Mori folium inhibits interleukin-1β-induced expression of matrix metalloproteinases and inflammatory mediators by suppressing the activation of NF-κB and p38 MAPK in SW1353 human chondrocytes

Abstract

The pro-inflammatory cytokine interleukin-1β (IL-1β) is known to play a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. Mori folium, the leaves of Morus alba L., has long been used in traditional medicine to treat diabetes, protect the liver, and lower blood pressure; however, the role of Mori folium in OA is not yet fully understood. Therefore, in the present study, we investigated whether Mori folium water extract (MF) inhibited the catabolic effects of IL-1β in vitro, and also whether it inhibited the matrix metalloproteinases (MMPs), inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) through the attenuation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) pathways in SW1353 human chondrocytes. MMP proteins in culture medium were determined using a cytokine‑specific enzyme-linked immunosorbent assay (ELISA). The production of NO and prostaglandin E2 (PGE2) were evaluated using Griess reagent and ELISA. Subsequently, the mRNA and protein levels of MMPs, iNOS, COX-2, NF-κB and MAPKs were examined by RT-qPCR and/or western blot analysis. The results indicate that MF significantly reduced the IL-1β‑induced release of MMP-1 and -13 in SW1353 cells, which was associated with the inhibition of MMP-1 and -13 mRNA and protein expression in a concentration‑dependent manner at concentrations with no cytotoxicity. MF also attenuated the IL-1β-induced production of NO and PGE2, and reduced iNOS and COX-2 expression. Furthermore, we noted that MF markedly suppressed the IL-1β‑induced nuclear translocation of NF-κB, which correlated with the inhibitory effects of MF on inhibitor-κB (IκB) degradation, and the phosphorylation of p38 MAPK was selectively restored by MF upon IL-1β stimulation. These results indicate that MF inhibited the production and expression of MMP-1 and -13 and inflammatory mediators, at least in part, through suppressing the activation of either NF-κB or p38 MAPK in IL-1β-treated SW1353 chondrocytes. Therefore, the novel findings of the present study suggest that MF is a potential therapeutic choice for chondroprotection against the collagen matrix breakdown in the cartilage of diseased tissues, such as those found in patients with arthritic disorders.

Sargassum serratifolium Extract Attenuates Interleukin-1β-Induced Oxidative Stress and Inflammatory Response in Chondrocytes by Suppressing the Activation of NF-κB, p38 MAPK, and PI3K/Akt

“…Furthermore, to investigate whether EESS can regulate upstream NF-κB signaling pathways, we examined the effects of EESS on MAPKs and PI3K/Akt pathways. Consistent with the results of previous studies [29,30,31], it was found that ERK, JNK, and p38 MAPK were activated in IL-1β treated chondrocytes, as evidenced by their phosphorylation. However, by pretreatment of EESS, only the activation of p38 MAPK was attenuated, and EESS did not affect the activation of ERK and JNK.…”

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

“…In addition, Mori folium possesses free radical-scavenging activities (Kim and Jang 2011, Iqbal et al 2012, Raman et al 2016, which may explain its antioxidant ability (Khan et al 2013, Raman et al 2016. Previous studies, including our recent data, indicated that the extracts and components of Mori folium have strong anti-inflammatory properties (Hong et al 2002, Shibata et al 2007, Chao et al 2009, Jeong et al 2016. Despite these encouraging studies, the effects and molecular mechanisms responsible for the anti-inflammatory and antioxidant potentials of Mori folium have remained elusive.…”

“…The dried leaves of M. alba were obtained from Bio-Port Korea, Inc. (Busan, Republic of Korea), and WEMF was prepared as previous described (Jeong et al 2016). WEMF was dissolved in a 100 mg/ml concentration with distilled water, and the stock solution was then diluted with culture medium to the desired concentration prior to use.…”

The Effect of the Prethanol Extract of <b><i>Trifolium pratense</i></b> Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

“…In our studies of the anti-inflammatory effect of 40% PeTP and in many other research papers, IL-1β has been shown to induce OA through the nuclear translocation of the NF-κB p65 sub-DOI: 10.1159/000496108 unit and MAPK phosphorylation [van den Berg, 2000;Goldring et al, 2011;Kim et al, 2011;Jeoun et al, 2016]. We thus confirmed the anticatabolic effects of 40% PeTP on the IL-1β-induced phosphorylation of MAPKs (ERK1/2, JNK, and p38) and the nuclear translocation of the NF-κB p65 subunit.…”

“…In addition, IL-1β-induced increase in expression is found in the synovial fluid and cartilage tissue of patients with OA [Dieppe et al, 1999;Zheng et al, 2017]. Thus, a reduction in the activity of cartilage-degrading enzymes and inflammatory mediators is expected to have beneficial effects, such as chondroprotection, against pathological conditions like OA [Jeoun et al, 2016]. In OA, cartilage destruction is closely related to chondrocyte dedifferentiation, which is modulated by multiple signaling pathways, including the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) pathways, such as ERK-1/2, JNK, and p38 [Kim et al, 2011;Goldring et al, 2011].…”