A molecular network analysis and in silico docking of beta-eudesmol, atractylodin and hinesol in patients with advance stage intrahepatic cholangiocarcinoma

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 alpha (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.