OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Malignancies are a difficult to treat disease in clinical practice.At present,there are many cases of differentiation and treatment based on qi and yin deficiency,the coagulation of phlegm,blood stasis and cancer toxin,there are few theories on the treatment of yang deficiency and yin excessiveness,as well as the coagulation of cold and dampness.On the basis of inheriting the cancer toxin theory of Chinese medicine master ZHOU Zhongying,combined with the theory of promoting yang and our own practice,we believe that malignancy is caused by yang deficiency as the foundation,cold dampness,phlegm-turbidity stagnation and toxin transformation as the manifestation,and the key pathogenesis can be summarized as yang deficiency and yin binding.Based on this,it is proposed to differentiate and treat malignancies from promoting yang and eliminating yin.The method of promoting yang and eliminating yin is people-oriented,with harmony as the value,based on the whole,with a focus on adjusting harmony,constantly promoting yang and timely eliminating yin.The specific differentiation and treatment strategies are as follows:in the early stages of malignancy,it is important to seize the opportunity to warm and dredge,or eliminate yin;malignancy is already present,balancing deficiency and excess,supplementing,eliminating,and harmonizing appropriately;after malignancy surgery,it is important to strengthen the foundation and regulate the spleen and kidney,and strengthen both congenital and acquired constitution;treating the zang-fu organs accordingly,elevating and lowering,and conforming to the physiology of the organs.Unlike simple malignancy treatment and detoxification,promoting yang and eliminating yin is a method of examining symptoms and identifying etiology and pathogenesis.It involves macroscopic regulation of yin and yang,dynamic management of medication,and orderly treatment,which can significantly improve the quality of life of patients and increase long-term survival rates.Exploring the theory and strategy of promoting yang and eliminating yin in the differentiation and treatment of malignancy can provide new ideas and references for the clinical differentiation and treatment of malignancies.