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( 12 ) United States Patent US010183048B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 183, 048 B2 Cho et al . (45 ) Date of Patent : Jan . 22 , 2019 ( 54 ) COMPOSITION FOR PROMOTING THE FOREIGN PATENT DOCUMENTS ACTIVITY OF PEROXISOME PROLIFERATOR -ACTIVATED CN 1544018 A 11 / 2004 JP 2006016312 A * 1 / 2006 RECEPTOR - DELTA KR 1993 -0008763 B1 9 / 1993 KR 2001110003 A * 12 / 2001 (75 ) Inventors : Si Young Cho , Seoul (KR ) ; Pil Joon KR 2004065427 A * 7 / 2004 Park , Yongin - si (KR ) ; Ji Hae Lee , KR 10 - 2005 - 0121775 A 12 / 2005 Yongin - si (KR ) ; Dae Bang Seo , KR 10 - 0645385 B1 11 /2006 KR 10 - 0659138 B1 12 / 2006 Yongin -si (KR ) ; Sang Jun Lee , KR 10 - 2007 - 0042405 A 4 / 2007 Seongnam - si (KR ) KR 10 - 2007 -0091964 A 9 / 2007 KR 10 - 2008 - 0050348 A 6 / 2008 (73 ) Assignee : AMOREPACIFIC CORPORATION , KR 10 - 2008 - 0054682 A 6 / 2008 Seoul (KR ) KR 10 - 2008 - 0065234 A 7 / 2008 ( * ) Notice : Subject to any disclaimer , the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U . S . C . 154 ( b ) by 653 days . Wang et al. , Bioactives of Artemisia dracunculus L enhance cellular insulin signaling in primary human skeletal muscle culture , 2008 , (21 ) Appl . No. : 13/ 511 , 964 Metabolism Clinical and Experimental, 57 : S58 - 564 . * 2016 https : // examine .com /supplements / artemisia - iwayomogi / ( 22 ) PCT Filed : Nov. 25, 2010 # ref8 . * U . J . Jung et al. , “ The Anti - Diabetic Effects of Ethanol Extract from ( 86 ) PCT No .: PCT/ KR2010 / 008404 Two Variants of Artemisia Princeps Pampanini in C57BL / KSJ -db /db Mice, " Food and Chemical Toxicology , vol. 45 , pp . 2022 - 2029 , $ 371 ( c ) ( 1 ), 2007 . ( 2 ) , ( 4 ) Date : May 24 , 2012 S . Lim et al. , " Effect of Artemisia princeps Var orientalis and Circium japonicum Var ussuriense on Serum Lipid of Hyperlipidemic ( 87 ) PCT Pub . No. : W02011/ 065767 Rat, ” The Korean Nutrition Society , vol. 30 ( 1 ), pp . 12 - 18 , 1997 . PCT Pub . Date : Jun . 3 , 2011 V . A . Narkar et al. , “ AMPK and PPARS Agonists are Exercise Mimetics, ” Cell , vol. 134 , pp . 1 - 11 , Aug . 8 , 2008 . (65 ) Prior Publication Data Y . Wang et al ., “ Peroxisome- Proliferator- Activated Receptor 8 Activates Fat Metabolism to Prevent Obesity ,” Cell, vol. 113, pp . US 2013 /0045289 A1 Feb . 21, 2013 159 - 170 , Apr. 18 , 2003 . G . D . Barish , et al. , “ PPARS : A Dagger in the Heart of the Metabolic ( 30 ) Foreign Application Priority Data Syndrome, " The Journal of Clinical Investigation , vol. 116 , No. 3 , pp . 590 - 597 , Mar . 2006 . Nov. 26 , 2009 (KR ) .. 10 -2009 -0115024 * cited by examiner (51 ) Int. Cl. A61K 36 / 282 ( 2006 . 01 ) Primary Examiner — Terry A McKelvey A23L 33 / 105 ( 2016 .01 ) Assistant Examiner — Catheryne Chen ( 52 ) U .S . CI. ( 74) Attorney , Agent, or Firm — Blank Rome LLP CPC . .. A61K 36 /282 ( 2013 .01 ) ; A23L 33 / 105 ( 2016 . 08 ) ; A23V 2002 /00 (2013 . 01 ) (57 ) ABSTRACT ( 58 ) Field of Classification Search Disclosed is a composition for promoting the activity of None peroxisome proliferator - activated receptor - 8 (PPAR - 8 ) , See application file for complete search history . which contains Artemisia vulgaris extracts or Artemisia capillaris extracts as active ingredients . The composition is ( 56 ) References Cited effective in strengthening muscles , improving endurance and memory , and preventing and alleviating the symptoms U . S . PATENT DOCUMENTS of dementia or Parkinson ' s disease . 8 , 741 ,364 B2 * 6 / 2014 Ninomiya .. A61K 31/ 205 424 / 725 3 Claims, 4 Drawing Sheets U . S . Patent Jan . 22, 2019 Sheet 1 of 4 US 10 , 183 ,048 B2 Fig . 1 EC50 : 7ppm EmissionRatio(520:495) 0 .0 0. 2 0. 4 0. 6 0. 8 1. 0 1. 2 11 . 4 16 18 Artemisia iwayomogi extract ( ug /ml ) U . S . Patent Jan . 22, 2019 Sheet 2 of 4 US 10 , 183 ,048 B2 Fig . 2 600000 500000 400000 RUL 300000 200000 F000001 to Control GW5015161uM Artemisiaiwayomogi Artemisiaextract 50iwayomogiug / ml extract Artemisia 100ugiwayomogi /ml extract 200ug /ml U . S . Patent Jan . 22, 2019 Sheet 3 of 4 US 10 , 183 ,048 B2 Fig . 3 Control N Artemisia iwayomogi Relativeexpression II CPT1 PDK4 U . S . Patent Jan . 22 , 2019 Sheet 4 of 4 US 10 , 183 , 048 B2 Fig . 4 productionRelative3H20 Control Artemisia iwayomogi US 10 , 183 ,048 B2 COMPOSITION FOR PROMOTING THE memory . The composition may be variously used in the field ACTIVITY OF PEROXISOME of food , health - food supplements or pharmaceuticals . PROLIFERATOR - ACTIVATED RECEPTOR - DELTA DESCRIPTION OF DRAWINGS TECHNICAL FIELD FIG . 1 shows fluorescence data showing PPAR - 8 - LBD binding affinity of Artemisia iwayomogi extract in a test The present disclosure relates to a composition including tube ; Artemisia extract as an active ingredient. FIG . 2 shows expression level of the reporter gene 10 luciferase as a result of PPAR - S activation by Artemisia BACKGROUND ART iwayomogi extract ; FIG . 3 shows expression level of the target genes of Peroxisome proliferator- activated receptors (PPARs ) are PPAR - O , CPT1B and PDK4, in muscle cells treated with 200 ligand -activated transcription factors belonging to the ug /mL Artemisia iwayomogi extract; and nuclear receptor superfamily activated by fatty acids. The 15 FIG . 4 shows fatty acid oxidation in muscle cells pro PPAR family consists of PPAR - Q , PPAR - B / 8 and PPAR - Y , moted as a result of treating with 200 ug /mL Artemisia which show different ligand specificity and tissue distribu iwayomogi extract. tion . PPAR - a is expressed the most in the liver and promotes fatty acid oxidation in peroxisomes and mitochondria . 20 BEST MODE PPAR - y is expressed in adipose tissues and regulates storage A composition according to an exemplary embodiment of of fats. The ligand of PPAR - a , fibrate , is used as hypolipi- the present disclosure comprises Artemisia extract as an demic agent, and the ligand of PPAR - y , thiazolidinedione , is active ingredient. The composition comprising . Artemisia used in the treatment of diabetes mellitus type 2 . extract promotes the activity of peroxisome proliferator PPAR - 8 is expressed in muscles , brown adipose tissues , 25 activated receptor delta ( PPAR - 8 ) and is effective in pro etc . This transcription factor shows anti- obesity effect since moting muscular metabolism and / or improving memory . fatty acid oxidation in adipocytes is promoted in mice in In the present disclosure, Artemisia ( ssuk , Artemisia prin which it is overexpressed (Wang Y X et al . , Cell, 113 , pp . ceps ) collectively refers to dicotyledonous perennial grasses 159 - 170 , 2003 ) . An activator of PPAR - S promotes metabo - belonging to the family Asteraceae of the order Asterales . lism in skeleton muscle cells , improves insulin sensitivity , 30 Artemisia grows naturally in the whole area of Korea and reduces adipocytes and inhibits inflammatory response by has been widely used for food as vegetable , soup , porridge , increasing expression of such proteins as carnitine palmi cake , etc . toyltransferase 1B (CPT1B ) and pyruvate dehydrogenase In an exemplary embodiment, the Artemisia extract may kinase isozyme 4 ( PDK4 ) ( Barish G D et al ., J . Clin . Invest. , be Artemisia iwayomogi extract . Artemisia iwayomogi is a 116 . pp . 590 -597 , 2006 . 116 : 590 ) . When the ligand of 35 perennial grass belonging to the genus Artemisia of family PPAR - , GW501516 , was administered together with the Asteraceae . It is also called saengdang ssuk , aedang ssuk , AMP - activated protein kinase ( AMPK ) activator AICAR to sacheol ssuk , injincho , heat reliever , heuinsan ssuk or teol a mouse , the mouse showed strengthened muscles even san ssuk . In particular , the young leaves are called injin or without exercise as well as anti -obesity effect (Vihang AN heat reliever and traditionally have been used as food or folk et al ., Cell, 134 , pp . 1 - 11 , 2008 ). 40 medicine owing to peculiar fragrance and medicinal effect . However , activator or ligand of PPAR - S with proven Injin , the young bud of sacheol ssuk which is a perennial stability has not been found yet. The inventors of the present grass belonging to the family Asteraceae , has been known disclosure have found out that Artemisia iwayomogi extract from old times to be beneficial for the liver . Especially , it is contains a novel ligand capable of activating PPAR - d . known to be highly effective in jaundice. Injin promotes 45 secretion of bile and clears the liver by excreting lumps , DISCLOSURE cholic acid and bilirubin in the bile . Also , it reduces blood pressure , relieves fever, and kills various germs including Technical Problem tubercle bacillus . In addition , it is effective in degrading lipids, dilating coronary arteries and promoting urination . An embodiment of the present disclosure is directed to 50 In an exemplary embodiment, the composition has the providing a composition including Artemisia extract . effect of regulating the expression of enzymes that promote Another embodiment of the present disclosure is directed fat and sugar metabolism in muscle cells . Specifically , the to providing food , health - food supplement and pharmaceu composition which comprises Artemisia princeps or Artemi tical compositions that include the composition including sia iwayomogi extract as an active ingredient is effective in 55 promoting the expression of proteins that promote fat and Artemisia extract. sugar metabolism in muscles , as ligand activating PPAR - d . Technical Solution In an exemplary embodiment, the composition may be a composition for strengthening muscles and
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