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

Background: Based on the anti-inflammatory and anti-oxidant properties of kaempferol and apigenin, we hypothesized that co-injection of these phytochcmicals would increase the effectiveness of cell therapy in knee osteoarthritic rats. Methods: Anterior crutiate ligament transection (ACLT) was used to induce osteoarthritis (OA). Animals were treated by weekly intra-articular injections of kaempferol (10 or 20 mu M) and/or isolated MSCs from synovial membrane (SMMSCs) (3 x 106 cells), a mixture of apigenin (0.1 mu M) and kaempferol alone or SMMSCs, hyaluronic acid or PBS (group size n 6), for three weeks. After three months, the levels of IL-1 beta, tumor necrosis factor alpha (TNF-alpha), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in the cartilage homogenate. Furthermore, relative expressions of collagen II2a1, aggrecan, IL-1 beta, TNF-alpha, 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. Results: Non-toxic concentrations of kaempferol and apigenin determined to be 10, 20 mu M and 0.1, 03 mu M, respectively. In comparison with the OA group, the levels of TNF-alpha, IL-1 beta and MDA significantly decreased in OA MSCs + kaempferol + apigenin group and a significant in- crease in SOD level was observed. The levels of MMP-13, MMP-3, TNF-alpha, IL-1 beta, iNOS were significantly decreased in the groups of OA + MSCs + A0.1 mu M + K10 mu M and OA + MSCs K20 mu M. Co-treatment of kaempferol and apigenin increased the gene expression levels of collagen 11a1, aggrecan and SOX-9 genes. Conclusion: We showed that kaempferol and apigenin potentially increase the efficiency of OA cell therapy in the rat model of ACLT-induced OA. (C) 2020 Elsevier B.V. All rights reserved.