Xueliang Zhang

Background: Irritable bowel syndrome (IBS) is a chronic disorder of the gut-brain axis with significant morbidity. Triptolide, an active compound extracted from Tripterygium wilfordii Hook F (TwHF), has been widely used as a major medicinal herb in the treatment of inflammatory disease. Methods: The chronic-acute combined stress (CAS) stimulation was used to establish IBS rat model. The model rats were then gavaged with triptolide. Forced swimming, marble-burying, fecal weight and abdominal withdrawal reflex (AWR) score were recorded. Pathologic changes in the ileal and colonic tissues were validated by hematoxylin and eosin staining. The inflammatory cytokines and Ornithine Decarboxylase-1 (ODC1) in the ileal and colonic tissues were performed by ELISA and WB. Results: Triptolide didn’t have antidepressant- and antianxiety- effects in rats caused by CAS, but decreased fecal weight and AWR score. In addition, Triptolide reduced the release of IL-1, IL-6, and TNF-α and the expression of ODC1 in the ileum and colon. Conclusion: The therapeutic efficacy of triptolide for IBS induced by CAS was revealed in this study, which may be related to the reduction of ODC1.

The aim of this study is to establish and validate a rapid, selective, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine tubeimoside I (TBMS-I) in ICR (Institute of Cancer Research) mouse whole blood and its application in the pharmacokinetics and bioavailability study. The blood samples were precipitated by acetonitrile to extract the analytes. Chromatographic separation was performed on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm). The mobile phase consisted of water with 0.1% formic acid and methanol (1 : 1, v/v) at a flow rate of 0.4 mL/min. The total eluting time was 4 min. The TBMS-I and ardisiacrispin A (internal standard (IS)) were quantitatively detected by a tandem mass spectrometry equipped with an electrospray ionization (ESI) in a positive mode by multiple reaction monitoring (MRM). A validation of this method was in accordance with the US Food and Drug Administration (FDA) guidelines. The lower limit of quantification (LLOQ) of TBMS-I was 2 ng/mL, and the calibration curve was linearly ranged from 2 to 2000 ng/mL (r² ≥ 0.995). The relative standard deviation (RSD) of interday precision and intraday precision was both lower than 15%, and the accuracy was between 91.7% and 108.0%. The average recovery was >66.9%, and the matrix effects were from 104.8% to 111.0%. In this assay, a fast, highly sensitive, and reproducible quantitative method was developed and validated in mouse blood for the first time. The absolute availability of TBMS-I in the mouse was only 1%, exhibiting a poor oral absorption.