Twelve Shugan Lidan Granules from traditional Chinese medicine can improve liver function in patients with postoperative hepatolithiasis by inhibiting the Hippo signaling pathway.

Abstract

Introduction: Hepatolithiasis (HL) is a complex liver and biliary disorder characterized by high rates of recurrence. This study aimed to evaluate the efficacy of Twelve Shugan Lidan Granules (TSLG), a compound herbal traditional Chinese formulation, in the treatment of HL, as well as to investigate its underlying mechanism.

Methods: A retrospective analysis was conducted involving 157 patients diagnosed with HL, who were divided into two groups: the control group and the research group. In the control group, no treatment was given postoperatively, while in the research group, TSLG was orally administered three times a day postoperatively for two months. Both groups were followed up by telephone at 1 month, 2 months, and 3 months postoperatively. Liver function indicators were measured before and after surgery, and miRNA expression profiling was analyzed using high-throughput sequencing (HTS). Additionally, the expression levels of related proteins were assessed through western blots.

Results: Postoperative liver function indicators were significantly lower in the research group compared to the control group (P < 0.05). Additionally, 64 miRNAs were differentially expressed in HL patients. Further analysis of 64 miRNAs revealed their abnormal targeting of the Hippo signaling pathway. Further experimental results indicate that TAZ protein expression is elevated in HL patients, reflecting abnormal activation of the Hippo signaling pathway in these patients. TSLG treatment significantly reduced the expression of YAP, TAZ, and SREBP-2 proteins, while increasing the expression of p-YAP and p-TAZ proteins (all P < 0.05). Furthermore, TSLG inhibited the Extracellular Acidification Rate (ECAR) in LPS-induced WRL68 cells.

Conclusion: TSLG effectively improved postoperative liver function by downregulating sterol regulatory element-binding protein-2 (SREBP-2) and inhibiting the Hippo signaling pathway.