Arctigenin prevents the progression of osteoarthritis by targeting PI3K/Akt/NF‐κB axis: In vitro and in vivo studies

Abstract

Osteoarthritis (OA), which is principally featured by progressive joint metabolic imbalance and subsequent degeneration of articular cartilage, is a common chronic joint disease. Arctigenin (ATG), a dietary phyto-oestrogen, has been described to have potent anti-inflammatory effects. Nevertheless, its protective effects on OA have not been clearly established. The target of our following study is to evaluate the protective effects of ATG on IL-1β-induced human OA chondrocytes and mouse OA model. Our results revealed that the ATG pre-treatment effectively decreases the level of pro-inflammatory mediators, such as prostaglandin E2 (PGE2), nitrous oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6 and tumour necrosis factor alpha (TNF-α) in IL-1β-induced human chondrocytes. In addition, ATG protects against the degradation of extracellular matrix (ECM) under the stimulation of IL-1β and the possible mechanism might be connected with the inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor-kappa B (NF-κB) axis. Furthermore, a powerful binding capacity between ATG and PI3K was also uncovered in our molecular docking research. Meanwhile, ATG may act as a protector on the mouse OA model. Collectively, all these findings suggest that ATG could be utilized as a promising therapeutic agent for the treatment of OA. K E Y W O R D Sarctigenin, chondrocyte, inflammation, NF-κB, osteoarthritis Shangkun Tang and Weijun Zhou contributed equally to this work.

Lignans as Pharmacological Agents in Disorders Related to Oxidative Stress and Inflammation: Chemical Synthesis Approaches and Biological Activities

“…Arctigenin protected against LPS-induced lung inflammatory and oxidative damage [ 153 ], and, in IL-1β–induced human osteoarthritis (OA) chondrocytes and mouse OA model, the lignan effectively decreased the level of pro-inflammatory mediators attenuating the progression of OA [ 189 ]. Arctigenin inhibited allergic inflammation type I as heterologous passive cutaneous anaphylaxis, type II as reversed cutaneous anaphylaxis, type III as the sheep red blood cell-induced Arthus reaction and contact dermatitis (type IV hypersensitive inflammation) in vivo as well as suppressed pro-inflammatory enzymes, such as COX, LOX, phospholipase A2 (PLA 2 ), and phosphodiesterase (PDE), in vitro [ 186 ].…”

Compounds from Natural Sources as Protein Kinase Inhibitors

“…The IC 50 value for MKK1 in vitro was 1 nM [ 186 ]. In another study, it was demonstrated that arctigenin interacts with PI3K, and IL-1β-stimulated PI3K and Akt phosphorylation could be inhibited by pre-treatment with arctigenin [ 187 ].…”

CCAL1 enhances osteoarthritis through the NF‐κB/AMPK signaling pathway

“…Osteoarthritis (OA) is a common chronic joint disease [8] and is characterized by the destruction of articular cartilage, sclerosis of subchondral bone, and inflammation of the synovium [11]. Aging is a primary risk factor for OA [12].…”

“…AMPK signaling plays a regulatory role in the chondrocyte apoptosis and cartilage degeneration of OA rat models [7]. In addition, lots of studies have suggested that the occurrence and development of osteoarthritis are related to the excessive activation of NF‐κB [8]. NF‐κB signaling pathway is implicated in the proliferation and apoptosis of OA chondrocytes [9] and has been suggested as the therapeutic target for OA [10].…”