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 the 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 (MIC_50/90, 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 antibiotic metronidazole. In mouse models of multidrug-resistant H. pylori infection, dual therapy with DHT and omeprazole showed in vivo killing efficacy superior to that of the standard triple-therapy approach. Moreover, DHT treatment induces negligible toxicity against normal tissues and exhibits a relatively good safety index. These results suggest that DHT could be suitable for use as an anti-H. pylori agent in combination with a proton pump inhibitor to eradicate multidrug-resistant H. pylori.

中文翻译：

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二氢丹参酮 I 在体外和体内对耐药性幽门螺杆菌有效

幽门螺杆菌是一种主要的全球病原体，与胃炎、消化性溃疡和胃癌有关。用抗生素广泛治疗幽门螺杆菌感染的疗效受到对人类肠道微生物群的耐药性和毒性的发展，这迫切需要新的和选择性的抗菌策略。本研究主要用于评估天然草药化合物二氢丹参酮 I (DHT) 对标准和临床幽门螺杆菌菌株的体外和体内作用。DHT在体外表现出对幽门螺杆菌的有效抗菌活性(MIC _50/90 , 0.25/0.5 μg/ml)，在连续连续传代期间没有产生抗性。时间-杀灭曲线对 DHT 显示出强的时间依赖性杀菌活性。此外，与传统抗生素甲硝唑相比，DHT 可以更有效地消除预先形成的生物膜并杀死被生物膜包裹的幽门螺杆菌细胞。在耐多药幽门螺杆菌感染的小鼠模型中，DHT 和奥美拉唑的双重治疗显示出优于标准三联疗法的体内杀灭效果。此外，DHT处理对正常组织的毒性可忽略不计，并表现出相对较好的安全指数。这些结果表明 DHT 可能适合用作抗幽门螺杆菌与质子泵抑制剂联合使用以根除耐多药幽门螺杆菌。