title: Torilin ameliorates type II collagen-induced arthritis in mouse model of rheumatoid arthritis.
abstract: Advancements in rheumatoid-arthritis-(RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential agents with relative safety and efficacy continues and natural compounds have been considered as alternatives to identify new entities. Since previous in-vivo data and our in-vitro findings showed that torilin has a strong anti-inflammatory property, we further investigated its effect against collagen-induced-arthritis-(CIA) in mice. CIA-induced DBA/1J mice were treated with torilin or methotrexate (MTX) for 5-weeks. Arthritis severity was evaluated by arthritic score and joint histopathology. Draining lymph node (dLN), joint and peripheral-blood mononuclear-cell (PBMC) counts, and activation/localization of T-/B-lymphocytes, dendritic cells (DCs) and neutrophils were examined by FACS analysis. Serum anti-type-II-collagen-(CII) antibody levels and cultured-splenocyte and serum cytokines were also evaluated. Torilin markedly reduced CIA-induced arthritic score, histopathology and leukocyte counts. Besides, torilin suppressed CIA-activated T-cells including CD3+, CD3+/CD69+, CD8+, CD4+ and CD4+/CD25+ in dLNs or joints. It also modified CD19+ or CD20+/CD23+ (B-cells), MHCII+/CD11c+ (DCs) and Gr-1+/CD11b+ (neutrophil) subpopulations. It further depressed total anti-CII-IgG, anti-CII-IgG1 and anti-CII-IgG2a antibody productions. Moreover, while IFN-γ and IL-10 were not affected, torilin suppressed CIA-induced serum TNF-α, IL-1β and IL-6 levels. Interestingly, torilin also blocked IFN-γ, IL-17 and IL-6 cytokines while it did not affect IL-10 but enhanced IL-4 in splenocytes. These results show that torilin attenuated arthritis severity, modified leukocyte activations in dLNs or joints, and restored serum and splenocyte cytokine imbalances. Torilin may have immunomodulatory and anti-inflammatory properties with the capacity to ameliorate the inflammatory response in CIA-mice.
authors.affiliation: Deparment of Molecular & Cellular Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Mehari
authors.initials: M
authors.lastname: Endale
authors.forename: Whi Min
authors.initials: WM
authors.lastname: Lee
authors.forename: Yi-Seong
authors.initials: YS
authors.lastname: Kwak
authors.forename: Na-Mi
authors.initials: NM
authors.lastname: Kim
authors.forename: Bok-Kyu
authors.initials: BK
authors.lastname: Kim
authors.forename: Seung-Hyung
authors.initials: SH
authors.lastname: Kim
authors.forename: Jaeyoul
authors.initials: J
authors.lastname: Cho
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
authors.forename: Seung-Chun
authors.initials: SC
authors.lastname: Park
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Dukhwan
authors.initials: D
authors.lastname: Ko
authors.forename: Manhee
authors.initials: M
authors.lastname: Rhee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005528:Foot / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007596:Joints / Q000166:cytology; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D045789:Sesquiterpenes, Guaiane / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; D045789:Sesquiterpenes, Guaiane; C112694:torilin