Metabolome alterations in Clonorchis sinensis after treatment with tribendimidine and praziquante in vivo.

Tribendimidine (TBD) is a broad-spectrum anthelmintic drug that is also significantly effective in treating clonorchiasis. In this study, the altered metabolomes of Clonorchis sinensis (C. sinensis) in rats after TBD administration were quantified by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) to explore the possible active sites of TBD against clonorchiasis through altered metabolites and metabolic pathway analysis, and the results are expected to provide a target for the future design of anti-Clonorchis sinensis drugs. The worm burden reduction rate and scanning electron microscopy demonstrated that praziquantel (PZQ, positive control drug) and TBD had significant effects on C. sinensis in rats after treatment at a single dose of 200 mg/kg for 24 h. For the MS-based metabolomic analysis, a total of 173 standard metabolites (126 amino acids, 10 phospholipids and 37 fatty acids) were utilized as a reference metabolite database for metabolome identification. In total, 32 amino acids, 71 phospholipids and 27 fatty acids were detected in the C. sinensis of each group. Among these metabolites, 10 amino acids were significantly decreased in both drug-treated groups. Four lysophosphatidyl cholines (LPCs), six lysophosphatidyl ethanolamines (LPEs) and one phosphatidyl inositol (PI) were significantly increased after treatment with TBD. There were no significant changes in fatty acids among the control group and the two drug-treated groups. The results indicated that TBD administration caused a decrease in amino acids involved in the metabolic pathways of energy consumption and an increase in lysophospholipids, which are the hydrolysis products of phospholipase2 (PLA2) in the phospholipid metabolic pathways. The increased lysophospholipid content can destroy the cell membrane, increase membrane permeability, and even cause exposure to internal antigens that can be attacked by host antibodies. Perhaps the destroyed membrane, the exposed internal antigens and the consumed energy are the cause of the damage and death of C. sinensis after TBD administration. This is an interesting problem that can be examined in future research.

GC/MS-based dynamic analysis of Eucalyptus camaldulensis extract on corre-lation of chromatography-activity against Oncomelania hupensis / 中国血吸虫病防治杂志

Objective To determine the contributions of main chemical compositions of extracts of Eucalyptus camaldulensis represented by GC/MS elute peaks to the molluscicidal activities,and explore a shortcut of looking for the effective components from natural products. Methods E. camaldulensis leaves were collected consecutively in 12 months at the same place,extracted with dichloromethane,analyzed by GC/MS,and their LC50(s)of molluscicidal activities were tested according to the method rec-ommended by WHO. The correlation of the main components in 12 extracts and their molluscicidal activities were analyzed by the grey relative correlation analysis model with software GTMS 3.0. Result All the dichloromethane extracts of eucalyptus leaves showed excellent molluscicidal activities with the highest LC50 of 0.257mg/L and 0.242mg/L for the samples in June and July and the lowest LC50 of 6.802 mg/L and 5.406 mg/L in December and January respectively. The structures of 16 main chemical compo-nents were elucidated by GC/MS and NIST Mass Spectral Library,most of which were monoterpenes and sesquiterpenoids. The gray correlation coefficients with activity were all over 0.5,the first five over 0.9 were 4,4,8-Trimethyltricyclo[6.3.1.0(1,5)]do-decane-2,9-diol,(-)-Spathulenol,a structural isomer of(-)-Spathulenol,Eucalyptol and Ledol. Conclusion The most main in-gredients in the dichloromethane extracts of E. camaldulensis leaves show good correlations with the molluscicidal activity,which suggests that the molluscicidal role is synergistically played by the multiple components together.

Research Progress on the Efficacy,Metabolism and Bioavailability of Mebendazole in Hydatid Disease / 中国寄生虫学与寄生虫病杂志

Mebendazole is currently used in the treatment of hydatid disease.Its poor absorption from the gastro-intestinal tract and low bioavailability aroused further research on new formulations of mebendazole to increase the bioa-vailability and improve the therapeutic efficacy.This review summarizes the recent research progress.

Application of HPLC-MS to analysis of muscone / 中草药

Object To determine the content of muscone in preparation Methods Standard addition, DNP derivatization and HPLC with electrospray ionization tandem mass spectrometry (LC/ESI MS/MS) were utilized Results Identification of muscone hydrazone in the sample was based on the unique mass spectra of the standard Under an optimum condition peak corresponding to + ion and characteristic fragments for muscone hydrazone were observed ESI and APCI full scan m/z 419 MS/MS had the same relative molecular mass and fragmentation pattern The recovery was 102 5% with RSD ≤ 2 76% (n=5) Conclusion The qualitative and quantitative determination on muscone could be fulfilled simultaneously