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.

Design strategies,advances and future perspectives of colon-targeted delivery systems for the treatment of inflammatory bowel disease

Inflammatory bowel diseases(IBD)significantly contribute to high mortality globally and negatively affect patients’qualifications of life.The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations.Moreover,certain natural or synthetic anti-inflammatory drugs are associated with poor targeting,low drug accumulation at the lesion site,and other side effects,hindering them from exerting their therapeutic effects.Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment.This review mainly discusses the treatment status of IBD,obstacles to drug delivery,design strategies of colon-targeted delivery systems,and perspectives on the existing complementary therapies.Moreover,based on recent reports,we summarized the therapeutic mechanism of colon-targeted drug delivery.Finally,we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.

Letter to the editor: Comment on the Regulatios of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine

To the Editor:On Oct 9,2017,China Food and Drug Administration announced1~ the Regulations of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine(Exposure Draft)which has been stirring up intense debate in the West.The article China to Roll Back Regulations for Traditional Medicine Despite Safety Concerns lately

Realgar toxicity in terms of its chemical characterization, pharmacological mechanisms, and metabolic profile: A review

Realgar is an arsenic-containing Chinese medicine known for its toxin-removing,phlegm-dispelling,and malaria-intercepting effects.It has proven to be effective in the treatment of acute promyelocytic leukemia.However,because of the harmful nature of arsenic to human health,realgar is considered a“poison”in many countries,raising concerns about the toxicity and safety of realgar and its preparations.The Shuifei process(grinding with water)of realgar plays a crucial role in ensuring its safety as a Chinese medicine.The major ingredient of realgar,As_(4)S_(4),is water insoluble and poorly absorbed by the human body.Therefore,it is important to note that the toxicity and health risks of realgar to humans are overestimated by solely considering the amount of arsenic.Realgar processing is an indispensable method to ensure the quality of medicinal realgar,involving purification,powdering,detoxification,and synergism.This article not only highlights possible mechanisms through which realgar exerts pharmacological effects but also reviews the literature regarding its toxic features and potential mechanisms.Currently,realgar toxicity research primarily relies on animal experiments,and clinical data on its adverse reactions are relatively limited.The toxicity of arsenic is closely related to the form and valence of itsmajor metabolites in the body.Animal studies have confirmed that,when realgar enters the body,the major form of arsenicmetabolized is dimethylarsenic acid;therefore,it was considered that the toxicity of realgar induced by high doses might be associated with the accumulation of dimethylarsenic acid produced in the methylation pathway of inorganic arsenic.Realgar is generally less toxic when used in safe doses,but prolonged use may pose a significant risk.It is rarely used alone and is often combined with other Chinese medicines in an attempt to reduce toxicity.Scientifically and reasonably limiting the arsenic content of realgar-containing Chinese patent medicines is an effective way to improve the safety of realgar in clinical medication.