Processing-induced detoxification of toxic Traditional Chinese Medicines: a systematic review of attenuation mechanisms at physical, chemical, and in vivo levels

The “toxicity” of Traditional Chinese Medicines (TCMs) carries a dual connotation, referring both to the potent nature of certain medicinal substances and a critical constraint on their safe clinical application. Processing is the core approach to achieving the goal of “attenuating toxicity while preserving efficacy” for toxic TCMs. A systematic elucidation of the detoxification mechanisms of processing is essential for inheriting traditional processing theories and ensuring clinical medication safety. Current research predominantly focuses on individual toxic TCMs, specific toxic constituents, or single processing methods, a fragmented paradigm that hinders a comprehensive understanding of the complex detoxification mechanisms and the extraction of universal principles. Therefore, this paper systematically reviews the toxic TCMs listed in the Chinese Pharmacopoeia (2025 Edition), summarizing their natural sources, types of toxic constituents, and traditional processing methods for toxicity reduction. Furthermore, by integrating existing research evidence, the detoxification mechanisms of processing are categorized into three interrelated yet distinct levels: physical detoxification (including the physical removal of toxic constituents and changes in the physical properties of decoction pieces), chemical transformation of toxic constituents, and modulation of in vivo processes. At the chemical transformation level, common patterns within the same family or genus are explored based on natural sources. At the physical level, the focus is on universal processing methods across different families and genera; at the in vivo level, the focus is on common regulatory pathways across families and genera. This review aims to integrate fragmented research findings, reveal potential common patterns underlying processing‑induced detoxification, and propose an integrated research strategy combining “physical detoxification – chemical transformation of toxic constituents – modulation of in vivo processes.” It thereby provides a theoretical basis for a deeper understanding of the scientific principles of processing‑induced detoxification and for guiding the optimization and innovation of processing technologies.