千年老树发新芽：古方黄芩汤在肿瘤化疗中的胃肠保护作用 

阿甘对祖国传统医学也是有感情的，上中学和大学时都曾经痴迷过，曾经为了学习所谓经络在自己身上扎过很多针（现在还后怕呢）；但是， 民族感情不能代替理性，文化不能代替科学呀，因此阿甘认为：

1. 废医验药的提法是合适的，中医是思辨的产物，缺乏明确的概念、没有实证的入路，根本不靠谱；而中药是经验的产物，还是有一定的挖掘潜力。

2. 要用现代医学规范的研究方法去“验”，要有质量控制手段，如监测药物的基本组成；动物或人体实验的对照设置与随机双盲；作用机理的探索等。

3. 毒性试验和用药安全，这是中药目前最为人所诟病的地方。中医以“是药三分毒”来偷懒和推脱责任，要学习人家做更多必要的功课。

4. 长路漫漫，任重而道远。

下面是憨人阿甘的粗译，欢迎各位高手拍砖、

 

译文：

新闻标题：看1800年的古老草药如何让损伤的肠胃愈合

作者：Ewen Callaway 2010年8月19日

一种古老的四种草药混合物可以化解癌症化疗对病人的一些副作用。这种“鸡尾酒药方”组成分别是：中国产的牡丹（或芍药）、甘草、大枣和黄芩花。在人们称之为“黄芩汤”，用于治疗胃肠疾病，至今已有1800年的历史。

一家叫做“PhytoCeutica”的新制药企业已经为该公司所属的复方进行编号命名为PＨY906，并在初期临床试验中展示了这种混合方剂对多种肿瘤化疗药物引起的腹泻症状的缓解。化疗药物除了能破坏杀死肿瘤细胞，也会伤害快速分裂的肠道细胞。

目前，该制药公司的研究人员与同在康州纽黑文市的耶鲁大学医学院的研究人员（合作）获得了PHY906发挥治疗作用的线索，虽然该复方药的绝大多数单体成分还不清楚。

PHY906还需要有更大规模的临床试验来证实其疗效。2004年美国FDA（食品药物管理局）降低对草药混合物的管理和审批的门槛，对那些单体成分还不清楚但已证明安全和有效的药物，容许批准通过。

德国一家名为MediGene的企业生产一种绿茶提取物，并将其用于治疗生殖器疣，该药是在这样的新规则下第一个得到FDA 批准的药物。

 “这是药物研发的一个新的范例”耶鲁大学药理学家、PhyCeutica公司首席科学顾问程永麒（音译）说，“它也是东方和西方（文明）交汇的典范。

分而治之（分头攻克）

围绕PHY906（作用机制）的最新研究结果提供了其发挥作用的分子细节，这些研究或能够有助于PhytoCeutica公司将其他草药的开发纳入相同的轨道。上述研究结果以在线形式发表于8月18日的“Science Translational Medicine”(科学转化医学)上。

依立替康（irinotecan）是一种化疗药物，它阻断一种被称为拓扑异构酶的酶，这种酶对DNA复制十分重要。当小鼠接受一定剂量的化疗药物依立替康时，肠道细胞开始相继死亡。然而， 程的研究组发现，在化疗的同时给予一定剂量的PHY906，则在四天内肠道内这些受到损伤的细胞却存活了下来。服用草药的小鼠肠道趋于死亡的细胞数要比未服用草药的要少，相反，正在分裂的细胞数则增加了。

研究人员检测了服用了PHY906 和依立替康小鼠肠道细胞的基因活性，发现促进肠道前体祖先细胞分裂的Wnt信号通路的基因表达被上调（表达增加）。程介绍说，PHY906不只是通过增加肠道干细胞数来对抗腹泻，依立替康也会导致炎症反应，而这也似乎是草药所针对的。

与单用化疗药物的小鼠相比，服用PHY906的小鼠肠道内的一种炎症细胞-巨噬细胞的数量减少，而且肠道内三个和炎症反应相关的基因（Cox2, NF-kB和iNOS）的活性也都降低。

治疗考虑

程认为，PHY906的多重效应可归结为其不同的化学组成，他还希望他的研究组能够分别鉴定出引起某一特定变化的化学成分，他说：“这将最终简化质控流程”。

目前，程和他在PhytoCeutica的同事们正在应用液相色谱、质谱以及细胞培养等手段尝试建立PHY906的生物学和化学“指纹”。他说，这种方式将保证每一批（药物）都含有相同的活性成分。

广告

英国伦敦帝国学院的化学生物学家伊莱恩. 福尔摩斯说：“就成分的活性而言，该研究组似乎在质量控制的技术上已经十分老练了。”然而，她又补充说“令人担心的是你无法控制它的毒性”。土壤化学、湿度，甚至是一天内不同的收集时间也会影响草药的化学组成。福尔摩斯指出：“我认为我们不得不对中药和其他民族的草药的应用方式持谨慎态度”。

程的研究组将在下周香港举行的一个学术会议上宣讲PHY906用于胰腺癌治疗的I/II 期临床研究结果，程也希望能在美国和欧洲尽快开展II期和III期临床试验。他还补充说，他乐于搞清楚这个方剂中的每一个分子成份，因为这可以帮助他的小组开发出新的药物，但是，在现阶段，“更重要的事情是考虑那些正在经受化疗的病人”。

 

 

 

附原文：

http://www.nature.com/news/2010/100818/full/news.2010.417.html

How an 1,800-year-old herbal mix heals the gut

Ewen Callaway

An age-old mixture of four herbs could spare patients with cancer some of the side effects of chemotherapy.

 

The cocktail comprises Chinese peonies, Chinese liquorice, the fruit of the Chinese date tree and flowers of the Chinese skullcap plant. In China, they call it 'Huang Qin Tang' and have used it to treat gastrointestinal problems for about 1,800 years.

 

A start-up pharmaceutical company called PhytoCeutica has dubbed its proprietary pill of the blend 'PHY906', and shown in early clinical trials that the mix can combat the severe diarrhoea caused by many chemotherapy drugs, which destroy fast-dividing gut cells in addition to tumour cells.

Now, researchers at PhytoCeutica and Yale University School of Medicine, both in New Haven, Connecticut, have some early leads on how PHY906 does this, despite the fact that most of its individual chemical components remain unknown.

 

PHY906 still needs to prove itself in larger clinical trials. In 2004, the US Food and Drug Administration (FDA) eased regulations on herbal mixtures, allowing the approval of medicines that have been proved to be safe and effective, even if their individual components aren't known.

A green-tea extract produced by the German firm MediGene in Martinsried, and used against genital warts, was the first such medicine to be approved by the FDA under these rules.

"This is a new paradigm of drug development," says Yung-Chi Cheng, a pharmacologist at Yale and head scientific adviser to PhytoCeutica. "It's a typical example of West meets East."

Divide and conquer

The latest results for PHY906, which provide molecular details indicative of how it might repair chemotherapy-damaged guts, could help PhytoCeutica to take its herbal drug down the same road. The results are published online today in Science Translational Medicine1.

When mice receive a dose of the chemotherapy drug irinotecan, which blocks an enzyme, called topoisomerase, that is important to DNA replication, their gut cells begin to die off. However, a dose of PHY906 given with the chemotherapy restored these cells within four days, Cheng's team found. The guts of mice taking the herbal medicine contained fewer dying cells and more dividing cells than those of control animals.

The researchers measured the activity of genes in the gut cells of mice on PHY906 and irinotecan and found that genes in the Wnt pathway, which encourages progenitor cells in the gut to divide, were upregulated.

But ramping up the gut's stem cells isn't the only way that PHY906 combats diarrhoea, Cheng says. Irinotecan also causes inflammation, which the herbal medicine seems to prevent. The guts of mice on PHY906 contained fewer inflammatory immune cells called macrophages than did those of rodents on chemotherapy alone, and the activity of three genes linked to inflammation — Cox2, NF-κB and iNOS — was also down.

Cure concerns

Cheng thinks that PHY906's multitude of effects can be explained through its different chemical constituents, and hopes that his team can identify which chemical is responsible for which change. "This will eventually simplify the procedures used for quality control," he says.

For now, Cheng and his colleagues at PhytoCeutica are using liquid chromatography, mass spectrometry and cell culture to try to establish a chemical and biological fingerprint for PHY906. This approach, he says, will ensure that each batch contains the same active ingredients.

ADVERTISEMENT

"This group seems to have got quality control down to a fine art in terms of the components' activity," says chemical biologist Elaine Holmes of Imperial College London. But, she adds, "the worrying thing is that you're not controlling for toxicity."

Soil chemistry, humidity and even when during the day a plant is harvested affect its chemical make-up, Holmes notes. "I think we have to be cautious with the way we use traditional Chinese medicines and other herbal remedies."

Cheng's team will present phase I/II clinical trial results for PHY906 in patients with pancreatic cancer at a conference in Hong Kong next week. And Cheng hopes to get phase II and III trials going in the United States and Europe soon.

He adds that he would love to account for every last molecule in the medicine; it could even help his team to develop new drugs. However, at this stage, "the importance is for patients undergoing chemotherapy", he says.

 

 

 Corrected:

An earlier version of this story stated that the fruit of the Buckthorn tree is a component of the Chinese herbal medicine Huang Qin Tang. It is actually the fruit of the Chinese date tree, a member of the buckthorn family.

·       References

1.       Lam, W. et al. Sci. Trans. Med. 2, 45ra59 (2010).

 

 

转载本文请联系原作者获取授权，同时请注明本文来自李福洋科学网博客。
链接地址：https://blog.sciencenet.cn/blog-475066-363327.html

上一篇：旧文重发：大肠呼吸，肚脐喘气，稀奇稀奇
下一篇：知耻而后勇，脓包须戳破！