PDF(Pubmed)
Abstract：
UNASSIGNED: Allicin, a bioactive compound derived from garlic (Allium sativum), demonstrates antibacterial activity against a broad spectrum of bacteria including the most common meningitis pathogens. In order to advocate for allicin as a potential therapeutic candidate for bacterial meningitis, the present study aimed to assess the ability of allicin to cross the blood-brain barrier (BBB) using an in vitro model.
UNASSIGNED: The cell viability of the human brain endothelial cell line hCMEC/D3 after incubation with various concentrations of allicin was investigated using an MTT assay at 3 and 24 h. Additionally, reactive oxygen species (ROS) production of allicin-treated hCMEC/D3 cells was examined at 3 h. The concentrations of allicin that were not toxic to the cells, as determined by the MTT assay, and did not significantly increase ROS generation, were then used to investigate allicin\'s ability to traverse the in vitro BBB model for 3 h. High-performance liquid chromatography (HPLC) analysis was utilized to examine the allicin concentration capable of passing the in vitro BBB model. The cellular uptake experiments were subsequently performed to observe the uptake of allicin into hCMEC/D3 cells. The pkCSM online tool was used to predict the absorption, distribution, metabolism, excretion, and pharmacokinetic properties of allicin and S-allylmercaptoglutathione (GSSA).
UNASSIGNED: The results from MTT assay indicated that the highest non-toxicity concentration of allicin on hCMEC/D3 cells was 5 µg/ml at 3 h and 2 µg/ml at 24 h. Allicin significantly enhanced ROS production of hCMEC/D3 cells at 10 µg/ml at 3 h. After applying the non-toxicity concentrations of allicin (0.5-5 µg/ml) to the in vitro BBB model for 3 h, allicin was not detectable in both apical and basolateral chambers in the presence of hCMEC/D3 cells. On the contrary, allicin was detected in both chambers in the absence of the cells. The results from cellular uptake experiments at 3 h revealed that hCMEC/D3 cells at 1 × 104 cells could uptake allicin at concentrations of 0.5, 1, and 2 µg/ml. Moreover, allicin uptake of hCMEC/D3 cells was proportional to the cell number, and the cells at 5 × 104 could completely uptake allicin at a concentration of 5 µg/ml within 0.5 h. The topological polar surface area (TPSA) predicting for allicin was determined to be 62.082 Å2, indicating its potential ability to cross the BBB. Additionally, the calculated logBB value surpassing 0.3 suggests that the compound may exhibit ease of penetration through the BBB.
UNASSIGNED: The present results suggested that allicin was rapidly taken up by hCMEC/D3 cells in vitro BBB model. The prediction results of allicin\'s distribution patterns suggested that the compound possesses the capability to enter the brain.
UNASSIGNED: The cell viability of the human brain endothelial cell line hCMEC/D3 after incubation with various concentrations of allicin was investigated using an MTT assay at 3 and 24 h. Additionally, reactive oxygen species (ROS) production of allicin-treated hCMEC/D3 cells was examined at 3 h. The concentrations of allicin that were not toxic to the cells, as determined by the MTT assay, and did not significantly increase ROS generation, were then used to investigate allicin\'s ability to traverse the in vitro BBB model for 3 h. High-performance liquid chromatography (HPLC) analysis was utilized to examine the allicin concentration capable of passing the in vitro BBB model. The cellular uptake experiments were subsequently performed to observe the uptake of allicin into hCMEC/D3 cells. The pkCSM online tool was used to predict the absorption, distribution, metabolism, excretion, and pharmacokinetic properties of allicin and S-allylmercaptoglutathione (GSSA).
UNASSIGNED: The results from MTT assay indicated that the highest non-toxicity concentration of allicin on hCMEC/D3 cells was 5 µg/ml at 3 h and 2 µg/ml at 24 h. Allicin significantly enhanced ROS production of hCMEC/D3 cells at 10 µg/ml at 3 h. After applying the non-toxicity concentrations of allicin (0.5-5 µg/ml) to the in vitro BBB model for 3 h, allicin was not detectable in both apical and basolateral chambers in the presence of hCMEC/D3 cells. On the contrary, allicin was detected in both chambers in the absence of the cells. The results from cellular uptake experiments at 3 h revealed that hCMEC/D3 cells at 1 × 104 cells could uptake allicin at concentrations of 0.5, 1, and 2 µg/ml. Moreover, allicin uptake of hCMEC/D3 cells was proportional to the cell number, and the cells at 5 × 104 could completely uptake allicin at a concentration of 5 µg/ml within 0.5 h. The topological polar surface area (TPSA) predicting for allicin was determined to be 62.082 Å2, indicating its potential ability to cross the BBB. Additionally, the calculated logBB value surpassing 0.3 suggests that the compound may exhibit ease of penetration through the BBB.
UNASSIGNED: The present results suggested that allicin was rapidly taken up by hCMEC/D3 cells in vitro BBB model. The prediction results of allicin\'s distribution patterns suggested that the compound possesses the capability to enter the brain.
摘要：
■大蒜素，一种来源于大蒜的生物活性化合物，对包括最常见的脑膜炎病原体在内的广谱细菌具有抗菌活性。为了倡导大蒜素作为细菌性脑膜炎的潜在治疗候选药物，本研究旨在使用体外模型评估大蒜素穿过血脑屏障(BBB)的能力.
在3和24小时使用MTT测定法研究了与各种浓度的大蒜素一起孵育后人脑内皮细胞系hCMEC/D3的细胞活力。在3小时检查大蒜素处理的hCMEC/D3细胞的活性氧（ROS）产生。如MTT测定法所确定，并且没有显着增加ROS的产生，然后用于研究大蒜素穿越体外BBB模型3小时的能力。高效液相色谱（HPLC）分析用于检查能够通过体外BBB模型的大蒜素浓度。随后进行细胞摄取实验以观察大蒜素对hCMEC/D3细胞的摄取。pkCSM在线工具用于预测吸收，分布，新陈代谢，排泄,大蒜素和S-烯丙基巯基谷胱甘肽（GSSA）的药代动力学特性。
■MTT测定结果表明，大蒜素对hCMEC/D3细胞的最高无毒性浓度为3h时5µg/ml，24h时2µg/ml。大蒜素在3h时10µg/ml显着增强hCMEC/D3细胞的ROS产生。在存在hCMEC/D3细胞的情况下，在顶端和基底外侧腔室中均未检测到大蒜素。相反,在没有细胞的情况下，在两个腔室中都检测到了大蒜素。3小时的细胞摄取实验结果表明，1×104个细胞的hCMEC/D3细胞可以摄取浓度为0.5、1和2µg/ml的大蒜素。此外，hCMEC/D3细胞的大蒜素摄取与细胞数成正比，5×104的细胞可以在0.5小时内以5µg/ml的浓度完全摄取大蒜素。大蒜素的拓扑极性表面积（TPSA）预测为62.082µ2，表明其潜在的穿越BBB的能力。此外,计算的logBB值超过0.3表明该化合物可能表现出易于渗透通过BBB。
■目前的结果表明，在体外BBB模型中，大蒜素被hCMEC/D3细胞迅速吸收。大蒜素分布模式的预测结果表明，该化合物具有进入大脑的能力。
在3和24小时使用MTT测定法研究了与各种浓度的大蒜素一起孵育后人脑内皮细胞系hCMEC/D3的细胞活力。在3小时检查大蒜素处理的hCMEC/D3细胞的活性氧（ROS）产生。如MTT测定法所确定，并且没有显着增加ROS的产生，然后用于研究大蒜素穿越体外BBB模型3小时的能力。高效液相色谱（HPLC）分析用于检查能够通过体外BBB模型的大蒜素浓度。随后进行细胞摄取实验以观察大蒜素对hCMEC/D3细胞的摄取。pkCSM在线工具用于预测吸收，分布，新陈代谢，排泄,大蒜素和S-烯丙基巯基谷胱甘肽（GSSA）的药代动力学特性。
■MTT测定结果表明，大蒜素对hCMEC/D3细胞的最高无毒性浓度为3h时5µg/ml，24h时2µg/ml。大蒜素在3h时10µg/ml显着增强hCMEC/D3细胞的ROS产生。在存在hCMEC/D3细胞的情况下，在顶端和基底外侧腔室中均未检测到大蒜素。相反,在没有细胞的情况下，在两个腔室中都检测到了大蒜素。3小时的细胞摄取实验结果表明，1×104个细胞的hCMEC/D3细胞可以摄取浓度为0.5、1和2µg/ml的大蒜素。此外，hCMEC/D3细胞的大蒜素摄取与细胞数成正比，5×104的细胞可以在0.5小时内以5µg/ml的浓度完全摄取大蒜素。大蒜素的拓扑极性表面积（TPSA）预测为62.082µ2，表明其潜在的穿越BBB的能力。此外,计算的logBB值超过0.3表明该化合物可能表现出易于渗透通过BBB。
■目前的结果表明，在体外BBB模型中，大蒜素被hCMEC/D3细胞迅速吸收。大蒜素分布模式的预测结果表明，该化合物具有进入大脑的能力。
