Study on the mechanism of cantharidin-induced hepatotoxicity in rat using serum and liver metabolomics combined with conventional pathology methods.

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.

TMT-based proteomics analysis of the blood enriching mechanism of the total Tannins of Gei Herba in mice.

Lanbuzheng (LBZ) is the traditional seedling medicine in Guizhou, which has the effect of tonifying blood. It has been found that the main active ingredient is tannin, however, the blood-replenishing effect of tannin and its mechanism are still unclear. The study was to explore the mechanisms underlying the therapeutic effects of the total Tannins of Lanbuzheng (LBZT) against anemia in mice. Anemia mice was induced by cyclophosphamide, the effect of LBZT against anemia was determined by analyzing peripheral blood and evaluating organs indexes. Tandem mass tag (TMT)-based quantitative proteomics technology coupled with bioinformatics analysis was then used to identify differentially expressed proteins (DEPs) in spleen. Compared to the model, number of RBCs, PLTs and WBCs, HCT ratio and HGB content were increased, the indexes of thymus, spleen and liver were also increased, after LBZT intervention. A total of 377 DEPs were identified in LBZT group, of which 206 DEPs were significantly up-regulated and 171 DEPs were significantly down-regulated. Bioinformatics analysis showed that hematopoietic function has been restored by activating the complement and coagulation cascade signaling pathways. Results suggest that LBZT exerts it therapeutic effects against anemia by regulating complement and coagulation cascade signaling pathways and provides scientific basis for further mechanistic studies for LBZT.

Exploring the protective mechanisms of total tannins from Geum japonicum var. chinense F.Bolle in mice with hematopoietic dysfunction via the JAK2/STAT3/5 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Geum japonicum var. chinense F.Bolle (Rnglish name Gei herba, GH), a traditional Miao medicine, promotes hematopoiesis. Emerging evidence shows that total tannins of GH (TGH) can treat ischemic diseases. AIM OF THE STUDY: To explore the protective mechanism of TGH in hematopoietic dysfunction (HD) mice. MATERIALS AND METHOD: Forty-eight female mice were randomly assigned to 6 groups: control, model, Zhenqi Fuzheng positive, and three doses TGH. Cyclophosphamide was injected in mice to establish an HD model. Spleen tissue was examined histomorphologically, peripheral hemograms and organ index were calculated, and serum hematopoietic factor levels were determined. The expression of proteins in the Janus kinase 2 (JAK2)/transcription 3/5 (STAT3/5) pathway, as well as upstream and downstream proteins, was examined using western blot to elucidate the underlying protective mechanisms of TGH. RESULTS: TGH could effectively alleviate spleen tissue damage in HD mice, improve peripheral hemogram and antagonize organ atrophy, and increase levels of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) and Erythropoietin (EPO) in HD mouse serum. Furthermore, after TGH treatment, the protein expression levels of P-JAK2, P-STAT3, P-STAT5, M-CSF, G-CSF, Bcl-2, and Bcl-xL were significantly higher than in the model group. At the same time, following TGH treatment, the protein expression levels of LC3 A/B, Beclin1, ATG5, and ATG7 were significantly lower than in the model group. CONCLUSIONS: TGH has been shown to protect HD mice through a mechanism linked to the activation of the JAK2/STAT3/5 pathway, as well as autophagy inhibition and apoptosis activation.

Protective effects of aqueous extract from Gei Herba on blood-deficiency mice: insights gained by a metabolomic approach.

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.