A new study published in the Journal of Ethnopharmacology reports that gandouling improves hepatic fibrosis in Wilson’s disease (WD) model mice by blocking the Wnt-1/β-catenin signaling pathway, indicating Wnt-1 to be a new target for the diagnosis and treatment of WD.
Gandouling (GDL) is a traditional Chinese medicine developed by the First Affiliated Hospital of the Anhui University of Chinese Medicine. It has been found to have anti-inflammatory and antioxidant properties that can effectively treat WD by reducing the activation of hepatic stellate cells and controlling the progression of hepatic fibrosis.
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The study used RT-qPCR, Western blot, immunofluorescence, and other research methods in combination with network pharmacological prediction and molecular docking, to identify the expression changes of Wnt-1 and the roles of GDL in TX mice and human HSC (LX-2). They further investigated whether the activation.
Wnt/β-catenin signaling pathway in WD hepatic fibrosis is affected by Wnt-1 and to analyze whether GDL blocks the Wnt/β-catenin signaling pathway by binding to Wnt-1, resulting in WD hepatic fibrosis inhibition. Study results revealed that GDL could improve liver function, inhibit the activation of HSC in TX mice, and reduce hepatic fibrosis. Moreover, network pharmacology results predicted that the GDL targeted Wnt-1/β-catenin, and molecular dynamics further demonstrated that GDL has good binding ability with Wnt-1 and inhibits the Wnt/β-catenin signaling pathway through Wnt-1.
In addition, GDL blocked the Wnt-1/β-catenin signaling pathway in TX mice liver in vivo, while in vitro, the serum containing GDL inhibited the Cu2+ ion-induced Wnt-1/β-catenin signaling pathway in LX-2 cells. Taking it all together, GDL blocked the Wnt-1/β-catenin signaling pathway, improved WD hepatic fibrosis by binding to Wnt-1, and inhibited the HSC activation.
“We found that the levels of serum inflammatory factors and liver function indexes of TX mice in the GDL group were decreased after treatment, suggesting that GDL has better therapeutic effects on the liver function and hepatic fibrosis of TX mice, “the authors highlighted. “This reveals a new mechanism of GDL against WD and promotes the clinical promotion of GDL, ” the authors wrote.
WD is an autosomal recessive genetic disorder caused by the mutation of the ATP7B gene, resulting in the accumulation of copper ions in various organs, including the liver, brain, and cornea, and leading to tissue and organ damage. The clinical symptoms of this disease are divided into those related to the liver and those associated with the nervous system. Liver disease is often the first manifestation of the disease in a majority of patients.
Hepatic fibrosis is an early occurrence in liver involvement caused by the exorbitant accumulation of extracellular matrix and the replacement of liver parenchyma by fibrous tissue, leading to severe consequences like cirrhosis and liver failure.
Reference
Chenglong C, Qiang W, Yurong H, et al. Gandouling inhibits hepatic fibrosis in Wilson’s disease through Wnt-1/β-catenin signaling pathway. Journal of Ethnopharmacology. Published online April 2, 2023. doi:10.1016/j.jep.2023.116445.
