Yang Eun-Ju, Kim Seo-Hyun, Lee Kyeong-Yeoll, Song Kyung-Sik
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea.
College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
J Microbiol Biotechnol. 2018 Jan 28;28(1):12-21. doi: 10.4014/jmb.1708.08067.
(PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (), 1,3,8-trihydroxy-9,10-anthraquinone (), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, 75 µM significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, Ca²⁺ influx, and lipid peroxidation. Additionally, and effectively suppressed the interferon-γ-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-α. Anthraquinones and derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound is reported for the first time in this study.
嗜线虫致病杆菌（PT）是一种革兰氏阴性菌，与昆虫病原线虫共生。从PT中提取的杀虫化合物在农业中用作生物农药。然而，其生理特性尚未得到充分表征。在我们从天然产物中筛选神经保护和抗神经炎症物质的过程中，PT的培养液显示出相当大的活性。通过活性导向纯化，从PT培养液的乙酸乙酯馏分中分离出五种蒽醌，即3-甲氧基吖嗪（）、1,3-二甲氧基-8-羟基-9,10-蒽醌（）、1,3,8-三羟基-9,10-蒽醌（）、3,8-二羟基-1-甲氧基-9,10-蒽醌（）和1,3,4-三甲氧基-8-羟基-9,10-蒽醌（）。在分离出的化合物中，75µM的 通过抑制活性氧生成、Ca²⁺内流和脂质过氧化，显著保护小鼠海马神经元细胞（HT22）免受5 mM谷氨酸诱导的细胞死亡。此外， 和 在10 ng/ml时通过降低一氧化氮、白细胞介素-6和肿瘤坏死因子-α，有效抑制了小鼠小胶质细胞（BV2）的干扰素-γ诱导的神经炎症。源自PT培养液的蒽醌 和 是发现神经保护和抗神经炎症药物先导物的潜在起点。新型化合物 在本研究中首次报道。
