Toxicity Of Traditional Chinese Medicine Research Articles

The role of SDF2 (Stromal cell derived factor-2) in gestational diseases through PERK- branch of the Unfolded Protein Response/ER stress.

Tripterygium hypoglaucum (Levl.) Hutch (THH) is the source plant of a traditional Chinese medicine named Kunmingshanhaitang, which was first recorded in Compendium of Materia Medica. Like Tripterygium wilfordii Hook f. (TWH), THH is also widely used in the treatment of various autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and psoriasis. The therapeutic effect of THH is closely related to its special compound composition. By now, about 300 compounds have been isolated and identified from THH, including sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, lignans, alkaloids, fatty acids, steroids and others. Further studies found that many compounds originated from THH showed a wide range of biological activities, such as immunosuppression, anti-inflammatory, antitumor, neuroprotection and the others. It is worth noting that THH belongs to the toxic traditional Chinese medicine, commonly known as gut-break grass. Although there have been a lot of studies on the toxic doses of some extracts or isolated compounds of THH, their mechanism remains unclear. Further study on the structure and function relationship of each active and/or toxic compound, analysis of their unique mechanism of action or toxicity mechanism, and exploration of its detoxification methods and new clinical uses will contribute to its better use for human health. In order to better explore the pharmaceutical potential of THH, this paper systematically reviewed its traditional uses, botany, phytochemistry, pharmacology, pharmacokinetics, toxicology and detoxification, which is convenient for further understanding and research.

Ancient Literature Literature study on Timing Medication for Chest Stuffiness and Pains Based on Chrono-Medicine(Traditional Chinese Medicine)

Objective Based on the analysis of the ancient literatures about chest stuffiness and pains in Chrono-Medicine of traditional Chinese medicine,to study the content of timing medication in chest stuffiness and pains. Methods According to the database of Chinese Medical Code, searching the ancient literatures and establishing the database, extracting the contents of chest stuffiness and pains’s prescription which covering timing medication. And the statistical analysis and content discussion were carried out according to the choice of taking medicine. Results The 67 kinds of traditional Chinese medicine included were qi regulating agent, dispelling cold agent, expectorant agent and blood regulating agent. Besides,the time of taking medicine is used to be3:00-5:00,7:00-9:00,11:00-13:00,17:00-19:00, 19:00-21:00, 21:00-23:00.Take medicine once a day in the morning, twice a day, three times a day, three times a day and once a night. It is recommended that timing medication in clinical should be increased in time of 21:00-23:00 and 11:00-13:00, and paying more attention to the heart channel corresponding and the heart pericardium channel in time of 11:00-13:00 and 19:00-21:00. Conclusion Timing medication is beneficial to the optimization of therapeutic effect and minimization of toxicity of traditional Chinese medicine, which needs to provide the best evidence for further multi-center clinical trial research, and promote the popularization of timing medicine in clinical practice. Key words: Chrono-Medicine (Traditional Chinese Medicine); Chest stuffiness and pains; Timing Medication; Ancient literature

Analysis and consideration based on first classical prescriptions

Classical prescriptions are precious wealth left by ancient Chinese medical scientists. Moreover,they are also the important part of the treasure-house in Chinese medicine. Classical prescriptions have a long and rich history for human-use in China and play an important role in keeping people healthy. The state administration of traditional medicine of China published the Catalogue of Classical Prescriptions(first batch) in 2018. This measure has inspired the enthusiasm of Chinese medicine manufacturers to study ancient classical prescriptions and develop classical compound prescriptions. Based on the first batch of classical prescriptions, the dosage forms, sources, prescription components, decocting degree, use of toxic drugs and processing methods of classical prescriptions. The results showed that most of the classical prescriptions in the first batch were decoction and boiled powder,while only four of them were powder and paste forms,all of which were originated from representative classics in the past dynasties. The dosage and decocting degree of decoction were greater than those of boiled powder. The dosage and decocting degree of decoction in Han and Tang Dynasties was close to that in Ming and Qing Dynasties,higher than that in Song and Jin Dynasties. Moreover,the average number of herbs in the prescriptions in Han Dynasty was the smallest. The use of toxic traditional Chinese medicine was the most frequent in Han Dynasty, and Pinellia ternata was the most common toxic medicine. There were various processing methods, including cleansing, cutting, stir-frying, roasting and so on. In this paper, the dosage forms of traditional paste, the time concept of decoction in the ancient times, the traditional roasting method and the processing method of toxic drugs were summarized to provide ideas and reference for further development of classical prescriptions.

Development of quantitative structure-activity relationship models to predict potential nephrotoxic ingredients in traditional Chinese medicines

The broad use of traditional Chinese medicines (TCMs) and the accompanied incidences of kidney injury have attracted considerable interest in investigating the responsible toxic ingredients. It is challenging to evaluate toxicity of TCMs since they contain complex mixtures of phytochemicals. Quantitative structure-activity relationship (QSAR) is an efficient tool to predict toxicity and QSAR study on TCMs-induced nephrotoxicity remains lacked. We developed QSAR models using three datasets of 609 compounds: natural products, drugs, and mixed (contained both kinds of data) datasets. Each dataset was used for modelling by utilizing artificial neural networks (ANN) and support vector machines (SVM) algorithms separately. Both internal and external validations were performed on each model. Six QSAR models were developed and yielded reliable performance in the internal validation. For external validation, 30 ingredients in the TCMs were predicted well by the natural product models (accuracy: ANN 96.7%, SVM 93.3%). The mixed models (accuracy: ANN 76.7%, SVM 66.7%) showed a better performance than the drug models (accuracy: ANN 50%, SVM 53.3%). Particularly, natural product models produced the most reliable results. It has the application not only on screening the nephrotoxic ingredients in TCMs, but it is also helpful at prioritizing the subsequent toxicity testing of natural products.

Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution.

With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.

Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Abstract Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics; methods to identify dose–toxicity relationships in TCM; and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

Discussions on toxic traditional chinese medicine and new perspectives

Along with the increase in the consumption of traditional Chinese medicine (TCM), the safety of TCM has dramatically attracted the attention and concern of the public. Here, we review previous studies, which focused mainly on the toxicity of toxic TCM and the interpretations for combination, to elaborate on advances and important issues existing in the safety evaluation of TCM, aiming to provide scientific advice for the clinical use. Moreover, we emphasize the importance of a safe evaluation system for TCM based on the material basis for toxicity, which integrates new toxicity testing strategy and is launched under the guidance of TCM theories in future researches.

Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injuryIssued by China Food and Drug Administration

Drug-induced liver injury (DILI), defined as liver injury caused by a drug and/or its metabolites, is a common clinical adverse drug reaction1, 2, 3, 4. This type of injury can cause acute liver failure and even death in severe cases5. DILI accounts for many drug warnings and is an important cause of failure in the clinical development of new drugs and new forms of traditional Chinese medicine (TCM). Thus, liver injury from drugs has attracted close attention from medical professionals, the pharmaceutical industry, and the general public6, 7, 8. For thousands of years, TCM has contributed to the prevention and treatment of disease, to the development of the Chinese nation, and to the quality of life of Chinese people. For many individuals, TCM remains an essential component of modern life. However, continuous improvements in monitoring adverse drug reactions/events (ADRs/ADEs), along with increased TCM use worldwide has frequently identified TCM-associated safety issues such as DILI9, 10. This situation imposes serious obstacles to the research and development of new, safe TCM drugs and the viability of TCM industries. Due to the lack of specific diagnostic indicators, an exclusion diagnosis of DILI has been commonly adopted, but this approach has shown a high rate of misdiagnosis. TCM DILI is often overlooked because of the pharmaceutical complexity of TCM, the limited basic information on the quantities of TCM components, as well as the increasingly common use of drug combinations. The causal relationship between liver injury and TCM is also difficult to clarify. In addition, potential TCM toxicity is often overlooked by the public since TCM preparations are commonly regarded as “natural, without toxic and side effects”. For these reasons and because developers and enterprises have paid insufficient attention to ADRs, the prevention and control of TCM safety risks is extremely difficult11. Therefore, the establishment of an objective and scientific technical system for assessing and identifying TCM DILI is needed. To this end, with strengthening the risk management of the entire drug life cycle as the main goal, the China Food and Drug Administration (CFDA)of China organized experts in related fields to develop the Guidance for Clinical Evaluation of Traditional Chinese Medicine-Induced Liver Injury. This task was accomplished by integrating the consensus of Chinese and international experts with research progress in the fields of medicine and pharmacy as well as in clinical and scientific research. This document aims to provide advice and assistance to relevant institutions and personnel in identifying the risk signals of TCM DILI; scientifically assess the causal relationship between patients׳ liver injury and TCM; effectively reduce misdiagnosis; fully evaluate the safety, risks and benefits of relevant TCM; and purposefully develop prevention and control measures for TCM DILI. These activities are needed to reduce the failure rate of new TCM drug research and development (R&D) and the risk of clinical use as well as to promote a viable TCM industry in China. This guide is designed for the evaluation of DILI and for risk control throughout the entire life cycle of TCM products, including the research and development stages of new drugs and post-marketing stage. It should also be used for TCM R&D, as well as by medical and regulatory agencies. Each drug marketing authority must carry the main responsibility for the product and not only strengthen the management of the entire lifecycle of the product but also take realistic and effective risk control measures to ensure the safety of public drug use. The TCMs (including ethnomedicines) in this guide consist of the TCM preparations that are being studied and those already on the market. This guide can be used as a reference for clinically used TCM decoctions and tablets, formulated TCM granules, TCM extract, homemade herbal medicines, TCM-containing health products and TCM health foods as well as relevant excipients. Many problems that urgently require in-depth study and solutions still exist in the field of TCM DILI. This guidance will be continuously revised and improved in accordance with research progress on TCM DILI and regulatory requirements.

Changes in the properties of Radix Aconiti Lateralis Preparata (Fuzi, processed aconite roots) starch during processing.

Radix Aconiti Lateralis Preparata (Fuzi) is an important, toxic traditional Chinese medicine that has been widely used in clinical practice. Due to the toxicity of its raw materials, it needs to be processed before application. The changes in the physicochemical properties of Fuzi starch during processing were evaluated by scanning electron microscopy, X-ray diffraction and differential scanning calorimetry. The results showed the following: morphological properties changed from spherical to irregular and polygonal particles, while the particle size increased significantly; amylose content and solubility decreased significantly; swelling power and water-binding capacity increased significantly; the X-ray diffraction peak disappeared, and the crystallinity decreased; and the gelatinization temperature and enthalpy decreased significantly. The properties of Fuzi starch were similar to those of pregelatinized starch. These results indicated that Fuzi starch undergone repeated processes of gelatinization and aging, which destroyed the original crystal structure of the starch.

Euphorbia kansui fry-baked with vinegar modulates gut microbiota and reduces intestinal toxicity in rats

Ethnopharmacological relevanceEuphorbia kansui (EK), a kind of toxic traditional Chinese medicine (TCM), is used in the treatment of edema, ascites and asthma. EK fry-baked with vinegar (VEK) is regularly used to reduce the toxicity in TCM. Previous studies have confirmed that fry-baking with vinegar could significantly reduce the significant gastrointestinal toxicity of EK. The toxic side-effects of EK are closely associated with intestinal tract, but existing research results could not provide practical measures for detoxification in terms of the biological effects of EK fry-baked with vinegar. Aim of the studyThis study aimed to investigate the gastrointestinal toxicity of EK and detoxification of VEK through the regulation of gut microbiota. Thirty male Sprague Dawley (SD) rats were randomly divided equally into 3 groups and received by oral gavage 0.5% CMC-Na (C group), EK (EKC group) or VEK (VEKC group) powder at 680 mg/kg for seven consecutive days. ResultsThe ten toxic components in VEK were reduced significantly compared with those in EK. After fry-baked with vinegar, those side effects associated with VEK were significantly relieved in terms of histopathology and inflammatory injury indices of intestinal tissues, liver function and oxidative damage indices. The toxicity of EK might be highly correlated with Lactobacillus and Blautia genera. In addition, EK fry-baked with vinegar increased the production of short-chain fatty acids (SCFAs), which are regulated by gut microbiota. ConclusionsThe proportion of main probiotics increased and potentially pathogenic bacteria decreased after EK was fry-baked with vinegar. It turned out that effective detoxification could be achieved by fry-baking with vinegar.

Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine

Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine

Application of Toxic Chinese Medicine in Chinese Pharmacopoeia

Objective: Explore the application characteristics of proprietary Chinese medicine prescriptions containing toxic herbs in pharmacopoeia. Methods: In this paper, according to the clinical application of pharmacopoeia proprietary Chinese medicine is divided into table agent, Qushu agent, diarrhea agent, heat agent, Wen Li agent, cough and asthma agents, resuscitation agent, Gutian agent, Fuzheng agent, Anshen agent, hemostatic agent, The traditional Chinese medicine prescription and the clinical application of the Chinese herbal medicine containing the toxic Chinese medicine were analyzed and sorted out., Summed up the compatibility of toxic herbs and application characteristics. Results: Toxic Chinese herbal medicine in the cure of traditional Chinese medicine to play a long-standing role, through the overall thinking, dialectical thinking, and thinking of toxic Chinese medicine in the analysis of Chinese medicine that [2], toxic Chinese medicine in the application of proprietary Chinese medicine can not lack. Conclusion: Pharmacopoeia included proprietary Chinese medicine not only in the clinical treatment of good, but also the application of its toxic traditional Chinese medicine and its understanding of the enrichment of the toxic characteristics of traditional Chinese medicine and treatment-related disease pathology between the points of contact for patients with clinical applications Based on and theoretical guidance of Chinese medicine [3].

Predicting acute toxicity of traditional Chinese medicine wastewater using UV absorption and volatile fatty acids as surrogates

In this study, the applicability of UV absorbance at 254 nm (UV254) and volatile fatty acids (VFAs) to serve as reliable surrogates to predict acute toxicity of traditional Chinese medicine (TCM) wastewater was investigated. The medicine residues and VFAs were identified as main components of the TCM wastewater, and their individual and joint toxicity assays were operated with luminescent bacteria. The median effective concentration (EC50) values of medicine residues and VFAs were in the range of 26.46–165.55 mg/L and 11.45–20.58 g/L, respectively. The joint toxicity action modes of medicine residues, VFAs and medicine residues-VFAs were identified as additive, additive and synergistic respectively. UV254 and VFAs showed better correlations with acute toxicity according to the correlation analysis, compared with other conventional parameters. The regression model was a good fit for toxic unit (TU50) as a function of UV254 and VFAs according to the stepwise regression method (adjusted R2 = 0.836). Validation of the model to the pilot-scale samples provided satisfactory prediction results in the influent and hydrolysis acidification effluent samples tests, but for EGSB effluent and final effluent samples, the model needed further optimization. Surrogates prediction using UV254 and VFAs provided a valuable and cost-saving tool for rapid or on-line monitoring of acute toxicity of TCM wastewater.

Study and opinion on toxicity of aristolochic acid

On October 18th, 2017, a research article named "Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia" was published on Science Translational Medicine. This article pointed out that herbs containing aristolochic acids could cause liver cancer by inducing the specific "aristolochic acids mutational signature". The public was also suggested to avoid the intake of herbs containing aristolochic acids. Since 2000, CFDA has gradually abolished the medicinal standards for herbs containing aristolochic acids such as caulis aristolochiae manshuriensis, aristolochia heterophylla and radix aristolochiae. Related drugs have been strengthened supervision since then. Chinese Pharmacopoeia has also removed the records of a series of related herbs. State Administration of Traditional Chinese Medicine held a conference on the "toxicity" of aristolochic acids as soon as the article was published. After a discussion of the studies on the toxicity of aristolochic acids, experts attending the meeting discovered several problems, including the unclearness of exposure history, tumor-producing dose and latent period, the absence of some key factors such as hepatitis B, the small sample size, miscellaneous factors, incomplete evidence chains, the missing of analyses between data with huge differences, the insufficiency of fundamental research arguments, etc. In order to understand the toxicity of aristolochic acids and the carcinogenic risks, as well as guide clinical safe medication, the experts suggested that：①Complete the systematical evaluation of aristolochic acids carcinogenicity as soon as possible. Scientifically elucidate the relationship between aristolochic acids and the genesis of liver cancer. ②Establish medication risk warnings of aristolochic acids and strengthen the supervision. ③Make an in-depth study of the toxicity of traditional Chinese medicine. Find out the adverse effects of all traditional Chinese medicine step by step.

Relationship between pre-clinical toxicity and efficacy of traditional Chinese medicine

Based on the different category of syndromes between traditional Chinese medicine(TCM) and Western medicine, the relationship between the efficacy and non-clinical toxicity of the TCM was analyzed. If TCM preparations have the same pharmacological targets to treat disease with modern medicine or the Chinese herbal preparations treat the diseases with its toxicity, their toxicity often exhibits the amplification and extension of activity; on the other hand, if TCM preparations have overlapped pharmacological targets but not completely the same with modern medicine, or if they have totally different pharmacological targets, the toxicity of TCM could not be inferred by pharmacological activity. With the great progress in extraction and separation technique for active parts of TCM as well as the application of some novel technique and excipients, some toxicity may be from the reactions unrelated with the pharmacological activity. In conclusion, better design and quality control could be obtained by understanding the relationship between pharmacological and toxicological study for the investigation of new traditional medicine.

Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.

The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.

Pharmacovigilance of Chinese medicine: practice of cognition, application, prevention and rescue of drug toxicity

Toxicity of traditional Chinese medicine(TCM) is the core of pharmacovigilance of Chinese medicine, whose initiation, development and practice revolves around the toxicity of TCM. Toxicity of TCM has rich meanings, and are influenced by three factors: drug composition, clinical use and patient constitution. With the increasingly deep understanding of toxicity of TCM, the cognition of clinicians is more objective, and the application, prevention and rescue are more complete. Therefore, based on the analysis of large numbers of ancient books, we put forward the whole pharmacovigilance theoretical frame that is formed by cognition, application, prevention and rescue of drug toxicity, which comprehensively reflects the academic Characteristics of safety medication in TCM.

Assay for the developmental toxicity of safflower (Carthamus tinctorius L.) to zebrafish embryos/larvae

ObjectiveTo explore the developmental toxicity and the potential toxicological mechanism of safflower (Carthamus tinctorius L.) on zebrafish embryos/larvae. MethodsMortality, malformations and increased apoptosis induced by safflower were assessed in zebrafish embryos from 6 to 96 hours post-fertilization. Enzymes and genes in the anti-oxidative and apoptotic pathways were also assayed. ResultsThe lethal concentration 50 of safflower to zebrafish embryos was 345.6 mg/L. Hatching inhibition, abnormal spontaneous movement, depressed heart rate, pericardial edema, yolk sac edema, abnormal head-trunk angle, inhibition of melanin release, enlarged yolk, and short body length were observed in safflower-treated zebrafish. Additional apoptotic cells mainly appeared around the heart. Safflower exposure changed the activities of defense enzymes (SOD↑, CAT↑, MDA↑, GPX without trend), increased MDA content, decreased caspase-3 activity, and altered mRNA levels of related genes (ogg1↓, p53↓, Cu/Zn-sod↑, Mn-sod↓, cat↓, gpx↑). ConclusionSafflower exhibits developmental toxicity for zebrafish embryos/larvae. The developing heart was speculated as the target organ of toxicity. Oxidative stress and increased apoptosis have roles in the developmental toxicity of safflower. This article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method.

The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs). Realgar, a toxic traditional Chinese medicine (TCM), does have curative effect on acute promyelocytic leukemia (APL). Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

Research and application of hepatotoxicity evaluation technique of traditional Chinese medicine

The safety of traditional Chinese medicine (TCM) has received the widespread attention in recent years. Hepatotoxicity of TCM is one of the key problems of the safety of TCM. This article summarized research progress and application prospect in the mechanism of TCM hepatotoxicity, biomarkers, toxic omics database, prevention of hepatotoxicity of the liver cell lines, subcellular fraction, three-dimensional cultivation models, the model animals, aiming to provide theoretical basis for TCM toxicity evaluation and technical guidelines, thus promoting the development of TCM toxicity studies. Hope for Chinese medicine liver toxicity evaluation method provides the theoretical foundation and technical guidelines, promote the development and improvement of TCM liver toxicity research system.