Multilevel molecular analysis of the hepatoprotective effect of medicinal herbs extracts in prevention of liver dysfunction caused by aflatoxin B1 in pig as an animal model (in-vivo), and hepatocyte cell culture analysis in human and pig (invitro)

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The project aims to investigate the hepatoprotective effect of medical herbs on hepatotoxic effects of aflatoxin B1 (AFB1) in vivo in piglets and in comparison in human hepatocyte cultures in vitro. For precise and comprehensive elucidation, a multilevel molecular analysis is performed at the levels of the transcriptome, proteome and metabolome. The motivation for the project arose from recurrent accidental contamination of feed and food with aflatoxin, especially AFB1. We hypothesised that hepatoprotective medical herbs [Andrographis paniculata AP, Silybum Marianum SM, Curcuma Longa CL], which have a beneficial effect on liver cells, could also attenuate the adverse effects of a diet contaminated with AFB1. A hepatotoxic dose of AFB1, specified in a pilot project with subclinical symptoms is fed in combination with extracts of the medical herbs (WP1). The hepatotoxic effect of aflatoxin B1 (AFB1) and the hepatoprotective effect of medical herb extracts on liver function are characterized by histological and (laboratory) clinical investigations (WP1) as well as analysis of the proteome (WP2), the mitochondrial functional and structural variation (WP3), the miRNA- (WP4) and mRNA- (WP6, WP7) expression and the metabolome (WP8) in vivo. In vitro experiments with human (THLE2) and porcine (JSNK-1) cells underpin the excursion of various molecular pathways and the specific functional role of key genes by expression analysis and siRNA experiments (WP8). The detection of detailed changes at the molecular level and interpretation of the data is ensured by a comprehensive bioinformatics integration and analysis of all data (WP9). A wide range of modern molecular methods provides insights into the fundamental changes in biological and metabolic processes in response to aflatoxins and in combination with the potential hepatoprotective effects of medical herbs offered as health-promoting dietary supplements. The study provides results relevant to the design of diets for pigs and whether the effects of accidental aflatoxin contamination can be prevented. Furthermore, by comparing the reaction of human and porcine cells, the study allows statements to be made about the potential of using medical herbs in the sense of a healthy diet.