Computational insight into the protective mechanism of Allium iranicum Wendelbo. Alliaceae in a mouse model of Staphylococcosis: focus on dietary phytocannabinoid trans-caryophyllene.

This study was aimed to investigate the prophylactic effects of hydro-alcoholic extract derived from bulbs of Allium iranicum Wendelbo. (Alliaceae; AI) on mouse model of Staphylococcosis, and to decipher which phytochemicals of AI may involve in its anti-staphylococcal property. Male mice were allocated into four groups, i.e. normal control (NC) and three other groups received AI at 0.192, 0.384 and 0.768 mg/ml in drinking water for 9 days. Thereafter, mice were intravenously injected 106 colony forming unites (CFUs/ml) of Staphylococcus aureus suspension at 10th day and tissue homogenates were colony counted for S. aureus 9 days post-inoculation. Molecular docking among cardinal proteins involved in Staphylococcosis and phytochemicals of AI has been performed using PyRx software and the best ligand submitted to compute molecular and biological attributes. Induction of murine Staphylococcosis and inclusion of AI did not adversely alter bodyweights of mice while colony counts in selected tissues of mice infected with S. aureus were different among groups (PANOVA = 0.016). Generally, the colony counts tended to decrease in AI 0.192 (P = 0.099) and AI 0.768 (P = 0.818) groups as compared to NC, however AI 0.384 (P = 0.005) group showed lesser colony counts than NC. In addition, colony counts decreased in AI 0.384 as compared to AI 0.768 (P = 0.009). The colony counts in kidneys of AI 0.0384 group were lesser than those of NC (P = 0.051) and AI 0.768 (P = 0.048). Among target proteins, trans-caryophyllene (TCP) showed reliable binding affinities (kcal/mol) to three hydrolase enzymes [beta toxin (sphingomyelin phosphodiesterase - 8.1), sortase B (protease - 8.1), and FtsZ (GTPase - 8.7) of S. aureus]. The ADMET properties of TCP showed that it followed the Lipinski's rule of five with one violation with respect to its miLogP 5.17. In addition, Molinspiration bioactivity score indicated ion channel modulatory and enzyme inhibitory effect for TCP. Computational findings of admetSAR software revealed that TCP leads to carcinogenicity, Tetrahymena pyriformis, fish, rat, and honey bee toxicities, weak inhibition of human ether-a-go-go-related gene, and cytochromes inhibitory promiscuity. The TCP showed promising in human intestinal absorption, blood-brain barrier permeability, Caco-2 penetration, and solubility. The results of Toxtree software showed that TCP is not an endogenous molecule of the body and contains no functional groups associated with enhanced toxicity and considered as class I toxic compound close to terpenes. In conclusion, we found the hydro-alcoholic extract derived from of bulbs AI has a significant protective effect against Staphylococcosis in mouse model. In silico findings demonstrated that TCP has acceptable ADMET score to be considered as a bioactive compound for designing phytobiotics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00078-x.