CA2874696A1

CA2874696A1 - Pharmaceutical composition for anti-obesity comprising extract of a mixture comprising saururi chinensis baill., curcumae longae rhizoma, and polygalae radix

Info

Publication number: CA2874696A1
Application number: CA2874696A
Authority: CA
Inventors: Jin Yeul Ma; Dong Hoon Kwak; Ji Hye Lee; Dong Gun Kim; Tae Soo Kim
Original assignee: Korea Institute of Oriental Medicine KIOM
Current assignee: Korea Institute of Oriental Medicine KIOM
Priority date: 2014-12-12
Filing date: 2014-12-12
Publication date: 2016-06-12

Abstract

Disclosed herein are a pharmaceutical composition for the prevention or treatment of obesity comprising an extract of a mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, or an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Mori Gramineri Rhizoma; a food composition comprising the extract of the mixture; and a method of manufacturing the extracts of the mixture. The extracts of the present invention can inhibit fat generation without adverse effects such as cellular toxicity and thus can be widely used for the prevention, improvement, or treatment of obesity or obesity-related diseases.

Description

CA Application Blakes Ref: 11886/00001 PHARMACEUTICAL COMPOSITION FOR ANTI-OBESITY COMPRISING EXTRACT OF

2 A MIXTURE COMPRISING SAURURI CHINENSIS BAILL., CURCUMAE LONGAE

3 RHIZOMA, AND POLYGALAE RADIX

4 BACKGROUND OF THE INVENTION

7 1. Field of the Invention 8 The present invention relates generally to a composition for preventing or treating obesity comprising an extract of a mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and more particularly, to a pharmaceutical composition and a food composition for preventing or treating obesity comprising an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, or an extract of a mixture comprising Saururi chinensis 13 Bail., Curcumae Longae Rhizoma, Polygalae Radix and Acori Gramineri Rhizoma, and a method for 14 manufacturing the extracts.
16 2. Description of the Related Art 17 As well known in the art, obesity generally refers to a medical condition of excess fat accumulation in the body. Obesity is a phenomenon where the energy surplus resulting from an imbalance between energy input from food intake and energy consumption by physical acitivities accumulates in the body as body fat. A long-term abnormal accumulation of body fat resulting from an 21 energy surplus can cause various metabolic diseases and adult diseases such as diabetes, hyperlipidemia, 22 heart diseases, strokes, atherosclerosis, and fatty liver, and has become a serious global issue Obesity can occur due to various reasons, including genetic factors, environmental factors such 24 as westernized dietary patterns, psychological factors due to stresses, disorders in energy metabolism, etc.
The types of obesity-causing factors may be divided into simple obesity due to overeating and lack of exercise, and symptomatic obesity such as endocrine obesity, hypothalamic obesity, genetic obesity, and 22654729.1 CA Application Blakes Ref: 11886/00001 1 metabolic obesity.
2 The degree of obesity can be evaluated by measuring body weight or the thickness of 3 skin folds. In general, a person with an obesity index of 25 or higher is defined as being obese.
4 Obesity index (body mass index; BMI) is a value obtained by dividing a person's body weight (in kg) over the square of his/her height (m2). For westerners, people with a BMI of 30 or higher 6 are considered obese, and in South Korea, people with a BMI of 25 or higher are considered 7 obese considering racial differences.
8 Multilateral studies have been performed globally in order to develop therapeutic agents 9 for treating obesity. The drugs for treating obesity, depending on their working mechanisms, may be largely divided into those for inhibiting fat absorption, promoting fat decomposition and 11 heat generation, controlling appetite and satiety, inhibiting protein metabolism, and controlling 12 emotions relating to food intake. Examples of representative therapeutic agents for obesity 13 include XenicalTm, which, being prepared using orlistat as a raw ingredient, inhibits fat absorption, 14 and ReductilTM, which, being prepared using sibutramine as a main raw ingredient, inhibits appetite by stimulating the sympathetic nervous system. However, XenicalTM is known to have side 16 effects such as steartorrhea, abdominal pain, vomiting, pruritus, and liver damage, whereas 17 RedliCtiiTm is known to have side effects such as headaches, anorexia, insomnia, and constipation, 18 and also serious cardiovascular diseases, and thus their administration guidelines have been 19 recently strengthened.
In addition to drug therapies, there are other therapies for preventing and treating obesity 21 such as diet therapy to restrict food intake, exercise therapy to increase energy consumption, 22 psychotherapy, behavior therapy, and surgical therapy.
23 Preferably, a combined therapy of exercising to promote energy consumption while 24 administrating a therapeutic drug for treating obesity with few side effects is suggested as the safest and most effective method for the treatment of obesity. However, the saftety issue on the 26 therapeutic drugs for treating obesity has not been resolved as described above in the serious side 22654729.1 CA Application Blakes Ref: 11886/00001 1 effects of XenicalTM and ReductilTM. Accordingly, there is a need to develop a substance capable with 2 advanced safety as well as anti-obesity efficacies in the human body.

4 As such, the present inventors, while endeavoring to find a substance having an excellent therapeutic effect on obesity without any side effects in the human body, discovered that an extract of a 6 mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, exhibits 7 effects of preventing and treating obesity within the range of not causing cell toxicity, thereby completing 8 the present invention.

SUMMARY OF THE INVENTION

Accordingly, the present invention has been made keeping in mind the above problems 13 occurring in the prior art, and an objective of the present invention is to provide a method for preventing 14 and treating obesity comprising administering an effective amount of an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix; or a fraction thereof to a subject 16 in need thereof.

Another objective of the present invention is to provide a method for the prevention and 18 treatment of obesity comprising administering an effective amount of an extract of a mixture comprising 19 Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineii Rhizoma; or a fraction thereof to a subject in need thereof.
21 Still another objective of the present invention is to provide a method of manufacturing an extract 22 from a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix by 23 extracting with water, a C1 ¨ C4 alcohol, or a mixed solvent thereof.
24 Still another objective of the present invention is to provide a method of manufacturing an extract from a mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and 26 Acori Gramineri Rhizoma by extracting with water, a C1 ¨ C4 alcohol, or a mixed solvent thereof.

22654729.1 CA Application Blakes Ref: 11886/00001 1 Still another objective of the present invention is to provide a composition comprising an 2 extract of a mixture comprising Saururi chinensis Bail!., Curcumae Longae Rhizoma, and 3 Polygalae Radix; or a fraction thereof.
4 Still another objective of the present invention is to provide a composition comprising an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, 6 Polygalae Radix, and Acori Gramineri Rhizoma; or a fraction thereof.

8 In an aspect of the present invention, in order to accomplish the above objectives, the 9 present invention provides a pharmaceutical composition for the prevention and treatment of obesity comprising an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae 11 Rhizoma, and Polygalae Radix; an extract of a mixture comprising Saururi chinensis Baill., 12 Curcumae Longae Rhizoma, Polygalae Radix, and Mori Gramineri Rhizoma; or a fraction 13 thereof.

BRET DESCRIPTION OF THE DRAWINGS

17 FIG. 1 A is a graph illustrating the inhibitory effects of KI0M-20120b(1) hot-water 18 extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 19 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(1) and each of the hot-water extracts of the herbal components constituted in 21 the KI0M-20120b(1) while inducing differentiation from 3T3-L1. In the graph (FIG 1A), the 22 treatment concentration was shown as the concentration of KI0M-20120b(1), and Saururi 23 chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma 24 constituted in KI0M-20120b(1) were treated in the same manner as in the contents of the composition. `*' denotes the significance (P<0.05) of the decrease in the accumulation of 26 triglycerides relative to that of the control group (0 lig/mL).

22654729.1 CA Application Blakes Ref: 11886/00001 1 HG. 1B
is a graph illustrating the inhibitory effects of KI0M-20120b(2) hot-water extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(2) 4 and each of the hot-water extracts of the herbal components constituted in the KI0M-20120b(2) while inducing differentiation from 3T3-Ll. In the graph (FIG 1B), the treatment concentration was shown as the concentration of KI0M-20120b(2), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 7 Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(2) were treated in the same manner as 8 in the contents of the composition. denotes the significance (P<0.05) of the decrease in the 9 accumulation of triglycerides relative to that of the control group (0 ptg/mL).
FIG. 1C is a graph illustrating the inhibitory effects of KI0M-20120b(3) hot-water extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(3) 13 and each of the hot-water extracts of the herbal components constituted in the KI0M-20120b(3) while inducing differentiation from 3T3-Ll. In the graph, the treatment concentration was shown as the concentration of KI0M-20120b(3), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 16 Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(3) were treated in the same manner as 17 in the contents of the composition. denotes the significance (P<0.05) of the decrease in accumulation of 18 triglycerides relative to that of the control group (0 pg/mL).
19 HG. 1D
is a graph illustrating the effect of KI0M-20120b(1) hot-water extracts on the viability of the cells differentiated from 3T3-L1. The viability of the cells differentiated from 3T3-L1 was shown 21 after measurement via WST method. In the graph, the treatment concentration was shown as the concentration of KI0M-20120b(1), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 23 Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(1) were treated in the same manner as 24 in the contents of the composition. `$' denotes the significance (P<0.05) of the decrease of the cell viability relative to that of the control group (0 pg/mL).
26 FIG.
lE is a graph illustrating the effect of MOM-20120b(2) hot-water extract on the viability of

5 22654729.1 CA Application Blakes Ref: 11886/00001 1 the cells differentiated from 3T3-L1. The viability of the cells differentiated from 3T3-L1 was 2 shown after measurement via WST method. In the graph, the treatment concentration was shown 3 as the concentration of KI0M-20120b(2), and Saururi chinensis Baill., Curcumae Longae 4 Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(2) were treated in the same manner as in the contents of the composition. `$' denotes the significance

6 (P<0.05) of the decrease of the cell viability relative to that of the control group (0 pg/mL).

7 FIG. 1F is a graph illustrating the effect of KI0M-20120b(3) hot-water extract on the

8 viability of the cells differentiated from 3T3-Ll. The viability of the cells differentiated from 3T3-

9 Li was shown after measurement via WST method. In the graph, the treatment concentration was shown as the concentration of KI0M-20120b(3), and Saururi chinensis Baill., Curcumae Longae 11 Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(3) were 12 treated in the same manner as in the contents of the composition. `$' denotes the significance 13 (P<0.05) of the decrease of the cell viability relative to that of the control group (0 ptg/mL).
14 FIG. 2A is a graph illustrating the inhibitory effects of KI0M-20120b(1) warm- extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 via Oil 16 Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the 17 KI0M-20120b(1) and each of the warm-water extracts of the herbal components constituted in the 18 KI0M-20120b(1) while inducing differentiation from 3T3-Ll. In the graph, the treatment 19 concentration was shown as the concentration of KI0M-20120b(1), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in 21 KI0M-20120b(1) were treated in the same manner as in the contents of the composition.
22 denotes the significance (P<0.05) of the decrease in accumulation of triglycerides relative to that of 23 the control group (0 pg/mL).
24 FIG. 2B is a graph illustrating the inhibitory effects of KI0M-20120b(2) warm-water extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 26 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with 22654729.1 CA Application Blakes Ref: 11886/00001 the KI0M-20120b(2) and each of the warm-water extracts of the herbal components constituted in the KI0M-20120b(2) while inducing differentiation from 3T3-L1. In the graph (FIG
2B), the treatment concentration was shown as the concentration of KI0M-20120b(2), and Saururi chinensis Bail!., 4 Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in MOM-S 20120b(2) were treated in the same manner as in the contents of the composition. denotes the significance (P<0.05) of the decrease in accumulation of triglycerides relative to that of the control group (0 7 fig/mL).

FIG. 2C is a graph illustrating the inhibitory effects of KI0M-20120b(3) warm-water extracts against the accumulation of triglycerides within the adipocytes differentiated fium 3T3-L1 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(3) and each of the warm-water extracts of the herbal components constituted in the KI0M-20120b(3) while inducing differentiation from 3T3-L1. In the graph (FIG 2C), the treatment concentration was shown as the concentration of KI0M-20120b(3), and Saururi chinensis Bail!., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(3) were treated in the same manner as in the contents of the composition. denotes the significance (P<0.05) of the decrease in accumulation 16 oftriglycerides relative to that of the control group (0 gg/mL).

FIG. 2D is a graph illustrating the effect of KI0M-20120b(1) warmwater extract on the viability 18 of the cells differentiated from 3T3-Ll. The viability of the cells differentiated from 3T3-L1 was shown after measurement via WST method. In the graph, the treatment concentration was shown as the concentration of KI0M-20120b(1), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(1) were treated in the same manner as 22 in the contents of the composition. `$' denotes the significance (P<0.05) of the decrease of the cell viability 23 relative to that of the control group (0 Rg/mL).

FIG. 2E is a graph illustrating the effect of KI0M-20120b(2) warm-water extract on the viability of the cells differentiated from 3T3-L1. The viability of the cells differentiated from 3T3-L1 was shown after measurement via WST method. In the graph, the treatment concentration was shown as the 22654729.1 CA Application Blakes Ref: 11886/00001 1 concentration of KI0M-20120b(2), and Saururi chinensis Baill., Curcumae Longae Rhizoma, 2 Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(2) were treated in 3 the same manner as in the contents of the composition. `$' denotes the significance (P<0.05) of the 4 decrease of the cell viability relative to that of the control group (0 RgimL).
FIG. 2F is a graph illustrating the effect of KI0M-20120b(3) warm-water extract on the 6 viability of the cells differentiated from 3T3-Li. The viability of the cells differentiated from 3T3-7 Li was shown after measurement via WST method. In the graph, the treatment concentration was 8 shown as the concentration of KI0M-20120b(3), and Saururi chinensis Bail!., Curcumae Longae 9 Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(3) were treated in the same manner as in the contents of the composition. `$' denotes the significance 11 (P<0.05) of the decrease of the cell viability relative to that of the control group (0 pg/mL).
12 FIG. 3A is a graph illustrating the inhibitory effects of KI0M-20120b(1) 25% Et0H
13 extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 14 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(1) and each of the 25% Et0H extracts of the herbal components constituted in 16 the KI0M-20120b(1) while inducing differentiation from 3T3-L1. In the graph, the treatment 17 concentration was shown as the concentration of KI0M-20120b(1), and Saururi chinensis Bail!., 18 Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in 19 KI0M-20120b(1) were treated in the same manner as in the contents of the composition. `4=' denotes the significance (P<0.05) of the decrease in accumulation of triglycerides relative to that of 21 the control group (0 g/mL).
22 FIG. 3B is a graph illustrating the inhibitory effects of KI0M-20120b(2) 25% Et0H
23 extracts against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 24 via Oil Red 0 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(2) and each of the 25% Et0H extracts of the herbal components constituted in 26 the KI0M-20120b(2) while inducing differentiation from 3T3-Li. In the graph, the treatment 22654729.1 CA Application Blakes Ref: 11886/00001 1 concentration was shown as the concentration of KI0M-20120b(2), and Saururi chinensis Baill., 2 Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in MOM-3 KI0M-20120b(2) were treated in the same manner as in the contents of the composition. "" denotes the 4 denotes the significance (P<0.05) of the decrease in accumulation of triglycerides relative to that of the control group (0 pg/mL).
6 HG. 3C
is a graph illustrating the inhibitory effects of KI0M-20120b(3) 25% Et0H
extracts 7 against the accumulation of triglycerides within the adipocytes differentiated from 3T3-L1 via Oil Red 0 8 Staining. The Oil Red 0 Staining was performed 8 days after treating the cells with the KI0M-20120b(3) 9 and each of the 25% Et0H extracts of the herbal components constituted in the KI0M-20120b(3) while inducing differentiation from 3T3-L1. In the graph, the treatment concentration was shown as the 11 concentration of KI0M-20120b(3), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 12 Radix, and Aeon i Gramineri Rhizoma constituted in KI0M-20120b(3) were treated in the same manner as 13 in the contents of the composition. denotes the significance (P<0.05) of the decrease in accumulation of 14 triglycerides relative to that of the control group (0 pg/mL).
HG. 3D is a graph illustrating the effect of KI0M-20120b(1) 25% Et0H extract on the viability 16 of the cells differentiated from 3T3-Ll. The viability of the cells differentiated from 3T3-L1 was shown 17 after measurement via WST method. In the graph, the treatment concentration was shown as the 18 concentration of KI0M-20120b(1), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 19 Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(1) were treated in the same manner as in the contents of the composition. `$' denotes the significance (P<0.05) of the decrease of the cell viability 21 relative to that of the control group (0 i.tg/mL). `$$' denotes the significance (P<0.01) of the decrease of the 22 cell viability relative to that of the control group (0 pg/mL).
23 HG. 3E
is a graph illustrating the effect of KI0M-20120b(2) 25% Et0H extract on the viability 24 of the cells differentiated from 3T3-Ll. The viability of the cells differentiated from 3T3-L1 was shown after measurement via WST method. In the graph, the treatment concentration was shown as the 26 concentration of KI0M-20120b(2), and Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae 22654729.1 CA Application Blakes Ref: 11886/00001 1 Radix, and Acori Gramineri Rhizoma constituted in KI0M-20120b(2) were treated in the same 2 manner as in the contents of the composition. '$' denotes the significance (P<0.05) of the 3 decrease of the cell viability relative to that of the control group (0 pg/mL). denotes the significance (P<0.05) of the increase of the cell viability by KI0M-20120b(2) 25% Et0H extract relative to that by Polygalae Radix 25% Et0H extract.
6 FIG. 3F
is a graph illustrating the effect of KI0M-20120b(3) 25% Et0H extract on the viability of the cells differentiated from 3T3-Li. The viability of the cells differentiated from 3T3-8 Li was shown after measurement via WST method. In the graph, the treatment concentration 9 was shown as the concentration of KI0M-20120b(3), and Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma constituted in MOM-ii were treated in the same manner as in the contents of the composition. '$' denotes the significance (P<0.05) of the decrease of the cell viability relative to that of the control group (0 13 pg/mL).
'$$' denotes the significance (P<0.01) of the decrease of the cell viability relative to that 14 of the control group (0 1.tg/mL). "" denotes the significance (P<0.05) of the increase of the cell viability by KI0M-20120b(3) 25% Et0H extract relative to that by Polygalae Radix 25% Et0H
16 extract.
17 FIG. 4 is a graph illustrating the effect of KI0M-20120b 25% Et0H extracts on the 18 decrease of body weight in an obesity animal model. A normal control group fed a diet with only 19 10% fat content, a negative control group fed a diet with only 60% fat content (HFD), and a positive control group fed with [Xenical (62.5 mg/kg) + diet with 60% fat content] were used. In 21 the graph, 'ix' indicates the dose of the extract for an adult male based on the daily administration 22 of the herbal decoction, and '4X' indicates four times the 1X dose. The graph shows a distinct 23 decrease in body weight in KI0M-20120b-4X groups.
24 FIG. 5 is a graph illustrating the amount of dietary intake of the mice treated with KI0M-20120b 25% Et0H extracts. "" denotes the significance (P<0.05) of the decrease in the 22654729.1 CA Application Blakes Ref: 11886/00001 1 amount of dietary intake in mice treated with KI0M-20120b(3) Et0H extract relative to the amount of 2 dietary intake of mice fed with 60% HFD.
3 FIG. 6 is a graph illustrating the effect of KI0M-20120b 25% Et0H
extracts on the fat 4 accumulation. A normal control group fed a diet with only 10% fat content, a negative control group fed a diet with only 60% fat content (HFD), and a positive control group fed with [Xenical (62.5 mg/kg) + diet 6 with 60% fat content] were used. In the graph, '1X' indicates the dose of the extract for an adult male 7 based on daily administration of the herbal decoction and '4X' indicates four times the '1X' dose. For the 8 weight of the fat tissues of the mice, their abdominal fat and subcutaneous fat were measured. '**' denotes 9 the significance (P<0.05) of the decrease in the weight of abdominal fat of the mice treated with MOM-20120b(3) Et0H extract relative to the body weight of the mice fed with 60%
FWD.
11 FIG. 7 is a graph illustrating the effect of the KI0M-20120b 25%Et0H
extracts on the liver.
12 The liver tissues were fixed on formalin and their H & E Staining and pathological findings were requested, 13 wherein FIG. 7A shows the increase of microvesicular steatosis in the liver tissues, and the inhibition of 14 the increase of the microvesicular steatosis in the group treated with KI0M-20120b, whereas FIG. 7B
shows the increase of chronic inflammation inliver tissues. The group treated with KI0M-20120b 16 showed a significant decrease in inflammation (P<0.05, P<0.01) than the groups treated with other herbal 17 drugs, in particular the group treated with Polygalae Radix extract.
'$$' denotes the significance (P<0.01) 18 of the increase of microvesicular steatosis relative to that of the normal control group, whereas '$' denotes 19 the significance (P<0.05) of the increase of microvesicular steatosis relative to that of the normal control group. `**' denotes the significance (P<0.01) of the decrease of chronic inflammation in the group treated 21 with KI0M-20120b relative to the group treated with Polygalae Radix extract (4X), whereas '*' denotes 22 the significance (P<0.05) of the decrease of chronic inflammation in the group treated with KI0M-20120b 23 relative to the group treated with Polygalae Radix extract (4X). '0' denotes the significance (P<0.01) of 24 the increase of chronic inflammation relative to the negative control group, whereas '#' denotes the significance (P<0.05) of the increase of chronic inflammation relative to the negative control group.

22654729.1 CA Application Blakes Ref: 11886/00001 1 FIG. 8 is a graph illustrating the effect of the KI0M-20120b 25% Et0H extracts on the 2 kidney. The kidney tissues were fixed on formalin and their H & E Staining and pathological 3 findings were requested, wherein FIG. 7A shows the increase of microvesicular steatosis in the 4 liver tissues, and the inhibition of the increase of the microvesicular steatosis in the group treated with KI0M-20120b, whereas FIG. 7B shows the increase of chronic inflammation in the liver 6 tissues. The graph shows an increase of chromic inflammation in the kidney. The group treated 7 with KI0M-20120b showed a significant decrease in inflammation (P<0.05, P<0.01) than the 8 groups treated with other herbal drugs, and in particular, the group treated with Polygalae Radix 9 extract `**' denotes the significance (P<0.01) of the decrease of chronic inflammation in the to group treated with KI0M-20120b relative to the group treated with Polygalae Radix extract (4X), 11 whereas `*' denotes the significance (P<0.05) of the decrease of chronic inflammation in a group 12 treated with KI0M-20120b relative to the group treated with Polygalae Radix extract (4X).
`111111' 13 denotes the significance (P<0.001) of the increase of chronic inflammation relative to the negative 14 control group, whereas `4,Nr denotes the significance (P<0.01) of the increase of chronic inflammation relative to the negative control group, and denotes the significance (P<0.05) of 16 the increase of chronic inflammation relative to the negative control group.
17 FIG. 9 is a graph illustrating the comparison result of the body weight of an animal 18 model according to the administered dose of an extract of a mixture comprising Saururi 19 chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri Rhizoma or clover.
21 FIG. 10 is a graph illustrating the comparison result of the amount of dietary intake of 22 an animal model according to the administered dose of an extract of a mixture comprising 23 Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively 24 comprising Acori Gramineri Rhizoma or clover.
FIG. 11A is a graph illustrating the comparison result of the weight of abdominal 26 gonadal fat of an animal model according to the administered dose of an extract of a mixture 22654729.1 CA Application Blakes Ref: 11886/00001 comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively 2 comprising Aeon Gramineri Rhizoma or clover.
3 FIG. 11B is a graph illustrating the comparison result of the weight of mesenteric fat of an 4 animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri 6 Rhizoma or clover.
7 FIG. 11C is a graph illustrating the comparison result of the weight of subcutaneous fat of an 8 animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis 9 Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri Rhizoma or clover.
11 FIG. 11D is a graph illustrating the comparison result of the total fat of an animal model 12 according to the administered dose of an extract of a mixture comprising Saururi chinensis Bail., 13 Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri Rhizoma 14 or clover.
FIG. 12A is a graph illustrating the comparison result of the level of activated Ghrelin of an 16 animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis 17 Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri 18 Rhizoma or clover.
19 FIG. 12B is a graph illustrating the comparison result of the level of activated desacyl-ghrelin of an animal model according to the administered dose of an extract of a mixture comprising Saururi 21 chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori 22 Gramineri Rhizoma or clover.
23 FIG. 12C is a graph illustrating the comparison result of the level of activated ghrelin ratio of an 24 animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Aeon Gramineri 26 Rhizoma or clover.

22654729.1 CA Application Blakes Ref: 11886/00001 1 FIG. 13 is a graph illustrating the comparison result of the level of leptin in the blood 2 plasma of an animal model according to the administered dose of an extract of a mixture 3 comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and 4 selectively comprising Acori Gramineri Rhizoma or clover.
FIG. 14A is a graph illustrating the comparison result of the level of triglycerides in the 6 blood of an animal model according to the administered dose of an extract of a mixture 7 comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 8 selectively comprising Acori Gramineri Rhizoma or clover.
9 FIG. 14B is a graph illustrating the comparison result of the level of total cholesterol in the blood of an animal model according to the administered dose of an extract of a mixture 11 comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 12 selectively comprising Acori Gramineri Rhizoma or clover.
13 FIG. 14C is a graph illustrating the comparison result of the level of LDL-cholesterol in 14 the blood of an animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 16 selectively comprising Acori Gramineri Rhizoma or clover.
17 FIG. 14D is a graph illustrating the comparison result of the level of HDL-cholesterol 18 in the blood of an animal model according to the administered dose of an extract of a mixture 19 comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri Rhizoma or clover.
21 FIG. 14E is a graph illustrating the comparison result of the level of glucose in the 22 blood of an animal model according to the administered dose of an extract of a mixture 23 comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 24 selectively comprising Acori Gramineri Rhizoma or clover.
FIG. 14F is a graph illustrating the comparison result of the level of creatinine in the 26 blood of an animal model according to the administered dose of an extract of a mixture 22654729.1 CA Application Blakes Ref: 11886/00001 1 comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively 2 comprising Acori Gramineri Rhizoma or clover.
3 FIG.
14G is a graph illustrating the comparison result of the level of urea in the blood of an 4 animal model according to the administered dose of an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri 6 Rhizoma or clover.
7 FIG.
14H is a graph illustrating the comparison result of the level of LDH (Lactate 8 dehydrogenase) in the blood of an animal model according to the administered dose of an extract of a 9 mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising Acori Gramineri Rhizoma or clover.
11 FIG.
141 is a graph illustrating the comparison result of the level of ALP
(alkaline phosphatase) 12 in the blood of an animal model according to the administered dose of an extract of a mixture comprising 13 Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively comprising 14 Acori Gramineri Rhizoma or clover.
FIG. 14J is a graph illustrating the comparison result of the level of GPT
(glutamic-pyruvic 16 transaminase) in the blood of an animal model according to the administered dose of an extract of a 17 mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 18 selectively comprising Acori Gramineri Rhizoma or clover.
19 FIG.
14K is a graph illustrating the comparison result of the level of GOT
(glutamic-oxaloacetic transaminase) in the blood of an animal model according to the administered dose of an extract of a 21 mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and 22 selectively comprising Acori Gramineri Rhizoma or clover.

Features and advantages of the present invention will be more clearly understood by the 26 following detailed description of the present preferred embodiments by reference to the accompanying 22654729.1 CA Application Blakes Ref: 11886/00001 1 drawings. It is first noted that terms or words used herein should be construed as meanings or 2 concepts corresponding with the technical sprit of the present invention, based on the principle 3 that the inventor can appropriately define the concepts of the terms to best describe his own 4 invention. Furthermore, it should be understood that detailed descriptions of well-known functions and structures related to the present invention will be omitted so as not to unnecessarily 6 obscure the important point of the present invention.

8 As used herein, the term "Saururi chinensis Bail." refers to a perennial plant belonging to 9 the Saururaceae Family, Piperales Order, which has been used as herbal raw ingredients in herbal to medicines. Saururi chinensis Baill. is known to have a bitter and spicy tastes, white flowers and 11 roots, the top two or three leaves turn white when in bloom, and bears a single round fruit in each 12 flower bud between September and October in the northern hemisphere.
13 In the present invention, Saururi chinensis Bail. may be used as an active ingredient of a 14 pharmaceutical composition for the prevention or treatment of obesity;
The parts used are leaves, stems, roots or the entire plant.
16 As used herein, the term "Curcumae Longae Rhizoma" refers to a perennial plant 17 belonging to Zingiberaceae Family, Zingiberales Order, which has been used as herbal raw 18 ingredients in herbal medicines. Curcumae Longae Rhizoma is known to have bitter and spicy 19 tastes, the surface of its rhizome takes on a light yellow while its inner side is vermillion and emits a camphor-like aroma, its flower pettles come out before the leaves, and its yellow flowers bloom 21 from the axils of leaves between April and June in the northem hemisphere.
22 In the present invention, Curcumae Longae Rhizoma may be used as an active ingredient 23 of a pharmaceutical composition for the prevention or treatment of obesity, and the parts used are 24 stems or roots of the plant.
As used herein, the term "Polygalae Radix" refers to a perennial plant belonging to the 26 Polygalaceae Family, Geraniales Order, which has been used as herbal raw ingredients in herbal 22654729.1 CA Application Blakes Ref: 11886/00001 1 medicines. Polygalae Radix is known that it has bitter and spicy tastes, long and thick roots with a ridge but 2 almost no hairs except some slightly curled hairs on the upper part, and its flowers bloom in violet between 3 July and August in the nothem hemissphere, and its fruits have many seeds contained in the partitioned 4 space therein.
In the present invention, Polygalae Radix may be used as an active ingredient of a pharmaceutical 6 composition for the prevention or treatment of obesity, and the parts used are roots of the plant.
7 As used herein, the term "Acori Gramineri Rhizoma" refers to a perennial plant belonging to the 8 Araceae Family, Arales Order, which has been used as herbal raw ingredients in herbal medicines. Acori 9 Gramineri Rhizoma is known to have laterally extending rhizomes, fibrous roots coming out of its joints, wherein the space between joints is relatively shorter above ground while that under ground is longer, is 11 green overall, have a hermaphrodite flower including both pistils and stamens, its flowers bloom between 12 June and July in yellow, and its fruits have many seeds contained in the partitioned space therein.
13 In the present invention, Polygalae Radix may be used as an active ingredient of a pharmaceutical 14 composition for the prevention or treatment of obesity, and the parts used are stems and roots of the plant As used herein, the term "extract of a mixture" refers to an extract of a mixture by extracting a 16 mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma and Polygalae Radix, or a 17 mixture comprising Saururi chinensis Bail!., Curcumae Longae Rhizoma, Polygalae Radix and Acori 18 Gramineri Rhizoma.
19 Depending on the plant part(s) for extraction, the activities of each of the extract(s), fraction(s) thereof, and the specific ingredients contained therein may differ from each other. Accordingly, the present 21 inventors firstly identified that an extract of a mixture comprising the entire plant of Saururi chinensis Baill., 22 stems and roots of Curcumae Longae Rhizoma, and roots of Polygalae Radix; and an extract of a mixture 23 comprising the entire plant of Saururi chinensis Bail., stems and roots of Curcumae Longae Rhizoma, 24 roots of Polygalae Radix, and stems and roots of Acori Gramineri Rhizoma exhibit the effect of preventing or treating obesity.

22654729.1 CA Application Blakes Ref: 11886/00001 1 In the present invention, the extract may be used as an active ingredient of a pharmaceutical composition for preventing or treating obesity. The amounts of Saururi chinensis 3 Bail, Curcumae Longae Rhizoma, and Polygalae Radix included in the mixture for obtaining the 4 extract are not particularly limited as long as they can be used in manufacturing a composition for preventing or treating obesity. Preferably, Saururi chinensis Bail!., Curcumae Longae Rhizoma, 6 and Polygalae Radix may be mixed at a ratio of 1: 0.2 through 1: 0.2 through 1 (w/w/w), more 7 preferably, 1: 0.4 through 1: 0.4 through 1 (w/w/w), and most preferably, 1: 0.6: 1 (w/w/w).

Additionally, when an extract of a mixture is obtained from the mixture including 9 Saururi chinensis Bail!., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma, the amounts of Saururi chinensis Bail!., Curcumae Longae Rhizoma, Polygalae Radix, 11 and Acori Gramineri Rhizoma are not particularly limited as long as they can be used in manufacturing a composition for the prevention or treatment of obesity.
Preferably, Saururi 13 chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma 14 may be mixed at a ratio of 1 : 0.2 through 1 : 0.2 through 1 : 0.2 through 1 (w/w/w/w), more preferably, 1: 0.4 through 1 : 0.4 through 1: 0.4 through 1 (w/w/w/w), and most preferably, 1 :
16 0.6 : 1 :
0.4 (w/w/w/w). Additionally, Saururi chinensis Bail!., Curcumae Longae Rhizoma, 17 Polygalae Radix, and Acori Gramineri Rhizoma may be purchased from the market or those 18 cultivated in nature may be used.
19 Examples of the extraction methods may include, although not limited thereto, preferably boiled-water extraction, hot-water extraction, cold immersion extraction, reflux cooling extraction, 21 or ultrasonification extraction, etc.
22 The extract may be obtained by extracting using an extraction solvent, or by fractionating 23 the extract obtained by extracting using an extraction solvent. The extraction solvent may include, 24 although not limited thereto, water, an organic solvent, or a mixed solvent thereof. The organic solvent may include a C1 ¨ C4 alcohol, a polar solvent such as ethyl acetate or acetone, a non-polar 26 solvent such as hexane or dichloromethane, or a mixed solvent thereof. Additionally, preferably, 22654729.1 CA Application Blakes Ref: 11886/00001 1 water, a C1 ¨ C4 alcohol, or a mixed solvent thereof may be used, more preferably, ethanol. In an 2 exemplary embodiment of the present invention, the extract was obtained using 25% ethanol (Et0H) as the 3 (Et0H) as the solvent.
4 The extract may be contained in an amount from 0.001 wt% to 100 wt%
relative to the total weight of the respective pharmaceutical composition, more preferably 0.1 wt%
to 80 wt%.

7 As used herein, the term "fraction" refers to a resultant product obtained by the fractionation 8 method for separating a specific component or specific group from the respective extract 9 In the present invention, the fraction may be obtained via various methods for fractionating the extract, and may include solvent fractionation performed by treating various solvents, ultrafiltration 11 fractionation performed by passing through an ultrafiltration membrane having a certain molecular cut-off 12 value, chromatography fractionation performed by various chromatographies (manufactured for separation 13 according to size, electric charge, hydrophobicity, or affinity), etc. , although not limited thereto. In 14 particular, the solvent to be used in the solvent fractionation may be a polar or non-polar solvent, although not limited thereto, and preferably a non-polar solvent. The solvent fractionation may be performed by 16 fractionating the extract using the fractionation solvent in a sequential order from a higher non-polarity 17 solvent to a lower non-polarity solvent For example, the extract may be sequentially fractionated using 18 hexane or ethyl acetate.
19 The fraction may be contained in an amount from 0.001 wt% to 100 wt%
relative to the total weight of the respective pharmaceutical composition, more preferably 0.1 wt%
to 80 wt%.

22 As used herein, the term "pharmaceutical composition" refers to something manufactured for the 23 purpose of preventing or treating a disease(s), and may be prepared in various types of formulations 24 according to the corresponding conventional method. For example, it may be prepared in oral-type formulations such as powders, granules, tablets, capsules, suspensions, and syrups, and also used in the 26 form of external formulations, suppositories, and sterile injection solutions.

22654729.1 CA Application Blakes Ref: 11886/00001 2 As used herein, the term "obesity" refers to an abnormal health condition caused by the 3 increase of body weight, in which, due to an excess energy intake over energy consumption, the 4 unconsumed surplus energy can accumulate as body fat in various forms of lipids or a physical state with an elevated lipid content in the blood. Once obesity occurs, it may induce various 6 metabolic diseases and adult diseases such as diabetes, hyperlipidemia, heart diseases, strokes, 7 atherosclerosis, and fatty liver.
8 The composition provided in the present invention can not only treat obesity by 9 inhibiting fat production, but also improve, prevent or treat obesity-related diseases derived from obesity, for example, various metabolic diseases such as diabetes, hyperlipidemia, heart diseases, 11 strokes, atherosclerosis, and fatty liver.
12 As used herein, the term "prevention" refers to all kinds of activities associated with the 13 inhibition or delay of obesity or obesity-related diseaseas by administering the compositon of the 14 present invention.
As used herein, the term "treatment" refers to all kinds of actions associated with the 16 improvement or advantageous changes in symptoms of obesity or obesity-related diseaseas 18 In an exemplary embodiment of the present invention, hot-water extracts (an extract of a 19 mixture and individual extracts), warm-water extracts (an extract of a mixture and individual extracts), and ethanol extracts (an extract of a mixture and individual extracts) of a mixture 21 including Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix and Acori 22 Gramineri Rhizoma, and a mixture including each of them separately were obtained, respectively 23 (Table 1), and 3T3-L1 cells were treated with each of the extracts at varied concentrations (Table 24 2) and their in vitro anti-obesity effects were examined. As a result, it was confirmed that, among the hot-water extracts (FIGS. 1A through 1C), warm-water extracts (11GS. 2A
through 2C), and 26 ethanol extracts (FIGS. 3A through 3C), the extracts of a mixture and Polygalae Radix extracts 22654729.1 CA Application Blakes Ref: 11886/00001 1 showed the effects of reducing fat content and the number of the cells, whereas Saururi chinensis Baill.
2 extracts, Curcumae Longae Rhizoma extracts and Aeon Gramineri Rhizoma extracts showed no reducing 3 effects of fat content and the number of the cells at all. Additionally, among the hot-water extracts, the 4 warm-water extracts, and the ethanol extracts, the ethanol extracts were shown to have the most superior effects of reducing fat contents and safety. Additionally, high fat diet containing each of the extracts at 6 varied concentrations was administered to mice (Table 3), and their in vivo anti-obesity effects were 7 examined. As a result, it was shown that, the mice treated with Polygalae Radix extracts and the extracts of 8 a mixture showed the most superior effect of reducing body weight, and of them in particular, the Polygalae 9 Radix extracts showed severe toxicities, whereas the extract of a mixture (ethanol extracts) showed alleviated toxicities (PIG. 4). Additionally, the measurement of fat weight revealed that the Polygalae 11 Radix extracts exhibited the most significant inhibitory effect against fat increase, followed by the 12 Curcumae Longae Rhizoma extracts, and the Acori Gramineri Rhizoma extracts showed the least 13 inhibitory effect against fat increase (FIG. 6); and the extract of a mixture (ethanol extracts) showed higher 14 safety than the Polygalae Radix extracts in liver tissues (FIG. 7) and kidney tissues (FIG. 8).
In another exemplary embodiment of the present invention, in order to examine the inhibitory 16 effects of the extract of a mixture including Satuuri chinensis Baill., Curcumae Longae Rhizoma and 17 Polygalae Radix against obesity, exclusive of Acori Gramineri Rhizoma, which was analyzed to have the 18 least inhibitory effect against fat increase among the components included in the extract of a mixture, 19 ethanol extracts were obtained for each of the components from the mixture essentially including Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, and selectively including Acori 21 Gramineri Rhizoma and clover, respectively (Table 4). Each of the thus-obtained ethanol extracts was 22 administered to mice at varied doses, and the experimental animals were collected thereafter (Table 5) and 23 subjected to evaluations regarding their body weight (I-41G. 9), dietary intake (FIG. 10), fat weight (FIGS.
24 11A through 11D), ghrelin level (FIGS. 12A through 12C), leptin level (FIG. 13), and levels of components in blood (FIGS. 14A through 14K). As a result, it was confirmed that not only the extract of a 26 mixture including Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix but also the 22654729.1 CA Application Blakes Ref: 11886/00001 1 extract of a mixture, which additionally includes Acori Gramineri Rhizoma thereto, exhibited 2 improved anti-obesity effects compared to that of the control group.
3 Accordingly, it was confirmed that the extract of a mixture of the anti-obesity 4 composition may be obtained from a mixture essentially including Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, or a mixture additionally including Acori 6 Gramineri Rhizoma thereto.

8 The pharmaceutical composition of the present invention may further include a 9 pharmaceutically acceptable diluent, excipient or carrier. The pharmaceutical composition including the pharmaceutically acceptable carrier may be prepared in various formulations for oral 11 or parenteral administration. Formulations may be prepared using a conventional filler, binder, 12 humectant, disintegrant, diluent, surfactant or excipient. Examples of the solid formulations for 13 oral administration may include tablets, pills, powders, granules, capsules, etc., and the solid 14 formulations may include at least one excipient, e.g., starch, calcium carbonate, sucrose or lactose, gelatin, etc., to be mixed therein. Additionally, lubricants such as magnesium stearate and talc 16 may be also used in addition to the simple excipient. Examples of the liquid formulations for oral 17 administration may include suspensions, liquid medicines for internal use, emulsifiers, syrups, etc., 18 which may include various kinds of excipients, e.g., a humectants, a sweetener, a fragrant, a 19 preservative, etc., in addition to the commonly used simple diluents such as water and liquid paraffin. Examples of the formulations for parenteral administration may include sterile aqueous 21 solutions, non-aqueous solvents, suspensions, emulsifiers, lyophilized formulations, and 22 suppositories. Examples of the non-aqueous solvents and suspensions may include propylene 23 glycol, polyethylene glycol, a vegetable oil such as olive oil, injectable estersuch as ethyl oleate, 24 etc. Examples of the bases for the suppositories may include witepsol, macrogol, tween 61, cacao butter, laurinum, g,lycerogelatin, etc.

22654729.1 CA Application Blakes Ref: 11886/00001 1 The pharmaceutical composition may be prepared in any one of the formulations selected from 2 the group consisting of tablets, pills, powders, granules, capsules, suspensions, liquid medicines for internal 3 use, emulsifiers, syrups, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsifiers, 4 lyophilized formulations and suppositories.
6 In another aspect of the present invention to accomplish the objectives, there is provided a method 7 for the prevention or treatment of obesity including administering an effective amount of a 8 pharmaceutical composition comprising the extract of a mixture or a fraction thereof as an active 9 ingredient to a subject having a risk of obesity or a subject having obesity. In particular, the respective active ingredient to be contained in the extract of a mixture is the same as described above.

12 As used herein, the term "subject" refers to all kinds of animals including humans having a risk of 13 obesity or having obesity.
14 As used herein, the term "administration" refers to an activity of introducing the pharmaceutical composition of the present invention to a subject by an appropriate method.

17 In the present invention, the pharmaceutical composition may be administered via any routes as 18 long as they can deliver the same to the target tissues. According to the intended purposes, the 19 pharmaceutical composition of the present invention may be administered via oral administration, rectal administration, local administration, intraperitoneal administration, intravenous administration, intraarterial 21 administration, intramuscular administration, intranasal administration, subcutaneous administration, 22 intracutaneous administration, dermal administration, intranasal administration, intrapulmonary 23 administration, intrarectal administration, ocular administration, etc., but is not limited thereto.
24 Additionally, the pharmaceutical composition may be administered via any apparatus that enables to transport the the active ingredient to a target cell.

22654729.1 CA Application Blakes Ref: 11886/00001 1 In an exemplary embodiment, the pharmaceutical composition of the present invention 2 includes an extract of a mixture. The amount of the extract of a mixture contained in the 3 composition may be in the range from 0.1 wt% to 50 wt% relative to the total weight of the 4 pharmaceutical composition, although not limited thereto.
6 The pharmaceutical composition of the present invention may be administered in a 7 pharmaceutically effective amount, and as used herein, the term "pharmaceutically effective amount" refers 8 to an amount sufficient to sufficient for the treatment of diseases at a reasonable benefit/risk ratio applicable 9 to a medical treatment without causing any adverse effects, and the level of the effective dose may be determined factors including the kind of a subject, severity of illness, age, sex, drug activity, drug sensitivity, 11 administration time, administration route and dissolution rate, length of treatment, drug(s) used in 12 combination, and other factors well known in the medical field. The pharmaceutical composition of the 13 present invention may be administered as an individual therapeutic agent or in combination with other 14 therapeutic agent, and also sequentially or simultaneously with the conventional therapeutic agent.
Additionally, the pharmaceutical composition of the present invention may be administered as a single dose 16 or in multiple divided doses. Additionally, it is important that an amount which can achieve the maximum 17 effect with the least amount without any adverse effects be administered in consideration of all the factors 18 described above.

The dose of the pharmaceutical composition of the present invention may be determined 21 by a skilled person in the art considering the intended use(s), addiction level of disease(s), age, 22 body weight, sex and anamesis of a subject, or the kinds of ingredients usd as active ingredient(s), 23 etc. In an exemplary embodiment, the pharmaceutical composition of the present invention may 24 be administered in the range from about 1 jig/kg/day to about 100 mg/kg/day for an adult, preferably from 20 mg/kg/day to 30 mg/kg/day. The pharmaceutical composition of the present 22654729.1 CA Application Blakes Ref: 11886/00001 1 invention may be administered once daily or in a few divided doses, although not particularly limited 2 thereto.

4 In still another aspect of the present invention to achieve the objectives, there is provided a food composition for the prevention or improvement of obesity comprising the extract or a fraction thereof.

7 The Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix and Acori Gramineri 8 Rhizoma included in the extract of a mixture have long been used as herbal raw ingredients and their safety 9 has been approved accordingly. Therefore, they may be prepared in the form of foods for preventing or treating obesity for ingestion. In particular, the extract of a mixture or a fraction thereof may be included in 11 the range from 0.01 wt% to 100 wt% relative to the total weight of the food composition, preferably from 1 12 wt% to 80 wt%, although not limited thereto. When the food is beverage it may be included in the range 13 from 1 g to 30 g per 100 mL of the food composition, preferably from 3 g to 20 g. Additionally, the 14 composition may further include additional ingredients which may be conventionally used in food compositions to improve smell, taste, sight, etc., e.g., vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, 16 folate, panthotenic acid, etc. Additionally, the composition may further include minerals such as Zn, Fe, 17 Ca, Cr, Mg, Mn, Cu, etc. Additionally, the composition may further include amino acids such as lysine, 18 tryptophan, cysteine, valine, etc. Addtionally, the composition may further include food additives such as 19 preservatives (potassium sorbate, sodium benzoate, salicylic acid, dehydro sodium acetate, etc.), disinfectants (bleaching powder, higher bleaching powder, sodium hypochlorite, etc.), antioxidants 21 (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.), coloring agents (tar color, etc.), color-22 developing agents (sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (monosodium 23 glutamate (MSG), etc.), sweeteners (dukin, cyclemate, saccharin, sodium, etc.), flavors (vaniline, lactones, 24 etc.), swelling agents (alum, potassium D-hydrogn tartate, etc.), fortifiers, emulsifiers, thickners (adhesive pastes), film-forming agents, gum base agents, antifoaming agents, solvents, improvers, etc. The food 26 additives may be selected according to the food kinds and used in an appropriate amount.
22654729.1 CA Application Blakes Ref: 11886/00001 2 Additionally, functional foods for preventing or improving obesity may be manufactured 3 using a food compositin comprising the extract or a fraction thereof.
4 Specifically, processed foods for preventing or improving obesity may be manufactured using the food composition. Examples of the processed foods may include cookies, beverages, 6 alcoholic beverages, fermented foods, canned foods, milk-processed foods, meat-processed foods, 7 noodles, etc. Examples of the cookies include biscuits, pies, cakes, breads, candies, jellies, gums, 8 cereals (meal substitutes such as grain flakes). Examples of the beverages include drinking water, 9 carbonated soft drinks, functional isotonic drinks, juices (e.g., apple-, pear-, grape-, aloe-, tangerine-, peach-, carrot-, tomato juices, etc.), sweet rice drinks, etc.
Examples of the alcoholic 11 beverages include refined rice wine, whisky, beer, liquors, fruits wine, etc. Examples of the 12 fermented foods include soy sauce, bean paste, red pepper paste, etc.
Examples of the canned 13 foods include seafood canned foods (e.g., canned tuna, mackerel, mackerel pike, conch, etc.), 14 livestock canned foods (canned beef, pork, chicken, turkey, etc.), agricultural canned foods (canned corn, peach, pineapple, etc.). Examples of milk-processed foods include cheese, butter, 16 yogurt, etc. Examples of meat-processed foods include pork cutlets, beef cutlets, chicken cutlets, 17 sausages, sweet and sour porks, nuggets, neobiani, etc. Examples of the noodles include sealed 18 and packed fresh noodles. Additionally, the composition may be used for manufacturing retort 19 foods, soups, etc.
As used herein, the term "functional food", which has the same meaning as the term "for 21 special health use (FoSHU)", refers to a food with high effects of medicinal and medical treatment 22 modulated so as to efficiently exhibit body modulating function as well as provision of nutrients.
23 The functional food may be manufactured in various forms including tablets, capsules, powders, 24 granules, liquids, pills, etc., in order to obtain useful effects for the prevention or improvement of bone diseases.

22654729.1 CA Application Blakes Ref: 11886/00001 1 In still another aspect of the present invention to achieve the objectives, there is provided a method 2 for manufacturing the extract of a mixture including obtaining the extract from a mixture including Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix using water, a CI ¨ C4 alcohol, or a 4 mixed solvent thereof.
6 In the method for manufacturing the extract of a mixture, the method may further include a conventional extraction method used in the art such as hot-water extraction, warm-water extraction, ethanol extraction, ultrasonification extraction, filtration and reflux extraction, and after obtaining the extract, the 9 extract may be further subjected to filtration, concentration, or lyophilization.
11 In particular, each of the active ingredients included in the extract of a mixture is the same as 12 described above.

14 The mixture may include Saururi chinensis Baill., Curcumae Longae Rhizoma and Polygalae Radix mixed therein at a ratio of 1 : 0.2 through 1: 0.2 through 1 (w/w/w).

17 In still another aspect of the present invention to achieve the objectives, there is provided a method 18 for manufacturing an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma, which includes obtaining the extract from a mixture including Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix and Acori Gramineri Rhizoma using water, a C1 ¨ C4 alcohol, or a mixed solvent thereof. In particular, each of the active 22 ingredients included in the extract of a mixture is the same as described above.

24 The mixture may include Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix and Acori Gramineri Rhizoma mixed therein at a ratio of 1 : 0.2 through 1 :
0.2 through 1: 0.2 through 1 26 (w/w/w/w).

22654729.1 CA Application Blakes Ref: 11886/00001 2 In still another aspect of the present invention to achieve the objectives, there is provided 3 a composition including an extract of a mixture comprising Saururi chinensis Baill., Curcumae 4 Longae Rhizoma, and Polygalae Radix or a fraction thereof. In particular, each of the active ingredients included in the extract of a mixture is the same as described above.
6 The composition may be used for treating obesity.
7 The extract of a mixture may be an extract of a mixture, in which Saururi chinensis 8 Bail., Curcumae Longae Rhizoma, and Polygalae Radix are mixed therein at a ratio of 1: 0.2 9 through 1: 0.2 through 1 (w/w/w).
The extract of a mixture may be obtained using 25% ethanol.

12 In still another aspect of the present invention to achieve the objectives, there is provided 13 a composition including an extract of a mixture comprising Saururi chinensis Baill., Curcumae 14 Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma or a fraction thereof. In particular, each of the active ingredients included in the extract of a mixture is the same as 16 described above.
17 The composition may be used for treating obesity.
18 The extract of a mixture may be an extract of a mixture, in which Saururi chinensis 19 Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma are mixed therein at a ratio of 1: 0.2 through 1: 0.2 through 1: 0.2 through 1 (w/w/w).
21 The extract of a mixture may be obtained by extracting the mixture with 25% ethanol.

24 The extract of a mixture of the present invention can inhibit fat production without the side effect of cell toxicity, and thus can be widely used for the prevention, improvement, or 26 treatment of obesity or obesity-related diseases.

22654729.1 CA Application Blakes Ref: 11886/00001 The present invention will be explained in greater detail through the following examples as set forth herein below, but they are disclosed for illustrative purposes only and are not to be construed as 4 limiting the scope of the present invention.

Example 1: Preparation of Individual Extracts of Saururi chinensis Bail., Curcumae Longae Rhizoma, Polvgalae Radix, and Acori Gramineri Rhizoma, and extract of a mixture thereof Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma were respectively ground and mixed according to the ratio shown in Table 1 below to prepare 30 g mixtures. The mixtures were then subjected to hot-water extraction, warm-water extraction, and ethanol extraction, respectively, and obtained the respective extract therefrom. Each of the thus-obtained extracts was subjected to filtration to obtain a liquid component, and the liquid component was lyophilized to obain powdered extracts (hot-water extract, warm-water extract, and ethanol extract), which were then dissolved in distilled water at a concentration of 100 mg/mL to be used later as samples for experiments. Specifically, the hot-water extraction was performed by adding 1 L of drinking water to the mixture, followed by heating to a final volume of 100 mL. The warm-water extraction was performed for 24 hours after adding 300 mL

of distilled water to the mixture while maintaining the temperature at 38 C.
The ethanol extraction was performed for 24 hours after adding 300 mL of 25% ethanol to the mixture while maintaining the 19 temperature at 38 C.
Additionally, each 30 g of Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma was subjected to the same method as described above, and the individual extracts for each component (hot-water extract, warm-water extract, and ethanol extract) were prepared 23 therefrom.

22654729.1 CA Application Blakes Ref: 11886/00001 1 [Table 1] Composition of Extracts Curcumae Saururi Acori Longae Polygalae Extract chinensis Gramineri Total (%) Rhizoma Radix (%) Bail. (%) Rhizoma (%) (go) MOM-20120b(1) lOg (33.3) lOg (33.3) 6g (20) 4g (13.4) 30g (100) MOM-20120b(2) lOg (33.3) 6g (20) lOg (33.3) 4g (13.4) 30g (100) MOM-20120b(3) lOg (33.3) 4g (13.4) lOg (33.3) 6g (20) 30g (100) 3 Example 2: In Vtro Anti-obesity Effects of Individual Extracts of Saururi chinensis 4 Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma and extract of a mixture 6 3T3-L1 cells distributed by American Type Culture Collection (ATCC, USA) were 7 inoculated into a Dulbcco's Modified Eagle's Medium (DMEM, Lonza) containing 10% bovine 8 serum (BS; Gibco) and 1% penicillin-streptomycin, cultured at 37 C under 5% CO2, subcultured 9 at intervals of from 3 to 4 days and thereby obtained preadipocytes.
The thus-obtained preadipocytes were collected, adjusted to a concentration of 1 x 104 11 cells/mL, aliquoted into a 96-well plate in the amount of 100 pL/well, and cultured at 37 C under 12 5% CO2 for 4 days until they were saturated. Then, the thus-cultured cells were added with a 13 medium for inducing differentiation of preadipocytes containing the individual extracts and the 14 extract of the mixture (DMEM, 0.25 jiM dexamethansone, 0.5 mM 3-isobuty1-1-methylxanthine,

10 fig/mL insulin, and fetal bovine serum (1-BS)) and cultured further for 2 days. In particular, the 16 concentrations of the individual extracts and the extract of the mixture included in the medium for 17 inducing differentiation of preadipocytes are shown in Table 2 below.
18 [Table 2] Treated Concentrations of Individual Extracts and Extract of the mixture 22654729.1 CA Application Blakes Ref: 11886/00001 Extract Treated Concentration ( g/mL) KI0M-2012b(1) 0 10 50 100 Saururi chinensis 0 3.3 16.7 33.3 Bail, extract Curcumae Longae Rhizoma 0 3.3 16.7 33.3 extract Polygalae Radix extract Acori Gramineri 0 1.4 6.6 13.4 Rhizoma extract KI0M-2012b(2) 0 10 50 100 Saururi chinensis 0 3.3 16.7 33.3 Bail, extract Curcumae Longae Rhizoma 0 2 10 20 extract Polygalae Radix 0 3.3 16.7 33.3 extract Acori Gramineri 0 1.4 6.6 13.4 Rhizoma extract KI0M-2012b(3) 0 10 50 100 Saururi chinensis 0 3.3 16.7 33.3 Bail. extract Curcumae Longae Rhizoma 0 1.4 6.6 13.4 extract Polygalae Radix 0 3.3 16.7 33.3 extract Mori Gramineri Rhizoma extract 22654729.1 CA Application Blakes Ref: 11886/00001 1 Then, the medium was removed from the plate and DMEM medium containing only 10 2 pig/mL
insulin was added thereto, and cultured for two days. Subsequently, the resultant was 3 cultured for 8 days while replacing with DMEM medium containing only FBS at two day 4 intervals.
Upon completion of the culture, the resulting cells were collected, washed with PBS, and 6 fixed with 10% formalin. The fixed cells were stained with Oil Red 0 and washed with 70%
7 isopropyl alcohol. The washed cells were dried, added with 100% isopropyl alcohol to dissolve 8 the Oil Red 0 stained in the cells. The absorbance of the resulting cells was measured at 490 nm, 9 and their content of fat accumulated in the body was calculated based on the measured absorbances. In particular, the fat content was indicated as a percentage relative to the average

11 absorbance value of the control group.

12

13 Meanwhile, the cell viability of the differentiated cells was measured via water-soluble

14 tetrazolium (WST) method, the sodium salt of 443-(4iodopheny1)-2-(4-nitropheny1)-2H-5-tetrazolio]-1,3-benzene disulfonate, and evaluated the cell toxicities of each of the extract of the 16 mixture and the individual extracts. Roughly, the culture-completed cells were treated with WST
17 solution (10 11100 L), cultured further for 1 hour, and the amount of formazan released as a 18 culture liquid was calculated based on the absorbance at 520 nm, thereby measuring the level of 19 the live cells, and the result was indicated as a ratio relative to the value of the control group.
21 First, upon analysis of the inhibitory effect of the hot-water extract on fat accumulation, 22 as illustrated in FIGS. 1A through 1C, it was confirmed that each of the extract of the mixture 23 (KI0M-20120b(1), KI0M-20120b(2), and KI0M-20120b(3)) reduced fat content in a concentration-dependent manner at concentrations of 50 Rg/mL and 100 mg/mL, whereas, among the individual extracts, only the Polygalae Radix extract reduced the fat content similar to that of 26 the extract of the mixture, but Saururi chinensis Baill. extract, Curcumae Longae Rhizoma extract, 22654729.1 CA Application Blakes Ref: 11886/00001 1 and Acori Gramineri Rhizoma extract failed to show any noticeable reduction in fat content regardless of 2 their treated concentrations. Additionally, the fat reduction rates when treated with each of the extract of the mixture (KI0M-20120b(1), KI0M-20120b(2), and KI0M-20120b(3)) at a concentration of 50 g/mL
4 were 10, 13 and 17%, respectively, and those treated at a concentration of 100 lag/mL were 25%, 28%, and 26%, respectively.

Additionally, upon analysis of the cell toxicity of the hot-water extract, as illustrated in FIGS. 1D

through 1F, it was confirmed that each of the extract of the mixture (KI0M-20120b(1), MOM-20120b(2), and KI0M-20120b(3)) reduced the number of cells in a concentration-dependent manner at concentrations of 50 ,g/mL and 100 ug/mL, whereas, among the individual extracts, only the Polygalae Radix extract singificantly reduced the number of cells, but Saururi chinensis Baill. extract, Curcumae Longae Rhizoma extract, and Acori Gramineri Rhizoma extract failed to show a reduction in the number of 12 cells regardless of their treated concentrations.

14 In addition, upon analysis of the inhibitory effect of the warm-water extract on the fat accumulation, as illustrated in FIGS. 2A through 2C, it was confirmed that each of the extract of the 16 mixture (KI0M-20120b(1), KI0M-20120b(2), and KI0M-20120b(3)) reduced fat content in a concentration-dependent manner at concentrations of 50 pg/mL and 100 g/mL, whereas, among the individual extracts, only the Polygalae Radix extract reduced the fat content similar to that of he extract of 19 the mixture, but Saururi chinensis Bail. extract, Curcumae Longae Rhizoma extract, and Acori Gramineri Rhizoma extract failed to show any noticeable reduction in fat content regardless of their treated 21 concentration.

Additionally, upon analysis of the cell toxicity of the hot-water extract, as illustrated in FIGS. 2D

through 2F, it was confirmed that each of the extract of the mixture (KI0M-20120b(1), MOM-20120b(2), and KI0M-20120b(3)) reduced the number of cells in a concentration-dependent manner at concentrations of 50 fig/mL and 100 g/mL, whereas, among the individual extracts, only the Polygalae 26 Radix extract singificantly reduced the number of cells, but Saururi chinensis Baill. extract, Curcumae 22654729.1 CA Application Blakes Ref: 11886/00001 1 Longae Rhizoma extract, and Acori Gramineri Rhizoma extract failed to show a reduction in the 2 number of cells regardless of their treated concentrations.

4 Finally, upon analysis of the inhibitory effect of the ethanol extract on the fat accumulation, as illustrated in FIGS. 3A through 3C, it was confirmed that each of the extract of 6 the mixture (KI0M-20120b(1), KI0M-20120b(2), and KI0M-20120b(3)) reduced fat content 7 in a concentration-dependent manner at concentrations of 10 14/mL, 50 prg/mL, and 100 j.rgimL, 8 whereas, among the individual extracts, only the Polygalae Radix extract reduced the fat content 9 similar to that of the extract of the mixture, but Saururi chinensis Baill. extract, Curcumae Longae Rhizoma extract, and Acori Gramineri Rhizoma extract failed to show any noticeable reduction in 11 fat content regardless of their treated concentration.
12 Additionally, upon analysis of the cell toxicity of the ethanol extract, as illustrated in 13 FIGS. 3D through 3F, it was confirmed that each of the extract of the mixture (KI0M-20120b(1), 14 KI0M-20120b(2), and KI0M-20120b(3)) reduced the number of cells in a concentration-dependent manner at a concentration of 100 1.1g/mL, whereas, among the individual extracts, only 16 the Polygalae Radix extract singificantly reduced the number of cells at concentrations of 50 17 1.tg/mL and 100 ttg/mL, but Saururi chinensis Baill. extract, Curcumae Longae Rhizoma extract, 18 and Acori Gramineri Rhizoma extract failed to show a reduction in the number of cells regardless 19 of their treated concentrations.
21 Consequently, based on the above results of the extract of the mixture (the hot-water 22 extract, the warm-water extract, and the ethanol extract), it was confirmed that the ethanol extract 23 has the most superior effects in terms of the inhibition of fat accumulation and safety of cells.

22654729.1 CA Application Blakes Ref: 11886/00001 Example 3: In Vivo Anti-obesity Effects of Individual Extracts of Saururi chinensis Baill., Curcumae Longae Rhizoma, Polvgalae Radix, and Acori Gramineri Rhizoma and Extract of the 3 mixture 4 From the result of Example 2, it was confirmed that ethanol extracts of Sauntri chinensis Bail!., Curcumae Longae Rhizoma, Polygalae Radix, and Aeon Gramineri Rhizoma have excellent in vitro effects in terms of the inhibition of fat accumulation and safety of cells.
Accordingly, the present example 7 was performed in order to confirm whether the ethanol extracts are still effective under in vivo condition.
8 To this end, mice were bred while feeding them with the individual extracts and the extract of the mixture obtainded via ethanol extraction. The body weight, the amount of dietary intake, and fat weight of the thus-bred mice were measured, and their liver tissues and kidney tissues were analyzed by comparison.

13 Example 3-1: Obtaining Mice Bred under Separate Breeding Conditions 14 One hundred seventy 5-week old male C57BL/6N mice were purchased, adapted for a week, and bred while feeding them with 60% high fat diet (IiFD) for 5 weeks. The thus-bred mice were divided into groups (10 mice/group) and bred for additional 6 weeks while feeding them with different feeds containing different test substances (Table 3). In particular, the positive control group was determined to be treated with XenicalTm, an agent for treating obesity, and the extract of the mixture were administered into 19 the normal diet group (1X) and excess diet group (4X). Additionally, the breeding room was set at a temperature of 22 1 C with a humidity of 50 5%, and the fight-dark cycle was controlled at 12 hour intervals. The 10% high fat diet and 60% high fat diet were purchase from the Central Lab. (Animal Inc., 22 Korea).

22654729.1 CA Application Blakes Ref: 11886/00001 1 [Table 3] Diet Conditions for Mice Test Substance Test Name High Fat Diet Dose Group Rate Kind (mg/kg) 1 normal control 10% -2 negative control 60% -3 positive control 60% Xenicalim 62.5 4 Saururi chinensis Bail. (1X) 60%
Saururi chinensis Bail. extract 36.4 Saururi chinensis Bail. (4X) 60% Saururi chinensis Bail.
extract 145.6 Curcumae Longae Rhizoma Curcumae Longae Rhizoma 6 60%
278.5 (1X) extract Curcumae Longae Rhizoma Curcumae Longae Rhizoma 7 60%
111.4 (4X) extract 8 Polygalae Radix (1X) 60%
Polygalae Radix extract 97.2 9 Polygalae Radix (4X) 60%
Polygalae Radix extract 388.8 Acori Gramineri Rhizoma Acori Gramineri Rhizoma 60% 50.9 (1X) extract Acori Gramineri Rhizoma Acori Gramineri Rhizoma 11 60%
203.6 (4X) extract 12 KI0M-20120b(1) (1X) 60% KI0M-20120b(1) 106.2 13 KI0M-20120b(1) (4X) 60% KI0M-20120b(1 ) 424.8 14 KI0M-20120b(2) (1X) ' 60% KI0M-20120b(2) 106.2 KI0M-20120b(2) (4X) 60% KI0M-20120b(2) 424.8 16 KI0M-201206(3) (1X) 60% KI0M-201206(3) 146.4 17 KI0M-20120b(3) (4X) 60% KI0M-20120b(3) 584.4 3 Example 3-2: Evaluation of Body Weight 4 The body weight of the 17 different kinds of experimental mice bred in Example 3-1 was 5 measured and analyzed by comparison (FIG. 4). As illustrated in FIG. 4, experimental group 9 (Polygalae Radix (4X)) showed the highest decrease in body weight closest to that of the normal 7 control group, followed by experimental group 15 (KI0M-20120b(2) (4X)) and experimental 8 group 17 (KI0M-20120b(3) (4X)). The remaining experimental groups also showed a lower 22654729.1 CA Application Blakes Ref: 11886/00001 1 level compared to that of the negative control group, thus generally showing the effect of decrease of body 2 weight.

However, in the case of experimental group 9 (Polygalae Radix (4X)), four out of 10 mice in the 4 group died during the 6 week period, and one of them showed a significant deterioration in its health condition thus showing the damage caused by toxicity. In contrast, experimental group 15 (MOM-20120b(2) (4X)) and experimental group 17 (KI0M-20120b(3) (4X)) did not show any damage caused 7 by toxicity.

9 Example 3-3: Evaluation of the Amount of Dietary Intake The amount of dietary intake of the 17 different kinds of experimental mice bred in Example 3-1 11 was measured and analyzed by comparison (FIG. 5). As illustrated in FIG. 5, no significance was observed except experimental group 9 (Polygalae Radix (4X)), although there was a difference in the amount of 13 dietary intake among the experimental groups.

Example 3-4: Evaluation of the Amount of Fat Weight 16 The 17 different kinds of experimental mice bred in Example 3-1 were fasted for 5 hours to allow 17 them to digest all the foods intaken, sacrificed by cervial dislocation, and the abdominal fat and subcutaenous fat were collected from each mouse. The thus-obtained abdominal fat and subcutaenous fat 19 were washed with saline solution, placed on a filter paper to remove water therefrom, and the total weight of the fats was measured and analyzed by comparison (FIG. 6). As illustrated in FIG. 6, experimental 21 group 9 (Polygalae Radix (4X)) and experimental group 15 (KI0M-20120b(2) (4X)) showed a significant decrease in their fat weight compared to that of the negative control group.
Additionally, in experimental groups 12 (KI0M-20120b(1) (1X)), 14 (KI0M-20120b(2) (1X)) and 16 (KI0M-20120b(3) (1X)), 24 which were treated with the same level of the extract of the mixture, the fat weight increased in the order of experimental groups 14, 16 and 12, whereas in experimental groups 13 (KI0M-20120b(1) (4X)),

15(KI0M-20120b(2) (4X)) and 17(KI0M-20120b(3) (4X)), the fat weight increased in the order of 22654729.1 CA Application Blakes Ref: 11886/00001 1 experimental groups 15, 17, and 13. Accordingly, considering the contents of Saururi chinensis 2 Bail!., Curcumae Longae Rhizoma, Polygalae Radix and Acori Gramineri Rhizoma included in 3 each of the extract of the mixture, it was analyzed that the Polygalae Radix has the most 4 significant inhibitory effect against fat increase, followed by Curcumae Longae Rhizoma, whereas Acori Gramineri Rhizoma has the least inhibitory effect against fat increase.

7 Example 3-5: Pathological Analysis of Liver Tissues 8 Liver tissues were collected from the mice sacrificed in Example 3-4, fixed in fonnalin, 9 and then subjected to pathological analysis thereby analyzing the levels of microvescicular steatosis and chronic inflammation included in the liver tissues by comparison (HG. 7). As 11 illustrated in FIG. 7A, the microvescicular steatosis included in the liver tissues showed low values 12 both in experimental groups 8 and 9, which were treated with the Polygalae Radix extract, and 13 experimental groups 12 through 17, which were treated with the extract of the mixture, compared 14 to that of the negative control group, thus confirming the significant decrease of the level of the microvescicular steatosis included in the liver tissues.

16 Additionally, as illustrated in FIG. 7B, the level of the chronic inflammation in the liver

17 tissues was higher in all experimental groups than the negative control group, and in particular, the

18 highest in experimental groups 8 and 9, which were treated with the Polygalae Radix extract. In

19 contrast, the mice in experimental groups 12 through 17, which were treated with the extract of the mixture, showed a lower level of the chronic inflammation than the mice treated with the 21 Polygalae Radix extract.

23 Example 3-6: Pathological Analysis of Kidney Tissues 24 Kidney tissues were collected from the mice sacrificed in Example 3-4, fixed in formalin, and then subjected to pathological analysis thereby analyzing the levels of 26 microvescicular steatosis and chronic inflammation included in the kidney tissues by comparison 22654729.1 CA Application Blakes Ref: 11886/00001 1 (HG. 8). As illustrated in FIG. 8, the level of the chronic inflammation in the kidney tissues was higher in 2 all experimental groups than the negative control group and even higher than the normal control group, and 3 in particular, relatively higher in experimental group 9, which was treated with the Polygalae Radix extract.
4 In contrast, the mice in experimental groups 12 through 17, which were treated with the extract of the mixture, showed an equal or lower level of the chronic inflammation than the mice treated with the 6 Polygalae Radix extract.

8 Consequently, based on the results from Examples 3-2 through 3-6, the Polygalae Radix extract 9 and the extract of the mixture showed in vivo inhibitory effects against obesity. Unlike the Polygalae Radix extract, which showed excellent inhibitory effect agasint obesity but has serious toxicities, the extract of the 11 mixture showed improved safety along with the relatively superior inhibitory effects against obesity.

13 Example 4: Effects of the Extract of the mixture derived from Saururi chinensis 14 Curcumae Longae Rhizoma and Polygalae Radix From the result of Example 3-4, it was confirmed that Mori Gramineri Rhizoma, among the 16 components included in the extract of the mixture, has the least inhibitory effect agasint fat increase.
17 Accordingly, the present example was performed in order to confirm whether the extract of the mixture 18 obtained from a sample including only Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae 19 Radix, exclusive of Acori Gramineri Rhizoma, has an inhibitory effect against obesity.
21 Example 4-1: Obtaining Natural Extracts 22 Mixtures essentially including ground Saururi chinensis Bail., Curcumae Longae Rhizoma, and 23 Polygalae Radix, and selectively including Acori Gramineri Rhizoma and clover were obtained (Table 4).
24 The mixtures were subjected to extractions for 24 hours after adding 300 mL of 25% ethanol to each of the mixtures while maintaining the temperature at 38 C, and the respective extract of the mixture was obtained 26 therefrom. Each of the thus-obtained extracts was subjected to filtration to obtain a liquid component, and 22654729.1 CA Application Blakes Ref: 11886/00001 1 the liquid component was lyophilized to obain powdered extracts, which were then dissolved in 2 distilled water at a concentration of 100 mg/mL to be used later as samples for experiments.
3 Additionally, a green tea extract to be used in a comparative group was obtained in the 4 same manner.
6 [Table 41 Composition Ratio of Extract of the mixture Saururi Curcumae Acori Polygalae Extract chinensis LongaeGramineri Clover Radix Bail. Rhizoma Rhizoma 8g 8g 8g KS 8g 8g 8g 4g KC 8g 8g 8g 4g 8 Example 4-2: Obtaining Mice Bred Under Various Conditions 9 One hundred twenty six 5-week old male C57BU6N mice were purchased, adapted for a week, and bred while feeding them with 60% high fat diet (1-1FD) for 8 weeks. The thus-bred 11 mice were divided into 14 groups (9 mice/group) and bred for additional 6 weeks while feeding 12 them with different feeds containing different test substances (Table 5). In particular, the breeding 13 room was set at a normal temperature of 22 1 C with a humidity of 50 5%, and the light-dark 14 cycle was controlled at 12 hour intervals. Saline solution was used as an excipient.

22654729.1 CA Application Blakes Ref: 11886/00001 i [Table 5] Diet Conditions for Mice Test Substance Name Test Group High Fat Diet Rate Dose Kind (mg/kg) 21 normal control 10%
22 negative control 60%
23 positive control 1, PC1 60% green tea extract 200 24 positive control 1, PC2 60% L-carnitine 30 25 positive control 1, PC3 60% Xenicall 26 positive control 1, PC4 60% XenicaIlm 27 K150 60% K 150 28 K300 60% K 300 29 KS 150 60% KS 150 30 K5300 60% KS 300 31 KC 150 60% KC 150 32 KC 300 60% KC 300 33 KCL 60% KC + L-camitine 300 + 30 34 KSL 60% KS + L-camitine 300 + 30 3 Example 4-3: Evaluation of Body Weight 4 The body weight of the experimental mice of 14 different kinds bred in Example 4-2 was measured and analyzed by comparision (HG. 9). As illustrated in FIG. 9, the body weight of all the 6 experimental groups (experimental groups 27 through 34) was lower than that of the negative control 7 group, and experimental group 34 (KSL) showed the highest reduction in body weight to a level closest to 8 that of the normal control group, followed by experimental groups 28 (K
300), 30 (KS 300), 33 (KCL), 29 9 (KS 150), 27 (K 150), 31 (KC 150), and 32 (KC 300), in that order.
From the above results, it was confirmed that the extract of the mixture obtained from a sample 11 including Saururi chinensis Bail., Curcumae Longae Rhizoma, and Polygalae Radix can exhibit the 12 inhibitory effect against increase of body weight.

22654729.1 CA Application Blakes Ref: 11886/00001 1 Example 4-4: Evaluation of Dietary Intake 2 The amount of dietary intake of the experimental mice of 14 different kinds bred in 3 Example 4-2 was measured and analyzed by comparision (FIG. 10). As illustrated in FIG. 10, no 4 significance was observed although there was a difference in the amount of dietary intake among the experimental groups.

7 Example 4-5: Evaluation of Fat Weight 8 The 14 different kinds of the experimental mice bred in Example 4 were fasted for 5 9 hours to allow them to digest all the foods intaken, sacrificed by cervial dislocation, and the abdominal gonadal fat and mesenteric fat were collected from each mouse. The thus-obtained i abdominal gonadal fat and mesenteric fat were washed with saline solution, placed on a filter 12 paper to remove water therefmm, and each and the total weight of the fats was measured and 13 analyzed by comparison (FIGS. 11A through 11D).

As illustrated in FIG. 11A, the level of the abdominal gonadal fat in all the experimental 16 groups (experimental groups 27 through 34) was lower than that of the negative control group, 17 and experimental group 28 (K 300) showed the highest reduction in fat weight to a level closest to 18 that of the normal control group, followed by experimental groups 34 (KSL), 30 (KS 300), 19 (KCL), 27 (K 150), 32 (KC 300), 29 (KS 150) and 31 (KC 150), in that order.
As illustrated in FIG. 11B, the level of the mesenteric fat in all experimental groups (experimental groups 27 through 34) was lower than that of the negative control group, and 22 experimental group 30 (KS 300) showed the highest reduction in fat weight to a level closest to 23 that of the normal control group, followed by experimental groups 34 (KSL), 28 (K 300), 33 24 (KCL), 32 (KC 300), 29 (KS 150), 27 (K 150) and 31 (KC 150), in that order.
As illustrated in FIG. 11C, the level of the subcutaneous fat in all the experimental 26 groups (experimental groups 27 through 34) was lower than that of the negative control group, 22654729.1 CA Application Blakes Ref: 11886/00001 1 and experimental group 28 (K 300) showed the highest reduction in fat weight to a level closest to that of 2 the normal control group, followed by experimental groups 34 (KSL), 30 (KS 300), 33 (KCL), 29 (KS
3 150), 27 (K 150), 32 (KC 300) and 31 (KC 150), in that order.
4 As illustrated in HG. 11D, the level of the total fat in all the experimental groups (experimental groups 27 through 34) was lower than that of the negative control group, and experimental group 28 (K
6 300) showed the highest reduction in fat weight to a level closest to that of the normal control group, 7 followed by experimental groups 34 (KSL), 30 (KS 300), 33 (KCL), 27 (K
150), 29 (KS 150), 32 (KC
8 300), and 31 (KC 150), in that order.

Consequently, based on the above results (FIGS. 11A through 11D), it was confirmed that the 11 extract of the mixture obtained from a sample including Saururi chinensis Baill., Curcumae Longae 12 Rhizoma, and Polygalae Radix can exhibit the inhibitory effect against fat accumulation.

14 Example 4-6: Evaluation of Ghrelin Level The level of ghrelin, known as a hunger hormone secreted in the stomach, was evaluated in details 16 in terms of activated ghrelin, desacyl-ghrelin, and ghrelin ratio, using the experimental mice of 14 different 17 kinds bred in Example 4-2.

19 First, the level of the activated ghrelin present in the blood plasma was measured using a ghrelin measurement kit (Active Ghrelin EL1SA kit, SCETI, Japan). Roughly, the blood collected from the mice 21 of each experimental group was added into a tube containing EDTA and aptotinin and mixed. The mixture 22 was centrifuged to obtain blood plasma. The thus-obtained plasma was added with 1 mol/L HC1 in a 23 volume corresponding to 10% of the plasma volume to thereby prepare a sample. The thus-prepared 24 sample was added to the ghrelin measurement kit and reacted. The absorbance of the resultant was measured at 450 nm, and the level of the activated ghrelin was calculated based on the measured 26 absorbance value (FIG. 12A).

22654729.1 CA Application Blakes Ref: 11886/00001 1 As illustrated in FIG. 12A, regarding the level of activated ghrelin, experimental group 2 32 (KC 300) showed a higher level than the negative control group, and experimental groups 3 (K 150) and 34 (KSL) showed similar levels to that of the negative control group.
Experimental 4 groups 29 (KS 150), 28 (K 300), 33 (KCL), 30 (KS 300) and 31 (KC 150) showed a lower level than the negative control group, and experimental group 29 (KS 150) showed the lowest level.
6 Then, the level of desacyl-ghrelin present in blood plasma was measured in the same 7 manner as described above except that desacyl-ghrelin measurement kit (desacyl-Ghrelin ELISA
8 kit, SCETI, Japan) was used instead of the ghrelin measurement kit (Active Ghrelin ELISA
kit, 9 SCETI, Japan) (FIG. 12B).
As illustrated in FIG. 12B, regarding the level of desacyl-ghrelin, experimental group 32 11 (KC 300) showed a lower level than the negative control group, experimental groups 29 (KS 150) 12 and 34 (KSL) showed a similar level to that of the negative control group, and experimental 13 groups 27 (K
150), 28 (K 300), 33 (KCL), 30 (KS 300), and 31 (KC 150) showed higher levels 14 than the negative control group, wherein experimental group 33 (KCL) showed the highest level.
16 Finally, the ghrelin ratio was calculated as a percentage of the activated ghrelin relative to 17 the level of the measured desacyl-ghrelin (FIG. 12C).
18 As illustrated in FIG. 12C, experimental group 32 (KC 300) showed a higher level of the 19 ghrelin ratio than the negative control group, experimental group 27 (K 150) showed a similar level to that of the negative control group, and experimental groups 34 (KSL), 29 (KS 150), 28 (K
21 300), 33 (KCL), 30 (KS 300) and 31 (KC 150) showed lower levels of desacyl-ghrelin than the 22 negative control group, wherein experimental group 33 (KCL) showed the lowest level.

Consequently, based on the above results (FIGS. 12A through 12C), it was confirmed that the extract obtained from the mixture comprising Saururi chinensis Bail., Curcumae Longae 26 Rhizoma, and Polygalae Radix showed similar or lower levels of activated ghrelin, desacyl-22654729.1 CA Application Blakes Ref: 11886/00001 1 ghrelin, and ghrefin ratio than the negative control group, thus suggesting that the anti-obesity effect of the 2 extract of the mixture was apparently not due to the inhibition of appetite.

4 Example 4-7: Evaluation of Leptin The level of leptin in the blood plasma was evaluated using the experimental mice of 14 different 6 kinds bred in Example 4-2.
7 Specifically, the level of leptin present in the blood plasma was measured using a leptin 8 measurement kit (Mouse and Rat Leptin ELISA kit, mediagnost, Germany).
Roughly, the blood collected 9 from the mice of each experimental group was added into a tube containing EDTA and aptotinin, mixed, and centrifuged to thereby obtain blood plasma. The thus-obtained blood plasma was added with a dilution 11 buffer included in the leptin measurement kit, and the diluted solution was added to the leptin measurement 12 kit and reacted. The absorbance of the resultant was measured at 450 nm, and the level of leptin was 13 calculated based on the measured absorbance value (FIG. 13).

As illustrated in FIG. 13, regarding the level of leptin in the blood plasma, all the experimental 16 groups (experimental groups 27 through 34) showed lower levels than the negative control group, and 17 experimental group 28 (K 300) showed the highest reduction in leptin level to a level closest to that of the 18 normal control group, followed by experimental groups 33 (KCL), 34 (KSL), 30 (KS 300), 29 (KS 150), 19 27 (K 150), 32 (KC 300), and 31 (KC 150), in that order.
21 In fact, it is generally known that obesity-induced experimental animals show an increased leptin 22 resistance thereby elevating the leptin level in the blood. Experimental group 28 (K 300), which were 23 treated with the extract obtained from the mixture consisting of Saururi chinensis Baill., Curcumae Longae 24 Rhizoma, and Polygalae Radix, showed the lowest level of leptin, thus implying the lowest leptin resistance. Accordingly, it was confirmed that the extract of the mixture is effective in preventing obesity 26 from occurring.
22654729.1 CA Application Blakes Ref: 11886/00001 2 Example 4-8: Evaluation of Level of Blood Components 3 The levels of blood components including triglycerides, total cholesterol, LDL-4 cholesterol, HDL-cholesterol, glucose, creatinine, urea, LDH, ALP, GPT, GOT, etc., were evaluated according to the known method using the experimental mice of 14 different kinds bred 6 in Example 4-2 (FIGS. 14A through 14K).

8 As illustrated in FIG. 14A, regarding the level of triglycerides in the blood, only 9 experimental group 34 (KSL) showed a lower level than the negative control group, and the remaining experimental groups showed similar or higher levels than the negative control group, 11 wherein experimental group 32 (KC 300) showed the highest level.

13 As illustrated in FIG. 14B, regarding the level of total cholesterol in the blood, 14 experimental groups 27 (K 150) and 34 (KSL) showed lower levels than the negative control group, experimental groups 28 (K 300) and 30 (KS 300) showed similar levels to that of the 16 negative control group, experimental groups 29 (KS 150), 33 (KCL), 32 (KC 300) and 31 (KC
17 150) showed higher levels than the negative control group, and experimental group 33 (KCL) 18 showed the highest level.

As illustrated in FIG. 14C, regarding the level of LDL-cholesterol in the blood, 21 experimental groups 31 (KC 150), 32 (KC 300) and 33 (KCL) showed higher levels than the 22 negative control group, experimental groups 29 (KS 150) and 30 (KS 300) showed similar levels 23 to the negative control group, experimental groups 27 (K 150), 28 (K
300) and 34 (KSL), and 24 experimental group 34 (KSL) showed the lowest level.

22654729.1 CA Application Blakes Ref: 11886/00001 As illustrated in FIG. 14D, regarding the level of HDL-cholesterol in the blood, only experimental 2 group 28 (K 300) showed a lower level than the negative control group, and the remaining experimental groups showed similar or higher levels than the negative control group, and experimental group 31 (KC
4 150) showed the highest level.
6 As illustrated in FIG. 14E, regarding the level of glucose in the blood, experimental groups 28 (K
7 300) and 29 (KS 150) showed lower levels than the negative control group, experimental group 34 (KSL) showed a similar level to that of the negative control group, experimental groups 27 (K 150), 31 (KC 150), (KC 300), 33 (KCL) and 30 (KS 300) showed higher levels than the negative control group, and experimental group 32 (KC 300) showed the highest level.

12 As illustrated in FIG. 14F, regarding the level of creatinine in the blood, all the experimental groups (experimental groups 27 through 34) showed similar or higher levels than the negative control group. Specifically, experimental groups 29 (KS 150) and 31 (KC 150) showed higher levels than the negative control group, wherein experimental group 34 (KSL) showed the highest level.

17 As illustrated in FIG. 14G, regarding the level of urea in the blood, all the experimental groups (experimental groups 27 through 34) showed higher levels than the negative control group, and specifically, experimental group 33 (KCL) showed the highest improvement in urea level, followed by experimental groups 30 (KS 300), 34 (KSL), 27 (K 150), 31 (KC 150), 28 (K 300), 29 (KS 150) and 32 (KC 300), in that 21 order.

23 As illustrated in FIG. 14H, regarding the level of lactate dehydrogenase (LDH) in the blood, all the experimental groups (experimental groups 27 through 34) showed similar or higher levels than the negative control group. Specifically, experimental groups 30 (KS 300) and 34 (KSL) showed similar levels to that 22654729.1 CA Application Blakes Ref: 11886/00001 I of the negative control group, and the remaining experimental groups showed higher levels than 2 the negative control group, wherein experimental group 32 (KC 300) showed the highest level.

4 As illustrated in FIG. 141, regarding the level of alkaline phosphatase (ALP) in the blood, only experimental group 29 (KS 150) showed a higher level than the negative control group, and 6 the remaining experimental groups showed similar or higher levels than the negative control 7 group, wherein experimental group 31 (KC 150) showed the lowest level.

9 As illustrated in FIG. 14J, regarding the level of glutamic-pyruvic transaminase (GPI) in the blood, all the experimental groups (experimental groups 27 through 34) showed similar or 11 higher levels than the negative control group. Specifically, experimental groups 27 (K 150), 28 (K
12 300) and 30 (KS 300) showed higher levels than the negative control group, wherein experimental 13 group 31 (KC 150) the highest level.

As illustrated in FIG. 14K, regarding the level of glutamic-oxaloacetic transaminase 16 (GOT) in the blood, all the experimental groups (experimental groups 27 through 34) showed 17 similar or higher levels than the negative control group. Specifically, experimental groups 29 (KS
18 150) and 34 (KSL) showed similar levels to that of the negative control group, and the remaining 19 experimental groups showed higher levels than the negative control group, wherein experimental group 31 (KC 150) showed the highest level.

22 As illustrated in FIGS. 141 through 14K, the experimental groups treated with the extract 23 obtained from the mixture consisting of Saururi chinensis Baill., Curcumae Longae Rhizoma, and 24 Polygalae Radix provided in the present invention, in general failed to show significance regarding the ALP, GPT and GOT levels in the blood compared to the control group thus 26 implying that the extract of the mixture does not exhibit hepatotoxicity.

22654729.1 CA Application Blakes Ref: 11886/00001 2 Although the prefened embodiments of the present invention have been disclosed for illustrative 3 illustrative purposes, those skilled in the art will appreciate that various modifications, additions and 4 and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

22654729.1

Claims

WE CLAIM:

1. A pharmaceutical composition for the prevention or treatment of obesity comprising an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix; or a fraction thereof.

2. The pharmaceutical composition of claim 1, wherein the extract is an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix mixed at a ratio of 1 : 0.2 through 1 : 0.2 through 1 (w/w/w) therein.

3. A pharmaceutical composition for the prevention or treatment of obesity comprising an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma; or a fraction thereof.

4. The pharmaceutical composition of claim 3, wherein the extract is an extract of a mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma mixed at a ratio of 1 : 0.2 through 1 : 0.2 through 1 : 0.2 through 1 (w/w/w/w) therein.

5. The pharmaceutical composition of claim 1 or claim 3, wherein the extract is obtained by extracting the mixture with 25% ethanol.

6. The pharmaceutical composition of claim 1 or claim 3, wherein the fraction is obtained by applying the extract to a method selected from the group consisting of solvent fractionation, ultrafiltration fractionation, chromatography fractionation, and a combination thereof.

7. A food composition for the prevention or improvement of obesity comprising an extract of a mixture comprising a Saururi chinensis Baill., a Curcumae Longae Rhizoma, and a Polygalae Radix;
or a fraction thereof.

8. The food composition of claim 7, wherein the extract is an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix mixed at a ratio of 1 : 0.2 through 1 : 0.2 through 1 (w/w/w) therein.

9. A food composition for the prevention or improvement of obesity comprising an extract of a mixture comprising Sauntri chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma; or a fraction thereof.

10. The food composition of claim 9, wherein the extract is an extract of a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma mixed at a ratio of 1 : 0.2 through 1 : 0.2 through 1 : 0.2 through 1 (w/w/w/w) therein.

11. The food composition of claim 7 or claim 9, wherein the extract is obtained by extracting the mixture with 25% ethanol.

12. The food composition of claim 7 or claim 9, wherein the fraction is obtained by applying the extract to a method selected from the group consisting of solvent fractionation, ultrafiltration fractionation, chromatography fractionation, and a combination thereof.

13. A method of manufacturing an extract from a mixture comprising Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix, comprising extracting the mixture with water, a C1 -C4 alcohol, or a mixed solvent thereof.

14. The method of claim 13, wherein the mixture comprises Saururi chinensis Baill., Curcumae Longae Rhizoma, and Polygalae Radix at a ratio of 1 : 0.2 through 1 :
0.2 through 1 (w/w/w).

15. A method of manufacturing an extract from a mixture comprising Saururi chinensis Bail., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma, comprising extracting the mixture with water, a C1 - C4 alcohol or a mixed solvent thereof.

16. The method of claim 15, wherein the mixture comprises Saururi chinensis Baill., Curcumae Longae Rhizoma, Polygalae Radix, and Acori Gramineri Rhizoma at a ratio of 1 : 0.2 through 1 : 0.2 through 1 : 0.2 through 1 (w/w/w/w).