Fenugreek Extract Rich in 4-Hydroxyisoleucine and Trigonelline Activates PPARα and Inhibits LDL Oxidation: Key Mechanisms in Controlling the Metabolic Syndrome

Abstract

Fenugreek ( Trigonella foenum-graecum L.) has properties which are hypolipidemic, hypocholesterolemic, hypoglycemic, insulinotropic, and antioxidant. These properties are related to the control of the Metabolic Syndrome, a disorder of carbohydrate and lipid metabolism which increases the risk of diabetes and cardiovascular disease. The purpose of this study was to evaluate the effect of fenugreek extract (Hydroxylean®, Naturex) containing 25% of 4-hydroxyisoleucine (4-OH-Ile, isomer 2 S,3 R,4 S) and 15.7% of trigonelline on peroxisome proliferator-activated receptor alpha (PPARα) transcriptional activity and Cu2+-induced low-density lipoprotein (LDL) oxidation in vitro. The activation of PPARα is linked to controlling lipidemia, cholesterolemia and glycemia, all associated with diabetes and cardiovascular disease. Also, the inhibition of LDL oxidation reduces the risk of stroke. 1,000 μg/mL of fenugreek extract showed a 31.2% activation of PPARα as compared with the positive control, 100 μM of fenofibrate. Fenugreek extract also inhibited LDL oxidation induced by Cu2+ at concentrations higher than 5 μg/mL (P<0.01). To our knowledge, this is the first report on PPARα transcriptional activity and Cu2+-induced LDL oxidation in vitro for fenugreek extract rich in 4-OH-Ile and trigonelline. The findings support the current evidence on fenugreek's capacity to control the Metabolic Syndrome.