Liquiritin reduces chondrocyte apoptosis through P53/PUMA signaling pathway to alleviate osteoarthritis.

AIMS: The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. MATERIALS AND METHODS: Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. KEY FINDINGS: Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. SIGNIFICANCE: This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.

Amygdalin Delays Cartilage Endplate Degeneration and Improves Intervertebral Disc Degeneration by Inhibiting NF-κB Signaling Pathway and Inflammatory Response.

Background: Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), in which inflammatory is frequently involved. Amygdalin (AMD) is a naturally occurring compound that exerts anti-fibrotic, anti-inflammatory, analgesic, and immunomodulatory effects in various diseases. The purpose of this study was to investigate the therapeutic effects and molecular mechanisms of AMD on Lumbar spine instability (LSI)-induced IDD in mice. Methods: In this study, we first explored the effects of AMD in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old male C57BL/6J mice were administrated with AMD. At 10 weeks after LSI, spinal were collected for tissue analyses, including histology, micro-CT, and immunohistochemistry for Col2, Mmp-13, TNF-α, and p-P65. Additionally, we also evaluated the mRNA and protein expression level of p-P65 and p-IKBα after being treated with AMD in vitro. Results: Histological staining, micro-CT and immunohistochemical analysis showed that AMD treatment significantly inhibited the expression of TNF-α and Mmp-13, increased the expression of Col2 as well as attenuated the calcification of cartilage endplates, eventually to delayed the progression of IDD. Meanwhile, in vivo and in vitro fluorescence imaging revealed that AMD markedly inhibited the AMD significantly inhibited the LSI-induced increase in TNF-α expression and P65and IKBα phosphorylation. Discussion: Our findings suggest that AMD partly inhibits the activation of NF-κB signaling pathway to reduce the release of inflammatory mediators and delay the degeneration of cartilage endplate in IDD model mice. Therefore, AMD may be a potential candidate for the treatment of IDD.