Cho Seong-Jun, Rhee Dong-Kwon, Pyo Suhkneung
Division of Immunopharmacology, College of Pharmacy, University of Sungkyunkwan, Suwon, Kyunggi-do, South Korea.
Nutrition. 2006 Nov-Dec;22(11-12):1177-84. doi: 10.1016/j.nut.2006.08.011. Epub 2006 Oct 4.
Allicin is believed to be the main component responsible for the biological activity of garlic. The regulation of cell death might have therapeutic potential in many diseases, and previous studies have demonstrated that allicin stimulates the functional activity of macrophages. Therefore, this study examined the effects of allicin on the apoptosis of macrophages induced by serum- and amino acid-free culture.
The apoptosis of peritoneal macrophages was examined after pretreating them with allicin and incubating them in a depleted nutritional state. The rate of apoptosis was determined using propidium iodide staining analysis using flow cytometry, DNA fragmentation, and a caspase-3 assay. Western blot analysis was used to examine the changes in the pro- or antiapoptotic protein expression levels.
DNA fragmentation and propidium iodide staining analyses revealed that allicin decreased the malnutrition-induced apoptosis of macrophages. The level of Bax expression, the amount of cytochrome-c released from the mitochondria, and the caspase-3 activity were also lower in the allicin-treated macrophages than in the untreated macrophages in a depleted nutritional state. Moreover, the MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase-kinase) inhibitor suppressed the allicin-induced inhibition of apoptosis in a depleted nutritional state and allicin increased the level of ERK1/2 phosphorylation.
Allicin inhibits the apoptosis of macrophages in a depleted nutritional state through the MEK/extracellular signal-regulated kinase pathway.
大蒜素被认为是大蒜具有生物活性的主要成分。细胞死亡的调控在许多疾病中可能具有治疗潜力，并且先前的研究表明大蒜素可刺激巨噬细胞的功能活性。因此，本研究检测了大蒜素对无血清和无氨基酸培养诱导的巨噬细胞凋亡的影响。
用大蒜素预处理腹膜巨噬细胞，并使其在营养缺乏状态下孵育后，检测其凋亡情况。使用流式细胞术、DNA片段化分析和半胱天冬酶-3检测，通过碘化丙啶染色分析确定凋亡率。采用蛋白质免疫印迹分析检测促凋亡或抗凋亡蛋白表达水平的变化。
DNA片段化分析和碘化丙啶染色分析显示，大蒜素可减少营养不良诱导的巨噬细胞凋亡。在营养缺乏状态下，经大蒜素处理的巨噬细胞中，Bax表达水平、从线粒体释放的细胞色素c量以及半胱天冬酶-3活性也低于未处理的巨噬细胞。此外，MEK（丝裂原活化蛋白激酶/细胞外信号调节激酶激酶）抑制剂可抑制大蒜素在营养缺乏状态下诱导的凋亡抑制作用，且大蒜素可提高ERK1/2磷酸化水平。
大蒜素通过MEK/细胞外信号调节激酶途径抑制营养缺乏状态下巨噬细胞的凋亡。
