β-桉叶醇、苍术素与茅术醇在晚期肝内胆管癌患者中的分子网络分析与计算机模拟对接

Cholangiocarcinoma (CCA), the bile duct cancer, is associated with a high burden and poor prognosis. This is due to the lack of early diagnostic tools and effective chemotherapy. Molecular networking is a promising tool for investigating the molecular mechanisms of drugs or candidate molecules for various diseases.

This study investigated molecular targets and signaling pathways of the three components (atractylodin, beta-eudesmol, and hinesol) of Atractylodes lancea Thunb. (DC.) (AL), the promising candidate for patients with advanced-stage intrahepatic CCA (iCCA). The independent-sample T-test or Mann-Whitney U test was used to identify significant gene targets in (i) patients with advanced-stage iCCA who received AL treatment and those who received palliative care alone, and (ii) patients with progressive and non-progressive diseases. A molecular network was constructed using Cytoscape to identify AL signaling action pathways. Fifty-two genes were identified as the essential targeted genes in patients with advanced-stage iCCA.

The most critical gene hubs were TNF (1st rank), NRAS (2nd rank), and PI3KCA (3rd rank). The false discovery rate (FDR) identified PI3K/AKT, NK cell-mediated cytotoxicity, and apoptosis as the top three significant pathways. Hinesol showed the highest binding affinity compared with other components of AL and the standard anti-CCA drugs gemcitabine and 5-FU.

Molecular networking is a valuable tool for investigating molecular signaling networks of herbal medicine with multiple active and non-active ingredients. With multi-signaling targets linked to all tumor development and progression stages, the study supports AL as a promising candidate for patients with advanced-stage iCCA.