Processing methods and the underlying detoxification mechanisms for toxic medicinal materials used by ethnic minorities in China: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Various toxic medicinal materials have been used by different ethnic minorities in China for thousands of years because of their extraordinary pharmacological activities. However, the improper use and complex toxicity-efficacy relationship could cause poisoning and even death. Therefore, the study of toxicity-attenuating methods and mechanisms is necessary. AIM OF THE STUDY: This review aims to summarize commonly used toxic ethnomedicines and their processing methods as well as the underlying mechanisms to potentially reduce toxicity and even enhance or preserve efficacy. Prospective for possible future investigations is also discussed. MATERIALS AND METHODS: Processing methods and mechanisms are investigated mainly through literature review. RESULTS: Processing methods with heating (boiling, stir frying, and steaming, etc.) and without heating (soaking) are usually used by Chinese ethnic minorities to attenuate the toxicity of ethnomedicines. Wheat bran, vinegar, wine, and herbal decoction are commonly used processing excipients. The mechanisms of detoxification by processing can be briefly summarized into three major categories: (1) direct elimination of impurities or reduction of toxic constituents' contents of ethnomedicines by cutting, washing, soaking or frosting; (2) chemical structure transformation of toxic constituents, such as alkaloids, glycosides, toxic proteins, animal toxicants, and mineral components, during heating and/or soaking; and (3) biological synergism or antagonism effects between the chemical constituents of processing excipients and ethnomedicines in vivo, to reduce toxicity and protect target organs. CONCLUSION: Toxic ethnomedicines have long been used in China, and detoxification by processing is the prerequisite for their safe clinical application. However, understanding on the special processing methods and detoxification mechanisms of ethnomedicines in China remains insufficient. Investigations on quality control of toxic ethnomedicines, as well as evaluation of processing methods and studies of the corresponding mechanisms should be further strengthened for safe and effective clinical application.

Aconitum pendulum and Aconitum flavum: A narrative review on traditional uses, phytochemistry, bioactivities and processing methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. AIM OF THE STUDY: This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. MATERIALS AND METHODS: Relevant information about Tiebangchui (A. pendulum and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra, and Jing Zhu Materia Medica, and official drug standards were reviewed. RESULTS: A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. CONCLUSIONS: The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored.

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking.

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.

Effect of Etiasa on the expression of matrix metalloproteinase-2 and tumor necrosis factor-α in a rat model of ulcerative colitis.

The aim of this study was to determine the disease activity index (DAI) and the colonic mucosa damage index (CMDI), and to detect the colonic mucosal expression levels of matrix metalloproteinase-2 (MMP-2) and tumor necrosis factor-α (TNF-α) in rats with ulcerative colitis (UC). We also aimed to investigate the protective role of Etiasa in UC. Sprague Dawley (SD) rats were randomly divided into three groups: the control, an Etiasa-treated group and a UC model group. Rats were sacrificed on days 14, 21, 35 or 56 following the administration of treatment by enema and the DAI, CMDI and colonic expression levels of MMP-2 and TNF-α were assessed. In the UC model group, the DAI and CDMI scores and the colonic expression levels of MMP-2 and TNF-α increased significantly compared with the control at all timepoints, and were also significantly higher than those in the Etiasa-treated group. In conclusion, the expression levels of MMP-2 and TNF-α increased significantly in rats with UC. Etiasa reduces colonic mucosal damage by downregulating the expression of MMP-2 and TNF-α.