Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections
Maolu Zhang, Shuqian Lin, Lianquan Han, Jiaming Zhang, Shaoning Liu, Xiu-Zhen Yang, Xiu-Zhen Yang, Ruiming Wang, Xiaohui Yang, Xiaohui Yang, Yunpeng Yi
Abstract
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 Clostridium perfringens ( C. perfringens ). 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 50 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 in vivo . Our study found that halicin had a good therapeutic effect on intestinal infection model of C . perfringens . These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.