A roadmap to unveil the mechanism(s) of natural indole-derived molecules against NAFLD-derived HCC via systems pharmacology
Year: 2025
Type: article
Abstract: BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is involved in non-alcoholic steatohepatitis (NASH), liver cirrhosis (LC), and even hepatocellular carcinoma (HCC). Hence, this study was to elucidate nuanced key mechanism(s), target(s), and Natural Indole-Derived Molecules (NIDMs) against NAFLD-derived HCC. METHODS: The NIDMs were retrieved by Natural Product Activity & Species Source Database (NPASS). The protein-protein interaction (PPI) networks, bubble plot on key signaling pathways, etiological spectrum-signaling pathways-targets-indoles (ESTI) networks, the verification of toxicity on key NIDMs, and MDE (Molecular Docking Evaluation) were performed with integrating perspective. RESULTS: The 141 NIDMs were identified by NPASS and SwissADME, suggesting that the NIDMs were associated with Similarity Ensemble Approach (SEA; 845 targets) and SwissTargetPrediction (STP; 1107 targets). On PPI analysis, JUN was the uppermost target with the highest DV (Degree Value). A bubble plot based on rich factor constructed to identify key mechanism(s), suggesting that AGE-RAGE signaling pathway in diabetic complications might be key antagonistic mode to hinder the spontaneous progression of NAFLD. The key targets were JUN, and AGTR1 on AGE-RAGE signaling pathway in diabetic complications, binding most stably to Marinacarboline D, and Fumitremorgin F, respectively. CONCLUSIONS: In closing, this study provides critical insights into the key mechanisms, targets, and NIDMs that may impede etiological spectrum of NAFLD.
Source: Translational Oncology
Institution: Hallym University
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,390
OpenAlex ID: W4416931409