The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study

Abstract

Background/Aims: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. Methods: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. Results: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/β and suppressed the IL-1β-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1β-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. Conclusion: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1β-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

Effect of mesenchymal stem cells combined with chondroitin sulfate in an osteoarthritis in vitro model

“…During the more advanced stages of OA the amount of Col2a1 and ACAN decreases by denaturation [59,60], which was in uenced by the increase in the expression of MMPs. Levels of type II collagen and aggrecan increased signi cantly when CS was added to chondrocytes in in amed co-cultures.…”

Rapid characterization the chemical constituents of Bergenia purpurascens and explore potential mechanism in treating osteoarthritis by ultra high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry combined with network pharmacology

“…Osteoarthritis (OA) is a degenerative joint disease characterized by chronic structural damage to articular cartilage, caused by aging, obesity, strain and trauma, resulting in cartilage destruction [1]. The main clinical manifestations of OA are joint pain, stiffness, limited movement, and joint deformity.…”

Ligustilide attenuates nitric oxide‐induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways

“…B, Chondrocytes were treated with LIG in a dose-dependent manner. 18 Nevertheless, the therapeutic mechanism of LIG in chondrocyte apoptosis has yet to be reported. C, D, Chondrocytes treated with SNP (0.75 mmol/L) were untreated or co-treated with or without LIG (25 and 50 μmol/L) and the JNK inhibitor SP600125 (10 μmol/L) or the p38 mitogen-activated protein kinase inhibitor SB203580 (10 μmol/L) for 24 h. The chondrocyte apoptotic rate was assessed through flow cytometry with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) dual staining.…”

“…17 LIG, as an effective chemotherapeutic agent, attenuates IL-1β-induced inflammation and promotes extracellular matrix synthesis in chondrocytes by suppressing NF-κB activation via the PI3K/AKT pathway. 18 Nevertheless, the therapeutic mechanism of LIG in chondrocyte apoptosis has yet to be reported. In the current study, we explored whether LIG prevented rat chondrocyte apoptosis and delayed the recessive process of cartilage degeneration.…”