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PPARγ agonists identified in extracts of elderflowers (Sambucus nigra) by bioassay-guided fractionation
Thiazolidinediones (TZDs) are insulin sensitizing drugs often prescribed in the treatment of Type 2 Diabetes. The TZDs function by binding to and activating the peroxisome proliferator-activated receptor-gamma (PPARγ), a key regulator of adipogenesis. Severe side effects of the TZDs may occur, as they are full PPARγ agonists. Partial PPARγ agonists are associated with fewer side effects but may still maintain the effect on insulin resistance. Recently, a screening for potential partial PPARγ agonists was carried out on a number of plant extracts. This resulted in a 60% hit rate among the tested plant species and one of the most promising ones was elderflowers (Sambucus nigra) . Black elder has traditionally been used for the treatment of diabetes but only limited evidence on the antihyperglycaemic effects exists. Based on the general screening a bioassay-guided fractionation of an extract of elderflowers was carried out. The fractionations were done by reverse phase flash column chromatography and semi-preparative HPLC for isolation of active constituents. Bioactivity of fractions and purified compounds were assessed using a PPARγ transactivation assay. Mouse embryonic fibroblasts were used for the assay and each sample was tested in triplicate in three different concentrations. Activation of PPARγ for each sample was compared to both vehicle (DMSO) and positive control (Rosiglitazone). Three active compounds being able to activate PPARγ were isolated and identified as linoleic acid, linolenic acid, and naringenin. Major phenolics in elderflowers such as 5-O-caffeoylquinic acid, quercetin-3-O-rutinoside, and kaempferol-3-O-rutinoside did not activate PPARγ. The active constituents of elderflowers have previously been identified as PPARγ agonists but this is the first time that their effect is documented in plant extracts .
References: 1. Christensen, K.B. et al. 2008, unpublished.
2. Huang, T.H. et al. (2005) Basic Clin. Pharmacol. Toxicol. 96:3–14.