Hepatoprotective properties of Gentiana SPP: Against non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterised by the accumulation of fat in the liver. It is estimated that 33 % of the UK population have NAFLD with 2-5 % progressing to non-alcoholic steatohepatitis (NASH). Due to a lack of an outright therapy for NAFLD, treatment has been mainly focussed on managing the conditions associated with the disease such as obesity, diabetes mellitus and hyperlipidaemia.

This study aimed to investigate the means by which hepatocyte protection is conferred by Gentiana plants (Gentiana lutea, Gentiana macrophylla, Gentiana scabra and Gentiana rigescens) used in herbal medicine for the management of non-alcoholic fatty liver diseases (NAFLD). The role played by some of the inherent Gentiana phytochemicals including: gentiopicroside, sweroside and swertiamarin in promoting hepatocyte protection against the cytotoxic effects of fatty acids were also investigated. Gentiana species: lutea, macrophylla, rigescens, and scabra are known to protect and enhance hepatocyte viability via their antioxidant, anti-inflammatory and bitter components including: amarogentin gentianine, iso-orientin, swertiamarin, gentiopicroside, and sweroside. This study was necessitated due to a lack of adequate research on the hepatoprotective effects of the above-named Gentiana species and phytochemicals with special emphasis on their effect on mitochondrial respiration in the presence of fatty acids.

At the time of submission, this was the first study to utilise the seahorse mitochondria stress assay to investigate the Gentiana species as well as phytochemicals: gentiopicroside, sweroside and swertiamarin. It was also found that the most abundant phytochemical in all four Gentiana species was gentiopicroside (up to 4.6% g/g), followed by swertiamarin (0.21–0.45% g/g), and sweroside (0.03- 0.4 % g/g). Furthermore, it was also observed that the methanolic extracts of all four Gentiana protected HepG2 and THLE-2 cells by inhibiting arachidonic acid from diminishing cell replication but showed a mitogenic effect mostly observed in gentiopicroside, Gentiana lutea and Gentiana macrophylla.

It was concluded that phytochemicals: gentiopicroside, sweroside and swertiamarin play key roles in the hepatocyte protection exerted by methanolic extracts of Gentiana lutea, Gentiana macrophylla, Gentiana scabra and Gentiana rigescens against the cytotoxic effects of fatty acids. This protection is conferred by enhancing mitochondrial function in terms of increasing maximal respiratory capacity in response to high influx of fatty acids, promoting ATP production as well as scavenging ROS produced as a result of high fatty acid influx and increased mitochondrial respiration. However, the mitogenic effect observed in gentiopicroside and Gentiana macrophylla requires further studies using unmodified primary hepatocytes to gain better understanding.