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: Lingpeng Zhu, Tong Chen, Xiayun Chang, Rui Zhou, Fen Luo, Jingyan Liu, Kai Zhang, Yue Wang, Ying Yang, Hongyan Long, Yu Liu, Tianhua Yan, Chunhua Ma
• Journal: Neuropharmacology (Neuropharmacology) Vol. 103 Pg. 134-42 (Apr 2016) ISSN: 1873-7064 [Electronic] England
• PMID: 26690894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Glucosides
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Phenols
• Tumor Necrosis Factor-alpha
• Collagen
• Freund's Adjuvant
• rho-Associated Kinases
• rhodioloside

Topics

• Animals
• Arthritis (chemically induced, complications)
• Brain Chemistry (drug effects)
• Cognition Disorders (etiology, metabolism, prevention & control)
• Collagen
• Freund's Adjuvant
• Glucosides (administration & dosage, blood, therapeutic use)
• Hippocampus (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Maze Learning (drug effects)
• NF-kappa B (metabolism)
• Phenols (administration & dosage, blood, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)
• rho-Associated Kinases (metabolism)