Multiscale Interactome–Guided Prioritization of Candidate Herbs and Active Compounds for Hepatic Cirrhosis Using a Biased Random Walk Algorithm

TL;DR

This paper uses a multiscale network approach to identify promising herbs and compounds for treating liver cirrhosis, focusing on inflammation and immune pathways.

Contribution

A novel multiscale interactome framework with a biased random walk algorithm to prioritize underexplored herbal candidates for hepatic cirrhosis.

Findings

Top-ranked herbs like Magnoliae Cortex and Notoginseng Radix et Rhizoma are supported by existing literature.

Underexplored herbs such as Saposhnikoviae Radix and Fritillariae Cirrhosae Bulbus were identified as potential candidates.

Enrichment analyses linked candidates to inflammatory, immune, and apoptosis-related pathways.

Abstract

Hepatic cirrhosis is a progressive chronic liver disease driven by sustained inflammation, cell death, and tissue remodeling, and effective disease-modifying options remain limited. Here, we applied a multiscale interactome framework to prioritize candidate herbs and active compounds for hepatic cirrhosis. Herb–compound associations were collected from the OASIS database and mapped to experimentally supported compound–target interactions (DrugBank/TTD/STITCH), while cirrhosis-related proteins were curated from DisGeNET. Using a biased random-walk algorithm, we generated disease and herb/compound diffusion profiles on the multiscale network and ranked candidates by profile similarity and target overlap. Among the top-ranked herbs, Magnoliae Cortex, Notoginseng Radix et Rhizoma, Polygoni Cuspidati Rhizoma et Radix, and Capsici Fructus were supported by prior literature, whereas several high-ranking herbs lacked curated evidence and were highlighted as underexplored candidates, including Saposhnikoviae Radix and Fritillariae Cirrhosae Bulbus. Enrichment analyses indicated convergence on inflammatory and innate-immune pathways (TNF, Toll-like receptor, NF-κB) and apoptosis-related processes, with additional signals involving HIF-1 and PI3K–Akt pathways. Disease-focused subnetworks suggested mechanistic hypotheses for evidence-lacking compounds, including bergapten, oleic acid, and octadecanoic acid. Overall, we systematically prioritize herbal candidates and provides a mechanistic basis for follow-up validation in hepatic cirrhosis.

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