Traditional medicines make delicate advance

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An indigenous Chinese herb similar to the popular garden sage in the West has been used to treat a variety of diseases since time immemorial.

It is called danshen, or Salvia miltiorrhiza in Latin.

Despite its popularity, Xuan Lijiang, a scientist at Shanghai Institute of Materia Medica (SIMM) under the Chinese Academy of Sciences, did not expect his research would herald a new wave in the study of traditional Chinese medicine (TCM) at the molecular level, when he took it up 13 years ago.

His assignment, along with his colleagues, was to study the chemical ingredients of the herbal plant.

A little more than a decade on, Xuan has been recognized for his contributions to the creation of an innovative drug that is licensed by the State Food and Drug Administration (SFDA).

The drug, called Depsides salts and extracted from the Chinese sage danshen, has also reportedly led dozens of institutes and pharmaceutical firms to launch research programmes to find effective molecules from other traditional medicines.

Danshen research

Before Xuan began his research, modern research into danshen had already continued for four decades.

Previous research had only revealed two effective compounds, but Xuan believed that the proportions of the two compounds in the herb were so low that they were hardly the most important curative ingredients of the herbal plant.

Danshen produced in different regions, picked in different seasons, and soaked with different liquids has shown varying effects in treating heart disease.

"I am not a TCM doctor and my major is chemistry. But I have a sense that if people cannot make clear what constitutes the variations, we may never know how to keep TCM a constantly effective treatment," Xuan said.

As a biological chemist, Xuan naturally thought of tracing the most effective and distinctive ingredients in danshen.

Danshen's curative effects have been recorded for several hundreds of years and there have been various documents in ancient medical books describing patients' different reactions after taking danshen.

"The records give us clues of knowing the chemical components of danshen," Xuan said.

Over the years, he and his colleagues extracted hundreds of compounds from roots of Chinese sage, and tested them one by one or by different combinations in cellular experiments in labs.

Xuan said his lab was much better equipped than that of older generations of researchers.

The fingerprint map technology helps maintain the stable contents of herbal plants. The state-of-the-art screening technology quickens the speed of testing on the curative effects of different compounds extracted from danshen.

Also, computer-based imaging systems facilitate research to trace the exact mutual reactions between target cells and curative compounds.

The research lasted more than a decade, before Xuan and his colleagues pinpointed the intermolecular compounds mainly formed with depsides - intermolecular esters formed from two or more molecules of the same or different component units.

Animal testing and three-stages of clinical trials proved the compounds with depsides being the most curative ingredients in the medicines.

Hope for a breakthrough

Xuan's work is not isolated.

Across the country, researchers at colleges or institutes and pharmaceutical firms have been trying to screen for effective compounds of other TCM for several years.

Yang Xiuwei, head of the school of pharmaceuticals at Peking University, said that trying to find effective curative ingredients in TCM might be the only hope for most Chinese drug makers to develop innovative medicines.

So far, more than 97 per cent of chemical drugs produced in China are generics. Of the more than 30 kinds of biological medicines licensed by SFDA, only five are independently developed by Chinese researchers or biopharmaceutical firms.

According to Yang, the average costs of developing a new chemical drug through synthesizing new compounds in the United States has reached US$800 million, which commonly requires eight years.

"It is apparent that most Chinese pharmaceutical firms cannot afford it, even though the costs in China might be much lower," Yang told China Daily.

By contrast, trying to extract chemical compounds of herbal plants having been recorded by ancient medical books is likely to be a shortcut for China to develop innovative medicines.

"Unlike Western pharmaceutical researchers who study compounds first, we have carried out 'clinical trials' for hundreds of years, which conversely makes it easier for us to trace the effective compounds from herbals," Yang said, speaking from the Natural Medicine Section of Beijing International Pharmaceutical Summit, held in late May.

Challenges ahead

Xuan's success in studying the chemical compounds of TCM at the molecular level has carved a trail for TCM manufacturers to take up challenges in the intense competition in alternative medicine world.

According to Wang Zhimin, director of natural drug lab of the Chinese Academy of TCM (CATCM), China's TCM industry kept an annual growth rate of 23.4 per cent in production value in the past 13 years.

In 2004, its production value was 95.8 billion yuan (US$11.57 billion), accounting for 26.1 per cent of the total production value in China's pharmaceutical industry.

However, most TCM makers simply try to standardize the production process of their medicines instead of investing in detecting the molecular contents of TCM.

This fact, together with the rising awareness of the major TCM markets in East Asian countries towards drug safety, Wang said, has led to a steady decline in China's TCM exports over the past 20 years.

By comparison, China's imports of Japanese or South Korean-made TCM have been surging, reaching US$1.29 billion in 2004.

Wang said one reason for the decline in exports and surge in imports of foreign TCM is South Korean and Japanese firms have done a better job revealing chemical components of some of their herbal plants.

He added that the threat of the lack of knowledge on the effective compounds of TCM has been much bigger than declining exports.

"It is clear that some TCM also has side effects, but we do not know why the side effects occur. This is always a potential danger to patients," Wang said.

Despite efforts taken to standardize herbal plants' growth and processing, Yang said, true standardization is not attained without knowing the effective compounds of the medicines.

But to detect molecular contents is not as simple as it appears.

Ancient medical books have recorded thousands of TCM prescriptions and more than 10,000 herbal materials. Many prescriptions use up to 20 herbal plants or other materials.

It has been quite difficult to make clear the chemical contents of one herbal plant - such as danshen - let alone tracing the complicated chemical and physical reactions of a compound TCM prescription.

Bian Baolin, director of research and development at the Institute of Herbal Medicine, CATCM, said TCM remedies rely on joint actions of different herbal materials.

Extracting only some of the ingredients from the herbs might impair the original effectiveness and harm the traditional conceptions of securing balance in human bodies.

Wang Xudong, a professor at Nanjing University of TCM, complained that under the name of TCM modernization, more and more TCM doctors began to pursue modern chemistry theories and medical practice, losing their basic skills in treating patients with rich and accumulated experience.

Solution on horizon

Yang said to deal with the complicated process of screening TCM compounds, one must combine nationwide resources to work out key herbs.

In the past 20 years, China has invested 8 billion yuan (US$966 million) in TCM research and education, according to the State Administration of TCM.

"But the problem is that the money has been spent too sparsely. Each of thousands of TCM institutes and firms can get a tiny bit of the money. As a result, few have enough resources to identify chemical compounds of a single type of herb," Yang said. "If the money can be concentrated into a few capable hands, the situation might be greatly changed."

Concerning the joint effects of compound TCM prescriptions, Yang said modern analytical chemistry is one method that can be employed.

"We can start with one or two herbs, then gradually expand to the complicated prescriptions," Yang said.

Wang Zhao, a professor of medicine at Tsinghua University's Natural Medicine Lab, welcomed the idea. Wang was originally a TCM doctor before he went to Germany for a chemistry PhD in early 1990s.

"It is natural that some of the old TCM theories might be lost, even if they are still effective in the contexts of traditional TCM practice. But on the whole, screening TCM compounds can give us new and more accurate knowledge, which can also be used scientifically to explain some of the complicated old theories," Wang said.

From ChinaDaily