Benzylideneacetophenone Derivative Alleviates Arthritic Symptoms via Modulation of the MAPK Signaling Pathway

Abstract

The benzylideneacetophenone derivative 3-(4-hydroxy-3-methoxy-phenyl)-1-{3-[1]-phenyl}-propenone (JC3 dimer) was synthesized through the dimerization of JC3. To investigate the inhibitory effects of JC3 dimer, the carrageenan/kaolin (C/K)-induced knee arthritis rat model was used in vivo and rheumatoid arthritis (RA) patient-derived fibroblast-like synoviocytes (FLS) were used in vitro. In the C/K rat model, JC3 dimer was given after arthritis induction for 6 days at the concentrations of 1, 5, or 10 mg/kg/day. Manifestation of arthritis was evaluated using knee thickness, weight distribution ratio (WDR), and squeaking test. The levels of prostaglandin E2 (PGE2), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the serum of JC3 dimer-treated arthritic rats were also analyzed. Histological examination of the knee joints was also done. For the FLS, the cells were stimulated using IL-1β and concentrations of 1, 5, and 10 μg/mL JC3 dimer were used. The levels of IL-8, IL-6, and PGE2 were measured in stimulated FLS treated with JC3 dimer. At days 5 to 6 after arthritis induction, JC3 dimer treatment significantly decreased arthritic symptoms and reduced the inflammation in the knee joints in the histology of knee tissues in C/K-arthritic rats. In stimulated FLS, JC3 dimer suppressed the increase of IL-8, IL-6, and PGE2. These findings suggest that JC3 dimer has suppressive effects on arthritis, and that JC3 dimer can be a potential agent for arthritis therapy.

Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production

“…The inhibition of pro-inflammatory cytokine, such as IL-1β and IL-6 is essential for the control of an inflammatory response [ 29 ]. We measured the levels of the relevant mRNAs via reverse transcription polymerase chain reaction (RT-PCR) [ 30 ]. Like the iNOS protein expression result, compound 4 treatment decreased the iNOS expression at the mRNA level, in a dose-dependent manner.…”

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

“…PGE 2 -increase suppression is important as due to its role in pain responses in inflammation ( Gomez et al ., 2013 ). The results presented are similar to other studies examining anti-inflammatory effects in arthritis animal models ( Hashizume and Mihara, 2011 ; Wojdasiewicz et al ., 2014 ; Dey et al ., 2016 ; Sur et al ., 2020 ).…”

Efecto protector del aceite de Sacha inchi (Plukenetía volubilis linneo) en ratas Holtzman con inducción de artritis experimental

“…Probablemente se origine en la incapacidad de los macrófagos para procesar la molécula de carragenina, la que se acumula dentro de los lisosomas, donde luego se produce una lisis de lisosomas, una respuesta inflamatoria y muerte celular con activación de células T, las que desempeñan un papel importante en la artritis reumatoide con niveles elevados de citocinas (7,9) . La inyección de carragenina por vía intraarticular en la articulación origina inflamación, lo que induce producción de mediadores como TNF, ciclooxigenasa-2 y prostaglandina E2 (PGE2) (10) .…”