Discovery of a Novel Silybin Derivative for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis
MASH has become the leading cause of liver disease worldwide, and the prevalence of MASH is steadily increasing. The development of new drugs for the treatment of MASH is urgent. Silybin has been used for decades in liver protection, but its insufficient antioxidant capacity and poor oral bioavailab...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , , , , , , , , , |
| منشور في: |
2025
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| الموضوعات: | |
| الوسوم: |
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| الملخص: | MASH has become the leading cause of liver disease worldwide, and the prevalence of MASH is steadily increasing. The development of new drugs for the treatment of MASH is urgent. Silybin has been used for decades in liver protection, but its insufficient antioxidant capacity and poor oral bioavailability have limited its clinical use. In this paper, we discovered a novel silybin derivative <b>A2</b> as a potent agent for MASH treatment. In vitro, <b>A2</b> showed excellent activity in inhibiting lipid accumulation, antioxidation, anti-inflammation, and antifibrosis. In the acute-liver-damage rat model experiment, <b>A2</b> showed notable hepatoprotective efficacy. In the MASH mouse model experiment, <b>A2</b>, better than silybin, significantly ameliorated the pathological features of the MASH liver including steatosis, inflammation, and fibrosis. In addition, <b>A2</b> displayed a good oral bioavailability and a good safety profile. Collectively, these findings demonstrated that <b>A2</b> serves as a promising candidate for MASH treatment. |
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