title: Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway.
abstract: The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling.
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lingpeng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiayun
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Nanjing Municipal Hospital of T.C.M, The Third Affiliated Hospital of Nanjing University of T.C.M, Nanjing 210001, China. Electronic address: hongyan3128@163.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liuyuyaoda@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yantianhuabest@126.com.
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: machunhuabest@126.com.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications*; D001923:Brain Chemistry / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D003094:Collagen; D005620:Freund's Adjuvant; D005960:Glucosides / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D010636:Phenols / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D005620:Freund's Adjuvant; D054460:rho-Associated Kinases; C009172:rhodioloside
keywords: Arthritis; Brain cognition deficits; Inflammation; Rho/ROCK/NF-κB; Salidroside