The effect of kaempferol and apigenin on allogenic synovial membrane-derived stem cells therapy in knee osteoarthritic male rats.

Based on the anti-inflammatory and anti-oxidant properties of kaempferol and apigenin, we hypothesized that co-injection of these phytochemicals would increase the effectiveness of cell therapy in knee osteoarthritic rats. Anterior cruciate ligament transection (ACLT) was used to induce osteoarthritis (OA). Animals were treated by weekly intra-articular injections of kaempferol (10 or 20 μM) and/or isolated MSCs from synovial membrane (SMMSCs) (3 × 106 cells), a mixture of apigenin (0.1 μM) and kaempferol alone or SMMSCs, hyaluronic acid or PBS (group size n = 6), for three weeks. After three months, the levels of IL-1β, tumor necrosis factor alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in the cartilage homogenate. Furthermore, relative expressions of collagen II2a1, aggrecan, IL-1β, TNF-α, inducible nitric oxide synthase (iNOS), SOX-9, MMP-3 and MMP-13 were assessed using real-time PCR. Radiological evaluation, before/after treatments, and histopathological assessments were carried out to evaluate the knees. Non-toxic concentrations of kaempferol and apigenin determined to be 10, 20 μM and 0.1, 0.3 μM, respectively. In comparison with the OA group, the levels of TNF-α, IL-1β and MDA significantly decreased in OA + MSCs + kaempferol + apigenin group and a significant increase in SOD level was observed. The levels of MMP-13, MMP-3, TNF-α, IL-1β, iNOS were significantly decreased in the groups of OA + MSCs + A0.1 μM + K10 μM and OA + MSCs + K20 μM. Co-treatment of kaempferol and apigenin increased the gene expression levels of collagen IIa1, aggrecan and SOX-9 genes. We showed that kaempferol and apigenin potentially increase the efficiency of OA cell therapy in the rat model of ACLT-induced OA.