COMPOSITION FOR INHIBITING SEBUM SECRETION COMPRISING FABP4 INHIBITOR

Abstract

The present invention relates to a composition for inhibiting sebum secretion comprising a FABP4 inhibitor, more specifically, relates to a composition for inhibiting sebum secretion capable of regulating sebum secretion by reducing lipid synthesis in sebocytes, inhibiting lipid synthesis-related signal transduction systems, and reducing the expression of lipid synthesis-related electronic factors. Also, the composition of the present invention can be used for preventing, treating or improving acne or seborrheic dermatitis.

Claims

1. A composition for inhibiting sebum secretion comprising a compound represented by Formula 1 as an active ingredient ##STR00006##

2. A pharmaceutical composition for preventing or treating diseases caused by sebum secretion, comprising a compound represented by Formula 1 as an active ingredient ##STR00007##

3. The pharmaceutical composition according to claim 2, wherein the diseases caused by sebum secretion are preferably one or more selected from the group consisting of acne, rosacea, seborrheic eczema, seborrheic dermatitis, and seborrheic alopecia.

4. The pharmaceutical composition according to claim 2, further comprising one or more components effective for diseases caused by sebum secretion.

5. The pharmaceutical composition according to claim 2, wherein the composition has a formulation selected from the group consisting of ointments, powders, tablets, capsules, powders, solutions, gels, pastes, patches and granules.

6. A cosmetic composition for preventing or improving skin conditions caused by sebum secretion, comprising a compound represented by Formula 1 as an active ingredient ##STR00008##

7. The cosmetic composition according to claim 6, wherein the skin conditions caused by sebum secretion are one or more selected from the group consisting of smudged makeup, glossiness, skin trouble, and scab.

8. The cosmetic composition according to claim 6, further comprising one or more components effective for skin conditions caused by sebum secretion.

9. The cosmetic composition according to claim 6, wherein the composition has a formulation selected from the group consisting of solutions, suspensions, emulsions, pastes, gels, creams, powders, soaps, cleansing containing surfactant, oils and sprays.

10. A method of inhibiting sebum secretion in a non-human animal, comprising a step of administering a compound represented by Formula 1 ##STR00009##

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIG. 1 shows changes in the expression of differentiation-related factors of sebocytes and changes in adipogenesis of sebocytes when FABP4 inhibitor was treated in sebocytes.

DETAILED DESCRIPTION

[0031] Hereinafter, examples are presented to aid understanding of the present invention.

[0032] However, the following examples are provided to more easily understand the present invention, and the content of the present invention is not limited by the following examples.

EXAMPLE 1 CELL CULTURE

[0033] Immortalized human sebocytes were used for the experiment. The cell lines were established as previously described. All procedures were approved by the Institutional Committee of Chungnam National University Hospital. The immortalized human sebocytes were cultured in Sebomed medium (Biochrom, Berlin, Germany) supplemented with 10% fetal bovine serum (Gibco BRL, Rockville, Md., USA) and 5 ng/mL of recombinant human EGF (Invitrogen, Grand Island, N.Y., USA).

EXAMPLE 2 FABP4 INHIBITOR

[0034] The FABP4 inhibitor of the present invention is a compound of Formula 1.

##STR00005##

EXAMPLE 3 WESTERN BLOTTING

[0035] After harvesting, the cells were lysed in protein extraction solution (Intron, Daejeon, Korea). Equal amounts of protein were then loaded and separated by SDA-PAGE, and then the proteins were transferred onto nitrocellulose membranes (Pall Corp., Port Washington, N.Y., USA). After blocking with 5% skim milk, the membranes were incubated with various primary antibodies. The blot was reacted with a secondary antibody conjugated with peroxidase, and were visualized for specific proteins with ECL (BIOMAX, Seoul, Korea). The primary antibodies used in western blot analysis were as follows: Actin, SREBP-1(Santa Cruz, Calif.), PPAR-γ, phospho-IGFR (p-IGFR), phospho-Akt (Cell Signaling Technology, Danvers, Mass.)

EXAMPLE 4 THIN-LAYER CHROMATOGRAPH, TLC

[0036] For quantitative analysis of intracellular lipids, the present invention used the TLC method as used in previous studies. Briefly, immortalized human sebocytes were cultured in a medium containing 2 μCi of .sup.14C-acetate and sodium salt (PerkinElmer, Boston, Mass., USA) and allowed to react for 4 hours. Intracellular lipids were extracted with chloroform and methanol (2:1, v/v). The solvent was evaporated and the lipid was resuspended in chloroform. TLC (TLC silica gel 60 F.sub.254, Merck KgaA) was used to separate intracellular lipids. After development with hexane and ethyl acetate (6:1, v/v), intracellular lipids were visualized by radioactivity measurement.

Test Example

[0037] The effect of BMS309403 on IGF-1-induced lipid synthesis was measured using an immortalized human sebaceous cell line established in a previous study. Immortalized human sebocytes were treated with 1, 2 or 5 μM of BMS309403. After treatment with BMS309403 for 1 hour, sebocytes were treated with 50 ng/mL of IGF-1 to induce differentiation and lipid synthesis.

[0038] To investigate the effect of BMS309403 on IGF-1-induced lipid synthesis in immortalized human sebocytes, transcription factors and enzymes related to sebocytes differentiation and lipid synthesis were investigated. In the group in which immortalized human sebocytes were treated with IGF-1, the levels of various transcription factors related to sebocyte differentiation, such as SREBP-1 and PPAR-γ were increased, but BMS309403 decreased their levels in a dose-dependent manner (see upper left of FIG. 1).

[0039] As the present inventors previously reported the role of the Akt/mTOR signaling pathway in sebocytes in IGF-1-induced fat synthesis, we examined whether BMS309403 regulates the Akt signaling pathway. In the present invention, IGF-1 increased the phosphorylation of IGFR and Akt, a downstream effector. On the contrary, BMS309403 markedly reduced phosphorylation of IGFR and Akt in a dose-dependent manner (see lower left of FIG. 1).

[0040] Through the results of TLC performed 48 hours after IGF-1 treatment, it was confirmed that IGF-1 treatment increased lipid accumulation in immortalized human sebocytes, and BMS309403 reduced intracellular lipid accumulation in a dose-dependent manner. IGF-1 increased the Intracellular lipid synthesis such as cholesterol, triglycerides, wax esters and squalene in immortalized human sebocytes. However, BMS309403 treatment reduced IGF-1-induced lipid synthesis. Among various lipids, the synthesis of squalene and wax esters was significantly reduced by BMS309403 (see the right side of FIG. 1).