| The dried roots and rhizomes of Sophora tonkinensis Gagnep.(Leguminosae),known as “Shan-Dou-Gen” in Chinese,is one of ten varieties geo-authentic traditional Chinese medicine of Guang Xi.Sophora Tonkinensis Radix et Rhizome(S.Tonkinensis)is cold in nature,bitter in taste,attributive to the lung and stomach meridians.It is commonly used in the treatment of fire-toxin amassment pattern,sore throat,swelling and aching of gum,sores of mouth and tongue.It is an essential medicine for the treatment of sore throat.In recent years,reports of liver injury induced by S.Tonkinensis have attracted widespread attention.However,the chemical composition of S.Tonkinensis and its mechanism of liver injury are still unclear,which restricts its clinical promotion and application.In this study,using UPLC coupled with quadrupole time-of-flight tandem mass spectrometry(Q-TOF MS)to identify the chemical components of S.Tonkinensis.A total of 152 chemical components were identified from the mass spectrometry data,including29 alkaloids,21 organic acids,75 flavonoids,1 quinone and 26 other types.The results showed that there are sequential four-centered H rearrangements and RDA reaction in the fragmentation pattern of matrine-type alkaloids,with characteristic fragment ion peaks including m/z 150.1278,m/z 148.1122 and m/z 136.1120.Subsequently,the HPLC fingerprints of S.Tonkinensis from different origins were established,from which 17 common peaks were selected.The results showed that all batches had good similarity,confirming the fingerprint quality control method established in this study is feasible.In this thesis,we focused on investigation of the mechanism of S.Tonkinensis and its quality marker matrine.On the one hand,using network pharmacology method to preliminarily clarify the biological connotation of liver injury induced by S.Tonkinensis and its quality marker matrine from the molecular perspective.PPI analysis showed that the key proteins IL6,TNF and STAT3 were closely related to inflammation.KEGG pathway enrichment analysis showed that metabolic pathways,such as bile acid secretion,IL-17 signaling pathway,and drug metabolism-cytochrome P450 were related to the liver injury process induced by S.Tonkinensis and its quality marker matrine.On the other hand,a strategy combining transcriptomics and metabolomics(GC-TOF MS and UPLC Q-TOF MS)was adopted to explore the mechanisms of matrine-induced liver injury in mice.The integrated analysis results showed that the downregulation of Gstps and Nat8f1 expression levels led to a disorder in glutathione metabolism,indicating that matrine-induced liver injury may be related to oxidative stress.Compared with the control group,there was no change in the expression level of HMGCS1 in low-dose group,while the expression level of HMGCS1 in high-dose group was down-regulated.HMGCS1 is a bridge between pyruvate metabolism and steroid biosynthesis,contributing to the homeostasis of the liver.Thus,HMGCS1 could be considered a marker gene in the development of matrine-induced liver injury.In addition,metabolites such as taurine,flavin mononucleotide(FMN)and Inosine 5’-monophosphate(IMP)also play an important role in the development of matrine-induced liver injury.The results of multi-omics showed that bile acid metabolism pathway may be an important trigger for matrine-induced liver injury,and further validating the predictive results of network pharmacology.This study completed the chemical composition analysis of S.Tonkinensis,and preliminarily explored the mechanism of S.Tonkinensis and its quality marker matrineinduced liver injury,which provided an analytical method for the construction of quality evaluation system of S.Tonkinensis,and a new insight for exploring the mechanism of matrine-induced liver injury. |
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