Treatment Mechanism of Gardeniae Fructus and Its Carbonized Product Against Ethanol-Induced Gastric Lesions in Rats.

Xue Zhang,Yejia Dai,Yinlian Ma,Xuezhu Gu,Dingrong Yu,Guoyou Wang,Xiaoqing Li,Yun Wang,Depeng Liu,Qinghao Wang,Cun Zhang

doi:10.3389/fphar.2019.00750

Abstract

Gardeniae Fructus (GF) and carbonized GF (GFC) have been shown to exert a gastrointestinal protective effect and are frequently used in clinical practice for the treatment of hemorrhage and brown stool. In this study, we employed a combination of pharmacological methods and metabolomics in a rat model of ethanol-induced acute stomach ulcer to investigate the gastroprotective effect of GF and GFC water extracts and the potential mechanism involved in this process. The levels of nitric oxide (NO) and interleukin 6 (IL-6) in the plasma of rats were determined. The results showed that both GF and GFC reduced the ethanol-induced gastric lesions and expression of NO and IL-6 in these rats. Of note, 16 and 11 feature metabolites were filtered and identified in the GF and GFC groups, respectively. Both GF and GFC act by restoring the biosynthesis of valine, leucine, and isoleucine, and the metabolism of glycerophospholipids. Moreover, histological evaluation revealed that heat processing of GF to create GFC enhanced the gastric mucosa protective effect. Furthermore, heat processing converted the main pathway from alanine, aspartate, and glutamate metabolism, associated with GF, to histidine metabolism, associated with GFC. GF and GFC ameliorated gastric mucosa lesions in rats via reductions in NO production and inflammatory cytokine secretion, and the induction of prostaglandin E2.

Highlights

Hematemesis and melena or hematochezia are signs and symptoms of acute upper gastrointestinal bleeding (AUGIB)
Microscopic observation of hematoxylin and eosin (H&E)-stained sections showed that administration of absolute ethanol induced gastric mucosal segmental hemorrhage, edema, and lymphocytic hyperplasia in rats of the M group
principal components analysis (PCA) Metabolomics data were obtained from the total ion current in hydrophilic interaction liquid chromatography (HILIC) and C18 separation. (Figure 2) The quality control samples (QCs) clustered together and there was no variable with a coefficient of variation (CV) beyond 15% in both the HILIC and C18 separation modes

Summary

Introduction

Hematemesis and melena or hematochezia are signs and symptoms of acute upper gastrointestinal bleeding (AUGIB). Natural products with antioxidant and gastroprotective properties have attracted the attention of complementary doctors and been used in the treatment of peptic ulcers which may lead to nonvariceal upper gastrointestinal hemorrhage (Repetto and Llesuy, 2002; Awaad et al, 2013). Such products have been in traditional Chinese medicine (TCM) for thousands of years in the treatment of similar syndromes to AUGIB. Gardeniae Fructus (GF) and its heat-processed products are commonly used in treatment of hematemesis and hematochezia

Methods

Results

Discussion

Conclusion