treated, the nerve cell death was inhibited to the level equivalent to that of DMSO treatment without rotenone.

[0038] In addition, as shown in FIG. 2, the treatment of the cP1P drug reduced the degree of cell death compared to the control group treated only with DMSO. This result appears to be because the treatment with the cP1P drug enhances the proliferation of SH-SY5Y nerve cells. From these results, it can be seen that the cP1P drug is useful as a therapeutic agent for Parkinson's disease.

Example 3: Effects of cP1P Drug in MPP.SUP.+.-Treated Parkinson's Disease Cell Model

[0039] To prepare a Parkinson's disease cell model by inducing oxidative stress with MPP.sup.+ (1-methyl-4-phenylpyridinium iodide, Sigma), MPP.sup.+ was dissolved in a phosphate buffer solution, diluted to a final concentration of 3 mM, and added to a nerve cell culture medium. To confirm the efficacy of the cP1P drug in the MPP.sup.+ environment, SH-SY5Y cells were pretreated with cP1P drug at concentrations of 10 nM, 100 nM, and 1000 nM, respectively, for 1 hour, and then exposed to oxidative stress by treatment with 3 mM MPP.sup.+ for 24 hours. The efficacy of the cP1P drug on the survival of SH-SY5Y cells after 24 hours of exposure to oxidative stress was determined by MTT assay.

[0040] The results are shown in FIG. 3.

[0041] As shown in FIG. 3, when the SH-SY5Y cell line was treated with MPP.sup.+ 3 mM, the nerve cells were killed. However, when the cell line was pretreated with the cP1P drug, the nerve cell death was significantly reduced. In particular, the nerve cell death was significantly reduced when the cP1P drug was treated at a concentration of 100 nM. From these results, it can be seen that the cP1P drug is useful as a therapeutic agent for Parkinson's disease.

Example 4: Effects of cP1P Drug on the Expression of Tyrosine Hydroxylase (TH) Required for Dopamine Formation in Nerve Cells

[0042] Tyrosine hydroxylase (TH) is an enzyme that converts amino acid tyrosine into L-DOPA, a precursor of dopamine, and plays an important role in the formation of dopamine in nerve cells.

[0043] In order to confirm the efficacy of the cP1P drug on TH expression in SH-SY5Y nerve cells, SH-SY5Y nerve cell culture was treated with the cP1P drug at concentrations of 10 nM and 100 nM, respectively. TH expression was determined by immunohistochemistry and western blot after 24 hours.

[0044] The results are shown in FIG. 4.

[0045] As shown in FIG. 4, the expression of the TH enzyme was increased when the cP1P drug was treated at concentrations of 10 nM and 100 nM. These results show that the cP1P drug can be used as a therapeutic agent for Parkinson's disease caused by the death of dopaminergic nerve cells.