A combination of silybin and carvedilol is more effective than either drug alone for treating liver fibrosis, found a new study published in Targetome.
Liver fibrosis is a chronic and multifactorial liver disease that can develop into cirrhosis or liver cancer over time. It happens when repeated or long-term liver damage, which may be caused by viral hepatitis, excessive alcohol use, metabolic disorders, toxins, or autoimmune disease, triggers an overactive healing response. Activation of hepatic stellate cells is a main driver of the condition, which, while inactive under normal conditions, switches into collagen-producing cells when injury occurs, which in turn leads to a build-up of scar tissue in the liver.
Currently, no antifibrotic drugs have been approved for the condition. As it involves many biological routes at once, drugs that target one pathway only often have limited success. This has fuelled interest in combination treatments that can target multiple drivers of disease at once.
In the current study, researchers combined lab experiments, animal studies, phenotype-based drug screening, and molecular analysis to uncover a new combination treatment. To begin, they assessed silybin on liver cell injury models, finding that the drug protected liver cells by restoring viability, lowering harmful reactive oxygen species, and lowering inflammatory gene activity. The drug, however, did not stop fibrosis- it did not directly block stellate cell activation.
To overcome this issue, the researchers next screened 397 FDA-approved drugs to identify compounds that could enhance silygin’s effects. Carvedilol emerged as the strongest contender. Tests in human and rat cell cultures, as well as hepatic stellate cells, showed that the drug combination reduced collagen production and stellate cell activation. In mouse models, the combination reduced liver injury, inflammation, and fibrosis severity.
Both silybin and carvedilol are widely used in clinical practice, have established safety records, and are low in cost. In their study, the researchers wrote that their findings point towards a ‘clinically feasible combination regimen with powerful synergistic and inhibitory effects on liver fibrosis.
Sources: Science Daily, Targetome
