Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.113
Fangchinoline Has an Anti-Arthritic Effect in Two Animal Models and in IL-1β-Stimulated Human FLS Cells
Thea Villa, Mijin Kim and Seikwan Oh*
Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea
*E-mail: skoh@ewha.ac.kr
Tel: +82-2-6986-6271, Fax: +82-2-6986-7014
Received: July 3, 2020; Revised: July 13, 2020; Accepted: July 13, 2020; Published online: July 27, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/ kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 μM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.
Keywords: Fangchinoline, Arthritis, Inflammation, FLS, ROS, NF-κB


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