Scientific understanding of toxicity and safety of Chinese medicines
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Abstract:
Scientific understanding of toxicity and safety of Chinese medicines Traditional Chinese medicine is a treasure of traditional culture and medicine which should be inherited and developed. How to correctly understand the toxicity of Chinese materia medica (CMM) is an important guarantee for safe drug use. The history of the application and research of the toxicity of CMM has been long, and the Chinese medicine community has never stopped exploring the issues related to the safety of CMM. As early as in the ancient time, the meaning of poison and medicine was the same, and poisons were commonly used as the term for "drug bait". During the pre-Qin period, a book on medicine and doctor “Zhou-Li: Tian-Guan Zai-Zhai” had recorded the words of "a physician's order of a doctor's prescription and a poison medicine". Although the words of the ancients may not be entirely correct, it reflects an unignorable aspect of the medicine world. With the development of society and science, the understanding of Chinese medicine has been continuously deepened, and the concept has gradually changed. The safety issue has also been paid attention to by the world's medical and pharmaceutical circles. We know that toxicity is a serious adverse effect of drugs on the body, which reflects the safety of a drug performance. Drug toxicity and adverse reactions can cause visceral tissue damage and dysfunction, and cause the body to undergo pathological changes or even death. The concept of complete toxicity of modern Chinese medicines should also include acute and sub-acute toxicity, chronic toxicity, and special toxicity such as carcinogenesis, mutagenesis, gene-toxicity, and addiction. Based on the above toxicological studies, in-depth toxicological mechanisms and health hazards can be beneficial to enhance the understanding of traditional medicines. Some research results published in domestic and foreign scientific journals are sufficient to illustrate the contribution of Chinese and foreign scientists to traditional medicine research. This special issue has published four articles on the toxicity and safety of Chinese medicine. From one aspect, we see the achievements of authors in this field. In a topic on "Application and prospect of toxicity quality markers (Q-markers) of Chinese materia medica based on metabolomics" (CHM 2018, 10(2): 108-116), authors reviewed that the toxicity Q-markers of CMM were explained from the following four aspects: 1) The establishment of toxicity prediction model of CMM based on metabolomics, recognition, and relative techniques; 2) The discovery of toxicity Q-markers of CMM based on metabolomic and toxicity mechanism research; 3) The research on the formation of toxicity Q-markers based on metabolomics from biosynthetic pathway and the secondary metabolites analysis of toxicity Q-markers; and 4) The susceptibility study of toxicity Q-markers based on metabolomics, key targets, and metabolic pathways of toxicity Q-markers to explain the target organ toxicity. Therefore, authors suggested that the application of metabolomics helped to systematically and comprehensively discover the quality control indicators related to the CMM safety, and it can provide rational evidences for the clinical toxicity of CMM. We know that the concept of Q-marker is possible to monitor the quality of Chinese Herbal medicines (CHMs) in the whole process, and control final products. However, as the complexity of CHM components and the great varieties of the extrinsic harmful residues, such as mycotoxins, pesticides, heavy metals, and sulfites, it is difficult to ensure the quality of CHMs. In the review paper "Extrinsic harmful residues in Chinese herbal medicines: types, detection and safety evaluation" (CHM 2018, 10(2): 117-136), authors summarized the potential harm, limit standards, detection methods of the harmful residues, and provided reference for the formulation or amendment of relative regulations to promote the healthy and stable development of CHMs, the information is value to establish a complete system with Q-marker evaluating the safety and quality of CHMs. In order to determine the toxic potential of Realgar-Indigo naturalis formula (RIF), Prof. Gao’s team performed a research titled "Synergistic effect and different toxicities of adjuvant components of Realgar-Indigo naturalis Formula" (CHM 2018, 10(2): 137-144). The assays acute toxicity and sub chronic toxicity were to evaluate the toxic potential of Realgar and the adjuvant components of RIF in addition to Realgar's synergy with these adjuvant components. Based on these experimental results presented, researchers found that the RIF toxicity was the result of the soluble arsenic in Realgar, and Indigo naturalis, and Salvia miltiorrhiza in the RIF exert completely opposite effects on the toxicity. Therefore, the intelligent explanation is not only a possible for the compatibility of the formula, but also the RIF study may be viewed as a classic case of CMM research on compatibility. The research paper of Prof. Zhang’s team titled “Toxicity-efficacy converting of ginseng combined with Fuzi Banxia incompatibility in heart failure stage of Cor pulmonale” (CHM 2018, 10(2): 145-151) used a heart failure model to evaluate the toxicity-efficacy and explore mechanism of ginseng combined with Fuzi Banxia. The study result exhibited that ginseng compatible environment could attenuate cardiac toxicity of Fuzi Banxia incompatibility intervening in the heart failure stage of Cor pulmonale, and improve cardiac function, which may be related to the expression of hypertrophy and apoptosis associated genes in the occurrence and development of heart failure. From the limited information and research results in these four articles, it can be understood the some safety issues of CMM from different perspectives, it can be seen that compatibility will affect their safety and effectiveness, and also affect the quality of medicines. Also, the effects are far more complex than those of single ingredient. Although the modern biology technology, such as genomics, proteomics and metabolomics technology, has been widely used in the study of mechanism of drug action, its mechanism research far fail to be elucidated and has a long way to go due to the complex components in CMM.