Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation.Zhiqiao(Fructus aurantii),the nearly mature fruit of Citrus aurantium L.,is widely used in traditional dietary therapy ...Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation.Zhiqiao(Fructus aurantii),the nearly mature fruit of Citrus aurantium L.,is widely used in traditional dietary therapy for intestinal health.Here,we extracted and purified neohesperidin from Zhiqiao and explored its alleviative effects on dextran sulfate sodium-induced colitis and related inflammatory pathways in mice.The results showed that neohesperidin administration significantly ameliorated symptoms of colitis and reduced the accumulation of inflammatory cytokines in mouse tissues and serum.Decreases in the TLR4,MyD88,and NF-κB p65 mRNA expression levels indicated that activity of the TLR4/NF-κB signaling pathway was downregulated.Molecular docking results showed that neohesperidin occupies the lipopolysaccharide-binding pocket of MD-2 and binds to the interacting surface of TLR4/MD-2 and that of the subsequently formed homodimer,thereby disrupting recognition of inflammatory ligands by the TLR4-mediated pathway.Neohesperidin holds promise for the adjunctive treatment of ulcerative colitis.展开更多
基金funded by the Key Lab of Aromatic Plant Resources Exploitation and Utilization in Sichuan Higher Education(Grant No.22XLZ03)the Natural Science Foundation of Chongqing(Grant No.CSTB2023NSCQ-MSX0282 and CSTB2023NSCQ-BHX0158)+3 种基金Chongqing Postdoctoral Research Project Special Support(Grant No.2023CQBSHTB3023)the Fundamental Research Funds for the Central Universities(Grant No.SWU-KR22050,SWU-KQ22057,and SWU113100)the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202201616)the University-Domestic Cooperation Project of Southwest University(2023001206 and 2021001318).
文摘Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation.Zhiqiao(Fructus aurantii),the nearly mature fruit of Citrus aurantium L.,is widely used in traditional dietary therapy for intestinal health.Here,we extracted and purified neohesperidin from Zhiqiao and explored its alleviative effects on dextran sulfate sodium-induced colitis and related inflammatory pathways in mice.The results showed that neohesperidin administration significantly ameliorated symptoms of colitis and reduced the accumulation of inflammatory cytokines in mouse tissues and serum.Decreases in the TLR4,MyD88,and NF-κB p65 mRNA expression levels indicated that activity of the TLR4/NF-κB signaling pathway was downregulated.Molecular docking results showed that neohesperidin occupies the lipopolysaccharide-binding pocket of MD-2 and binds to the interacting surface of TLR4/MD-2 and that of the subsequently formed homodimer,thereby disrupting recognition of inflammatory ligands by the TLR4-mediated pathway.Neohesperidin holds promise for the adjunctive treatment of ulcerative colitis.
