RESUMEN
Safety has always been an important issue affecting the development of traditional Chinese medicine industry, especially for toxic medicinal materials, the establishment of risk prevention and control measures for toxic herbs is of great significance to improving the use of traditional Chinese medicine in clinical. Fuzi is a kind of traditional Chinese medicine and its toxicity has become the most important obstacle of limit in clinical using. In this paper, network pharmacology and molecular docking technology were used to analyze the main toxic components of Fuzi, the key targets and the mechanism of neurotoxicity. We carried out CCK-8 and WB assays, and detected LDH release and SDH activity. It was verified that aconitine caused neurotoxicity through a variety of pathways, including MAPK signaling pathway, pathways related to Akt protein, destruction of cell membrane integrity, damage of mitochondrial function affecting energy metabolism and apoptosis. What's more, this study confirmed that aconitine could produce neurotoxicity by promoting apoptosis of hippocampus neuron and decreasing its quantity through Nissl Staining and TUNEL assay. This paper found and confirmed multiple targets and various pathways causing neurotoxicity of Fuzi, in order to provide reference for clinical application and related research.
RESUMEN
Gliomas are tumors of the primary central nervous system associated with poor prognosis and high mortality. The 5-year survival rate of patients with gliomas received surgery combined with chemotherapy or radiotherapy does not exceed 5%. Although temozolomide is commonly used in the treatment of gliomas, the development of resistance limits its use. MicroRNAs are non-coding RNAs involved in numerous processes of glioma cells, such as proliferation, migration and apoptosis. MicroRNAs regulate cell cycle, PI3K/AKT signal pathway, and target apoptosis-related genes (e.g., BCL6), angiogenesis-related genes (e.g., VEGF) and other related genes to suppress gliomas. Evidence illustrates that microRNAs can regulate the sensitivity of gliomas to temozolomide, cisplatin, and carmustine, thereby enhancing the efficacy of these agents. Moreover, traditional Chinese medicine (e.g., tanshinone IIA, xanthohumol, and curcumin) exert antiglioma effects by regulating the expression of microRNAs, and then microRNAs inhibit gliomas through influencing the process of tumors by targeting certain genes. In this paper, the mechanisms through which microRNAs regulate the sensitivity of gliomas to therapeutic drugs are described, and traditional Chinese medicine that can suppress gliomas through microRNAs are discussed. This review aims to provide new insights into the traditional Chinese medicine treatment of gliomas.