Anti‐hyperlipidemic actions of synthetic nordihydroguaiaretic acid analogs (767.1)

Abstract

Previous studies have shown that creosote bush‐derived NDGA exerts beneficial actions on the key components of the Metabolic Syndrome including dyslipidemia, and insulin resistance (IR) in several relevant rodent models. Here we screened several synthetic analogs of NDGA with selective modification of the aromatic groups of NDGA and tested their efficacy against hepatic lipid metabolism in a high‐fructose fed (HFrD) Sprague‐Dawley (SD) rat model of insulin resistance, dyslipidemia and hypertension. Oral gavaging of HFrD‐fed SD rats for 4 days with NDGA analogs 1 and 2 (100 mg/kg, q.d.) suppressed the hepatic TG content, whereas treatment of rats with NDGA analogs 2, 3 and 4, like NDGA, decreased the plasma TG levels by 70‐75%. QRT‐PCR measurements demonstrated that among the NDGA analogs 1, 2 and 4, analog 4 was most effective in inhibiting the mRNA levels of genes and transcription factors involved in lipogenesis, while all three analogs almost equally inhibited the genes involved in TG synthesis. Unlike NDGA, none of these three NDGA analogs affected the genes of hepatic fatty acid oxidation or transport. Our data suggest that these NDGA analogs possess more potent anti‐hyperlipidemic properties than NDGA and have therapeutic potential to ameliorate dyslipidemia and associated IR.Grant Funding Source: Supported by Office of Research and Development, Medical Service, Dpt. of Veterans Affairs