title: Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting the synovial joints. The currently available drugs for RA are effective only in a proportion of patients and their prolonged use is associated with severe adverse effects. Thus, new anti-arthritic agents are being sought. We tested Pristimerin, a naturally occurring triterpenoid, for its therapeutic activity against rat adjuvant arthritis. Pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin-treated rats exhibited a reduction in the pro-inflammatory cytokines (IL-6, IL-17, IL-18, and IL-23) and the IL-6/IL-17-associated transcription factors (pSTAT3 and ROR-γt), coupled with an increase in the immunomodulatory cytokine IL-10. Also increased was IFN-γ, which can inhibit IL-17 response. In addition, the Th17/Treg ratio was altered in favor of immune suppression and the RANKL/OPG ratio was skewed towards anti-osteoclastogenesis. This is the first report on testing Pristimerin in arthritis. We suggest further evaluation of Pristimerin in RA patients.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510510, China. Electronic address: tli59@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Siddaraju M
authors.initials: SM
authors.lastname: Nanjundaiah
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Shivaprasad H
authors.initials: SH
authors.lastname: Venkatesha
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Astry
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: kmoud001@umaryland.edu.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001327:Autoimmune Diseases; D016723:Bone Remodeling / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D018836:Inflammation Mediators / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053978:Pentacyclic Triterpenes; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D020780:Matrix Metalloproteinase 9; C050414:celastrol
keywords: Autoimmunity; Experimental arthritis; Mediators of inflammation; Natural products; T cell subsets (Th17/Treg); Therapy