Inhibition of Carrageenan/Kaolin-Induced Arthritis in Rats and of Inflammatory Cytokine Expressions in Human IL-1β-Stimulated Fibroblast-like Synoviocytes by a Benzylideneacetophenone Derivative

Abstract

The benzylideneacetophenone derivative JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] (JC3) was synthesized by modifying yakuchinone B obtained from the seeds of Alpinia oxyphylla , a member of the ginger family (Zingiberaceae), which are widely used as a folk remedy and as an anti-inflammatory. The aim of this study was to investigate the anti-arthritic effects of JC3 in rat models of carrageenan-induced paw pain and carrageenan/kaolin-induced knee arthritis. The anti-nociceptive effect of JC3 was assessed by measuring paw withdrawal pressure thresholds using an analgesy-meter. Arthritic symptoms in our monoarthritic rat model were evaluated using weight distribution ratios (WDR), paw thicknesses, and serum prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular endothelial growth factor (VEGF) levels (determined by ELISA). Histological analyses of knee joints were performed after injecting JC3 intraperitoneally into rats before carrageenan treatment at 5 or 10 mg/kg/day for 6 days. The anti-inflammatory effects of JC3 were investigated in vitro using interleukin-1beta (IL-1β)-stimulated fibroblast-like synoviocytes (FLS) derived from arthritis patients. PGE2, IL-6, and IL-8 levels were measured after treating FLS with JC3. In arthritis-induced rats, JC3 treatment significantly decreased nociceptive and arthritic symptoms at days 5 to 6 after carrageenan/kaolin injection. Histological staining of knee tissue showed that JC3 significantly reduced inflammatory areas in the knee joints. Furthermore, JC3 inhibited the expressions of IL-6 and IL-8 in FLS cells at concentrations of 5–10 μg/ml and decreased PGE 2 levels in FLS cells. These findings suggest JC3 has anti-arthritic effects in in vivo and in vitro , and that it might be useful for the treatment of arthritis.

In vitro and In vivo Models for Anti-inflammation: An Evaluative Review

“…The kaolin-induced edema model is suitable for sub-acute inflammation. The experiment is performed as described [27]. Edema was induced in the animals by the introduction of 5% suspension of Kaolin in normal saline (0.1 mL) into the plantar surface of the animal paw after 30 min of drug treatment.…”

Concomitant using of topical carrageenan-kappa and oral vitamin D against 7, 12-dimethylbenz[a]anthracene induced-oral cancer in rats: A synergism or an antagonism effects

“…Topical application κ-carrageenan or systemic oral administration of vitamin D produced an increment of TNF-α level in rats bearing tumor while concomitant administration of these agents does not produce considerable incremental. Carrageenan per se can induce inflammation and thereby increased the serum level TNF-α which explained our findings [23]. The explanation of systemic oral vitamin D produced an increment of TNF-α level is a little bit complicated.…”

Holistic approach to microwave-reflux extraction and thermo-analytical fingerprints of under-utilized Artocarpus heterophyllus seed wastes

“…This is an important spicy compound with flavouring attribute which could be a potential alternative for food preservations and as an anti-inflammatory agent when isolated as a single pure compound ( Li et al., 2019 ). Moreover, the presence of other secondary alkaloids such as Dendrocandin F (m/z = 315.13, RT = 6.72 min) ( Yang et al., 2018 ), Yakuchinone A (m/z = 357.17, RT = 12.38 min) ( Sur et al., 2019 ), Aspidinol (m/z = 269.10, RT = 6.45min) ( Wang et al., 2016 ), Saponin PA (m/z = 853.46, RT = 10.89 min) ( Xu et al., 2013 ) confirmed the activities of A. heterophyllus as anti-tumour agents which makes them potential drug candidates against cancerous cells.…”