Coumestrol as a new substance that may diminish lipid precursors of the inflammation in steatotic primary rat hepatocytes

Coumestrol is a phytoestrogen found in various plant foods. Increasing evidence ascertained its robust anti-inflammatory, anti-oxidative properties likewise ability to mitigate insulin resistance. Thus, it may be a potential medicine in the treatment of many metabolic disorders, including obesity, type 2 diabetes (T2D) as well as non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to shed some light on its influence on the accumulation of certain lipid fractions and the expression of pro-inflammatory proteins in primary rat hepatocytes during the lipid-overload state. The cells were isolated from the male Wistar rat's liver with the use of collagenase perfusion. It was followed by incubation of the cells with the presence or absence of palmitic acid and/or coumestrol. The accumulation of lipid fractions was assessed by gas-liquid chromatography (GLC) whereas the expression of the proteins was evaluated by the Western blot technique. Treatment with coumestrol in the state of increased fatty acids availability led to the deposition of triacylglycerols rather than diacylglycerols, significantly decreased expression of proinflammatory and profibrotic cytokines, especially interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), as well as transforming growth factor β (TGF-β), and nuclear factor κβ (NF-κβ). Also, we observed a substantial diminution in proinflammatory enzymes expression. Taking into consideration the direction of the aforementioned changes, we may assume that coumestrol can ameliorate the array of factors leading to the development of steatosis, likewise counteracting progression to steatohepatitis, thus it may be a step forward to the long-awaited breakthrough in the treatment of NAFLD.