Harnessing the potential of ginger/derivatives as therapeutic targets in the management of knee osteoarthritis: a molecular docking approach

Background: Amongst musculoskeletal diseases, knee osteoarthritis (KOA) form most critical chronic joint disorder being more prevalent in females than in males, increases markedly in elderly population and correlate significantly with obesity. The structural alterations underlining KOA includes cartilage degradation, subchondral bone lesion, osteophyte formation, and altered changes in synovium and joints capsule.Inflammation forms core player of KOA to set in progressive and degenerative changes of knee joints vis-a-vis up regulate battery of pro-inflammatory cytokines including (TNF-α,IL-1β) as well as inflammasome complex(NLRP3).We hypothesize that ginger/its derivatives which have been well documented for their culinary and anti-inflammatory functions would be effective as anti-inflammatory in KOA to protect the joint degeneration. Methods: In the present study we selected 15 ginger derivatives (literature survey) and with molecular docking approach screened the derivatives targeted against potent key inflammatory markers of KOA including TNF-α, IL-1β and inflammasome NLRP3complex. Subsequently we scored for highest binding energy and lowest binding distance (HBE-LBD) using Schrödinger software. Results: Interestingly, we show that 6-gingerol and Zingerone demonstrated highest HBE-LBD for TNF-α,6-gingerol and paradol for IL-1β, and 8-gingerol and 10-gingerol for NLRP3 receptor. Conclusions: Our findings are novel and report for the first time for the differential cross talk of ginger derivatives for a given Ligand displaying higher binding affinity and specificity to inflammatory targets. Way forward, we advocate carrying out efficacy studies using combinational approach 6-gingerol/Zingerone/paradol vis-à-vis 8-gingerol and 10-gingerol in KOA model to unravel target precision of the identified ginger derivatives so as to arrive for their therapeutic signatures in management of KOA.