Abstract
In recent years, drug-induced liver injury (DILI) has become an important issue of public health. Euodiae Fructus (EF) is a commonly used herb with mild toxicity in clinic, and large doses of EF can cause significant liver damage. Licorice processing might reduce the hepatotoxicity of CEF (crude EF), but up to now, studies on the hepatotoxicity of EF have been hardly reported, let alone its material basis and mechanism of detoxification by licorice processing. This work firstly established a stomach excess-cold syndrome animal model induced by intragastric administration of cold Zhimu (Anemarrhena asphodeloides Bge). Secondly, multiple approaches and indexes were used to evaluate the hepatotoxicity of the drugs in the rats including general behavior, biochemical analysis, protein expressions, and histopathological examination. Thirdly, the hepatotoxicity of three doses of three CEF and LPEF (licorice-processed EF) extracts was systematically investigated, and the hepatotoxicity differences were analyzed and compared comprehensively among the three extracts, three doses, and CEF and LPEF. Finally, the connotation of detoxification of EF by licorice processing was preliminarily discussed according to the changes in toxic components after processing, toxicological characteristics, and TCM (traditional Chinese medicine) theory. All extracts of EF were found to have dose-dependent hepatotoxicity, and the toxicity was in the descending order of water extract, ethanol extract, and volatile oil. The hepatotoxic mechanism of EF may be related to peroxidation damage, inflammatory factor, and mitochondrial injury. The CEF hepatotoxicity can be significantly reduced by licorice processing. EF should be safe for short-term use at pharmacopeial dose under the guidance of the TCM theory. The detoxification mechanism is probably related to the reduction of toxic components and antagonistic action of licorice.
Highlights
Throughout human history, traditional medicine has made important contributions to the prevention and treatment of the diseases all over the world
The toxicity of traditional Chinese medicine (TCM) is closely related to its efficacy and syndromes; the comprehensive evaluation and cognition of toxicity should be based on the syndromes of TCM
The model “stomach excess-cold syndrome” was found to be acute, its pathological process was short, and the symptoms could be self-healing after the discontinuation of Zhimu
Summary
Throughout human history, traditional medicine has made important contributions to the prevention and treatment of the diseases all over the world. Safety has always been the outstanding advantage of traditional Chinese medicine (TCM). With the widespread use of TCM in the world, the safety problems/issues are gradually increasing (Teschke and Eickhoff, 2015; Xiao et al, 2021). In recent years, the frequent occurrence of adverse events, such as drug-induced liver injury (DILI), has become an important issue for public health. The TCM safety has become a domestic and international focus, which has seriously affected the healthy and sustainable development as well as the modernization and internationalization process of TCM (Wang et al, 2018; Xiao, 2019). The safe use of herbal medicine and traditional medicine has been increasingly challenging. It is of great importance to study the toxic and side effects of TCM and explore the scientific connotation of detoxification
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