ABSTRACT
This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.
Subject(s)
Irritable Bowel Syndrome , Rats , Male , Animals , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/metabolism , Water , Chromatography, Liquid , Tryptophan , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Diarrhea/drug therapy , Biomarkers , RiboflavinABSTRACT
Cycloastragenol, a naturally occurring compound in Astragali Radix, has been demonstrated to possess various pharmacological actions including anti-aging, anti-inflammation, anti-fibrosis, antibacterial, liver and endothelium protection. However, whether cycloastragenol ameliorates heart failure remains unclear. Isoproterenol administration to rats triggered classic cardiac damage, as demonstrated by objective parameters of cardiac dysfunction. The treatment of cycloastragenol improved deranged cardiac parameters in the isoproterenol-induced heart damage model in a dose-dependent manner. At the same time, cycloastragenol markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Moreover, the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in rat heart were also inhibited by cycloastragenol. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by cycloastragenol. These results suggest that cycloastragenol ameliorates cardiac dysfunction and remodeling through promoting autophagy in myocardial cells and suppressing MMP-2 and MMP-9 expressions, indicating that it could be a drug candidate for patients with congestive heart failure.