Combination of kaempferol and azithromycin attenuates Staphylococcus aureus-induced osteomyelitis via anti-biofilm effects and by inhibiting the phosphorylation of ERK1/2 and SAPK

Abstract

ABSTRACT Osteomyelitis is bacterial infection of bone, commonly caused by Staphylococcus aureus. This work aims to study the potential of azithromycin and kaempferol against chronic osteomyelitis induced by azithromycin-resistant Staphylococcus aureus (ARSA). It was noticed that rats tolerated the treatments with no diarrhoea or weight loss; also, no deaths were observed in rats. The treatment by azithromycin alone failed to inhibit bacterial growth and also had no effect on the infection condition of bone, although the treatment decreased the levels of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), but did not improve the oxidative stress levels. Kaempferol monotherapy slightly inhibited bacterial growth and bone infection; the treatment also inhibited the levels of IL-6 and (TNF-α). The treatment also improved the antioxidant status. However, the combined treatment of azithromycin and kaempferol significantly suppressed bacterial growth and bone infection and modulated oxidative stress. In vitro, the combined treatment inhibited the levels of IL-6 and TNF-α, and also suppressed the phosphorylation of ERK1/2 and stress-activated protein kinase (SAPK). The combined treatment also showed anti-biofilm activity in ARSA. The combination attenuates ARSA-induced osteomyelitis in rats compared with their treatments alone by reducing oxidative stress, inhibiting the phosphorylation of ERK1/2 and SAPK and inhibiting biofilm formation.