Lee Seoung Rak, Lee Dahae, Lee Hae-Jeung, Noh Hyung Jun, Jung Kiwon, Kang Ki Sung, Kim Ki Hyun
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Department of Food and Nutrition, Gachon University, Seongnam 13120, Republic of Korea.
Bioorg Chem. 2017 Apr;71:67-73. doi: 10.1016/j.bioorg.2017.01.012. Epub 2017 Jan 19.
Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.
白灵侧耳(侧耳科)是一种可食用和药用的蘑菇,广泛分布于韩国、中国和日本。白灵侧耳子实体的甲醇提取物对顺铂诱导的肾细胞损伤具有肾脏保护作用。对甲醇提取物进行化学研究,分离并鉴定出12种化合物,包括去甲云芝素(1)、尿苷(2)、尿嘧啶(3)、(3β, 5α, 6β, 22E, 24S)-麦角甾-7, 22-二烯-3, 5, 6, 9-四醇(4)、(22E,24S)-麦角甾-7,22-二烯-3β,5α,6β-三醇(5)、(22E,24R)-麦角甾-8(14),22-二烯-3β,5α,6β,7α-四醇(6)、脑苷脂B(7)、(2R)-N-[(1S, 2R, 3E, 7E)-1-[(β-D-吡喃葡萄糖氧基)甲基]-2-羟基-8-甲基-3, 7-十七碳二烯-1-基]-2-羟基-十七烷酰胺(8)、脑苷脂D(9)、烟酰胺(10)、1,2-双(羟甲基)-4,5-二甲氧基苯(11)和苯甲酸(12)。其中,化合物1和11是首次作为天然产物分离得到,尽管它们在以前的文献中被报道为合成产物。所有化合物(除8和11外)均以剂量依赖性方式消除顺铂诱导的LLC-PK1细胞损伤。特别值得注意的是,化合物2、5、6和12在10μM时将顺铂诱导的肾毒性改善至对照值的80%。化合物2、5、6和12的保护作用是通过JNK-半胱天冬酶3凋亡级联的失活介导的。本研究首次证明白灵侧耳的化学成分对癌细胞药物诱导的肾细胞损伤具有肾脏保护作用。