Effect of peniocerol on human meniscal fibrochondrocyte inflammation induced by IL-1β and TNF-α through the NF-κB signaling pathway

It is currently known that meniscal damage has a bidirectional relationship with the onset/development of osteoarthritis (OA), making the development of new therapeutic strategies that comprehensively address both issues crucial. In this context, the present study aimed to evaluate the biological effect of peniocerol (PEN), an emerging phytopharmaceutical, in an in vitro model of inflammation induced by IL-1β and TNF-α in human meniscal fibrochondrocyte cells. Human meniscal fibrochondrocyte cells were isolated, cultured, and treated with different concentrations of PEN to determine those that promote cell proliferation and the IC₅₀ using the MTT assay. The cells were then stimulated with TNF-α (10 ng/mL) or IL-1β (5 ng/mL), with or without PEN (300 and 500 µM). Cell morphology and the expression of ACAN, type I+III collagen, type II collagen, MMP13, and p65 were evaluated by immunofluorescence. Treatment with TNF-α and IL-1β significantly reduced the expression of ACAN and type II collagen, while increasing MMP13 and p65, indicating a degenerative phenotype. Co-treatment with PEN at 300 μM showed partial improvements, while PEN at 500 µM normalized the levels of ACAN, Col2A1, and p65 to values similar to the control, while significantly inhibiting the markers for COL I+III and MMP3. In an in vitro degenerative fibrochondrocyte model, PEN at 500 μM demonstrated its ability to halt extracellular matrix degradation and actively promote its recovery, showing an optimal balance between efficacy and safety as a potential therapeutic strategy for the comprehensive treatment of OA progression.