A comprehensive review of herb-induced liver injury: Mechanisms, clinical management, and future perspectives in natural product safety.

BACKGROUND

The global surge in medicinal natural product use, driven by a "natural equals safe" belief, has led to a significant public health concern: herb-induced liver injury (HILI). As a growing contributor to herbal medicine safety issues, HILI presents challenges in risk assessment and clinical management.

PURPOSE: Based on current toxicological knowledge to address critical gaps in understanding HILI, this review provides an evidence-based roadmap for researchers, clinicians, and regulators to improve risk assessment, clinical management, and public health safeguarding.

STUDY DESIGN AND

METHODS

We systematically analyzed global HILI epidemiology, preclinical quality control challenges, and the toxicological pathways of prominent causative agents. Epidemiological and clinical challenges were used to formulate a multi-dimensional framework for HILI management, incorporating technological innovation, policy development, and enhanced education.

RESULTS

Multiple hepatotoxic mechanisms were elucidated, including mitochondrial dysfunction and metabolic bioactivation. We identified specific diagnostic challenges, including patient non-disclosure of herb use and the inadequacy of standard causality tools for multi-ingredient products. To address these gaps, we propose a multi-faceted approach, including the adoption of novel biomarkers for early detection. Furthermore, we outline future technological advances, such as liver-on-a-chip systems for mechanism elucidation, applying artificial intelligence for predictive toxicology, and using blockchain for supply chain verification.

CONCLUSION

Ensuring natural product safety requires integrated strategies that connects mechanistic toxicology with robust clinical management and forward-thinking regulatory science. A deeper, more specific understanding of HILI etiology is required for developing effective prevention strategies and enhancing the safety of herbal medicine for global public health.