Abstract
Periplaneta americana, a magic medicinal insect being present for over 300 million years, exhibits desirable therapeutic outcome for gastrointestinal ulcer treatment. Nowadays, P. americana ethanol extract (PAE) has been shown to ameliorate ulcerative colitis (UC) by either single-use or in combination with other therapeutic agents in clinics. However, its underlying mechanisms are still seldom known. Herein, we investigated the anti-UC activity of PAE by alleviating intestinal inflammation and regulating the disturbed gut microbiota structure in dextran sulfate sodium (DSS)-induced UC rats. Based on multiple constitute analyses by HPLC for quality control, PAE was administrated to DSS-induced UC rats by oral gavage for 2 weeks. The anti-UC effect of PAE was evaluated by inflammatory cytokine production, immunohistochemical staining, and gut microbiota analysis via 16S rRNA sequencing. As a result, PAE remarkably attenuated DSS-induced UC in rats. The colonic inflammatory responses manifested as decreased colonic atrophy, intestinal histopathology scores and inflammatory cytokines. In addition, PAE improved the intestinal barrier function via activating Keap1/Nrf-2 pathway and promoting the expressions of tight junction proteins. It was observed that the UC rats showed symptoms of gut microbial disturbance, i.e., the increased Firmicutes/Bacteroidetes ratio and the significantly decreased probiotics such as Lactobacillus, Roseburia, and Pectobacterium, which were negatively correlated with these detected pro-inflammatory cytokines (secreted by immune CD4+ T cells, and including IFN-γ, TNF-α, IL-6, IL-8, IL-17, IL-1β). Besides, PAE administration regulated the abnormal intestinal microbial composition and made it similar to that in normal rats. Therefore, PAE could attenuate the DSS-induced UC in rats, by means of ameliorating intestinal inflammation, improving intestinal barrier function, and regulating the disturbed gut microbiota, especially improving beneficial intestinal flora growth, modulating the flora structure, and restoring the intestinal-immune system.
Highlights
Ulcerative colitis (UC) is a representative chronic inflammatory bowel disease (IBD) with high morbidity worldwide, characterized by recurrent remission and relapse (Danese and Fiocchi, 2011)
We evaluated the anti-ulcerative colitis (UC) activity of ethanol extracts of P. americana (PAE), which were provided by GoodDoctor Pharmaceutical Co., Ltd., and widely used as the preparation materials for Kangfuxin liquid, in a dextran sodium sulfate-induced UC rat model that mimicked many histopathological and immune characteristics of human intestinal inflammation
Both high- and low-dose P. americana ethanol extract (PAE) could increase the mucin expressions, showing much more positive blue cells in both PAE-H and PAE-L groups. These results suggested that PAE could inhibit colonic inflammation and promote the restoration of intestinal mucosa
Summary
Ulcerative colitis (UC) is a representative chronic inflammatory bowel disease (IBD) with high morbidity worldwide, characterized by recurrent remission and relapse (Danese and Fiocchi, 2011). It is reported that the incidence of UC ranges from 35 to 100 per 100,000 people. A global epidemiology study has reported that compared to United States and United Kingdom, Southern Europe and Asia have a more rapid growth rate of UC incidence (Hanauer, 2006; Molodecky et al, 2012). Some potential side-effects of these drugs, such as anti-antibody reaction, allergy, infection and mutagenesis, could be brought by long-term use and compromise their clinical applications (Renna et al, 2014; Gu et al, 2017). To investigate the effective anti-UC drugs with higher drug safety is of great significance and urgency
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