Evidence for the Natural Toxins from the Mushroom Trogia venenata as a Cause of Sudden Unexpected Death in Yunnan Province, China
Evidence for the Natural Toxins from the Mushroom Trogia venenata as a Cause of Sudden Unexpected Death in Yunnan Province, China
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蘑菇 Trogia venenata 的天然毒素导致中国云南省突然意外死亡的证据
DOI：
10.1002/anie.201106502
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Liu, Ji-Kai
中科院分区：
文献类型：
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作者：
Zhou, Zhong-Yu;Shi, Guo-Qing;Liu, Ji-Kai
在过去的30年里，在云南省西南部的中国，有260多名看似健康的村民突然死于不明原因。[1]在雨季，从6月到8月，云南经常发生不明原因猝死(SUD)，发生在海拔1800到2400米的村庄。[1，2]2005年的流行病学研究表明采摘蘑菇是一个危险因素，2006年-2009年的研究进一步表明食用了一种以前没有描述过的蘑菇品种，我们将其命名为Trogia venenata朱L.Yang(图1，另见支持信息中的描述)。我们从这种蘑菇的子实体中分离并鉴定了三种有毒化合物，以进一步证实毒蛾是引起SUD的假说。在这里，我们描述了两种不寻常的有毒氨基酸(1和2，方案1)以及从蘑菇T.venenata中分离出来的已知毒素g-鸟嘌呤丁酸(3)。这些活性成分的分离以小鼠经口毒性试验为指导(所有动物实验均经昆明市植物研究所动物实验伦理委员会批准)。氨基酸毒素1和2可致小鼠死亡，LD50值分别为71和84mgkg±1。2009年7月，云南省腾冲县在云南省腾冲县附近采集了毒毛虫样本，在一个村庄附近曾发生过与毒毛虫相关的云南南德聚集性疾病。在室温条件下，用乙醇连续提取了9.7公斤的毒草鲜子实体。组合乙醇溶液减压浓缩得到粗提物(60.2g)，悬浮在水中，用乙酸乙酯分离。动物实验证实，有毒因素存在于水相中。水提物(40.5g)在反相C18色谱柱(RP-C18，甲醇/水，0-100%)上进行制备性中压液相色谱(MPLC)，得到16个馏分。组分A是
Over the past 30 years, more than 260 apparently healthy villagers in Yunnan Province, southwest China, have suddenly died of an unknown cause.[1] Yunnan Sudden Unexplained Death (SUD) often strikes in time-space clusters during the rainy season, from June to August, in villages between 1800 and 2400 m above sea level.[1, 2] Epidemiologic studies in 2005 implicated mushroom picking as a risk factor, and studies from 2006–2009 further implicated eating a previously undescribed species of mushroom, which we have named Trogia venenata Zhu L. Yang (Figure 1, see also the descriptions in the Supporting Information). We have isolated and characterized three toxic compounds from the fruiting bodies of this mushroom to further substantiate the hypothesis that T. venenata is responsible for SUD. Herein, we describe two unusual and toxic amino acids (1 and 2, Scheme 1) as well as the known toxin g-guanidinobutyric acid (3) that were isolated from the mushroom T. venenata. The isolation of these active constituents was guided by oral toxicity tests in mice (all animal experiments were performed with the approval of the Kunming Institute of Botany Ethical Committee for Experimental Use of Animals). Amino acid toxins 1 and 2 killed mice with an LD50 value of 71 and 84mgkgÀ1 respectively. T. venenata has been epidemiologically implicated as a contributing cause of Yunnan SUD, which is an important local health concern of hereto undefined etiology.In July 2009, samples of T. venenata were collected from Tengchong County in Yunnan Province, near to a village where several T. venenata-associated Yunnan SUD clusters had occurred. We subjected fresh fruiting bodies of T. venenata (9.7 kg) to three successive extractions with ethanol at room temperature. Concentration of the combined ethanol soltions under reduced pressure gave crude extract (60.2 g), which was suspended in water and partitioned with ethyl acetate. Animal testing confirmed that the toxic factor was present in the aqueous phase. The water extract (40.5 g) was subjected to preparative medium-pressure liquid chromatography (MPLC) on a reverse-phase C18 column (RP-C18, MeOH/H2O, 0–100%) to yield 16 fractions. Fraction A was