AUTHOR=Zhang Maolu , Lin Shuqian , Han Lianquan , Zhang Jiaming , Liu Shaoning , Yang Xiuzhen , Wang Ruiming , Yang Xiaohui , Yi Yunpeng 

TITLE=Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1389293

DOI=10.3389/fphar.2024.1389293

ISSN=1663-9812

ABSTRACT=<p>Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and <italic>Clostridium perfringens</italic> (<italic>C. perfringens</italic>). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD<sub>50</sub> of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated <italic>in vivo</italic>. Our study found that halicin had a good therapeutic effect on intestinal infection model of <italic>C</italic>. <italic>perfringens</italic>. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.</p>