Mohammed Layth Jasim, Chehri Khosrow, Karimi Isaac, Karimi Nasser
Department of Biology, Faculty of Science, Razi University, Kermanshah, 67149-67346 Iran.
In Silico Pharmacol. 2021 Feb 7;9(1):17. doi: 10.1007/s40203-021-00078-x. eCollection 2021.
This study was aimed to investigate the prophylactic effects of hydro-alcoholic extract derived from bulbs of 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 10 colony forming unites (CFUs/ml) of suspension at 10th day and tissue homogenates were colony counted for 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 were different among groups (P = 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, -caryophyllene () 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 ]. The ADMET properties of 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 . Computational findings of admetSAR software revealed that leads to carcinogenicity, , fish, rat, and honey bee toxicities, weak inhibition of human ether-a-go-go-related gene, and cytochromes inhibitory promiscuity. The showed promising in human intestinal absorption, blood-brain barrier permeability, Caco-2 penetration, and solubility. The results of Toxtree software showed that 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 has acceptable ADMET score to be considered as a bioactive compound for designing phytobiotics.
The online version contains supplementary material available at 10.1007/s40203-021-00078-x.
本研究旨在探讨温德尔博鳞茎（葱科；AI）的水醇提取物对葡萄球菌病小鼠模型的预防作用，并解读AI中的哪些植物化学物质可能与其抗葡萄球菌特性有关。雄性小鼠被分为四组，即正常对照组（NC），其他三组分别在饮用水中给予0.192、0.384和0.768毫克/毫升的AI，持续9天。此后，在第10天给小鼠静脉注射10个菌落形成单位（CFU/毫升）的悬浮液，并在接种后9天对组织匀浆进行菌落计数。使用PyRx软件对葡萄球菌病相关的主要蛋白质和AI的植物化学物质进行了分子对接，并提交最佳配体以计算分子和生物学属性。诱导小鼠葡萄球菌病并给予AI并未对小鼠体重产生不利影响，而感染小鼠选定组织中的菌落计数在各组之间存在差异（P = 0.016）。一般来说，与NC相比，AI 0.192组（P = 0.099）和AI 0.768组（P = 0.818）的菌落计数有下降趋势，然而AI 0.384组（P = 0.005）的菌落计数低于NC。此外，与AI 0.768组相比，AI 0.384组的菌落计数下降（P = 0.009）。AI 0.0384组肾脏中的菌落计数低于NC组（P = 0.051）和AI 0.768组（P = 0.048）。在目标蛋白中，β-石竹烯（）对三种水解酶[β毒素（鞘磷脂磷酸二酯酶 - 8.1）、分选酶B（蛋白酶 - 8.1）和葡萄球菌的FtsZ（GTP酶 - 8.7）]表现出可靠的结合亲和力（千卡/摩尔）。的ADMET特性表明，它遵循Lipinski的五规则，但在其miLogP 5.17方面有一个违反。此外，Molinspiration生物活性评分表明对离子通道有调节作用，对酶有抑制作用。admetSAR软件的计算结果表明会导致致癌性、对鱼类、大鼠和蜜蜂有毒性、对人类醚 - a - 去极化相关基因的抑制作用较弱以及对细胞色素的抑制作用具有混杂性。在人体肠道吸收、血脑屏障通透性、Caco - 2渗透性和溶解性方面表现出良好前景。Toxtree软件的结果表明不是体内的内源性分子，不包含与增强毒性相关的官能团，被认为是接近萜类的I类有毒化合物。总之，我们发现从AI鳞茎中提取的水醇提取物对小鼠模型中的葡萄球菌病有显著的保护作用。计算机模拟结果表明具有可接受的ADMET评分，可被视为设计植物源生物制剂的生物活性化合物。
在线版本包含可在10.1007/s40203 - 021 - 00078 - x获取的补充材料。
