PPARα Activation by Culinary Herbs and Spices

Abstract

Hyper- and dyslipidemia are risk factors for cardiovascular disease, the primary cause of death in industrialized countries. Peroxisome proliferators-activated receptor (PPAR)α activation is involved in various mechanisms that improve the lipid profile. We tested various plant extracts and their compounds to determine whether they stimulated PPARα activity in vitro. Out of 34 tested plant extracts, nine exhibited low to moderate PPARα transactivation, including caraway, chili pepper, nutmeg, licorice, black and white pepper, paprika, coriander, saffron, and stevia tea. The active components of black pepper and chili pepper, piperine, and capsaicin exerted the highest transactivational activities with EC₅₀ values of 84 µM and 49 µM, respectively. The chalcones, including 2-hydroxychalcone, 2′-hydroxychalcone, 4-hydroxychalcone, and 4-methoxychalcone, moderately transactivated PPARα. Resveratrol and apigenin only slightly transactivated PPARα. These results suggest that a diet rich in fruit, herbs, and spices provides a number of PPARα agonists that might contribute to an improved lipid profile.

Key words

PPARα - plants - spices - hyperlipidemia - dyslipidemia - chalcones

References

• 1 Alberti G, Zimmet P, Shaw J, Grundy S M. The IDF consensus worldwide definition of the metabolic syndrome. Available at. http://www.idf.org/home/index.cfm?node=14292006 Accessed April 02, 2009
• 2 Grundy S M. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds.  J Am Coll Cardiol. 2006;  47 1093-1100
• 3 Staels B, Fruchart J C. Therapeutic roles of peroxisome proliferator-activated receptor agonists.  Diabetes. 2005;  54 2460-2470
• 4 Zandbergen F, Plutzky J. PPARα in atherosclerosis and inflammation.  Biochim Biophys Acta. 2007;  1771 972-982
• 5 Forman B M, Chen J, Evans R M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.  Proc Natl Acad Sci USA. 1997;  94 4312-4317
• 6 Tsi D, Das N P, Tan B K H. Effects of aqueous celery (Apium graveolens) extract on lipid parameters of rats fed a high fat diet.  Planta Med. 1995;  61 18-21
• 7 Salgado J M, Curte F, Mansi D N. Effect of gala apples (Malus domestica Borkh) on lipidemia of hyperlipidemic rats.  Ciencia e Tecnologia de Alimentos. 2008;  28 477-484
• 8 Srinivasan K, Sambaiah K, Chandrasekhara N. Spices as beneficial hypolipidemic food adjuncts: a review.  Food Rev Int. 2004;  20 187-220
• 9 Ramadan M F, Amer M M A, Awad A E S. Coriander (Coriandrum sativum L.) seed oil improves plasma lipid profile in rats fed a diet containing cholesterol.  Eur Food Res Technol. 2008;  227 1173-1182
• 10 Lemhadri A, Hajji L, Michel J B, Eddouks M. Cholesterol and triglycerides lowering activities of caraway fruits in normal and streptozotocin diabetic rats.  J Ethnopharmacol. 2006;  106 321-326
• 11 Vijayakumar R S, Surya D, Senthilkumar R, Nalini N. Hypolipidemic effect of black pepper (Piper nigrum Linn.) in rats fed high fat diet.  J Clin Biochem Nutr. 2002;  32 31-42
• 12 Roghani M, Baluchnejadmojarad T, Sohrabi Z, Sadeghi M. Anti-hyperlycemic and hypolipidemic effect of oral administration of Capsicum frutescens in male STZ-diabetic rats.  J Med Plants. 2004;  3 23-30
• 13 Lee K. Transactivation of peroxisome proliferator-activated receptor alpha by green tea extracts.  J Vet Sci. 2004;  5 325-330
• 14 Li Y, Qi Y, Huang T H W, Yamahara J, Roufogalis B D. Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/gamma activator properties.  Diabetes Obes Metab. 2008;  10 10-17
• 15 Jungbauer A, Graumann K. The logistic dose-response function: a robust fitting function for transition phenomena in life sciences.  J Clin Ligand Assay. 2001;  24 270-274
• 16 Tenenbaum A, Fisman E Z, Motro M, Adler Y. Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins.  Cardiovasc Diabetol. 2006;  5 20
• 17 Dhanapakiam P, Joseph J M, Ramaswamy V K, Moorthi M, Kumar A S. The cholesterol lowering property of coriander seeds (Coriandrum sativum): mechanism of action.  J Environ Biol. 2008;  29 53-56
• 18 Arun Sam Lal A, Kumar T, Balakrishna Murthy P, Sadasivan Pillai K. Hypolipidemic effect of Coriandrum sativum L. in triton-induced hyperlipidemic rats.  Indian J Exp Biol. 2004;  42 909-912
• 19 Han K L, Choi J S, Lee J Y, Song J, Joe M K, Jung M H, Hwang J K. Therapeutic potential of PPAR-alpha/gamma dual agonist with alleviation of ER stress for the treatment of diabetes mellitus.  Diabetes. 2007;  57 737-745
• 20 Rau O, Wurglics M, Dingermann T, Abdel-Tawab M, Schubert-Zsilavecz M. Screening of herbal extracts for activation of the human peroxisome proliferator-activated receptor.  Pharmazie. 2006;  61 952-956
• 21 Ehala S, Vaher M, Kaljurand M. Characterization of phenolic profiles of Northern European berries by capillary electrophoresis and determination of their antioxidant activity.  J Agric Food Chem. 2005;  53 6484-6490
• 22 Proestos C, Chorianopoulos N, Nychas G J E, Komaitis M. RP-HPLC analysis of the phenolic compounds of plant extracts. Investigation of their antioxidant capacity and antimicrobial activity.  J Agric Food Chem. 2005;  53 1190-1195
• 23 Gupta P, Yadav D K, Siripurapu K B, Palit G, Maurya R. Constituents of Ocimum sanctum with antistress activity.  J Nat Prod. 2007;  70 1410-1416
• 24 Justesen U, Knuthsen P. Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes.  Food Chem. 2001;  73 245-250
• 25 Seguin P, Zheng W. Phytoestrogen content of alfalfa cultivars grown in eastern Canada.  J Sci Food Agric. 2006;  86 765-771
• 26 Winkel-Shirley B. Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology.  Plant Physiol. 2001;  126 485-493
• 27 Heber D. Vegetables, fruits and phytoestrogens in the prevention of diseases.  J Postgrad Med. 2004;  50 145-149
• 28 Jarvill-Taylor K J, Anderson R A, Graves D J. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes.  J Am Coll Nutr. 2001;  20 327-336
• 29 Kahle K, Huemmer W, Kempf M, Scheppach W, Erk T, Richling E. Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption.  J Agric Food Chem. 2007;  55 10605-10614
• 30 Harnly J M, Doherty R F, Beecher G R, Holden J M, Haytowitz D B, Bhagwat S, Gebhardt S. Flavonoid content of U.S. fruits, vegetables, and nuts.  J Agric Food Chem. 2006;  54 9966-9977
• 31 Honda K, Kamisoyama H, Tominaga Y, Yokota S, Hasegawa S. The molecular mechanism underlying the reduction in abdominal fat accumulation by licorice flavonoid oil in high fat diet-induced obese rats.  Anim Sci J. 2009;  80 562-569
• 32 Kang J H, Goto T, Han I S, Kawada T, Kim Y M, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet.  Obesity. 2010;  18 780-787
• 33 Rimando A M, Nagmani R, Feller D R, Yokoyama W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters.  J Agric Food Chem. 2005;  53 3403-3407