Health Promoting Bioactive Compounds in Plants: Identification of Bioactive Metabolites Modulating Glucose Uptake and Fat Accumulation

Type 2 diabetes is a heavy economic burden for the health care system as it is one of the major causes of death due to cardiovascular disease and other associated metabolic disorders it causes. Progressive development of IR leads to hyperglycemia and body tissue like muscle, adipose tissue, and liver fail to uptake and utilize glucose from the blood circulation. Different treatments are used for T2D, which include oral drugs which exert their hypoglycemic effect through different mechanisms. Because the antidiabetic medication sometimes involves prescribing more than one drug at the same time which includes a variety of side effects, efforts are being made to find suitable antidiabetic therapies. Ethnopharmacological surveys indicate that more than 1200 plants are used in traditional medical systems for their potential hypoglycemic activity. As the use of natural products for biological and medicinal investigation is getting more attention, many methods have been developed to scientifically validate the bioactivity of the plants and their bioactive metabolites. All steps in investigating plants of interest are important, such as correct identification, preparation, storage, and choice of extraction method and solvent. Different in vitro and in vivo bioassays are developed to investigate the bioactivities of interest. In vitro bioassays are generally faster and use relatively small amounts of materials than in vivo assays, and therefore they are favoured. In relation to diabetes research different procedures are recommended. This PhD thesis is based on three papers and revolves around identification of secondary metabolites from plant extracts with influence on glucose uptake and the activation of the nuclear receptor PPARγ. In the experimental part related to this thesis, which is discussed in PAPER I – III, mainly glucose uptake and PPARγ transactivation assays are used. The work presented in PAPER I provides a broad screening of different plant extract using a platform of bioassays related to glucose uptake and fat accumulation. Inspired by the results obtained in PAPER I, PAPER II and III focus on two promising extracts from the screening. In PAPER II the dichloromethane extract of carrot is investigated for the bioactive metabolites responsible for the observed activities, while in PAPER III the dichloromethane extract of Echinacea purpurea was set in focus.