Abstract
In this paper, the effect of skipjack (Katsuwonus pelamis) enzymatic peptide (SEP), which was prepared and purified from a byproduct of skipjack, on inflammation, ulcerative colitis and the regulation of intestinal flora was studied in a mouse ulcerative colitis model and a transgenic zebrafish inflammation model. The aggregation of transgenic granulocyte neutrophils in zebrafish from a normal environment and from a sterile environment was calculated, and the anti-inflammatory activity of SEP was evaluated. To evaluate the anti-ulcerative colitis activity of SEP, DSS-induced colitis mice were given SEP, salicylazosulfapyridine (SASP), or SASP + SEP. Then, the concentrations of IL-6, IL-10 and TNF-α in the serum were detected, the HE-stained colon tissue was examined by microscopy the species composition and abundance distribution of the intestinal flora was analyzed. The results showed that 500 μg/mL SEP treatment significantly alleviated neutrophil granulocyte aggregation in the zebrafish inflammation model; Diarrhea, hematochezia and body weight loss were alleviated to a certain extent in mice gavaged with SEP and SASP, and the combination of SASP with SEP was the most effective in mice. The damage to villi in the intestine was completely repaired, and the levels of IL-6, IL-10 and TNF-α, which are associated with inflammation, were all reduced. In addition, the proportion of intestinal probiotics or harmless bacteria increased, while that of pathogenic bacteria decreased, and the effect of the combined treatment was the most pronounced. These results show that SEP could relieve inflammation, cure ulcerative colitis, regulate intestinal flora and enhance the therapeutic effect of the clinical drug SASP. This study provides a theoretical basis for the development of SEP as an anti-inflammatory adjuvant therapy and intestinal flora regulator.
Highlights
The initiation of inflammation, the manifestation of infection or injury, is mediated by resident immune cells via pathogen recognition receptors (PRRs), such as Toll-like receptors (TLRs) [1], leading to the synthesis of soluble mediators such as proinflammatory cytokines, which activate downstream proinflammatory signaling pathways [2]
In treated with the combination of skipjack (Katsuwonus pelamis) enzymatic peptide (SEP) and SASP, the diversity of the intestinal flora was close to that mice treated with the combination of SEP and SASP, the diversity of the intestinal flora was close to of the normal group. These results indicate that SEP has a proliferation-inducing effect on intestinal that of the normal group. These results indicate that SEP has a proliferation-inducing effect on microbes in mice with Ulcerative colitis (UC), which is beneficial to the diversity of the intestinal flora
The physiological activity SEP was investigated based on the transgenic zebrafish model and the UC mouse model
Summary
The initiation of inflammation, the manifestation of infection or injury, is mediated by resident immune cells via pathogen recognition receptors (PRRs), such as Toll-like receptors (TLRs) [1], leading to the synthesis of soluble mediators such as proinflammatory cytokines (see Glossary), which activate downstream proinflammatory signaling pathways [2]. Mar. Drugs 2019, 17, 582; doi:10.3390/md17100582 www.mdpi.com/journal/marinedrugs. Mar. Drugs 2019, 17, 582 mononuclear phagocytes from the blood. Upon arrival at a site of inflammation, granulocytes such as neutrophils primarily phagocytose and eliminate tissue debris and microorganisms through distinct intracellular mechanisms, such as the production of reactive oxygen species (ROS), including hydrogen peroxide, superoxide anions, and hydroxyl radicals, and/or extracellular mechanisms via the release of neutrophil extracellular traps (NETS) [3]. The most widely used inflammation treatment approach is to inhibit the synthesis or action of mediators that drive inflammation using drugs including nonsteroidal anti-inflammatory drugs (NSAIDs) and anticytokine therapies, such as anti-tumor necrosis factor (TNF)-α [4]
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