《神经科学杂志》报道：UCLA梁京教授团队发现中草药对酗酒提供新治疗 - 学人动向 - 科技动向

《神经科学杂志》报道：UCLA梁京教授团队发现中草药对酗酒提供新治疗

来源：FW by UCLA Max Shao ｜ 2012/1/23 3:15:19 ｜浏览：5961 ｜评论：1

中国草药可能对酗酒提供新的治疗

从一个古老的草药枳椇子中提取出一种化合物，二氢杨梅素可以消除急性酒精中毒和戒断症状。研究报告发表在1月4日“神经科学杂志”。

如果一个化合物被证明在人类有类似的效果，它可以提供一个强大的方式来阻断酒精的令人眼花缭乱的效果，可怕的后遗症及对酒精依赖。在北卡罗莱纳医学院神经科学家A. Leslie Morrow教授说：“我认为这是真的很漂亮，令人难以置信的是一项研究能开辟从这么多角度的研究途径”。

《神经科学杂志》报道：UCLA梁京教授团队发现中草药对酗酒提供新治疗

梁京教授带领下的美国加州大学的研究人员进行了研究，他们筛选了大多数具有解酒作用的草药，从中找出有效的草药化合物。一个有高效的候选物引起了研究人员的注意：从亚洲的枳椇树的种子（枳椇子）中分离提取，历史记载作为一个主要的解酒药来描述至今已有数百年了。

在这项研究中，梁教授和她的团队找出了枳椇子的一个成分称为二氢杨梅素（DHM），对模拟人类酒精中毒及酒后综合症的大鼠进行研究。给予大鼠酒精（酒精量相当于人在两小时内喝10至15罐啤酒），动物马上酒醉并失去知觉及生理反射（不能自行翻转）。大鼠大约失去知觉及生理反射一个小时后才能开始重新控制自己的身体和自己翻转过来。

但是，当大鼠接受二氢杨梅素，这些老鼠失去知觉及生理反射仅约15分钟。

二氢杨梅素有更多的效益。在酒精狂欢两天后它有助于缓解酒精戒断症状，并且抑制焦虑和抑制癫痫发作的易感性。

在纽约市威尔康乃尔医学院的史蒂文保罗说，最出色的结果是，二氢杨梅素也抑制了酒精成瘾性。一般喝酒的大鼠逐渐产生酒精依赖症。该研究小组发现，喝酒加上二氢杨梅素，老鼠并未产生对酒精的依赖性。

“当你喝的酒精加上二氢杨梅素，你永远不会难以自拔，”梁教授说。

虽然结果是令人振奋的的，他们并不意味着二氢杨梅素可以使你不计后果的暴饮，A. Leslie Morrow教授说。酒精在大脑中有许多方面的影响。

更重要的是，梁京教授的团队还成功地发现了二氢杨梅素的药理作用原理。酒精通过改变大脑抑制系统的神经GABA受体的可塑性，来改变大脑的功能，也称酒精的毒性效应。二氢杨梅素使这些大脑中的受体少受酒精的的毒性效应影响。另一个已经开发多年的化学物质称为Ro15 - 4513的，是由史蒂文保罗和合作者发现的，也阻断酒精对GABA受体的作用。但它有很多副作用，会引起癫痫发作。

到目前为止，梁教授和她的团队已经发现二氢杨梅素无副作用。研究人员正计划测试二氢杨梅素对人的药理作用。

Chinese herb may provide alcoholism cure

Hovenia found to stop hangovers, reduce alcohol dependency：Scientists

By Thandi Fletcher, Postmedia News January 15, 2012

If you're having trouble reading this because your head is pounding from too many drinks last night, help may be on the way.

Of course, you'll have to wait until scientists perfect their theory.

Researchers have uncovered a compound in an ancient Chinese herbal medicine that has been found to stop hangovers and to reduce alcohol dependency in rats, according to a recent study published in the Journal of Neuroscience.

If the compound is proven to have the same effect in humans, it could help pave the way to a cure for alcoholism, said Dr. Jing Liang, the study's lead author and an associate professor of pharmacology at the University of California in Los Angeles, in an interview with Postmedia News.

For others who enjoy an occasional drink but would rather not endure the pounding hangover headache the next day, taking the compound also could be "an easy way to erase the uncomfortable feelings," said Liang.

Hovenia is an extract from the Chinese Raisin Tree.

In Asia, Liang said hovenia has been taken as an herbal supplement to treat hangovers for at least 500 years.

However, the effectiveness of hovenia as a drug to treat alcohol dependency has never before been closely studied.

Liang said she became interested in taking a closer look at hovenia when she noticed that when people consumed alcohol along with food cooked with hovenia - as it is also a spice used for cooking in Asia - they seemed to avoid getting drunk.

In order to study how hovenia works, Liang said she needed to isolate the specific compound that was blocking the effect of alcohol.

The answer turned out to be dihydromyricetin, or DHM.

Liang and her research team at UCLA began testing the compound on rats.

They devised a series of tests to determine what would happen to rats if they were given just alcohol, or alcohol along with DHM.

For the group given alcohol, the rats' behaviour when intoxicated was not unlike that of humans, she said.

When you give a rat alcohol, they act "totally like a human," said Liang. "You give an animal alcohol and then they're drunk, and they lose consciousness. They go to sleep."

But the rats who were given alcohol plus DHM, showed no signs of intoxication, Liang said.

"They don't（get）drunk," said Liang. "It was amazing. I was so excited."

The rats in the alcohol group slept for about 70 minutes, while those in the DHM group only slept for about 10 minutes. Others didn't sleep at all, she said.

In another test, the researchers administered DHM to rats who were given alcohol for a prolonged period of time. Their symptoms of alcohol dependency were significantly reduced.

"From this experiment, even if you establish a high drinking level of alcohol and then give them DHM, their dependence will reduce," said Liang.

The rats given DHM along with alcohol did not have any hangover symptoms either, she said.

The next step, if she is able to secure enough funding, is to test the study's findings in human clinical trials, said Liang. She expects to see the same results in humans, and without any negative side-effects.

"For more than 500 years（that hovenia has been used as a supplement）, there have been no reports of poison or toxicity," she said. "It's really safe."

Liang's goal is to turn DHM into a medication, possibly in a gum, patch or spray-form, she said. She already has patented her idea.

In her study, Liang wrote that there are only three medications - oral naltrexone, acamprosate and disulfiram - currently approved for treating alcohol dependence by the U.S. Food and Drug Administration. However, Liang said these drugs have major side-effects and have not been proven effective in treating the disorders.

Bernard Le Foll, a pharmacology professor at the University of Toronto, said the study's findings are "very promising" for the treatment of alcohol addiction.

"I think it's very interesting," he told Postmedia News. "It's building on the use of an old plant in Chinese medicine and they seem to have been able to isolate what seems to be the active ingredient."

However, Le Foll does not recommend people start taking hovenia to treat their hangovers just yet.

"More experiments need to be done. We need to validate this in human subjects," he said. "But what is clear from this experiment is that ... some drugs appear to accelerate the elimination of alcohol from the body, and also it seems to reduce the desire to drink alcohol."

Related report 1：Chinese Tree Offers Hope For Alcohol Antidote

By Eleanor Bell ABC - AustraliaNews.com.au

Researchers are investigating a 500-year-old Chinese hangover cure in the hope they can put its properties into a pill to help alcoholics and stave off sore heads. The researchers say the ancient Chinese remedy contains a compound which can prevent alcohol from having its usual intoxicating effects on the brain. The compound, DHM, which works by stopping alcohol from accessing the receptors in the brain, is extracted from an oriental raisin tree and has already proved its worth as an alcohol antidote in a series of experiments on rats. Researchers at the University of California injected rats with a dose of alcohol proportionate to the amount a human would get from downing 15 to 20 beers in two hours. Head researcher Dr Jing Liang said "when rats are drunk they behave like humans, just like that". In a bid to test coordination and clumsiness, Dr Liang looked at how long rats took to right themselves after being laid on their backs. Rats treated with DHM took just five minutes to recover, while those without the drug slept for more than an hour. As well as sobering them up, the treated rats also exhibited fewer hangover symptoms; for example, untreated rats were more likely to cower in the dark recesses of their maze. But Dr Liang says those dreaming of a magic antidote to drinking too much can think again. The presence of DHM also reduced the cravings for alcohol, a factor Dr Liang says could prove invaluable in treating alcoholism in humans. "If from the beginning you drink alcohol with DHM, you never go to a high level of drinking," she said. Direct antidote Dr Paul Haber from Australia's National Alcohol and Drug Research Centre welcomes the research. He says the development of a drug with these properties for humans could potentially save lives. "A direct antidote might be useful in the emergency department setting where people who are grossly intoxicated with alcohol sometimes are brought - Friday night, Saturday night situations - and this might wake them up quickly so they can go home," he said. "We do have patients like this who wind up in intensive care and there are deaths associated with direct alcohol poisoning." Risks Providing the drug is safe, effective and available, Dr Haber says there are still risks associated with an alcohol antidote. "Sometimes the antidote wears off too quickly," he said. "It works for a while but then it wears off and the person becomes intoxicated again, and if they have started driving home, for argument's sake, then becoming intoxicated again can be life-threatening." While a therapeutic drug may be some time away, Dr Liang is working on a supplement that could potentially prevent alcohol addiction. "You can take DHM with alcohol so you don't become addicted," she said. Dr Haber says while potential drugs often falter in human trials, the DHM discoveries are important. "So even if this particular compound does not prove to be a safe and effective treatment, it gives rise to a whole line of research into perhaps similar compounds," he said. Clinical trials on the effects of DHM on the human brain will begin soon.

Related Report 2：Chinese tree extract stops rats getting drunk

18:02 09 January 2012 by Andy Coghlan
For similar stories, visit the Drugs and Alcohol Topic Guide

For hardened drinkers, it sounds too good to be true：a natural substance that keeps them sober no matter how much they drink, neutralises hangovers and eventually breaks the cycle of alcohol addiction.

Alcoholism is a huge problem globally, killing 2.5 million people a year according to the World Health Organization. There has been serious research recently looking for drugs that stop people drinking, or at least encourage them to drink less.

Extracts of a Chinese variety of the oriental raisin tree（Hovenia dulcis）could be the answer. The extracts have been used for 500 years to treat hangovers in China. Now dihydromyricetin（DHM）, a component of the extract, has proved its worth as an intoxication blocker in a series of experiments on boozing rats. It works by preventing alcohol from having its usual intoxicating effects on the brain, however much is in blood.

Soon, a preparation containing DHM will be tested for the first time in people. "I would give it to problem drinkers who can't resist going to the pub and drinking," says pharmacologist Jing Liang of the University of California, Los Angeles, who led the research team.

"DHM will reduce the degree of drunkenness for the amount of alcohol drunk and will definitely reduce the hangover symptoms," says Liang. "In time, it will reduce their desire for alcohol."

Too drunk to stand

Liang first tested whether DHM blocks the clumsiness and loss of coordination caused by drinking too much. To do this, she measured how long it took for treated rats to right themselves after being laid on their backs in a V-shaped cradle.

After she injected rats' abdomens with a dose of alcohol proportionate to the amount a human would get from downing 15 to 20 beers in 2 hours by a human, they took about 70 minutes, on average, to right themselves. However, when an injection of the same amount of booze included a milligram of DHM per kilogram of rat body weight, the animals recovered their composure within just 5 minutes.

DHM also stopped rats in a maze from behaving in ways resembling anxiety and hangovers. Rats given heavy doses of alcohol cowered away in corners of the maze, whereas those given the extract with their alcohol behaved normally and were as inquisitive as rats given no alcohol at all, exploring the more open corridors of the maze.

Finally, DHM appeared to discourage rats from boozing when they had a free choice between drinking a sweetened solution of alcohol or sweetened water. Over a period of three months, rats will normally get addicted to increasing volumes of the hard stuff. Rats given DHM, though, drank no more than about a quarter of the amount that the "boozers" eventually built up to. Moreover, boozy rats that had worked up to the higher levels suddenly dropped down to a moderate intake when given DHM after seven weeks.

All the benefits of DHM were lost instantly when Liang also gave the rats a drug called flumazenil, which is known to block receptors in the brain for a neurotransmitter called gamma aminobutyric acid（GABA）. According to Liang, this proved that DHM works by stopping alcohol from accessing the same receptors. This, she says, explains why DHM kept the rats sober even when they had huge amounts of alcohol in their blood.

Good idea?

"This supports other data that GABA receptors are key in the actions of alcohol and that targeting this interaction is a viable approach to reducing alcohol intake," says David Nutt of Imperial College London, former head of the British government's advisory committee on drugs. "Let's hope it's safe to use in humans."

Other alcohol experts fear that the availability of a "sobriety pill" could encourage more, not less drinking. Markus Heilig, clinical director of the US National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, says that Roche abandoned development of a similar compound called Ro15-4513. "There was a lot of philosophical worry that an 'alcohol antidote' would entice people to consume alcohol and then count on being able to terminate the intoxicating effects on demand," says Heilig.

Ro15-4513 caused serious side effects, including anxiety and convulsions. Liang says there is no sign that DHM carries similar side effects.

Journal reference：The Journal of Neuroscience, DOI：10.1523/jneurosci.4639-11.2012

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