Schisandrin A Inhibits the IL-1β-Induced Inflammation and Cartilage Degradation via Suppression of MAPK and NF-κB Signal Pathways in Rat Chondrocytes

Abstract

Osteoarthritis (OA) is a common joint disease in the elderly population. Its development has been reported to be associated with cartilage degradation and inflammatory responses. Schisandrin A, a bioactive lignin in Schisandra sphenanthera, has shown its anti-inflammatory potential in various inflammation diseases. However, the effects of Schisandrin A on OA remain to explore. In this study, rat chondrocytes were treated with IL-1β (10 ng/ml) with or without different concentrations of Schisandrin A for 24 h. Cell viability was evaluated by CCK-8 assay. Production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reaction and ELISA. The MAPK/NF-κB-related signaling molecules expression and the protein production of inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, MMPs (MMP1, MMP3, MMP13), ADAMTS5, Collagen II, aggrecan, and Sox9 were detected by Western blot. Protein expression of Collagen II, aggrecan, and p65 nuclear translocation was evaluated by immunofluorescence. In vivo, intra-articular injection of 50 μM Schisandrin A or equal volume of vehicle was performed on rat OA models. Severity of cartilage damage was evaluated by HE and Safranin-O-Fast green staining. Our results revealed that Schisandrin A could suppress the IL-1β-induced production of NO and PGE2 in rat chondrocytes. Consistent with these findings, the upregulation of iNOS and Cox2 could also been decreased by Schisandrin A. Additionally, Schisandrin A could inhibit IL-1β-induced cartilage matrix catabolic enzymes including MMPs and ADAMTS5. Moreover, the IL-1β-induced downregulation of Collagen II, aggrecan, and Sox9 could be ameliorated by Schisandrin A. Mechanistically, Schisandrin A functioned by suppressing MAPK and NF-κB signal pathways. In vivo, Schisandrin A prevented cartilage damage in rat OA model. In conclusion, this study elucidates that Schisandrin A inhibits the IL-1β-induced inflammation and cartilage degradation via suppression of MAPK and NF-κB signal pathways, indicating its potential role in OA therapy.

Preventive Effects of Schisandrin A, A Bioactive Component of Schisandra chinensis, on Dexamethasone-Induced Muscle Atrophy

“…SNA supplementation improves the condition of nonalcoholic fatty liver disease in mice that were fed a high-fat/high-cholesterol diet [30]. Further, SNA suppresses inflammation, apoptosis, and oxidative stress by suppressing the PI3K/Akt, MAPK, and NF-κB signaling pathways in various cell types [28,31] and activates the Nrf2/HO-1 or AMPK/Nrf2 pathway [32,33]. Moreover, SNA prevents ROS-induced DNA damage and apoptosis in C2C12 cells [29].…”

Berberine inhibits the interleukin‐1 beta‐induced inflammatory response via MAPK downregulation in rat articular chondrocytes

“…In the degradation of the cartilage matrix, MMPs (MMP‐3 and MMP‐13) are involved as proteolytic enzymes (Klein & Bischoff, ). Meanwhile, matrix synthesizing related protein(Collagen II) was decreased in OA (Tu et al, ). Overproduction of MMPs and underproduction of Collagen II can disturb the balance between the degeneration and synthesis of the ECM in articular cartilage and decrease the ability to repair articular cartilage (Liu et al, ; Tetlow, Adlam, & Woolley, ).…”

Use of Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: a Sight Through the Prism of Pathogenesis

“…По данным T. Jia и соавт., при ОА в хондроцитах человека повышается концентрация интерлейкина 1-бета, а также индуцированная интерлейкином 1-бета продукция металлопротеиназ 1, 3 и 13, оксида азота и простагландина Е2 [10]. Аналогичные данные выявлены и в экспериментальных моделях ОА [11,12]. Известно, что при ОА происходит увеличение экспрессии ядерного фактора транскрипции NF-кB.…”