Reflections on the Toxicity and Safety of Traditional Chinese Medicine Combined with the Cases of Nephrotoxicity and Hepatotoxicity

This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.

Guideline for the diagnosis and treatment of rheumatoid arthritis with integrated traditional Chinese medicine and Western medicine to increase efficiency and reduce toxicity

Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.

A Brief Discussion on the Toxicity of Traditional Chinese Medicine

With the wide application of traditional Chinese medicine in the world,the related reports on the toxicity of traditional Chinese medicine are increasing,which makes the safety of traditional Chinese medicine receive wide attention.This paper analyzes the toxicity of traditional Chinese medicine with a fair and scientific attitude,in order to promote the benign and sustainable development of traditional Chinese medicine.

Advances in Research of Toxic Traditional Chinese Medicines in the Treatment of Malignant Tumors

Combating poison with poison is an important method of traditional Chinese medicine to treat malignant tumors.This study reviews the experimental research on anti-tumor effects of toxic traditional Chinese medicines in recent years.It summarizes the action mechanism of toxic traditional Chinese medicines for the treatment of malignant tumors,including:inhibiting tumor cell proliferation and angiogenesis,inducing tumor cell apoptosis and differentiation,reversing tumor cell multidrug resistance(MDR),inhibiting tumor cell invasion and metastasis,and enhancing the body's immune functions.Finally,it discusses the research and development prospects of toxic traditional Chinese medicines as new anti-tumor drugs.

Metabolomics and its application in the evaluation of toxicity of traditional Chinese medicine

Metabolomics is a newly developed discipline following genomics,transcriptomics,and proteomics.It is based on the theory of systems biology,supported by modern spectroscopy analysis technology and is analyzed by the external stimulation of organisms.By analyzing the overall changes of metabolites with low molecular weight in organism after being stimulated by the outside world,we can understand the physiological and pathological state of organism,and finally clarify the essence of biological changes of organism.In recent years,metabolomics has developed rapidly.It has been widely used in early toxicity screening of lead compounds,preclinical toxicity of drugs and toxicity evaluation of clinical drugs.The in-depth interpretation of metabolomics results is also developing.This article reviewed the progress of metabolomics technology and its application in the study of toxicity evaluation of traditional Chinese medicine.

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

某些药物在体内代谢过程中会生成反应性代谢物,并与体内的大分子物质结合产生毒副作用.这些亲电代谢产物或中间体,具有化学不稳定性和较短的半衰期,往往不易被检测到.谷胱甘肽作为天然的亲核物质,可以捕获亲电的反应性代谢产物,与之形成GSH共价结合物.利用液质联用技术对GSH结合物进行检测和分析,即可快速筛查和发现中药潜在毒性物质.本文简要介绍了谷胱甘肽捕获反应性代谢物的原理,列举了近年来 LC-MS 检测 GSH 结合物的定性和定量分析方法,例如用于检测谷胱甘肽特征碎片的中性丢失扫描、前体离子扫描和多反应监测等方法,并就该技术在一些含有吡咯里西啶生物碱类 （阿多尼弗林碱、毛果天芥菜碱）、呋喃类（黄独乙素）、醌类（黄樟素）中药毒性物质的发现进行了综述.概而述之,基于GSH 捕获反应性代谢物的 LC-MS 检测方法,可快速、灵敏地发现中药潜在的毒性反应性代谢物,具有较好的应用前景.

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.

The riddles of number nine in Chinese medicine processing method

The“nine cycles of steaming and shining”,“nine making”,“nine turns”and“nine cycles of calcining and quenching”methods that are recorded and used since ancient times are merely one aspect of the unique processing methods of traditional Chinese medicine.Inducing the Chinese medicine processing method“nine cycles of steaming and shining”from historical review and summarizing the practical wisdom based on the canonical aspects of traditional Chinese medicine and the experiences of ancient Chinese medicine sages to promote the new development of traditional Chinese medicine.After the long-term and multiple“nine”processing,the materials of traditional Chinese medicine exhibit significant beneficial changes in terms of taste,efficacy,and chemical composition contents,thus emphasizing that Chinese medicine processing plays a significant role in their efficacy enhancement and toxicity reduction.Heshouwu(Polygoni Multiflori Radix),Dihuang(Rehmanniae Radix),Huangjing(Rhizoma Polygonati),Dahuang(Radix et Rhizoma Rhei),and Xixiancao(Herba Siegesbeckiae)are representatives of Chinese medicinal materials prepared using the“nine-system”processing method.This review discovers the aim and the molecular mechanism of“nine”processing of the abovementioned herbs from the viewpoints of modern pharmacochemistry and pharmacology to provide a theoretical support for the“nine”processing method of traditional Chinese medicine and to promote the international market of traditional Chinese medicine.

Network toxicology and LC-MS-based metabolomics:New approaches for mechanism of action of toxic components in traditional Chinese medicines

Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines(TCMs).In this study,we reviewed the application of network toxicology based on LC-MS metabolomics,mainly in the study of toxic components and the toxicity mechanism of TCMs,which provides new ideas and methods for the further study of the toxicity mechanism of TCMs.

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

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.

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 cor- rectly understand the toxicity of Chinese materia medica （CMM） is an important guarantee for safe drug use. The history of the applica- tion and research of the toxicity of CMM has been long, and the Chi- nese medicine community ,has never stopped exploring the issues related to the safety of CMM.

A systematic review of treating Helicobacter pylori infection with Traditional Chinese Medicine

AIM: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of Helicobacter pylori (H pylori) infection. METHODS: We electronically and manually searched electronic databases, references lists and conferences compilations, and included all randomized clinical trials comparing the treatment of H pylori using TCM with proton pump inhibitor or colloidal bismuth subcitratebased triple therapy as controls. The Jadad score was used to assess trial quality, H pylori eradication rate and the incidence of side effects were taken as outcome measurements, and heterogeneity analysis, meta-analysis and funnel plot analysis were conducted. RESULTS: Sixteen trials were included. The Jadad scores of all the trials were not more than 2. Clinical heterogeneity and substantial statistical heterogeneity existed among the trials (P = 0.001, I 2 = 59%) and meta-analysis was not conducted. The average eradication rates following TCM and triple therapy were 72% and 78% and the incidence of side effects were 2% and 29%, respectively. The funnel plot was obviously asymmetric. CONCLUSION: Available evidence is not convincing enough to show that TCM has the same efficacy as triple therapy in H pylori treatment. TCM may be safer than triple therapy. TCM should not be recommended as monotherapy in H pylori infection.

A Histological Study on Subacute Toxicity of "Baikening" in Hy-Line Brown Roosters

[ Objective] A histological study was conducted to investigate the toxicity of ＂Baikening＂ and the toxic effect of ＂Baikening＂ on roosters after longer- term administration at different dose levels. [ Method] Thirty 21-day-old Hy-Line Brown roosters were administered with 0.5 and 1.0 ml of ＂Balkening＂ aqueous extract through drinking water once a day for continuous 14 d. Roosters in control group and experimental groups after drug administration for 14 d and drug with- dmwal for 7 d were euthatfized; livers, kidneys, thymuses, spleens and bursas of Fabricius were collected and weighed for comparative analysis. Various tissues were prepared into paraffin-embedded slices and stained by H. E. , to observe histological changes of various organs under an optical microscope. [ Result ] After drug administration for 14 d, all the roosters in experimental groups survived; there was no visible pathological change in various organs of Hy-Line Brown roosters in each group; organ weights of Fly-Line Brown roosters in various groups showed no significant difference; observation results of tissue slices indicated that there was no pathological change in fine structures, nuclei and cytoplasm of various organs of Hy-Line Brown roosters in different groups ; various blood vessels in different organs also presented no change in blood circulation or other pathological changes. [ Conclusion] ＂Baikening＂ aqueous extract （oral administration） has no toxic and side effect on roosters in the subacute toxicity experiment.

Chronic Toxicity Study in Rats Orally Exposed to Mulberry Sea-Buckthorn Beverage Concentrate

Objective: This study is designed to observe the chronic toxicity after the administration of mulberry sea-buckthorn beverage concentrate for 3 months on rats and to predict the possible adverse effect and the potential toxicity target organs. Method: The rats (SPF level) were randomly divided into high-dose (20 mL/kg BW), middle-dose (10 mL/kg BW), low-dose (5 mL/kg BW) groups and negative control group (20 mL/kg BW of purified water) with 30 rats in each group. Each group was orally given mulberry sea-buckthorn beverage concentrate for 3 months and recovered by stop feeding samples for 2 weeks for a recovery observation. The rats’ general condition, the organ coefficient, the indexes of hematology and blood biochemistry and the histological changes of the main organs were determined. Result: The appearance and behavior of activity in rats showed no anomalies in all these groups and all the rats put on weight during this period. Comparing to the negative control group, no obvious differences were observed in the weekly weight and organ coefficient of each dose group. After 3 months of administration, HGB in both mulberry sea-buckthorn beverage concentrate low-dose group and high-dose group were increased. No significant differences were observed in the indexes of hematology after 2 weeks of recovery. CREA in low-dose, middle-dose and high-dose groups were significantly increased after 3 months of administration and it remained in the high level in middle-dose and high-dose group even after 2 weeks of recovery. No drug-related lesions were observed in the histological changes of major organs. Conclusion: The results show that long term use of mulberry concentrated sea-buckthorn beverage can lead to increased CREA, which suggested kidney toxicity. Although no obvious pathological change was found in kidney, we should pay attention to chronic kidney damage in the further research.

Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report

Stevens-Johnson syndrome/toxic epidermal necrolysis(SJS/TEN)is a rare adverse cutaneous reaction with a low incidence and high mortality.Despite posing a serious threat to patients’health and lives,there is no high-quality evidence for a standard treatment regimen.Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN.After consensus-based regular treatments at a local hospital,his symptoms became worse.Thus,he consented to receive Chinese herbal medicine(CHM)therapy.The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day.After 7 days of treatment,the dead skin began peeling away from the former lesions that had covered his hands,feet,and lips,indicating that skin had regenerated.After 12 days of treatment,the patient’s skin was completely recovered.In this case,SJS/TEN was successfully treated with Pi-Yan-Ning,suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments.Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Non-thermal plasma treatment of Radix aconiti wastewater generated by traditional Chinese medicine processing

The wastewater effluent from Radix aconiti processing, an important step in the production processes of traditional Chinese medicine（TCM）, is a type of toxic wastewater and difficult to treat. Plasma oxidation methods have emerged as feasible techniques for effective decomposition of toxic organic pollutants. This study examined the performance of a plasma reactor operated in a dielectric barrier discharge（DBD） to degrade the effluent from R. aconiti processing. The effects of treatment time, discharge voltage, initial pH value and the feeding gas for the reactor on the degradation of this TCM wastewater were investigated. A bacterium bioluminescence assay was adopted in this study to test the toxicity of the TCM wastewater after non-thermal plasma treatment. The degradation ratio of the main toxic component was 87.77% after 60 min treatment with oxygen used as feed gas and it was 99.59% when the initial p H value was 8.0. High discharge voltage and alkaline solution environment were beneficial for improving the degradation ratio. The treatment process was found to be capable of reducing the toxicity of the wastewater to a low level or even render it non-toxic. These experimental results suggested that the DBD plasma method may be a competitive technology for primary decomposition of biologically undegradable toxic organic pollutants in TCM wastewater.

Use of Chinese herbal medicine to treat AD: advantageous efficacy and stimulation of PKA signaling at crossroad between neural plasticity enhancement and pTau clearance

OBJECTIVE Currently, almost all chemical compounds or biological reagents to reverse or slow down the AD process have failed in clinical trials. An integrative and multi-targeted strategy is increasingly appreciated to effectively combat this devastating disease. Traditional Chinese medicine(TCM) has been widely used for treatment of dementia, and thus the advantages of the potential therapeutic features of TCM treatment and associated mechanisms should be well taken. The Amnesia Remedy Formula(ARF) was invented by one of the most influential Master of TCM SUN Si-miao, who lived for about 100 year old. The aim of this research is to characterize the time course changes of the cognitive behaviors post a ARF, and the mechanism underlying the effects, focusing on PKA-centered signaling for both enhancement of neural plasticity and clearance of the phosphorylated Tau. RESULTS We tested the efficacy of ARF on two animal models of AD, and examine the central role of PKA signaling in the enhancement of neural plasticity via PKA/CREB/BDNF pathway as well as clearance of toxic p Tau via PKA/GSK3β/p Tau pathway. In the scopolamine model, ARF effectively reversed the memory in Morris water maze(MWM) test, with some features superior to anti-AD drug donepezil. In a battery test of MWM, novel object recognition or T maze in 5-month-old senescenceaccelerated mouse prone 8(SAMP8) strain mice, two weeks of administration of ARF showed overall better improvement in memory loss than donepezil, and the effect lasted for at least 1 week after termination of administration of the formula. ARF increased expression of PKA/CREB/BDNF and synaptic proteins PSD95 expression, as well as enhanced Ser9 phosphorylation of GSK3β, thus reduced p Tau in the hippocampus. Blockade of PKA signaling blunted the anti-AD-like effect of ARF, with reversal of CREB/BDNF signaling. Transcriptomic analysis indicated some changes of novel molecules along this pathway may be part of the pathological and therapeutic mechanism, which warrants further investigation. CONCLUSION ARF may display some advantageous features in treating AD with early onset, via multi-targeted manner including enhancement of neural plasticity and reduction in Tau toxicity.

Acute and Sub-chronic Toxicity of Tetrandrine in Intravenously Exposed Female BALB/c Mice

Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

飞龙掌血茎和根不同炮制品对小鼠的急性毒性试验

旨在了解飞龙掌血[Toddalia asiatica(Linn)Lam.]茎和根不同炮制对小鼠急性毒性作用。130只KM小鼠适应性喂养3 d后,随机分为13组,包括溶媒组和12个药物试验剂量组(1个药材茎生品组和5个茎炮制组,1个根生品组和5个根炮制组,其中5种药材炮制品包括水煮制品、水洗制品、水蒸制品、酒蒸制品和酒炙制品)。溶媒组小鼠按40 mL/kg给予纯净水灌胃,给药3次,间隔4~5 h;茎各炮制品试验组小鼠按40 mL/kg灌胃,给药3次,间隔4~5 h;根各炮制品试验组小鼠按30 mL/kg灌胃,给药2次,间隔4~5 h,记录给药后各组小鼠14 d的主要临床症状、体重变化,并统计死亡率。结果表明,飞龙掌血及各炮制品可对小鼠产生急性毒性作用,临床中毒症状有自主活动减少、安静怠动、俯卧和翻正反射消失。炮制品组与溶媒组比较,在14 d内茎和根各炮制品均可致小鼠体重明显降低,且死亡率显著高于溶媒组(P<0.05或P<0.01);而与生品组比较,茎和根的5种炮制品在14 d内对小鼠体重的影响不显著,可有效降低小鼠的死亡率,其中以水煮法效果最佳。水煮、水洗、水蒸、酒蒸、酒炙炮制方法可以减小飞龙掌血茎和根(生品)对小鼠的毒性作用,但对小鼠体脂影响不显著。