Coral-Derived Endophytic Fungal Product, Butyrolactone-I, Alleviates Lps Induced Intestinal Epithelial Cell Inflammatory Response Through TLR4/NF-κB and MAPK Signaling Pathways: An in vitro and in vivo Studies

Abstract

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

Butenolide derivatives from Aspergillus terreus selectively inhibit butyrylcholinesterase

“…In recent years, many efforts have been devoted to discovering potent and selective BChE inhibitors through chemical design and synthesis ( Li et al, 2021 ; Rossi et al, 2021 ), or screening of natural products (NPs) and their derivatives ( Orhan et al, 2017 ; Jabir et al, 2018 ; Wu et al, 2019 ; Chen et al, 2021 ; Onder et al, 2022 ). Galantamine, isolated from the bulbs and the flowers of Galanthus woronowii , is an approved drug used for treating AD as a natural AChE inhibitor with relatively weak BChE inhibitory activity ( Marucci et al, 2021 ).…”

Egg yolk phosphatidylcholine alleviates DSS-induced colitis in BALB/c mice

“…[55][56][57] Prior studies have shown that DSS reduced the expression of TJs in the gut epithelium of mice, and restoring the level of TJs could improve the homeostasis of the intestinal mechanical barrier and alleviate inflammatory bowel disease. [58][59][60] An in vivo study showed that DHAenriched PLs could increase the levels of TJ proteins ZO-1 and occludin, and thereby improved the intestinal barrier of DSS treatment injury. 61 This study is the first to show that EYPC can significantly inhibit DSS-induced reduction of colonic TJ expression and maintain intestinal barrier integrity.…”

Influence of Heat Stress on Intestinal Epithelial Barrier Function, Tight Junction Protein, and Immune and Reproductive Physiology

“…Ocaña-Guzman et al reported that stress could hinder the body's delayed hypersensitivity reaction and reduce T lymphocyte conversion function, which may be caused by endogenous opioids. Also, the stress-induced inhibition of T lymphocyte reaction may be related to the Under HS, the gastric emptying time and the intensity of intestinal peristalsis of animals are prolonged and weakened, which reduces the mechanical digestive function, resulting in accumulation of chyme and inhibition of appetite [47] 8…”