Rethinking Network Analysis in Ethnopharmacology: A Multi-omics and AI Roadmap to Overcome Homogeneity

Xuewen Diao^1,2Zhang Hao³Shiqi Wang¹Zulong Wang^1,2*Qi Zhang^1,2*

• ¹First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
• ²Henan University of Chinese Medicine, Zhengzhou, China
• ³Macau University of Science and Technology, Taipa, Macao, SAR China

Network analysis (NA) is a widely used computational tool for exploring the complex systems of interactions in ethnopharmacology, aiming to predict potential targets and generate mechanistic hypotheses. However, the predictive validity and biological relevance of its outputs are constrained by a pervasive methodological bottleneck: the recurrent identification of a narrow set of molecules— such as quercetin—across disparate natural products and diseases. Through a systematic analysis of 1,038 network-based studies, we establish "homogeneity" as a coherent, multi-level pattern, from "Flavonoid Centrality" to a "Hub-Target Core" and restricted "Canonical Pathways," transcending specific remedies or diseases. We conceptualize this as a self-reinforcing "convergent discovery pipeline," in which initial database biases are amplified by context-insensitive analytical approaches. Empirical evidence shows that integrating contextual experimental or multi-omics data mitigates homogeneity. To break this cycle and align network analysis more closely with pharmacological best practices, we propose an integrated framework that shifts from database dependency to empirically driven data acquisition, leverages bias-aware artificial intelligence for curation and prioritization, and advances dynamic, context-specific network modeling. This framework provides a clear roadmap to disrupt methodological inertia and steer network-based research in ethnopharmacology toward a more robust, diverse, and pharmacologically and clinically relevant future.