AI-Driven Plant-Derived Anti-Infectives: Integrating Traditional Wisdom into Precision Medicine Against AMR

The escalating antimicrobial resistance (AMR) crisis necessitates the development of innovative anti-infectives with novel mechanisms of action. Nevertheless, research on natural products remains constrained by low-throughput screening and limited mechanistic insights. Artificial intelligence (AI) is catalyzing a pivotal paradigm shift—from the mere isolation of active compounds to precisely deciphering their modes of action. This review highlights AI’s transformative role in bridging ethnopharmacological knowledge and modern pharmacology to decode the mechanisms of plant-derived anti-infectives. Case studies on berberine, baicalein, danshensu derivatives, and rosmarinic acid derivatives from Coleus amboinicus illustrate AI’s capacity to map traditional therapeutic concepts to specific pathways (e.g., biofilm inhibition, inflammasome modulation) and to predict precise binding interactions and pharmacophores with high precision. Leveraging statistical correlations between ethnobotanical usage patterns and chemical similarity, we propose a “Knowledge–Data–Mechanism” three-layer framework centered on deep mechanistic insight. Integrating Chinese initiatives, such as the CNDR (China’s National Drug Repository) database and the TCM-AI platform, with global traditional medicine wisdom, this strategy provides an actionable roadmap for modernizing anti-infective discovery. Validated applications of this paradigm have demonstrated order-of-magnitude acceleration in mechanistic characterization, rapidly yielding structurally novel agents with well-defined, target-specific actions—a critical advancement in addressing the urgent global threat of antimicrobial resistance.