Myricetin exerts anti-biofilm activity and attenuates osteomyelitis by inhibiting the TLR2/MAPK pathway in experimental mice.

To evaluate the potential of Myricetin against S.aureus induced osteomyelitis. Osteomyelitis is infected condition of bone by micro-organisms. The mitogen-activated protein kinase (MAPK), inflammatory cytokines and Toll-like receptor-2 (TLR-2) pathway are mainly involved in osteomyelitis. Myricetin is a plant-food derived flavonoid which shows anti-inflammatory activity. In the present study, we evaluated the potential of Myricetin against S.aureus induced osteomyelitis. MC3T3-E1 cells were used for in vitro studies. Murine model of osteomyelitis was developed in BALB/c mice by injecting S.aureus in the medullary cavity of the femur. The mice were studied for bone destruction, anti-biofilm activity, osteoblast growth markers alkaline phosphatase (ALP), osteopontin (OCN) and collagen type-I (COLL-1) were studied by RT-PCR, ELISA analysis for levels of proinflammatory factors CRP, IL-6 and IL-1 β. Expression of proteins by Western blot analysis and anti-biofilm effect by Sytox green dye fluorescence assay. Target confirmation was done by performing in silico docking analysis. Myricetin reduced bone destruction in osteomyelitis induced mice. The treatment decreased bone levels of ALP, OCN, COLL-1 and TLR2. Myricetin decreased serum levels of CRP, IL-6 and IL-1 β. The treatment suppressed activation of MAPK pathway and showed anti-biofilm effect. Docking studies suggested high binding affinity of Myricetin with MAPK protein in silico, by showing lower binding energies. Myricetin suppresses osteomyelitis by inhibiting ALP, OCN, COLL-1 via the TLR2 and MAPK pathway involving inhibition of biofilm formation. In silico studies suggested MAPK as potential binding protein for myricetin. • Present paper discus's role of Myricetin in S. aureus induced osteomyelitis. • Myricetin suppresses osteomyelitis by inhibiting ALP, OCN, COLL-1 via TLR2 & MAPK pathway involving inhibition of biofilm formation. • The results were well supported by in silico docking analysis. [ABSTRACT FROM AUTHOR]