Angelica sinensis aboveground part polysaccharide and its metabolite 5-MT ameliorate colitis via modulating gut microbiota and TLR4/MyD88/NF-κB pathway

The roots of Angelica sinensis have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this herb (aboveground part) are commonly discarded during the process of root preparations. A polysaccharide (ASP-Ag-AP) in the aboveground parts of A. sinensis was isolated and preliminarily characterized as typical plant pectin. ASP-Ag-AP exhibited noticeable protective effects against dextran sodium sulfate (DSS)-induced colitis, including reduction of colonic inflammation, modulation of barrier function, and alteration of gut microbiota and serum metabolite profile. Anti-inflammatory effects of ASP-Ag-AP were observed by inhibiting TLR4/MyD88/NF-κB signaling pathway in vitro and in vivo. Additionally, the level of serum metabolite 5-methyl-dl-tryptophan (5-MT) was reduced by DSS and restored by ASP-Ag-AP, which also negatively correlated with Bacteroides, Alistipes, Staphylococcus and pro-inflammatory factors. The protection from inflammatory stress on intestinal porcine enterocytes cells (IPEC-J2) of 5-MT was observed through the inhibition of TLR4/MyD88/NF-κB pathway. Besides, 5-MT also exhibited robust anti-inflammatory effect in colitis mice with improving colitis symptoms, barrier function and gut microbiota, which was the same as presented by ASP-Ag-AP. Therefore, ASP-Ag-AP could be a promising agent for colitis prevention and 5-MT could be the signal metabolite of ASP-Ag-AP on defending against intestinal inflammatory stress.