四种滇产乌头的发酵改性及发酵乌头的镇痛抗炎活性物质基础研究

Aconites displayed definite anti-inflammation and analgesia activities. In Yunnan Province, many people eat aconites to treat arthritis and various kinds of pains. However, eating aconities frequently led to poisoning and death of eaters because of cardiotoxicity and neurotoxicity of these medicinal materials. Improving the bioactivities and reducing the toxicities is the key to develop aconites.In recent years,fermented traditional medicines were gaining more and more attention. A lot of studies revealed that fermentation could improve the bioactivities and reduce the toxicities of traditional herbal medicine.Therefore, we proposed the idea of fermenting aconites to improve their bioactivities. In this study, four kinds of edible aconites from Yunnan, including Aconitum vilmorinianum, Aconitum vilmorinianum var. patentipilum, Aconitum austroyunanense and Aconitum nagarum var. heterotrichum f. dielsianum will be fermented by plant pathogen fungi and plant endophytic fungi, including some plant endophytic fungi isolated from Aconitums. According to the comparison of chemical constituents, toxicities, anti-inflammatory and analgesia activities with original marerial, potential inculants will be selected to perform large scale fermentation. And the chemical constituents and diterpenoid alkaloids of enlarged fermented aconites will be studied and the bioactivities of some separated compounds will be tested. This study is supposed to find low toxic lead compounds possessed anti-inflammatory and analgesia activities. Furthermore,this work will also provide a new idea for Yunnan aconites development.

乌头属药用植物具有明确的抗炎镇痛活性，在云南民间，人们通过食用乌头治疗关节炎和各类疼痛，取得了良好的疗效，但由于其神经毒性和心脏毒性也常导致食用者中毒甚至死亡。要想更好的开发乌头属药材，对其改性实现减毒增效是关键。近年来，采用微生物发酵改性中药逐渐受到重视，大量的研究已表明，微生物发酵是可以实现中药的减毒增效的。基于以上，申请人提出了通过微生物发酵改性乌头，实现减毒增效的研究思路，拟采用植物病原真菌和植物内生真菌包括乌头属植物内生真菌对黄草乌、展毛黄草乌、滇南草乌和无距小白撑等四种云南民间食用较多的滇产乌头进行纯种固态发酵，结合化学筛选、毒性筛选和抗炎镇痛活性筛选，选出能够使乌头减毒增效的优良发酵菌种。然后进行扩大发酵，并系统研究发酵乌头的化学成分，特别是二萜生物碱类化合物，阐明其镇痛抗炎活性物质基础，从而发现高效低毒的具有镇痛抗炎活性的药用先导化合物，为滇产乌头的开发提供一个新的思路。

乌头属药用植物具有明确的抗炎镇痛活性，在云南民间，人们通过食用乌头治疗关节炎和各类疼痛，取得了良好的疗效，但由于其神经毒性和心脏毒性也常导致食用者中毒甚至死亡。为了更好的开发滇产乌头，并对其进行减毒增效，本课题系统研究了10种滇产乌头的化学成分，从中分离鉴定了155个化合物，包括27个新化合物；并对5种乌头属植物进行了微生物发酵改性研究。探索了植物内生真菌与植物次生代谢产物的关系，从黄草乌和生附子中的分离鉴定了46株植物内生真菌，研究了其中一个植物内生真菌娄地青霉的化学成分，从中分离鉴定了8个化合物，包括3个新的二倍半萜化合物，并对部分所得化合物的抗肿瘤细胞毒性和抗氧化活性进行了测试。本课题的研究结果将对滇产乌头的开发提供重要的参考。

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