Abstract
Ethnopharmacological RelevanceDiarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD.ObjectiveThe aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy.Materials and MethodsWistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats.ResultsThe clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level.ConclusionGlycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.
Highlights
Diarrhea is one of the most common diseases and serves as a public health issue with potentially fatal implications
The levels of tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-2 in the model group were increased compared to the control group (P < 0.05) (Figure 4), while the levels of these serum inflammatory cytokines decreased in the pulsatilla decoction (PD) group when compared to the model group
Comparison of the Base Peak Spectra of Samples The ultra-high performance liquid chromatography (UHPLC)-Orbitrap MS base peak spectra (BPC) of samples were compared in Figures 7, 8
Summary
Diarrhea is one of the most common diseases and serves as a public health issue with potentially fatal implications. As diarrhea is a public health problem with potentially deadly effects, the WHO teamed up with other international organizations to launch a diarrheal disease control program with an emphasis on the use of traditional drug treatments to tackle the condition on a global scale (Xiong et al, 2018). Diarrhea can be divided into different forms such as dampness-heat, dampness-cold, spleen yang deficiency syndrome (Xiong et al, 2018) etc. DHD is one of the most common forms of diarrhea. This pathogenic form is developed by a collection of heat and wetness. The main clinical symptoms of DHD include pathological changes in the intestinal tract, intestinal mucosal injury and inflammation, as well as systemic inflammation (Zheng et al, 2016; Yao et al, 2017)
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