Gastroprotective Effects of Periplaneta americana L. Extract Against Ethanol-Induced Gastric Ulcer in Mice by Suppressing Apoptosis-Related Pathways.

Shu Fu,Jiamei Chen,Jinfeng Shi,Yichen Hu,Chen Zhang,Chaomei Fu,Xin Nie,Xiaofang Li,Jinming Zhang

doi:10.3389/fphar.2021.798421

Abstract

Although Periplaneta americana L. and its modern preparation, Kangfuxin liquid, have been extensively applied for ulcerative diseases in gastrointestinal tract (e.g., gastric ulcer (GU) and ulcerative colitis, the effective components and potential mechanisms) remain unclear. In accordance with the accumulating research evidences, the relieving/exacerbating of GU is noticeably correlated to focal tissue programmed cell death. Herein, gastro-protective effects of the effective Periplaneta americana L. extract (PAE) fraction were assessed in vitro and in vivo, involving in programmed cell death-related signaling channels. To screen the effective PAE fraction exerting gastroprotective effects, several PAE fractions were gained based on a wide range of ethanol solution concentration, and they were assessed on ethanol-induced ulcer mice. Based on HPLC investigation with the use of nucleosides, the chemical composition of screened effective PAE, extracted by 20% ethanol, was analyzed in terms of quality control. Based on CCK-8 assay, the protective effects on GES-1 cells, impaired by ethanol, of PAE were assessed. After 3 days pre-treatment with PAE (200, 400, 800 mg/kg), the gastric lesions were assessed by tissue morphology, and periodic acid-schiff (PAS) staining, as well as hematoxylin and eosin (H&E) based histopathology-related investigation. The levels for inflammation cytokines (IL1-β, TNF-α, IL-18, PGE2, and IL-6), antioxidant indices (SOD and MDA) were examined via ELISA. In the meantime, based on Western Blotting assay, the expression levels of some programmed cell death-related protein targets (NLRP3, caspase-1, NF-κB p65, MyD88, and TLR4) were analyzed. As revealed from the results, PAE is capable of alleviating gastric mucosa impairment, suppressing the inflammatory cytokines, and down-regulating the MyD88/NF-κB channels. Accordingly, 20% ethanol extract of Periplaneta americana L. would contribute its gastroprotective effects, thereby providing the evidence that its anti-GU mechanisms correlated with inhibiting programmed cell death channel.

Highlights

Gastric ulcer (GU) refers to a prevailing disorder relating to the stomach and intestines with effects on more populations globally (Boligon et al, 2014)
The 20% EE, 40% EE, and 60% EE could effectively prevent the severe gastric mucosa impairment attributed to ethanol
Mice pretreated with 20% EE before ethanol intoxication exhibited good protective effect against tissue impairment by ethanol, in which mucosa color was normally pink while not being thickened, hemorrhages and congestion were not identified

Summary

Introduction

Gastric ulcer (GU) refers to a prevailing disorder relating to the stomach and intestines with effects on more populations globally (Boligon et al, 2014). More and more research reported that programmed cell death is critical channels under the catalysis from caspases downstream pertaining to impairment of gastrointestinal mucosa epithelium (Ahmed et al, 2021). It acts via molecule signaling channels exhibiting the characteristics of the cell regulatory cycle’s initiating, mediating, executing and regulating processes. Mitochondrion channel mitigated programmed cell death had correlations to the act or process of causing or getting H. pylori. The act or process of causing or getting H. pylori up-regulated pro-apoptosis protein Bax, whereas it down-regulate anti-apoptosis protein Bcl condition within gastric mucosa (Liu et al, 2005). It is noticeable that stimulation for caspase three and nine is reported within one gastric adenocarcinoma cell line for responding H. pylori culture (Zhang et al, 2007)

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