Xanthohumol and Gossypol Are Promising Inhibitors against Babesia microti by In Vitro Culture via High-Throughput Screening of 133 Natural Products

Human babesiosis caused by Babesia microti is an emerging threat for severe illness and even death, with an increasing impact worldwide. Currently, the regimen of atovaquone and azithromycin is considered as the standard therapy for treating human babesiosis, which, however, may result in drug resistance and relapse, suggesting the necessity of developing new drugs to control B. microti. In this regard, natural products are promising candidates for drug design against B. microti due to their active therapeutic efficacy, lower toxicity, and fewer adverse reactions to host. Here, the potential inhibitors against B. microti were preliminarily screened from 133 natural products, and 47 of them were selected for further screening. Gossypol (Gp) and xanthohumol (Xn) were finally shown to effectively inhibit the growth of B. microti with IC(50) values of 8.47 μm and 21.40 μm, respectively. The cytotoxicity results showed that Gp and Xn were non-toxic to erythrocytes at a concentration below 100 μm. Furthermore, both of them were confirmed to be non-toxic to different types of cells in previous studies. Our findings suggest the potential of Gp and Xn as effective drugs against B. microti infection.