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Peroxisome proliferator-activated receptor (PPAR) activator, and drugs, supplements, functional foods and food additives using the same

一种过氧化物酶体、增殖物的技术，应用在有机活性成分、含有效成分的医用配制品、有机化学等方向，能够解决油脂卡路里高等问题

Inactive Publication Date: 2007-10-10
ARKRAY INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, even if it is a substance derived from natural ingredients, since fats and other calories are high, there is a problem with continuous intake
In addition, for daily intake, it is desirable to add it to foods, etc., but many substances derived from natural ingredients have a special taste, and such substances are not suitable for addition to foods, etc.

Method used

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  • Peroxisome proliferator-activated receptor (PPAR) activator, and drugs, supplements, functional foods and food additives using the same
  • Peroxisome proliferator-activated receptor (PPAR) activator, and drugs, supplements, functional foods and food additives using the same
  • Peroxisome proliferator-activated receptor (PPAR) activator, and drugs, supplements, functional foods and food additives using the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] As shown below, this example is an example in which the activation of PPARγ by nobiletin was confirmed.

[0036] First, inoculate CV-1 cells (cultured cells from male African green monkey kidney) in a 24-well culture plate to 0.2 μg / well at 37°C, 5% CO 2 Conditioned for 24 hours. As a medium, DMEM (Dulbecco's Modified Eagle Medium, GIBCO) containing 10% FBS (fetal bovine serum) and 10 mg / mL penicillin-streptomycin solution was used. Next, pM-hPPARγ and p4×UASg-tk-luc were transfected into cultured CV-1 cells using the Lipofectamine system (Invitrogen). In addition, the aforementioned pM-hPPARγ is a vector for expressing a fusion protein comprising residues 1 to 147 as the GAL4-binding domain and residues 204 to 505 as the ligand-binding domain of human PPARγ, and the aforementioned p4×UASg-tk-luc is a reporter plasmid containing 4 copies of the upstream activating sequence (UAS) for the GAL4-binding domain and the thymidine kinase gene promoter upstream of the lucifer...

Embodiment 2

[0042] As described below, this example is an example of confirming the secretion-promoting effect of adiponectin produced by nobiletin.

[0043] (differentiation induction of preadipocytes)

[0044] First, prepare the following 2 types of media.

[0045] 1. Differentiation induction medium (0.25 μM: DEX, 0.5 mM: MIX, 10 μg / mL: insulin / 10% FBS / DMEM)

[0046] 55 mL of FBS (fetal bovine serum (manufactured by GIBCO)) was added to 500 mL of DMEM (manufactured by SIGMA) to prepare 10% FBS / DMEM. 138.75 µL of 1 mM DEX (dexamethasone) / DMSO (manufactured by Nacalai) and 555 µL of 10 mg / mL insulin / PBS (manufactured by SIGMA) were added thereto. In the case of insulin / PBS, 1N HCl was previously added to PBS to make it acidic enough to dissolve insulin, and then the insulin was dissolved. A necessary amount of MIX (3-isobutyl-1-methylxanthine) (manufactured by Nakalai) was added to the medium to make it 0.5 mM just before use, thereby preparing a differentiation induction medium. Sin...

Embodiment 3

[0064] This embodiment is the use of naturally occurring diabetic mice (KKA y ) is an example of confirming the diabetes-improving effect of nobiletin.

[0065] First, 12 naturally occurring diabetic mice (6-week-old, female) were preliminarily bred with normal food for one week. Next, the above-mentioned mice were divided into two groups (n=6) of the control group and the NOB group in such a manner that the average body weight was equal. Then, the mice in the control group were given a high-fat diet alone, and the mice in the NOB group were given a high-fat diet containing 0.02% nobiletin. Sera were collected from these mice 27 or 28 days after the start of intake. In addition, as nobiletin, nobiletin derived from Lemon citrus extract was used.

[0066] (Adiponectin secretion measured by ELISA)

[0067] Adiponectin secretion was measured by enzyme-linked immunoassay (ELISA method) using mouse / rat adiponectin ELISA kit (trade name) (manufactured by Otsuka Pharmaceutical Co...

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Abstract

The present invention provides a peroxisome proliferator-activated receptor (PPAR) activator, which is free from the problem of side effects, can be taken over a long term and has no characteristics taste. Nobiletin is employed as a PPAR activator. Nobiletin has an excellent PPAR activity and has an excellent adiponectin secretion-promoting effect, and is contained in a large amount in citrus fruits, in particular, in Shiikuwasha (Citrus depressa HAYATA) indigenous to Okinawa (Japan). Since citrus fruits have been consumed for many years, the safety of nobiletin has been proven and besides, nobiletin has a low calorie content. Therefore, it can be taken over a long term. Moreover, because of being tasteless and odorless, nobiletin would not damage the unique taste of a food when added thereto. Therefore, it can be added to foods and taken.

Description

technical field [0001] The present invention relates to peroxisome proliferator-activated receptor (PPAR) activators and medicines, supplements, functional foods and food additives using the activators. Background technique [0002] The onset of diabetes is said to be associated with both decreased insulin secretion and insulin resistance. Recently, the number of diabetic patients has increased among Japanese people, but since the genetic factor of decreased insulin secretion is large, it is not considered to be the main cause of the increase in diabetic patients, and the main reason is insulin resistance. It is said that this is due to the Westernization of the Japanese diet, increased fat intake, lack of exercise, obesity, and stress. Recent studies have found that the mechanism of insulin resistance is caused by the hypertrophy of fat cells. That is, if adipocytes become hypertrophic, they secrete TNF-α and free fatty acids (FFA), which block the uptake of sugar in musc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P3/06A61P3/10A61P9/10A61P9/12A61P43/00C07D311/30
CPCC07D311/30A61K31/352A61K36/752A61P3/04A61P3/06A61P3/10A61P5/50A61P9/10A61P9/12A61P43/00
Inventor 佐佐木贵生
Owner ARKRAY INC
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