BackgroundRhaponticum cathamoides (RC) is an endemic wild Siberian herb with marked medicinal properties that are still poorly understood. The aim of this study is to investigate the therapeutic potential of RC extract (ERC) compared to the effects of Glycyrrhiza glabra (EGG) and Punica granatum extracts (EPG) in a rat model with high-fat diet-(HFD)-induced signs of metabolic syndrome; therefore, this study addresses a significant global public health problem.MethodsSix-month-old male Wistar Albino Glaxo rats were subjected to eight weeks of a standard diet (SD), HFD, or HFD in which ERC, EGG, or EPG powders were incorporated at 300 mg/kg/day. The serum lipid profile, corticosterone and cytokine concentrations, glucose tolerance, systolic blood pressure, triacylglycerol accumulation, and PPARα DNA-binding activities in the liver samples were determined.ResultsIn contrast to EGG and EPG, an ERC supplement significantly reduced the weight of epididymal tissue (19.0%, p < 0.01) and basal serum glucose level (19.4%, p < 0.05). ERC improved glucose intolerance as well as dyslipidemia more efficiently than EGG and EPG. EGG but not ERC or EPG supplementation decreased systolic blood pressure by 12.0% (p < 0.05). All of the tested extracts reduced serum IL6 and corticosterone levels induced by HFD. However, the lowering effects of ERC consumption on the serum TNF-α level and its restoring effect on the adrenal corticosterone level significantly exceeded the improvements induced by EGG and EPG. ERC intake also reduced triacylglycerol accumulation and increased the PPARα DNA-binding activity in the liver more significantly than EGG and EPG.ConclusionsERC powder supplementation improved glucose and lipid metabolism more significantly than EGG and EPG in rats fed on HFD, supporting the strategy of R. carthamoides use for safe relief of metabolic syndrome and its related disturbances such as inflammation, stress, and hepatic steatosis.