Yamaguchi Yusuke, Honma Ryosuke, Yazaki Tomoaki, Shibuya Takeshi, Sakaguchi Tomoya, Uto-Kondo Harumi, Kumagai Hitomi
Department of Chemistry and Life Science, Nihon University, 1866 Kameino, Fujisawa-shi 252-0880, Japan.
Department of Bioscience in Daily Life, Nihon University, 1866 Kameino, Fujisawa-shi 252-0880, Japan.
Antioxidants (Basel). 2019 Sep 10;8(9):385. doi: 10.3390/antiox8090385.
-Allyl-l-cysteine sulfoxide (ACSO) is a precursor of garlic-odor compounds like diallyl disulfide (DADS) and diallyl trisulfide (DATS) known as bioactive components. ACSO has suitable properties as a food material because it is water-soluble, odorless, tasteless and rich in bulbs of fresh garlic. The present study was conducted to examine the preventive effect of ACSO on hepatic injury induced by CCl in rats. ACSO, its analogs and garlic-odor compounds were each orally administered via gavage for five consecutive days before inducing hepatic injury. Then, biomarkers for hepatic injury and antioxidative state were measured. Furthermore, we evaluated the absorption and metabolism of ACSO in the small intestine of rats and NF-E2-related factor 2 (Nrf2) nuclear translocation by ACSO using HepG2 cells. As a result, ACSO, DADS and DATS significantly suppressed the increases in biomarkers for hepatic injury such as the activities of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH), and decreases in antioxidative potency such as glutathione (GSH) level and the activities of glutathione -transferase (GST) and glutathione peroxidase (GPx). We also found ACSO was absorbed into the portal vein from the small intestine but partially metabolized to DADS probably in the small intestine. In in vitro study, ACSO induced Nrf2 nuclear translocation in HepG2 cells, which is recognized as an initial trigger to induce antioxidative and detoxifying enzymes. Taken together, orally administered ACSO probably reached the liver and induced antioxidative and detoxifying enzymes by Nrf2 nuclear translocation, resulting in prevention of hepatic injury. DADS produced by the metabolism of ACSO in the small intestine might also have contributed to the prevention of hepatic injury. These results suggest potential use of ACSO in functional foods that prevent hepatic injury and other diseases caused by reactive oxygen species (ROS).
-烯丙基-L-半胱氨酸亚砜(ACSO)是大蒜气味化合物如二烯丙基二硫化物(DADS)和二烯丙基三硫化物(DATS)的前体,这些化合物被称为生物活性成分。ACSO具有作为食品原料的合适特性,因为它可溶于水、无味、无味且在新鲜大蒜鳞茎中含量丰富。本研究旨在考察ACSO对大鼠四氯化碳诱导的肝损伤的预防作用。在诱导肝损伤前,连续五天通过灌胃分别口服给予ACSO、其类似物和大蒜气味化合物。然后,测定肝损伤和抗氧化状态的生物标志物。此外,我们评估了ACSO在大鼠小肠中的吸收和代谢,以及使用HepG2细胞研究ACSO对NF-E2相关因子2(Nrf2)核转位的影响。结果显示,ACSO、DADS和DATS显著抑制了肝损伤生物标志物的增加,如天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和乳酸脱氢酶(LDH)的活性,以及抗氧化能力的降低,如谷胱甘肽(GSH)水平、谷胱甘肽-S-转移酶(GST)和谷胱甘肽过氧化物酶(GPx)的活性。我们还发现ACSO从小肠吸收进入门静脉,但可能在小肠中部分代谢为DADS。在体外研究中,ACSO诱导HepG2细胞中的Nrf2核转位,这被认为是诱导抗氧化和解毒酶的初始触发因素。综上所述,口服给予的ACSO可能到达肝脏并通过Nrf2核转位诱导抗氧化和解毒酶,从而预防肝损伤。ACSO在小肠中代谢产生的DADS也可能有助于预防肝损伤。这些结果表明ACSO在预防肝损伤和其他由活性氧(ROS)引起的疾病的功能性食品中具有潜在用途。