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Objective Bacterial drag resistance caused by effiux pump remains problematic.Our previous study showed that 20 (S)-ginsenoside Rh2 (20 (S)-Rh2) reversed multidrug resistance (MDR) in MCF-7 cells by inhibiting the effiux pump P-glycolprotein (P-gp) The present study is to investigate the activity of 20 (S)-Rh2 on the efflux pump and the drug resistance in bacteria.Methods (1) Antibiotic synergy analysis of 20 (S)-Rh2 and ciprofloxacin in S aureus-infected mice by determining survival rate and bacterial counts in blood.(2) Synergetic effects of 20 (S)-Rh2 on ciprofloxacin in S.aureus, P.aeruginosa and E.coli by determining MIC and antibacterial kinetics.(3) Pharmacokinetic analysis by determining the effectsof 20 (S)-Rh2 on ciproxacin accumulation and Pyronin Y effiux.(4) NorA experession was determined by Real-time PCR.Results In vivo, 20 (S)-Rh2 (25, 50, 100 mg/kg) combined with ciprofloxaein (2.5 mg/kg) exerted better therapeutic action and reduced bacteria in blood than single dose of ciprofloxacin.In vitro, 20 (S)-Rh2 reduced MIC of ciprofloxacin on some strains at non-toxic concentration and had synergistic effect on the antimicrobial kinetics of ciprofloxacin at these concentrations.20 (S)-Rh2 enhanced ciprofloxacin accumulation in ATCC 29213 significantly and concentration-dependently inhibited the function of effiux pump in ATCC 29213.Real-time PCR showed that norA expression was higher in these strains on which 20 (S)-Rh2 and ciprofloxacin had synergistic effects than those without synergistic effects.Conclusion 20 (S)-Rh2 has synergistic effect on antibiotic activity ofciprofloxacin in vivo and in vitro.This effect may be related to its inhibition on the function of efflux pump NorA and the subsequent enhancement of ciprofloxacin accumulation in ATCC 29213.