Ganoderic Acid A Attenuates IL-1ß-Induced Inflammation in Human Nucleus Pulposus Cells Through Inhibiting the NF-κB Pathway.

Intervertebral disc (IVD) degeneration is a major cause of low back pain associated with several pathological changes in the IVD, including dysfunction of nucleus pulposus (NP) cells. Ganoderic Acid A (GAA), one of triterpenoid extracts of Ganoderma lucidum (G. lucidum), has been reported to possess anti-inflammatory effect. In the current study, we aimed to evaluate the effect of Ganoderic Acid A (GAA) on the interleukin-1ß (IL-1ß)-induced inflammation in human NP cells. Our results showed that the IL-1ß-stimulated production of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were suppressed by GAA. In addition, treatment of NP cells with GAA significantly inhibited the production of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in IL-1ß-stimulated human NP cells. GAA improved the reduced expression levels of extracellular matrix (ECM) proteins, collagen II and aggrecan in IL-1ß-stimulated human NP cells. GAA also alleviated IL-1ß-induced the levels of matrix metalloproteinase (MMP)-3 and MMP-13. Furthermore, GAA inhibited the IL-1ß-induced upregulation of the phosphorylation of p65 and downregulation of IκBα. Taken together, these findings indicated that GAA alleviated IL-1ß-induced inflammation and ECM degradation in NP cells through regulating NF-κB pathway.

Icariin alleviates osteoarthritis by regulating autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling.

Osteoarthritis (OA) is a chronic degenerative disease that significantly impacts the quality of life of the elderly population. Recently, the pathogenesis of OA has been reported to involve autophagy in chondrocytes. Intriguingly, icariin, one of the main components of epimedium, exerts multiple pharmacological effects, including a protective effect against chondrocyte damage. Thus, we aimed to investigate the therapeutic effect of icariin on OA and its potential underlying mechanism by using a rat model of OA. After treatment with icariin or an autophagy activator (rapamycin) or inhibitor (3-methyladenine), OA chondrocyte viability was measured using the CCK-8 assay, apoptosis in the chondrocytes was evaluated using the acridine orange-propidium iodide assay and flow cytometry, and OA tissue pathological state was assessed using micro-CT scanning and safranin O staining. Furthermore, immunohistochemical staining was used to measure the expression level of Beclin-1 and immunofluorescence labeling was used to visualize LC3 expression, and western blotting was used to determine the expression levels of autophagy proteins and key proteins in the PI3K signaling pathway. The apoptotic rate of OA chondrocytes was markedly elevated by 3-methyladenine and suppressed by rapamycin and icariin; autophagy genes were drastically downregulated in the 3-methyladenine group and upregulated in the rapamycin and icariin groups; and the PI3K/AKT/mTOR signaling pathway was activated by 3-methyladenine and inhibited by rapamycin and icariin. Notably, following treatment with rapamycin and icariin, the severe pathological state in OA cartilage tissues was substantially alleviated, and this was accompanied by activated autophagy and inhibited PI3K signaling in the cartilage tissues. Taken together, these findings indicate that icariin alleviates OA by regulating the autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling.