Assessment of the synergistic anti-inflammatory effect of naringin/sulindac for the treatment of osteoarthritis: in vitro and in vivo

Osteoarthritis is a prevailing form of arthritis that affects more than two hundred million people globally. Current treatments depend mainly on reducing pain and improving movement; however, their adverse effects made their use problematic. Usually, a combination of more than one drug is used to alleviate chronic inflammation. Naringin is a natural plant flavonoid present in fruits and vegetables, having many biological actions as anti-inflammatory, antioxidant and anticarcinogenic actions. In our study, we inspected the anti-inflammatory action of naringin in silico then we evaluated its role individually or in combination with sulindac in vitro on RAW 264.7 cells and in vivo by measuring the levels of most common inflammatory mediators; Tumor Necrosis Factor-alpha (TNF-alpha), Interlukin-6 (IL-6) and nuclear factor kappa beta (NF-kappa B), and the inflammation related pathway mitogen-activated protein kinases/extracellular signal-regulator Kinase (MAPK/Erk1). We also investigated the wound healing effect, locomotor activity and coordination. Results indicated that the combination of low doses of naringin and sulindac restrained the release of IL-6 and NF-kappa B by 63% and 56% respectively. The combinative treatment significantly reduced the serum levels of MAPK and Erk1 by 90% and 91% respectively as compared to carrageenan group. Histological analysis revealed a decline of cellular infiltration, development of pannus, damage of bone and cartilage, which ensures the obtained antiarthritic effect of combination, the physical activity improved also. This study disseminates the effectiveness of naringin to enhance the therapeutic efficacy of sulindac in the treatment of osteoarthritis through attenuation of NF-kappa B levels and suppression of MAPK/Erk1 signaling pathway.