Fangchinoline Has an Anti-Arthritic Effect in Two Animal Models and in IL-1β-Stimulated Human FLS Cells

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.

Fangchinoline alleviates cognitive impairments through enhancing autophagy and mitigating oxidative stress in Alzheimer’s disease models

“…However, numerous lines of evidence have revealed that Fan induces autophagy via the activation of AMPK/mTOR/ULK1 signaling pathway ( Xiang et al, 2021 ). Meanwhile, Fan has also been reported to inhibit the PI3K/Akt and MAPK signaling pathways in several diseases ( Li et al, 2017 ; Jiang F. et al, 2020 ; Chen et al, 2020 ; Villa et al, 2020 ; Chen et al, 2022 ). However, the exploration of Fan’s impact on proteasome regulation remains relatively limited and restricted to human cancer cells and articular chondrocytes ( Chuu et al, 2015 ).…”

“…Fan has been demonstrated to possess significant anti-inflammatory properties in various inflammatory diseases. Notably, Fan has been shown to exert anti-arthritic effects via the inhibition of MAPK pathway and NF-κB pathway in cell and animal models of rheumatoid arthritis ( Villa et al, 2020 ). Meanwhile, Fan has exhibited the ability to attenuate LPS-induced endotoxemia by inhibiting ERK1/2 and NF-κB p65 phosphorylation ( Chen et al, 2020 ).…”

Phytoceramide Alleviates the Carrageenan/Kaolin-Induced Arthritic Symptoms by Modulation of Inflammation

“…Rats were induced with arthritis using C/K by following a protocol as described ( Hwang et al ., 2008 ; Villa et al ., 2020 ). 3% Isoflurane in N 2 O/O 2 mixture was used to anesthetize the rats, and an intra-articular injection of 100 μL of 5% C/K suspended in saline into the left knee joint was performed to induce arthritic inflammation.…”