# Isosilybin B: a potential novel therapeutic agent with hepatoprotective, anticancer and antifibrotic properties

## TL;DR

Isosilybin B shows strong potential as a new treatment for liver cancer and liver fibrosis, being more effective and less toxic than existing compounds.

## Contribution

The study reveals isosilybin B's superior anticancer and antifibrotic effects compared to silibinin and silymarin in liver cells.

## Key findings

- Isosilybin B is more cytotoxic to liver cancer cells and less harmful to healthy liver cells than silibinin.
- It induces G1 cell cycle arrest in liver cancer cells without affecting non-tumor cells.
- Isosilybin B reduces pro-fibrotic gene expression and ALT levels more effectively than silibinin in a liver fibrosis model.

## Abstract

Silybum marianum (milk thistle) is a plant for centuries well known for its hepatoprotective effects. The extract from seeds, silymarin, and its major compound, silibinin, are well studied for their hepatoprotective and antifibrotic effects. The role of other minor compounds, such as isosilybin B, remains underexplored.

This study aimed to compare the cytotoxic and antifibrotic properties of IB with those of silibinin and silymarin in vitro. It focuses on evaluating the cytotoxic effect of these substances on tumor and non-tumor liver cells. Moreover, antifibrotic potential of the three substances was determined in healthy liver cells treated with TGF-β1.

Isosilybin B exhibits greater cytotoxicity toward liver cancer cells while being less toxic to non-tumor hepatocytes compared to silibinin. At non-toxic concentrations, isosilybin B induced cell cycle arrest at the G1 phase in two types of liver cancer cells. In contrast, it did not impact the cell cycle of non-tumor cells under the same experimental conditions. In the model of liver fibrosis in vitro induced by TGF-β1, isosilybin B reduced the mRNA expression of pro-fibrotic genes as well as ALT level in the culture medium more effectively than silibinin.

Obtained results suggest that isosilybin B represents a promising anticancer agent for the treatment of liver cancer. Moreover, its anti-fibrotic properties emphasize its potential for treatment of many other liver diseases, which underline the strong potential of isosilybin B in future anticancer and antifibrotic therapeutic strategies.

The online version contains supplementary material available at 10.1007/s12672-025-03380-8.