Berberine functions as a negative regulator in lipopolysaccharide -induced sepsis by suppressing NF-κB and IL-6...

Sepsis is a deadly complication raised by bacterial pathogens-induced dysregulated innate inflammatory response. Thus, anti-inflammatory is a potential therapeutic treatment for septic patients. Numerous evidence exhibited that berberine possesses potent anti-inflammatory, anti-apoptotic and anti-oxidative activities. However, the effect of berberine on sepsis is not fully understood. The anti-inflammatory effect of berberine was evaluated using lipopolysaccharide (LPS)-induced macrophages differentiation model in vitro and using LPS/D-galactosamine-challenged septic mice model in vivo. The secreted protein levels were determined by ELISA assay. The multiple targets mRNA and protein levels were measured by quantitative RT-PCR and western blot assay, respectively. Our study demonstrated that administration of berberine significantly attenuated lung tissue injury, and potently increased the survival rate of septic mice by modulating excessive inflammatory response with negligible side-effects. We further found that berberine inhibited the expression of tumor necrosis factor (TNF)-α, interleukin-(IL)-1β and IL-6 via suppressing nuclear factor kappa B subunit 1 (NF-κB) signaling activation. Our study strongly supported the concept that berberine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medications for the treatment of septic patients.