Advances in Toxicity Risk Control and Modern Research of Highly Toxic Traditional Chinese Medicinal Materials
The toxicity of traditional Chinese medicines (TCMs) constitutes a core component of pharmacological theory, alongside the four natures and five flavors, ascending-descending-floating-sinking, and channel tropism, collectively guiding clinical TCM practice. Highly toxic medicinal materials present formidable challenges: their complex compositions impede full elucidation of toxic constituents and mechanisms, while diverse clinical regimens and significant individual variability further complicate research. This review systematically examines highly toxic medicinal materials listed in the 2025 edition of the Chinese Pharmacopoeia. Integrating herbal textual research with modern pharmacological investigations, it analyzes common toxic components and pathways, the bidirectional toxicity-efficacy relationship, and strategies for reducing toxicity while preserving efficacy. The application of modern analytical detection techniques in quality control is reviewed, and other potentially toxic substances and risk management strategies are discussed. The 2025 Pharmacopoeia classifies highly toxic materials primarily as plant-derived, imposing strict regulations on dosage forms, pregnancy contraindications, compatibility contraindications, usage, and special population restrictions. Historical toxicity grading has evolved; for instance, Chuanwu (Aconiti Lateralis Radix Praeparata) was recorded as 'toxic' in Wupu Bencao but as 'highly toxic' in Mingyi Bielu and Yaoxing Lun. Advanced analytical tools such as HPLC-MS have enabled fingerprinting and identification of over 50 highly toxic compounds, including aconitine-type alkaloids and brucine. Mechanistic studies based on apoptotic signaling pathways and metabolomics have revealed complex 'biphasic toxicity effects.' Traditional processing detoxification and compatibility antagonism have been scientifically validated and optimized. However, challenges persist, particularly the incomplete 'component-toxicity' association, which restricts clinical dosage ranges and elevates potential risks, constraining further clinical application. This review aims to provide a scientific reference for deepening quality standard research and promoting safe, rational clinical use of highly toxic medicinal materials.