licochalcone-a and Osteoarthritis

Osteoarthritis (OA), which is characterized by proliferation of subchondral bone and the degeneration of articular cartilage, is the most prevalent human arthritis. Nod-like receptor pyrin domain 3 (NLRP3) inflammasome is a hot spot in recent year and has been reported to be associated with OA synovial inflammation. However, there are few studies on NLRP3 inflammasome in chondrocyte. Licochalcone A (Lico A), a compound extracted from Glycyrrhiza species, has various biological effects such as anti-inflammation, anti-apoptotic, anti-cancer and anti-oxidation. In this study, we investigated the protective effect of Lico A on chondrocytes stimulated by lipopolysaccharide (LPS) and surgically induced OA models. In vitro, Lico A could reduce the expression of NLRP3, apoptosis-associated speck-like protein (ASC), Gasdermin D (GSDMD), caspase-1, interleukin-1beta (IL-1β) and IL-18, which indicated that Lico A attenuates LPS-induced chondrocytes pyroptosis. In addition, Lico A ameliorates the degradation of extracellular matrix (ECM) by enhancing the expression of aggrecan and collagen-II. Meanwhile, we found that Lico A inhibits NLRP3 inflammasome via nuclear factor erythroid-2-related factor 2 (Nrf2)/haeme oxygenase-1(HO-1)/nuclear factor kappa-B (NF-κB) axis. And the Nrf2 small interfering RNA (siRNA) could reverse the anti-pyroptosis effects of Lico A in mouse OA chondrocytes. In vivo, Lico A mitigates progression OA in a mouse model and reduces OA Research Society International (OARSI) scores. Thus, Lico A may have therapeutic potential in OA.

Topics: Animals; Apoptosis; Cartilage, Articular; Chalcones; Chondrocytes; Inflammasomes; Interleukin-18; Interleukin-1beta; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Osteoarthritis; Plant Extracts; Pyroptosis; RNA, Small Interfering; Signal Transduction

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. In this study, we evaluated the anti-inflammatory effects of Lico A on IL-1β-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that Lico A treatment significantly inhibited PGE2 and NO production induced by IL-1β. IL-1β-induced iNOS and COX-2 expression were also inhibited by Lico A. Lico A inhibited MMP1, MMP3, and MMP13 production in IL-1β-stimulated chondrocytes. Lico A also inhibited IL-1β-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, Lico A was found to upregulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of Lico A. In conclusion, our results suggested that Lico A showed anti-inflammatory effects in IL-1β-stimulated chondrocytes by activating Nrf2 signaling pathway.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Chalcones; Chondrocytes; Humans; Interleukin-1beta; NF-E2-Related Factor 2; Osteoarthritis; Signal Transduction