Fangchinoline eliminates intracellular Salmonella by enhancing lysosomal function via the AMPK-mTORC1-TFEB axis

作者：Mengping He, Hui‐Hui Wu, Tianqi Xu, Yurong Zhao, Zhiqiang Wang, Yuan Liu · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.015 · 被引用次数：6 · 研究领域：Autophagy in Disease and Therapy、NF-κB Signaling Pathways、Ginger and Zingiberaceae research

INTRODUCTION: Salmonella, a foodborne zoonotic pathogen, is a significant cause of morbidity and mortality in animals and humans globally. With the prevalence of multidrug-resistant strains, Salmonellosis has become a formidable challenge. Host-directed therapy (HDT) has recently emerged as a promising anti-infective approach for treating intracellular bacterial infections. OBJECTIVES: Plant-derived natural products, owing to their structural and functional diversity, are increasingly being explored and utilized as encouraging candidates for HDT compounds. This study aims to identify and screen natural compounds with potential as HDT for the treatment of intracellular Salmonella infections. METHODS: A cell-based screening approach was deployed to identify natural compounds capable of mitigating the intracellular replication of S. enterica. Safety and efficacy of the candidate compounds were evaluated using multiple animal models. RNA sequencing, ELISA, and immunoblotting analyses were conducted to elucidate the underlying mechanisms of action. RESULTS: Our results reveal that fangchinoline (FAN) effectively reduces S. enterica survival both in vitro and in vivo. Meanwhile, FAN also displays anti-infective activity against other intracellular pathogens, including multidrug-resistant isolates. A 14-day safety evaluation in mice showed no significant toxic or adverse effects from FAN administration. RNA sequencing analysis reveals an upregulation of lysosome pathways in S. enter...