解锁大自然的药房：中药研究焕发新活力-医疗器械网

解锁大自然的药房：中药研究焕发新活力

来源：广州云星科学仪器有限公司分类：科技文献 2024-03-20 10:00:09 15阅读次数

中药（Traditional Chinese Medicine, TCM）作为中国宝贵的医学资源已经在中国大地上使用了数千年，并且积累了大量的临床实践证据。但由于其化学成分复杂，大多数中药的活性化合物和靶点仍然不明确，这严重阻碍了现代医学对其的解释。另一方面，传统中医文献大多是用古汉语写作的，数量大且语言复杂，严重阻碍了临床医生或研究人员对有效信息的检索和挖掘，使得记载在经典中医文献中的知识可能会被忽视。青蒿素的低耐热性就是受到了一本古中医书籍的启发，并催生了诺奖成就，这也极大地鼓舞了科研人员向经典中医文献挖掘中药有效信息的动力。

浙江大学药学院王毅教授团队就利用信息挖掘、高内涵筛选及高分辨率质谱分析等手段，成功的在仲景方中筛选到了多种可以用于炎性肠病（Inflammatory Bowel Diseases, IBD）治疗的潜在中药组分 ^[1]。

研究团队首先通过 Python 的词频分析和词汇分类，在 40 多本中医古籍中找到了 248 个中医方剂，并以此为依据对中国国家知识基础设施和 NCBI Pubmed 进行进一步文献检索。另外，使用 Word2vec 模型进行知识挖掘，最终确定了与胃肠道炎症疾病最密切相关的十种仲景方。

图1. 仲景方知识挖掘

接下来，研究团队构建了用于 IBD 药物筛选的斑马鱼模型。TNBS 诱导的 IBD 斑马鱼模型表现出肠道形态的改变及中性粒细胞浸润等明显的 IBD 症状 ^{[2, 3]}。另外，经 5-ASA（5-ami- nosalicyclic acid）这一常规的 IBD 治疗药物干预后斑马鱼肠道的中性粒细胞积累及 ROS 信号均得到缓解，这也进一步说明 IBD 斑马鱼模型适用于 IBD 治疗药物的筛选。

图2. 5-ASA 缓解 TNBS 诱导的斑马鱼肠道中性粒细胞积累（A，红色荧光）及 ROS（D，绿色荧光），ImageXpress Micro Confocal (Molecular Devices, US.)拍摄

利用 IBD 斑马鱼模型及高内涵分析，研究人员对桃花汤、白头翁汤及葛根芩连汤 3 种仲景方中的 74 个组分（fractions）进行了筛选，科研人员把焦点锁定在了其中 6 种组分上。经过 LC-MS 方法分离鉴定，最终确定了 13 种化合物。经过又一轮 IBD 斑马鱼模型的筛选，科研人员最终发现了 6 种有效成分，其中调节中性粒细胞积累的化合物有 5 种（daidzin， palmatine，oroxyloside，chlorogenic acid 和 aesculin），降低 ROS 水平的化合物有 2 种（baicalin 和 oroxyloside）。

图3. 高内涵方法筛选仲景方化合物

王毅教授团队开发的这套中药成分筛选方法无疑为中药现代化做了良好的示范，这一系列方法不仅有效而且高效地完成了目标疾病治疗药物的筛选，也为后续筛选其他疾病治疗药物奠定了基础。

参考文献：

[1] Yu, Y. et al. (2021) Identification of anti-inflammatory compounds from Zhongjing formulae by knowledge mining and high-content screening in a zebrafish model of inflammatory bowel diseases. Chin Med 16 (1), 42.

[2] Fleming, A. et al. (2010) In vivo analysis of gut function and disease changes in a zebrafish larvae model of inflammatory bowel disease: a feasibility study. Inflamm Bowel Dis 16 (7), 1162-72.

[3] Oehlers, S.H. et al. (2013) Chemically induced intestinal damage models in zebrafish larvae. Zebrafish 10 (2), 184-93.

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Molecular Devices 始创于上世纪 80 年代美国硅谷，并在全球设有多个代表处和子公司。2005 年，Molecular Devices 在上海设立了中国代表处，2010 年加入全球科学与技术的创新者丹纳赫集团，2011 年正式成立商务公司：美谷分子仪器 (上海) 有限公司。Molecular Devices 以持续创新、快速高效、高性能的产品及完善的售后服务著称业内，我们一直致力于为客户提供在生命科学研究、制药及生物治疗开发等领域蛋白和细胞生物学的创新性生物分析解决方案。

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[8]未定义数组索引: page
[2]Declaration of app\common\model\TechNewsCategory::getList($filter = Array) should be compatible with app\common\model\BaseModel::getList($filter = Array, $sort = Array)
[8]未定义数组下标: 0
[2]Declaration of app\common\model\TechNews::getAllList($filter = Array, $limit = 10, $order = Array, $with = Array) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[2]Declaration of app\common\model\Company::getAllList($filter = Array, $limit = 20) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[8]未定义数组索引: center
[8]Only variables should be passed by reference
[2]Declaration of app\common\model\TechNewsComment::getAllList($filter = Array, $limit = 16) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[8192]Function create_function() is deprecated
[8192]Function create_function() is deprecated
[8]未定义数组索引: area
[8]未定义数组索引: st
[2]Declaration of app\common\model\Topic::getList($filter = Array) should be compatible with app\common\model\BaseModel::getList($filter = Array, $sort = Array)
[2]Declaration of app\common\model\Topic::getAllList($filter = Array, $field = 'id,md5,tit...', $limit = 0) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[2]Declaration of app\common\model\TopicInfoList::getAllList($filter = Array, $limit = 8) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[2]Declaration of app\common\model\News::getAllList($filter = Array, $limit = 16, $order = Array, $with = Array) should be compatible with app\common\model\BaseModel::getAllList($filter = Array, $with = Array, $limit = 0, $sort = Array, $field = 'a.*', $join = Array)
[8]未定义数组索引: center
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: cid
[8]未定义数组索引: goods_list
[8]未定义数组下标: 0
[8]未定义数组索引: center
[8]未定义数组索引: center
[8]未定义数组索引: center
[8]未定义数组索引: center
[8]未定义数组索引: center
[8]未定义数组索引: wtt_list

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[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 444 LIMIT 1 [ RunTime:0.000200s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 444 LIMIT 1 [ RunTime:0.000186s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 224 LIMIT 1 [ RunTime:0.000198s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 224 LIMIT 1 [ RunTime:0.000179s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 13 LIMIT 1 [ RunTime:0.000268s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 13 LIMIT 1 [ RunTime:0.000186s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 239 LIMIT 1 [ RunTime:0.000197s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 239 LIMIT 1 [ RunTime:0.000168s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 598 LIMIT 1 [ RunTime:0.000156s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 598 LIMIT 1 [ RunTime:0.000167s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 697 LIMIT 1 [ RunTime:0.000174s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 697 LIMIT 1 [ RunTime:0.000187s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 394 LIMIT 1 [ RunTime:0.000157s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 394 LIMIT 1 [ RunTime:0.000166s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `follow_user_id` = 285 LIMIT 1 [ RunTime:0.000168s ]
[ SQL ] SELECT COUNT(*) AS tp_count FROM `user_follow` WHERE `user_id` = 285 LIMIT 1 [ RunTime:0.000146s ]

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