title: CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage.
abstract: Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin (Pae), was evaluated in rats with adjuvant-induced arthritis (AA) to study its potential anti-arthritic activity. AA rats were treated with CP-25 (25, 50, or 100 mg/kg) from days 17 to 29 after immunization. CP-25 effectively reduced clinical and histopathological scores compared with the AA groups. CP-25-treated rats exhibited decreases in pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) coupled with an increase in the anti-inflammatory cytokine TGF-β1 in the serum. CP-25 treatment inhibited M1 macrophage activation and enhanced M2 macrophage activation by influencing cytokine production. Decreases in Th17-IL-17 and the Th17-associated transcription factor RAR-related orphan receptor gamma (ROR-γt) dramatically demonstrated the immunomodulatory effects of CP-25 on abnormal immune dysfunction. In addition, CP-25 suppressed the production of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase (MMP) 9, which supported its anti-osteoclastic effects. The data presented here demonstrated that CP-25 significantly inhibited the progression of rat AA by reducing inflammation, immunity and bone damage. The protective effects of CP-25 in AA highlight its potential as an ideal new anti-arthritic agent for human RA.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Jia
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Huaxun
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D016723:Bone Remodeling / Q000187:drug effects / Q000276:immunology; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005960:Glucosides / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D018448:Models, Immunological; D039821:Monoterpenes / Q000494:pharmacology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D005960:Glucosides; D018836:Inflammation Mediators; D039821:Monoterpenes; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand; C539902:Rorc protein, rat; C000610980:paeoniflorin-6'-O-benzenesulfonate; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat