# Azorella compacta Organic Extracts Exacerbate Metabolic Dysfunction-Associated Fatty Liver Disease in Mice Fed a High-Fat Diet

## TL;DR

A plant used in traditional medicine worsened liver disease in mice on a high-fat diet, suggesting potential risks for people with fatty liver disease.

## Contribution

This study is the first to investigate the effects of Azorella compacta extracts on fatty liver disease in a mouse model.

## Key findings

- A. compacta fractions increased serum levels of AST and ALT, indicating liver damage.
- The extracts did not reduce hyperglycemia or body weight in high-fat diet-fed mice.
- Liver histopathology showed no improvement in steatosis, inflammation, or necrosis.

## Abstract

Azorella compacta (A. compacta) is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. A. compacta is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of A. compacta diterpenoids on fatty liver disease has not been investigated. Therefore, A. compacta organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The A. compacta fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic A. compacta extracts may generate hepatic complications in patients with MAFLD.