Dihydrotanshinone I is effective against drug-resistant Helicobacter pylori in vitro and in vivo

Helicobacter pylori is a major global pathogen and has been implicated in gastritis, peptic ulcer and gastric carcinoma. The efficacy of the extensive therapy of H. pylori infection with antibiotics is compromised by development of drug resistance and toxicity toward human gut microbiota, which urgently demands novel and selective antibacterial strategies. The present study was mainly performed to assess the in vitro and in vivo effects of a natural herbal compound, dihydrotanshinone I (DHT), against standard and clinical H. pylori strains. DHT demonstrated effective antibacterial activity against H. pylori in vitro ((MIC50/90: 0.25/0.5 μg/mL) with no development of resistance during continuous serial passaging. Time-kill curves showed strong time-dependent bactericidal activity for DHT. Also DHT eliminated preformed biofilms and killed biofilm-encased H. pylori cells more efficiently than the conventional antibiotics, metronidazole. In mouse models of multi-drug resistant H. pylori infection, dual therapy with DHT and omeprazole showed superior in vivo killing efficacy to the standard triple therapy approach. Moreover, DHT treatment induces neglectable toxicity against normal tissues and exhibits a relative safety index. These results suggest that DHT could be suitable for use as an anti-H. pylori agent in combination with proton pump inhibitor to eradicate multidrug-resistant H. pylori.