Cancan Duan

Background: Norcantharidin (NCTD) has multiple antitumor effects. However, NCTD can induce significant hepatotoxicity and the mechanism of hepatotoxicity is not clear for now. Objective: This study aimed to explore the hepatotoxicity of NCTD in rat by ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight (Q-TOF)-MS (UPLC/Q-TOF-MS) metabolomics. Results: Serum biochemical indices including alanine aminotransferase (ALT) and total bilirubin (T-BIL) were significantly increased. Histopathological and ultrastructure results revealed that hepatocytes were damaged. Furthermore, the metabolomics results showed that 11 metabolites in serum and 8 metabolites in liver were differential metabolites for NCTD hepatotoxicity. Four metabolic pathways including the sphingolipid metabolism, purine metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were the key metabolic pathways related to NCTD hepatotoxicity. Conclusion: The metabolomics analysis in this study reveal new clues on the hepatotoxicity mechanism of NCTD in rats. These findings have potential applications in the toxicity study of NCTD.

Purpose. Compound banmao capsule (CBC), a well-known traditional Chinese medical material, is known to inhibit various tumors. However, its material basis and pharmacological mechanisms remain to be elucidated. This study aimed to investigate the effective material basis and mechanisms of action of CBC against tumors. Methods. Active compounds of CBC were identified using public database and reports to build a network. The corresponding targets of active compounds were retrieved from online databases, and the antitumor targets were identified by GeneCards database. The antitumor hub targets were generated via protein-protein interaction analysis using String, and key compounds and targets from the integrative network were detected by molecular docking and ADMET. Top targets in hepatocellular carcinoma were confirmed by quantitative real-time PCR (qPCR). Finally, the multivariate biological network was built to identify the integrating mechanisms of action of CBC against tumor cells. Results. A total of 128 compounds and 436 targets of CBC were identified successfully. Based on the generated multivariate biological network analysis, 25 key compounds, nine hub targets, and two pathways were further explored. Effective material bases of cantharidin, baicalein, scutellarin, sesamin, and quercetin were verified by integrative network analysis. PTGS2, ESR1, and TP53 were identified as hub targets via multivariate biological network analysis and confirmed using qPCR. Furthermore, VEGF and estrogen signaling pathways seem to play a role in the antitumor activity of CBC. Thus, breast cancer may be a potential clinical indication of CBC. Conclusion. This study successfully identified the material basis of CBC and its synergistic mechanisms of action against tumor cells.

Cantharidin (CTD), a compound secreted from Mylabris species, exhibits strong antitumor properties; however, hepatotoxicity restricts its clinical application. The mechanism by which CTD induces toxicity remains unclear. In the present study, the hepatotoxicity of CTD in the rat was investigated using a metabolomic approach combined with conventional pathology methods. A total of 30 rats were intragastrically treated with two doses of CTD (0.75 and 1.5 mg/kg) for 15 days to evaluate hepatotoxicity. Serum and liver samples were collected for biochemical dynamics analyses, histopathological examination and metabolomic analysis. It was found that liver index and serum biochemical indices were significantly increased. Furthermore, the pathology results showed that hepatocytes and subcellular organelles were damaged. Metabolomics analysis found 4 biomarkers in serum and 15 in the liver that were associated with CTD‐induced hepatotoxicity. In addition, these were responsible for CTD hepatotoxicity by glycerophospholipid metabolism, sphingolipid metabolism, and steroid hormone biosynthesis. In conclusion, conventional pathology and metabolomics for exploring hepatotoxicity can provide useful information about the safety and potential risks of CTD.

With increasing tumor incidence, anemia (categorized as a blood deficiency in traditional Chinese medicine) caused by chemotherapy has become a major side effect worldwide. Gei Herba, a traditional Miao nation herb, has a prominent effect on the treatment of blood deficiency (BD). However, its application is limited owing to little fundamental research. Therefore, a GC-MS metabolomic approach was used to study the protective effect of aqueous extract from Gei Herba (AEG) on BD mice and its putative mechanism. In this study, 32 male mice were divided into four groups: a control group, a BD model group, and two groups subjected to AEG treatment at a daily dose of 0.15 or 0.30 g kg⁻¹ for 8 d. After AEG treatment, the HGB and HCT levels in the blood of BD mice were significantly increased, the activity of superoxide dismutase was increased, and the histomorphology of the liver was improved. Furthermore, compared with those in the model group, the levels of eight significant metabolites [phosphoric acid, glycine, L-proline, ribitol, (Z,Z)-9,12-octadecadienoic acid, oleic acid, uridine and 4B2H-carbamic acid] in the liver were significantly changed by AEG. The findings of this study provide sound evidence regarding the protective effects of AEG in BD mice from both classical and metabolomic perspectives. The mechanisms of action of AEG could be related to regulation of linoleic acid metabolism and that of glycine, serine, and threonine metabolism.