Shadkchan Yona, Shemesh Einav, Mirelman David, Miron Talia, Rabinkov Aharon, Wilchek Meir, Osherov Nir
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
J Antimicrob Chemother. 2004 May;53(5):832-6. doi: 10.1093/jac/dkh174. Epub 2004 Mar 24.
The evaluation of allicin, the biologically active compound responsible for the antimicrobial activities of freshly crushed garlic cloves, in inhibiting Aspergillus spp. in vitro and in a murine model of disseminated aspergillosis.
Pure allicin was prepared by reacting synthetic alliin with a stabilized preparation of the garlic enzyme alliinase. We tested the in vitro efficacy of pure allicin against 31 clinical isolates of Aspergillus spp. using a microdilution broth method and following the NCCLS guidelines (document M-38P). Subsequently, the in vivo efficacy of allicin was tested in immunocompetent mice infected intravenously (iv) with Aspergillus fumigatus conidia. Allicin (5 mg/kg body weight) was administered iv once daily for 5 days post-infection or orally (po) (9 mg/kg body weight) for 5 days pre-infection and 10 days post-infection. No ill effects were observed in allicin-treated uninfected mice.
The in vitro MICs and MFCs of allicin were between 8 and 32 mg/L, indicating that allicin in its pure form may be an effective fungicide in vitro. Time-kill studies indicate that allicin exerts its fungicidal activity within 2-12 h of administration in vitro. Allicin treatment significantly prolonged survival of infected mice (P < 0.01) from mean survival time (MST) = 7.7 days in untreated mice to MST = 21.3 and 13.9 days for allicin iv and po treated mice, respectively. Allicin iv treatment led to a significant (P < 0.001) 10-fold reduction in fungal burden in A. fumigatus infected mice as evaluated by quantitative fungal cultures of kidney tissue samples.
These favourable results, despite the short half-life of this compound in vivo, support further studies of controlled sustained release or more prolonged administration of allicin as a treatment for aspergillosis.
评估大蒜素(新鲜压碎的蒜瓣中具有抗菌活性的生物活性化合物)在体外和播散性曲霉病小鼠模型中对曲霉属真菌的抑制作用。
通过使合成蒜氨酸与大蒜酶蒜氨酸酶的稳定制剂反应制备纯大蒜素。我们使用微量稀释肉汤法并遵循美国国家临床实验室标准委员会(NCCLS)指南(文件M - 38P)测试了纯大蒜素对31株曲霉属临床分离株的体外疗效。随后,在静脉注射烟曲霉分生孢子感染的免疫活性小鼠中测试大蒜素的体内疗效。感染后每天静脉注射大蒜素(5毫克/千克体重),持续5天;或在感染前5天和感染后10天口服(9毫克/千克体重)。在接受大蒜素治疗的未感染小鼠中未观察到不良影响。
大蒜素的体外最低抑菌浓度(MIC)和最低杀菌浓度(MFC)在8至32毫克/升之间,表明其纯形式在体外可能是一种有效的杀菌剂。时间 - 杀菌研究表明,大蒜素在体外给药后2至12小时内发挥其杀菌活性。大蒜素治疗显著延长了感染小鼠的存活时间(P < 0.01),未治疗小鼠的平均存活时间(MST)= 7.7天,而大蒜素静脉注射和口服治疗的小鼠分别为MST = 21.3天和13.9天。通过对肾组织样本进行定量真菌培养评估,大蒜素静脉注射治疗使烟曲霉感染小鼠的真菌负荷显著降低(P < 0.001)10倍。
尽管该化合物在体内半衰期较短,但这些良好结果支持进一步研究大蒜素的控释或更长时间给药作为曲霉病的治疗方法。