Liver drug’s mechanism finally revealed

Magnesium isoglycyrrhizinate (a compound derived from licorice root, approved as a liver treatment in China) has long demonstrated therapeutic effects without a well-characterised mechanism. The researchers, publishing in eLife, identified HSD11B1 as the direct molecular target of the compound.

HSD11B1 is a liver enzyme involved in regulating stress hormones such as cortisol. The researchers found that the compound binds directly to this enzyme at a specific site in its structure. They confirmed this using RNA sequencing (a technique that reveals which genes are active in a cell), molecular docking, and direct binding assays.

Downstream effects: less fat accumulation and inflammation

By binding to HSD11B1, the compound influences a signalling chain that reduces fat accumulation in liver cells, decreases inflammation, and lowers rates of cell death. In mice given chronic alcohol exposure, treatment with magnesium isoglycyrrhizinate visibly reduced liver damage: tissue architecture improved, liver-to-body weight ratios normalised, and inflammation markers declined.

A gene called IDI1 emerged as a key downstream link between enzyme inhibition and the protective effects on liver cells.

Relevance to aging

Alcohol-associated liver disease is not a classic longevity topic, but the connection exists. Liver dysfunction increases markedly with age and is associated with systemic inflammation and accelerated biological aging. HSD11B1 is also involved in cortisol regulation, and dysregulation of cortisol in older adults has been linked to metabolic disorders and cognitive decline.

The study identifies a new therapeutic target for liver disease. Whether it is also relevant to age-related liver dysfunction outside of alcohol use is a question that further research will need to address.

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