Expression promoter for scavenger receptor gene

Abstract

To provide a method for reducing cholesterol.SOLUTION: There is provided an agent which promotes expression of a class B scavenger receptor which is expressed on a lymphatic vessel endothelial cell. The expression decreases with age. More specifically, at least one plant extract selected from the group consisting of a camellia seed extract, a rosemary extract, a Chinese blackberry tea extract, and a citrus unshiu peel extract is identified as a component which promotes the expression of the class B scavenger receptor, resulting in provision of an expression promoter for the scavenger receptor.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to the regulation of the expression of scavenger receptor genes involved in the regulation of blood cholesterol.

Background Art

[0002] Scavenger receptors are receptors capable of binding to oxidized LDL. Since foam cell formation of macrophages also progresses in patients lacking LDL receptors, the scavenger hypothesis that there are receptors that bind to LDL other than LDL receptors was proposed, and thereafter, scavenger receptors were identified as receptors that bind and take up oxidized LDL. Since the expression of scavenger receptors by macrophages is involved in plaque formation, development of scavenger receptor gene expression inhibitors has been carried out to suppress the onset of atherosclerosis (Patent Document 1: Japanese Patent Application Laid-Open No. 2009-029727).

[0003] Currently, the structure responsible for scavenger receptor function has been identified, a scavenger receptor family having such a structure has been discovered, and it has been classified into eight classes (class A to class H). These scavenger receptors are involved in complications of arteriosclerosis, thrombosis, and cardiovascular diseases by interacting with oxidized LDL. Among these, CD36 classified as class B scavenger receptor and scavenger receptor B1 (SCARB1) are known as two-transmembrane scavenger receptors. It has been reported that class B scavenger receptors are expressed not only in macrophages but also in blood components such as platelets, and further in vascular cells and lymphatic vessel cells (Non-Patent Document 1: Lim et al., (2013) Cell Metabolism). In addition, it has been reported that class B scavenger receptors bind not only to oxidized LDL but also to HDL, long-chain fatty acids, and specific proteins.

[0004] Scavenger receptor B1 (SCARB1) has binding affinity for HDL and plays a role in reverse cholesterol transport in the liver. SCARB1 is also known to be expressed in lymphatic endothelial cells. In knockout mice of scavenger receptor B1 (SCARB1), an increase in HDL cholesterol levels has been reported (Non-Patent Document 2: N Engl. J. Med. 2011; 364:136-45).

[0005] CD36 has binding affinity not only for oxidized LDL but also for various molecules such as type I and type IV collagen, thrombospondin, and long-chain fatty acids. CD36 is known to contribute to hemostasis, thrombosis, inflammation, atherogenesis, and also to malaria infection. In malaria-infected patients, it is known that HDL cholesterol in the blood decreases, and it has been reported that malaria parasites parasitizing erythrocytes take up HDL cholesterol using exosomes containing platelet-derived CD36 and SCARB1 receptors (Non-Patent Document 3: Frontiers in Cell and Developmental Biology 2021). The expression of scavenger receptors in lymphatic endothelial cells functions as a system for recovering excess cholesterol supplied from blood vessels. HDL cholesterol recovered by lymphatic vessels is sent to the liver and excreted.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Non-Patent Documents

[0007]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0008] An object is to provide a method for reducing cholesterol.

Means for Solving the Problems

[0009] When the inventors studied vascular aging, they found that the expression of class B scavenger receptor expressed in lymphatic endothelial cells decreased with aging. Therefore, in order to counteract aging, screening was conducted for components that promote the expression of class B scavenger receptor. As a result, it was surprisingly found that at least one plant extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract promotes the expression of class B scavenger receptor in lymphatic endothelial cells, leading to the present invention. Thus, the present invention relates to the following: [1-1] An expression promoter of a scavenger receptor gene, comprising at least one extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract. [1-2] Use of at least one extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract for the production of an expression promoter of a scavenger receptor gene. [1-3] At least one extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract for use in promoting the expression of a scavenger receptor gene. [1-4] A method for promoting the expression of a scavenger receptor gene, comprising administering at least one extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract. [2] The invention according to any one of items 1-1 to 1-4, which promotes the expression of the scavenger receptor gene in lymphatic vessels. [3] The invention according to any one of items 1-1 to 2, wherein the scavenger receptor gene is a two-transmembrane scavenger receptor gene. [4] The invention according to item 3, wherein the two-transmembrane scavenger receptor gene is a SCARB1 gene or a CD36 gene. [5] The invention according to item 4, wherein the extract is selected from the group consisting of camellia seed extract, rosemary extract, and tentacle extract, and promotes the expression of the SCARB1 gene. [6] The invention according to item 4, wherein the extract is selected from the group consisting of chinpi extract and tentacle extract, and promotes the expression of the CD36 gene. [7] A food or a cosmetic containing the expression promoter according to any one of items 1-1 to 6.

Advantages of the Invention

[0010] By promoting the expression of scavenger receptors by vascular endothelial cells, cholesterol recovery becomes possible.

Brief Description of the Drawings

[0011]

Figure 1

Figure 2A

Figure 2B

Figure 3

Figure 4

Mode for Carrying Out the Invention

[0012] One aspect of the present invention relates to an expression promoter for scavenger receptor genes containing a plant extract. By using a plant extract whose safety to a living body has already been established as a food or a cosmetic, product development becomes easy. Examples of the plant extract that promotes the expression of scavenger receptor genes include at least one component selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract.

[0013] Examples of the scavenger receptor include, in particular, the two-transmembrane scavenger receptor gene. Such a two-transmembrane scavenger receptor can also be referred to as a class B scavenger receptor. Known class B scavenger receptors include SCARB1, SCARB2 (also called CD36), and SCARB3. More specifically, in the present invention, the class B scavenger receptor relates to SCARB1 and CD36.

[0014] Promotion of gene expression may occur in any cell expressing class B scavenger receptor, but from the perspective of cholesterol recovery in particular, it is preferable to promote expression in vascular cells, particularly cells of blood vessels or lymphatic vessels, especially endothelial cells of lymphatic vessels. More specifically, the promoter of the scavenger receptor gene of the present invention can act on vascular endothelial cells, particularly endothelial cells of lymphatic vessels. The present inventors have shown that endothelial cells of lymphatic vessels take up HDL into cells through the expression of CD36 (Figure 3). Chinpi extract and Tencha extract increase the gene expression of CD36 in endothelial cells of lymphatic vessels (Figures 1(D) and (E)) and increase the uptake of HDL (Figure 3). Further, the present inventors have shown that endothelial cells of lymphatic vessels take up oxidized LDL (oxLDL) into cells through the expression of SCARB1 (Figure 4). Rosemary extract, Tencha extract and Camellia seed extract increase the gene expression of SCARB1 in endothelial cells of lymphatic vessels (Figures 1(A) to (C)) and increase the uptake of oxidized LDL (oxLDL) (Figure 4).

[0015] Therefore, the promoter of the scavenger receptor gene of the present invention can also be referred to as a cholesterol-lowering agent. More specifically, rosemary extract, Tencha extract and Camellia seed extract can be referred to as promoters of SCARB1 expression, and further as agents for lowering LDL, particularly oxidized LDL. Chinpi extract and Tencha extract can be referred to as promoters of CD36 expression, and further as agents for lowering HDL. Tencha extract can suppress the expression of both scavenger receptors of CD36 and SCARB1 and can lower both HDL and LDL. Generally, the expression of scavenger receptors in macrophages is considered to contribute to atherogenesis, and suppression of scavenger receptor expression is desired, but the effects vary depending on the cell type expressing the scavenger receptor. In the present invention, while having little effect on the gene expression of scavenger receptors in macrophages, it can promote the gene expression of scavenger receptors in vascular endothelial cells.

[0016] The tissue fluid collected by the lymphatic vessels flows through the lymphatic vessels as lymph, and finally flows into the subclavian vein through the right lymphatic duct or thoracic duct, returns to the blood circulation system, and is sent to the liver. Lymphatic vessels contribute to lipid transport, and the lipids absorbed in the small intestine are sent to the blood circulation system through the lymphatic system as lipoproteins. It also has the role of returning HDL and LDL contained in the tissue fluid to the blood circulation system. In the present invention, when HDL and LDL are taken up by the endothelial cells of the lymphatic vessels, the total amount of cholesterol returning to the blood circulation system decreases, and as a result, cholesterol in the body, particularly in the blood, decreases.

[0017] In still another aspect of the present invention, it may also relate to the treatment or therapeutic agent for dyslipidemia through promoting the expression of scavenger receptors. Examples of dyslipidemia include angina pectoris, myocardial infarction, arteriosclerosis, hypertension, atherosclerosis, etc., and it can be used for the prevention, treatment or alleviation of these diseases. There has been no sufficient knowledge so far about the treatment method focusing on the expression of scavenger receptors in vascular endothelial cells, and it becomes possible to provide a treatment method based on a new action mechanism.

[0018] The administration route of the scavenger receptor expression promoter according to the present invention may be any administration route, and oral, transdermal, subcutaneous, intramuscular, intravenous, intra-arterial, oral, transmucosal administration are used. From the viewpoint of acting on lymphatic endothelial cells, transdermal administration, oral administration or subcutaneous administration is particularly preferred. The scavenger receptor expression administered transdermally or subcutaneously is collected by the capillary lymphatic vessels in the dermis layer and can act in the lymphatic vessels.

[0019] In a further aspect of the present invention, the present invention also relates to a method for screening a scavenger receptor expression promoter using the expression of the scavenger receptor according to the present invention in lymphatic endothelial cells as an index. The screening method of the present invention is more specifically as follows: A step of culturing lymphatic endothelial cells in a medium containing a candidate component, A step of measuring the expression of the scavenger receptor in the lymphatic endothelial cells after culturing, and A step of comparing the measured expression level of the scavenger receptor with the expression of the control scavenger receptor When the expression of the scavenger receptor is enhanced, the candidate component can be screened as an expression promoter of the scavenger receptor. The expression of the control scavenger receptor can use the expression of the scavenger receptor in lymphatic endothelial cells that is different only in that it does not contain the candidate component. For the control group, experiments can be conducted in advance to set a threshold based on the expression of the scavenger receptor in the control group, or the culture and measurement steps can be performed in parallel. The expression of the scavenger receptor may be the protein amount or mRNA amount of the scavenger receptor in cultured lymphatic endothelial cells, and can be measured using techniques well-known in the art such as immunological techniques or quantitative PCR, respectively.

[0020] In yet another aspect, it may relate to a method for screening an expression promoter of a scavenger receptor using the uptake of LDL and HDL in lymphatic endothelial cells as an index. More specifically, the following: A step of culturing lymphatic endothelial cells in a medium containing labeled LDL or HDL and a candidate component, A step of measuring the intracellular uptake amount of labeled LDL or HDL in the cultured lymphatic endothelial cells, and A step of comparing the uptake amount of labeled LDL or HDL with the uptake amount of control labeled LDL or HDL When the uptake amount of labeled LDL or HDL is enhanced, the candidate component can be screened as an expression promoter of the scavenger receptor. The control can use the uptake amount of labeled LDL or HDL in lymphatic endothelial cells that is different only in that it does not contain the candidate component. As the labeled LDL, particularly labeled oxidized LDL can be used.

[0021] Lymphatic endothelial cells may have suppressed expression of scavenger receptor expression. For example, siRNA of CD36 or siRNA of SCARB1 may be introduced to transiently suppress the expression of CD36 and SCARB1, or the genes of CD36 or SCARB1 may be deleted by techniques such as genome editing. The scavenger receptor expression promoter thus screened can also be used as a cholesterol-lowering drug.

[0022] As the candidate components used in the screening method of the present invention, any library such as a cosmetic material library, a food material library, or a pharmaceutical material library can be used. As such a library, a compound library, an extract library, or the like may be used. As the compounds and extracts contained in each library, commercially available compounds and extracts may be used, or synthesized compounds and prepared extracts may be used.

[0023] The plant extracts described in this specification can be obtained by conventional methods. For example, the plant from which they are derived can be heated at room temperature or under heating together with an extraction solvent for immersion or heating under reflux, followed by filtration and concentration. As the extraction solvent, any solvent commonly used for extraction can be arbitrarily used. For example, aqueous solvents such as water, physiological saline, phosphate buffer, borate buffer, or organic solvents such as alcohols like ethanol, propylene glycol, 1,3 - butylene glycol, glycerin, hydrous alcohols, chloroform, dichloroethane, carbon tetrachloride, acetone, ethyl acetate, hexane, etc. can be used alone or in combination. Preferably, a mixed solvent of water and an alcohol, such as 1,3 - butylene glycol, is used as the solvent. The extract obtained by extraction with the above solvent can be used as it is, or an extract concentrated by, for example, lyophilization can be used. If necessary, impurities can be removed by an adsorption method, for example, using an ion - exchange resin, or after adsorption on a column of a porous polymer (e.g., Amberlite XAD - 2) and elution with a desired solvent, and then further concentrated extracts can also be used. As the plant extract, commercially available extracts can also be used as cosmetic raw materials, and the commercially available extracts can be formulated at a predetermined concentration.

[0024] The camellia seed extract is an extract obtained from the seeds of plants belonging to the genus Camellia of the family Theaceae. In particular, it is an extract obtained from the seeds of Camellia japonica or Camellia sasanqua. Camellia japonica is native to Japan and is widely distributed not only in the Japanese archipelago but also in the Korean Peninsula, China, and Taiwan. It may be extracted directly from the camellia seeds themselves, or it can also be produced by further solvent extraction of the residue after squeezing camellia oil. It can be prepared by extraction using water, alcohol, or a mixed solution thereof. As the alcohol, ethanol, propylene glycol, or 1,3 - butylene glycol is used, and more preferably 1,3 - butylene glycol can be used. The camellia seed extract is formulated at a concentration of 0.005% - 1%, and 0.05% - 0.2% is more preferable.

[0025] Rosemary extract is an extract of the plant body of Rosmarinus Officinalis. The plant body may be leaves, stems, flowers, roots, or fruits, but leaves are particularly used. Rosemary is a plant native to the Mediterranean coastal region. It can be prepared by extracting the plant body, particularly the leaves, using water, ethanol, alcohol, or a mixed solution thereof. As the alcohol, ethanol, propylene glycol, or butylene glycol is used. More preferably, it can be extracted with a mixed solution of water and 1,3-butylene glycol in any ratio, for example, a mixed solution of 10:90 to 90:10, preferably 30:70 to 70:30, and more preferably 50:50. The rosemary extract is formulated at a concentration of 0.005% to 1%, and 0.05% to 0.2% is more preferable.

[0026] Tench extract refers to an extract obtained from the leaves of Rubus Suavissimus, a plant of the Rosaceae family. Rubus Suavissimus is a plant native to the mountains of Guangxi Province in southern China. It can be prepared by extracting the leaves of Rubus Suavissimus with water, ethanol, alcohol, or a mixed solution thereof. As the alcohol, ethanol, propylene glycol, or butylene glycol is used. More preferably, it can be extracted with a mixed solution of water and 1,3-butylene glycol in any ratio, for example, a mixed solution of 10:90 to 90:10, preferably 30:70 to 70:30, and more preferably 50:50. The tench extract is formulated at a concentration of 0.005% to 1%, and 0.05% to 0.2% is more preferable.

[0027] Chimpi extract refers to an extract obtained from the pericarp of plants of the Rutaceae family (Citrus), particularly Citrus unshiu. Rutaceae plants are distributed worldwide, and Citrus unshiu is native to Ehime. The pericarp of Rutaceae plants can be prepared by extraction with water, ethanol, alcohol, or a mixed solution thereof. As the alcohol, ethanol, propylene glycol, or butylene glycol is used. More preferably, it can be extracted with a mixed solution of water and 1,3-butylene glycol in any ratio, for example, a mixed solution of 10:90 to 90:10, preferably 30:70 to 70:30, and more preferably 50:50. Chimpi extract is formulated at a concentration of 0.005% to 1%, and 0.05% to 0.2% is more preferable.

[0028] The extracts of the present invention may be used alone or in combination of two or more. An extract that promotes the expression of SCARB1 and an extract that promotes the expression of CD36 may be used in combination. As an example, camellia seed extract and rosemary extract, camellia seed extract and tencha extract, camellia seed extract and chinpi extract, rosemary extract and tencha extract, rosemary extract and chinpi extract, tencha extract and chinpi extract may be combined.

[0029] The promoter for the expression of the scavenger receptor gene and the cholesterol-lowering agent of the present invention can be used interchangeably, and each may be formulated in cosmetics, pharmaceuticals, or quasi-drugs. They may also be formulated in foods, such as dietary supplements or functional foods with functional claims. These agents may be administered orally or parenterally, for example, by transdermal administration. When administered transdermally, it can be formulated into a topical skin preparation.

[0030] The topical skin preparation is not particularly limited as long as it can be applied to the skin. For example, any dosage form such as solution, emulsion, solid, semi-solid, powder, powder dispersion, water-oil two-layer separation, water-oil-powder three-layer separation, ointment, gel, aerosol, mousse, stick, etc. can be applied. When formulated into a topical skin preparation, bases and excipients commonly used in topical skin preparations, such as preservatives, emulsifiers, pH adjusters, etc., may be used.

[0031] When formulated into cosmetics, it can be formulated into facial or body cosmetics such as lotion, emulsion, beauty essence, cream, lotion, pack, essence, gel, etc., makeup cosmetics such as foundation, makeup base, concealer, etc., and further into bath preparations. When formulated into food, it can be formulated into capsules, tablets, beverages, etc. By using cosmetics, food, pharmaceuticals, and quasi-drugs containing the components of the present invention, cholesterol reduction can be achieved through promoting the expression of the scavenger receptor gene. The promoter for promoting the expression of the scavenger receptor gene can be administered as the food or cosmetics of the present invention over a long period of time. From the perspective of reducing cholesterol, it may be administered for several days or more, one week or more, two weeks or more, one month or more, three months or more, or six months or more. The upper limit is not particularly limited, but it may be several years or less, for example, one year or less.

[0032] The promoter for promoting the expression of the scavenger receptor gene of the present invention can arbitrarily select the concentration from the perspective of a desired effect, such as reducing cholesterol. From the perspective of formulating it as a topical skin preparation, the extract according to the present invention can be formulated at 0.0005% to 0.5%. From the perspective of fully exerting the effect, it is preferably formulated at 0.001% or more, and more preferably at 0.005% or more. From the perspective of economy, it is preferably formulated at 0.1% or less, and more preferably at 0.05% or less.

[0033] All documents mentioned in this specification are hereby incorporated by reference in their entirety into this specification.

[0034] The embodiments of the present invention described below are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the description in the claims. Changes to the present invention, for example, addition, deletion, and substitution of the constituent elements of the present invention, can be made on the condition that the gist of the present invention is not deviated from.

Example

[0035] Example 1: Cultivation of Human Skin Lymphatic Endothelial Cells Human skin lymphatic endothelial cells (HDLEC: PromoCell, Heidelberg, Germany) were seeded in a collagen-coated 12-well plate and incubated for 24 hours in Endothelial Cell Growth Medium MV2 medium (PromoCell, Heidelberg, Germany) supplemented with supplements (PromoCell, Heidelberg, Germany). The next day, the medium was changed to Endothelial Cell Growth Medium MV2 medium supplemented with 0.5% FBS, and the cells were starved for 24 hours. Thereafter, the test substances (0.07% Camellia seed extract, 0.1% Rosemary extract BG (Maruzen Pharmaceutical Co., Ltd.), 0.1% Tencha extract (Maruzen Pharmaceutical Co., Ltd.), and 0.1% Chinpi extract (Maruzen Pharmaceutical Co., Ltd.)), or a solvent as a control was added and treated for 24 hours.

[0036] Example 2: Measurement of SCARB1 and CD36 mRNA by Quantitative Real-Time RT-PCR Intracellular RNA was purified from cells using the RNeasy mini kit (QIAGEN, Valencia, CA). The expression of mRNA was examined by quantitative real-time RT-PCR using the LightCycler 480 (Roche Applied Science, Indianaporis, IN). FAM-labeled TaqMan gene expression probes for SCARB1 (Hs00901465_m1) and CD36 (Hs00354519_m1) were used together with the Taqman RNA-to-CtTM 1-step Kit (Thermo Fisher). Gene expression was normalized using FAM-labeled GAPDH (Hs02786624_g1) and ACTB (Hs99999903_m1) TaqMan Probes. The results are shown in Figure 1.

[0037] Example 3: Tissue Staining For the observation of the expression of SCARB1 and CD36 in human skin lymphatic vessels, frozen sections of human buccal skin of different ages fixed with 4% PFA / PBS for 15 minutes were used (n = 7 - 9). The fixed skin sections were permeabilized with 0.5% Triton-X100 / PBS for 30 minutes and blocked with 10% donkey serum / PBS for 1 hour, and then, as primary antibodies, anti-Lyve1 antibody (ReliaTech, 102-PA50), anti-SCARB1 antibody (R&D, MAB8114), and anti-CD36 antibody (R&D, MAB1955) diluted 100-fold with 5% Donkey serum / PBS were used and incubated overnight at 4°C. Then, after washing, Alexa568 anti-rabbit (H+L) and Alexa488 anti-rat (H+L) were used as secondary antibodies, diluted 1000-fold with 5% Donkey serum / PBS, and incubated for 1 hour. The immunostained skin sections were observed with an LSM880 (Zeiss) and digitized with ImageJ. The immunostaining results of a 33-year-old subject and a 57-year-old subject are shown in Figure 2A (SCARB1) and Figure 2B (CD36). Also, the expression level ratios of SCARB1 / Lyve1 and CD36 / Lyve1 in subjects of each age were graphed.

[0038] Example 4: Human dermal lymphatic endothelial cells (HDLEC) were seeded at 5×10 4 on collagen-coated coverslips and cultured for 24 hours. Then, SCARB1 stealth siRNA (Thermo Fisher Scientific, HSS101570, HSS101571, HSS190377) or CD36 stealth siRNA (Thermo Fisher Scientific, HSS101567, HSS190373, HSS190374), Stealth Negative Control (Thermo Fisher Scientific) were transfected into the cells using Lipofectamine RNAiMAX (Thermo Fisher Scientific) to a final concentration of 20 nM. After 6 hours, the medium was changed to Endothelial Cell Growth Medium MV 2 supplemented with 0.5% FBS. Twenty-four hours later, the test substance (0.07% camellia seed extract, 0.1% tencha extract & 0.1% chinpi extract) or the solvent as a control was added. After an additional 24 hours, 10 μg / mL DiО-oxLDL (Kalen Biomedical) or DiО-HDL (Kalen Biomedical) was added and incubated at 37 °C for 1 hour. After washing three times with PBS and fixing at room temperature with 4% PFA for 15 minutes, the cells were incubated with Hoechst (Thermo Fisher Scientific) diluted 1000-fold with PBS for 1 hour and washed twice with PBS. Then, the cells were observed with a confocal microscope (LSM880) and quantified with ImageJ. Transfection with CD36 siRNA decreased the uptake of DiО-HDL into endothelial cells, while the suppressed uptake of DiО-HDL increased when chinpi extract and tencha extract were added, respectively (Figure 3). Transfection with SCARB1 siRNA decreased the uptake of DiО-oxLDL into endothelial cells, while the suppressed uptake of DiО-oxLDL increased when chinpi extract and tencha extract were added, respectively (Figure 4).

Claims

1. A promoter for promoting the expression of a scavenger receptor gene, comprising at least one extract selected from the group consisting of camellia seed extract, rosemary extract, tentcha extract, and chinpi extract.

2. The promoter according to claim 1, which promotes the expression of the scavenger receptor gene in lymphatic vessels.

3. The promoter according to claim 1, wherein the promoter for promoting the expression of the scavenger receptor gene is a promoter for promoting the expression of a two-pass transmembrane scavenger receptor gene.

4. The promoter according to claim 3, wherein the two-pass transmembrane scavenger receptor gene is the SCARB1 gene or the CD36 gene.

5. The promoter according to claim 4, wherein the extract is selected from the group consisting of camellia seed extract, rosemary extract, and tentcha extract, and promotes the expression of the SCARB1 gene.

6. The promoter according to claim 4, wherein the extract is selected from the group consisting of chinpi extract and tentcha extract, and promotes the expression of the CD36 gene.

7. A food or a cosmetic comprising the promoter according to any one of claims 1 to 6.

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