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

Abstract

Osteoarthritis (OA) is a degenerative joint disease that is characterized by irreversible articular cartilage destruction by inflammatory reaction. Among inflammatory stimuli, interleukin-1β (IL-1β) is known to play a crucial role in OA pathogenesis by stimulating several mediators that contribute to cartilage degradation. Recently, the marine brown alga Sargassum serratifolium has been reported to exhibit antioxidant and anti-inflammatory effects in microglial and human umbilical vein endothelial cell models using lipopolysaccharide and tumor necrosis factor-α, but its beneficial effects on OA have not been investigated. This study aimed to evaluate the anti-osteoarthritic effects of ethanol extract of S. serratifolium (EESS) in SW1353 human chondrocytes and, in parallel, primary rat articular chondrocytes. Our results showed that EESS effectively blocked the generation of reactive oxygen species in IL-1β-treated SW1353 and rat primary chondrocytes, indicating that EESS has a potent antioxidant activity. EESS also attenuated IL-1β-induced production of nitric oxide (NO) and prostaglandin E2, major inflammatory mediators in these cells, which was associated with the inhibition of inducible NO synthase and cyclooxygenase-2 expression. Moreover, EESS downregulated the level of gene expression of matrix metalloproteinase (MMP)-1, -3 and -13 in SW1353 chondrocytes treated with IL-1β, resulting in their extracellular secretion reduction. In addition, the IL-1β-induced activation of nuclear factor-kappa B (NF-κB) was restored by EESS. Furthermore, EESS reduced the activation of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways upon IL-1β stimulation. These results indicate that EESS has the potential to exhibit antioxidant and anti-inflammatory effects through inactivation of the NF-κB, p38 MAPK, and PI3K/Akt signaling pathways. Collectively, these findings demonstrate that EESS may have the potential for chondroprotection, and extracts of S. serratifolium could potentially be used in the prevention and treatment of OA.

[RETRACTED ARTICLE] Ginsenoside Rd inhibits IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination

“…The activated complex can recruit intracellular adaptor proteins and kinases, including MyD88, IRAK4, and IRAK1, and consequently activates downstream kinases IKK-α and IKK-β, which phosphorylate IκB proteins and lead to activation of NF-κB. Although various plant extracts have been reported to inhibit NF-κB activation by suppressing cell inflammatory responses (15), it remains unclear how they suppress NF-κB activation. The present study showed that ginsenoside Rd decreased IL1RAP protein level but not the mRNA level in NP chondrocytes.…”

Valuing Bioactive Lipids from Green, Red and Brown Macroalgae from Aquaculture, to Foster Functionality and Biotechnological Applications

“…To our knowledge there are few publications that evaluated COX-2 inhibition by macroalgae lipid extracts, and the ones published used cell lines assays, but not in vitro COX-2 assays. Previous studies evaluated the COX-2 expression, evidencing a reduction of the enzyme expression in cell lines [ 72 , 73 , 74 , 75 ], but polar lipid extracts from terrestrial plants and microalgae showed modulation capacity of COX-2 using in vitro assays [ 75 , 76 ]. The ethanolic extract of the small herbaceous plant Polygonum minus (Huds) achieved 25% of COX-2 inhibition at concentration of 100 μg/mL [ 76 ] which is in the same order of magnitude we obtained in the present study (about 80% inhibition at a concentration of 500 μg/mL).…”

Cudratricusxanthone O Inhibits H2O2-Induced Cell Damage by Activating Nrf2/HO-1 Pathway in Human Chondrocytes

“…However, despite these various biological activities, prenylated xanthones have not been studied for OA. Previous studies have shown that hypoxia or inflammatory induction of SW1353 chondrocytes stimulated by IL-1β, monosodium iodoacetate (MIA), and H 2 O 2 is known as a representative in vitro model for OA studies [ 20 , 21 , 22 , 23 ]. In this study, we investigated the role of prenylated xanthones, cudratricusxanthone O (CTO), isolated from M. tricuspidata , on the suppression of H 2 O 2 -induced cell damage by promoting the Nrf2/HO-1 pathway in SW1353 cells.…”