# Psoralidin, a main compound in Psoraleae Fructus, induces hepatotoxicity by impeding lipid oxidative catabolism and aggravating lipid accumulation in mice

## TL;DR

This study shows that psoralidin, a compound in Psoraleae Fructus, causes liver damage in mice by increasing fat buildup and disrupting fat breakdown.

## Contribution

The study identifies psoralidin as a hepatotoxic component of Psoraleae Fructus and reveals its mechanism involving lipid metabolism disruption.

## Key findings

- Psoralidin increases ALT and AST levels and causes hepatic steatosis and lipid droplet accumulation in mice.
- Psoralidin promotes lipid synthesis and inhibits fatty acid oxidation, leading to lipid metabolism disorders.
- Psoralidin enhances Pla2g6 and Pla2g12b levels, promoting TG synthesis and glycerophospholipid metabolism disruption.

## Abstract

Psoralea corylifolia(PF) is widely utilized for the treatment of conditions such as kidney yang deficiency, frequent urination, and cold pain in the waist and knees. However, both basic research and clinical reports indicate that it induce hepatotoxicity. Our preliminary research has confirmed that PF has hepatotoxicity and in vitro research indicated that psoralidin is hepatotoxic. but it remains unclear whether psoralidin is the hepatotoxic component of PF and the mechanism of psoralidin induces hepatotoxicity. This study aimed to investigate the hepatotoxicity induced by psoralidin and its toxic mechanisms.

Kunming mice were used to conduct long-term toxicity experiments. Liver function indices, organ coefficients, and histopathological observations were employed to assess the hepatotoxicity of psoralidin. Non-targeted metabolomics and proteomics analyses were conducted to elucidate the potential pathways and targets associated with psoralidin-induced hepatotoxicity. Furthermore, immunofluorescence staining, molecular docking and Western blotting analyses were utilized to validate the mechanisms underlying psoralidin hepatotoxicity.

The elevation of ALT and AST, accompanied by hepatic steatosis and lipid droplet aggregation were observed after psoralidin treatement. Psoralidin affected biosynthesis of unsaturated fatty acid, fatty acid metabolism, arachidonic acid metabolism, phospholipid metabolism, and oxidative phosphorylation. Further validation research found that psoralidin induced the expressions of Acot4 and Plin5, which in turn caused up-regulations of TGs and FFA in mice, and increased the HSD17B12 level, thereby promoting the synthesis of long-chain fatty acids and facilitating lipid synthesis. And psoralidin catalyzed the conversion of phosphatidylcholine into LPC by enhancing Pla2g6 and Pla2g12b levels, which promoted the synthesis and accumulation of TGs, ultimately inducing disorders in glycerophospholipid metabolism. Furthermore, psoralidin caused upregulation of ROS and mitochondrial damage, leading to a decrease in FA oxidation.

Psoralidin is one of the hepatotoxic components of PF, which induced hepatotoxicity via promoting lipid synthesis and inhibiting lipid oxidative degradation.

The online version contains supplementary material available at 10.1186/s13020-026-01335-x.