Therapeutic mechanism of albendazole in treating pebrine disease of Bombyx mori based on GC-MS metabonomics analysis

【Objective】 GC-MS metabolomics was used to investigate the effect of albendazole on hemolymph metabolites of Bombyx mori with pebrine disease, and to clarify the action mechanism of albendazole from the perspective of metabolomics, so as to provide a theoretical basis for developing new therapeutic drugs for pebrine disease with albendazole as the main agent.【Method】 The model of pebrine disease was established by inoculating 5^th instar Bombyx mori larvae with Nosema bombycis(N.b). The mulberry leaves coating with albendazole suspension were fed at 12, 24, 48, 72 and 96 h after inoculation until cocooning. The silkworms without inoculation and administration was used as the control. The infection rate was investigated by individual microscopic examination at pupal stage and the therapeutic effect was evaluated;GC-MS was used to conduct the non-targeted metabonomics study to search the hemolymph related differential metabolites in silkworms with pebrine disease, and the related metabolic pathways were constructed by MetaboAnalyst 4.0.【Result】 The results showed that albendazole had a significant therapeutic effect on pebrine disease, and the key time was 24-48 h after inoculation. Compared with the control group, a total of 47 different metabolites were screened and identified from the hemolymph of B. mori in the model group, of which 27 metabolites showed a downward trend and 20 metabolites showed an upward trend. The comparative analysis of the hemolymph samples between the model group and the albendazole treatment group showed that albendazole had an intervention and regulation effect on most metabolites related to pebrine disease except xylulose, D-glucose 6-phosphate, inositol, pantothenic acid, methylsuccinic acid and oleic acid.Six metabolic pathways changed greatly after infection with N.b by MetaboAnalyst 4.0, which were as follows:① starch and sucrose metabolism;② biosynthesis of phenylalanine, tyrosine and tryptophan;③ phenylalanine metabolism;④ glycine, serine and threonine metabolism;⑤ glutathione metabolism;⑥ inositol phosphate metabolism. The albendazole suspension treatment could effectively reduce the changes of the above metabolic pathways, so as to promote the silkworms suffering from pebrine disease in a more normal physiological state.【Conclusion】 Albendazole had a significant therapeutic effect on pebrine disease of B. mori. The key time of drug action was 24-48 h after N.b infection. Combined with the life cycle of N.b, the mechanism of albendazole in the treatment of pebrine disease can be fully revealed. Albendazole can effectively reduce the the destruction of amino acid metabolism and energy metabolism by N.b infection by inhibiting the proliferation of the meronts in silkworms, thus maintaining the normal physiological state of B. mori and achieve healing effects.