title: Huaier aqueous extract protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NLRP3 inflammasome activation.
abstract: The use of Trametes robiniophila Murr. (Huaier) as a complementary therapy for cancer has recently become increasingly common in China. However, whether Huaier can regulate host immune responses, especially innate immunity, remains largely unknown. The NLRP3 inflammasome is a multimeric complex consisting of NLRP3, ASC and caspase-1. NLRP3 inflammasomes respond to a variety of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli, and play crucial roles in host defense against pathogens and multiple diseases such as ulcerative colitis (UC). In this study, we investigated the anti-inflammatory effect of Huaier in dextran sulfate sodium (DSS)-induced murine colitis and revealed the underlying mechanisms by targeting NLRP3 inflammasomes. In C57BL/6 mice, oral administration of Huaier attenuated DSS-induced colon shortening and colonic pathological damage. Furthermore, we analyzed the effect of Huaier on NLRP3 inflammasome activation in macrophages. Huaier inhibited NLRP3 inflammasome activation-induced IL-1β secretion and caspase-1 cleavage. Moreover, Huaier decreased NLRP3 protein expression via promoting NLRP3 degradation through the autophagy lysosome pathway. Therefore, our findings demonstrate a novel function for Huaier in the regulation of NLRP3 inflammasome activation and suggest a potential role for Huaier in NLRP3 inflammasome-associated diseases.
authors.affiliation: Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Second Hospital of Shandong University, Jinan, Shandong 250033, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wei
authors.affiliation: Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.|Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Medicine, Jinan, Shandong 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Song
authors.affiliation: Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Pathology Tissue Bank, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.|Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D045424:Complex Mixtures / Q000008:administration & dosage* / Q000494:pharmacology; D016264:Dextran Sulfate / Q000009:adverse effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D000074084:THP-1 Cells; D055454:Trametes
chemical_list: D000893:Anti-Inflammatory Agents; D045424:Complex Mixtures; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C000621679:huaier; D016264:Dextran Sulfate
keywords: Huaier; IL-1β; NLRP3; colitis; inflammasome