Silymarin and Its Isolated Flavanonol Lignans Are Liver X Receptor Antagonists

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Abstract
Silymarin is a mixture of bioactive natural products from milk thistle ( Silybum marianum ) fruit extracts, which have a long history as a phytotherapeutic agent in treating various liver‐related ailments. Even though important pharmacological effects of silymarin, such as the antioxidative properties, have been proven, the exact molecular mechanisms for its liver‐protective action remain elusive. Here, we provide in vitro pharmacological data showing that silymarin, as a mixture and also its individual flavanonol lignans, antagonize liver X receptor (LXR). In HepG2 cells, the isolated silymarin flavanonol lignans showed LXR‐mediated anti‐steatotic effects that may play a crucial role in the hepatoprotective action of silymarin. Our findings underscore the potential of silymarin, both as a mixture and in the form of its isolated flavanonol lignans, as therapeutic agents for liver disorders, including metabolic dysfunction‐associated steatotic liver disease (MASLD). There is an urgent need for well‐designed clinical trials engaging standardized milk thistle fruit extract to explore its efficacy in MASLD.

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