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

Shengwei Chen; Yi Zhang; Xueting Niu; Sahar Ghulam Mohyuddin; Jiayin Wen; Minglong Bao; Tianyue Yu; Lianyun Wu; Canyin Hu; Yanhong Yong; Xiaoxi Liu; A M Abd El-Aty; Xianghong Ju

doi:10.3389/fnut.2021.748118

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

Front Nutr. 2021 Oct 1:8:748118. doi: 10.3389/fnut.2021.748118. eCollection 2021.

Authors

Shengwei Chen^{1

2}, Yi Zhang^{2

3}, Xueting Niu^{1

2}, Sahar Ghulam Mohyuddin^{1

2}, Jiayin Wen^{1

2}, Minglong Bao^{1

2}, Tianyue Yu^{1

2}, Lianyun Wu^{1

2}, Canyin Hu^{1

2}, Yanhong Yong^{1

2}, Xiaoxi Liu², A M Abd El-Aty^{4

5

6}, Xianghong Ju^{1

2}

Affiliations

¹ Department of Veterinary Medicine, Guangdong Ocean University, Zhanjiang, China.
² Shenzhen Institute of Guangdong Ocean University, Shenzhen, China.
³ College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
⁴ State Key Laboratory of Bio Based Material and Green Papermaking, College of Food Science and Engineering, Qilu University of Technology, Shandong Academy of Science, Jinan, China.
⁵ Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
⁶ Department of Medical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.

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.

Keywords: IBD; MAPK; TLR4/NF-κB; anti-inflammatory; butyrolactone-I; intestinal barrier.