On February 4th, 1972, the Institute of Pharmacology established a new drug research group, with Liu as the team leader. At that time, the leaders' intention was to organize some people to carry out President Mao Zedong's call and create new medicine combining traditional Chinese and western medicine. As for the specific research content, you should choose your own topic. At the age of 40, Liu He and his colleagues in the group went deep into the relevant hospitals in Beijing to investigate and study, understand what the good signs of Chinese herbal medicine treatment are, and consulted a large number of Chinese herbal medicine research materials. After analysis and thinking, he put forward a train of thought: taking the combination of liver biochemistry and pharmacology with the theory of "strengthening the body resistance and consolidating the foundation" of traditional Chinese medicine as the research direction, and starting with the research of Schisandra chinensis and Ganoderma lucidum. There are three main reasons for putting forward the above ideas: ① Don't crash with others when choosing a topic, and have more space for research activities. Considering the theoretical research of strengthening the body resistance and consolidating the foundation by combining traditional Chinese and western medicine, Professor Kuang Ankun and others in Shanghai have done a lot of research on the essence of "kidney" in traditional Chinese medicine from the endocrine point of view. If we still follow the endocrine route, it is difficult to surpass them, and liver pharmacology has not been studied in China, so we will not repeat it with others, and there is a lot of room for research activities; ② Theoretical research should be combined with practical application as far as possible, instead of simply publishing papers, so as to solve some practical problems. The incidence of hepatitis in China is high and there are many patients, so new drugs for treating hepatitis are urgently needed. Through the study of liver biochemistry and pharmacology, new drugs for hepatitis may be found one day. At that time, it was found that Schisandra chinensis could reduce transaminase and improve symptoms in patients with chronic hepatitis. ③ The research work should be combined with the latest development of international pharmacology. Liver is an important organ for detoxification and metabolism, and the research abroad is quite active. At that time, the domestic research on liver biochemistry and pharmacology was still blank. Once you find something in liver research, you can combine the latest international progress in time to improve your research level. Based on the above ideas, he and Bao and others combined with Chinese herbal medicines such as Schisandra chinensis and Ganoderma lucidum to continue to study and expand liver pharmacology. During this period, Professor Song Zhenyu served as the project leader for a period of time, leading the whole team. They successively cooperated with plant chemists Chen, Li Lianniang and medicinal chemist Xie Jingxihe, and successfully developed new drugs for treating chronic hepatitis (DDB) on the basis of studying the pharmacology and chemistry of Schisandra chinensis. This drug has been widely used in China for nearly 20 years and exported to four countries. This is the beginning of active treatment of chronic hepatitis in China, which has produced good social and economic benefits. At the time of studying DDB, there was no patent system in China, so although DDB was the first new drug to treat hepatitis at home and abroad, there was no patent protection, which caused a lot of economic losses to the country. The lost gold should be found back. He began to develop new anti-hepatitis drugs with intellectual property rights in China, hoping that its curative effect would be better than that of bifendate. He led Li Yan, Wei Huailing and others to cooperate with the chemical group led by Zhang Chunzhen. After nearly 15 years' efforts, bicyclol, a second-generation new drug for treating hepatitis, was finally successfully developed, and applied for invention patent protection in 14 developed countries and Taiwan Province province of China. The drug has a significant effect on reducing transaminase in patients with chronic hepatitis B, and has a certain effect on inhibiting the replication of hepatitis B virus with few adverse reactions. In September of 20001year, it was approved by the state for trial production and marketing, which provided another new therapeutic drug for patients with chronic hepatitis in China.
The research process of Schisandra chinensis and DDB is not smooth sailing. There are different academic viewpoints and other factors. He persisted in his research and found that DDB can also induce the differentiation and apoptosis of tumor cells, and inhibit the secretion of alpha-fetoprotein (an important biochemical marker of liver cancer) and the expression of alpha-fetoprotein gene by liver cancer cells. These new results deepen the understanding of the pharmacological characteristics of DDB. Fortunately, 10 years, DDB has been widely used to treat chronic hepatitis in clinic, and its curative effect is better than other similar drugs at home and abroad, and no adverse reactions have been found.
In addition, he also made a comparative study on nearly 30 compounds extracted from Chinese herbal medicines such as Schisandra chinensis and wampee. It was found that these compounds have the same pharmacological characteristics, which can alleviate hepatocyte injury and induce liver drug enzyme (cytochrome P-450), which is different from the classic liver drug enzyme inducer phenobarbital. These results have not been reported before, thus greatly enriching people's understanding of traditional Chinese medicine such as Schisandra chinensis. Relevant research results have been written into many papers, published in famous foreign journals and reported at international conferences many times. Hundreds of foreign colleagues have written to ask for a pamphlet, and the deputy editor-in-chief of the internationally renowned Italian journal Pharmacology and Therapy has also written to Liu to write a literature review of "Cytochrome P-450 and Hypolipidemic Drugs" for the journal. An American professor wrote: "The publication of your research results further stimulated our long-term interest in studying the chemopreventive activity of China herbs." This shows that his research has attracted the attention of foreign counterparts.
Origin of pharmacological research on antioxidants
The pathogenesis of many diseases is related to oxygen free radical injury, such as radiation injury, organ ischemia reperfusion, toxic hepatitis, aging, cancer, inflammation, degenerative diseases of the central nervous system such as Parkinson's disease, Alzheimer's disease and epilepsy. Substances that can scavenge oxygen free radicals are called antioxidants. During the period of 1985, Liu studied the protective mechanism of Schisandra chinensis, and found that various components in Schisandra chinensis can inhibit the lipid peroxidation of liver microsomes caused by carbon tetrachloride, which is an important part of oxygen free radicals' damage to biofilm. Therefore, it is speculated that Schisandra chinensis may also inhibit membrane lipid peroxidation caused by oxygen free radicals. He used a variety of in vitro and in vivo models to study, and found that many components of Schisandra chinensis had significant antioxidant effects, which were extended from Schisandra chinensis to other Chinese herbal medicines, and became the first research on antioxidation in China pharmacological circles. Some people think that antioxidants have a wide range of functions and are not specific. However, Liu has his own opinion. Because oxygen free radical damage is closely related to diseases such as aging, Parkinson's disease and Alzheimer's disease, and there is a lack of satisfactory therapeutic drugs at home and abroad, it may be a promising field to study the preventive and therapeutic effects of antioxidants on these diseases from the perspective of neuroprotection. Therefore, he closely combined the research of antioxidants with the prevention and treatment of antioxidants, and cooperated with the research team led by Academician Liang to screen a new compound with novel structure and strong antioxidant activity from dozens of synthetic compounds. Oral administration can obviously improve the behavior disorder of several experimental tremor model mice and increase the content of dopamine and its metabolites in brain striatum of MPTP model mice. It has a significant protective effect on the injury and apoptosis of dopaminergic nerve cells (PC- 12 cells) caused by dopamine and the formation of intracellular protein polymers and neuromelanin caused by dopamine autooxidation. The compound also has the effect of improving learning and memory dysfunction in mice, and has applied for patent protection, so it may be developed into a new neuroprotective drug for treating Parkinson's disease.
A preliminary study on the mystery of "Cao Xian" Ganoderma lucidum and Ganoderma lucidum spore powder
Ganoderma lucidum is a precious nourishing and strong traditional Chinese medicine. It is said that it can cure all diseases and is called "Cao Xian". 1970 or so, many domestic units study the cultivation, fermentation culture, pharmacology, chemistry and clinic of Ganoderma lucidum. Considering the traditional Chinese medicine "strengthening the body resistance", Liu first made a comparative study on the pharmacological effects of wild ganoderma lucidum, cultivated ganoderma lucidum and fermented ganoderma lucidum mycelium, and found that the ganoderma lucidum preparation studied had various pharmacological effects. Ganoderma lucidum emits spore powder during its growth. Whether these spore powders have pharmacological activities has not been reported in the paper. Scientific research is to explore things that have not been studied before, so he cooperated with Zhai Yunfeng and Hou in the plant chemistry room to compare the pharmacology and chemistry of Ganoderma lucidum spore powder and Ganoderma lucidum mycelium. It was found that the water extracts of both of them had various pharmacological effects and contained similar chemical components, which were basically the same as those of Ganoderma lucidum. On this basis, Ganoderma lucidum spore powder and Ganoderma lucidum mycelium were processed into injections (trade name: Shengji Zhi Bo Injection) respectively. Clinical trials show that it has a certain therapeutic effect on dermatomyositis, polymyositis, alopecia areata, localized scleroderma, neurosis, progressive muscular dystrophy, atrophic myotonia and other diseases refractory to western medicine. Since 1973, it has been used clinically for nearly 30 years, and no toxicity or adverse reaction has been found. The above diseases generally belong to skin and muscle diseases. Shengji injection can treat these diseases. How to prove its effect in pharmacology? What is the mechanism of action? At that time, there were no suitable experimental models at home and abroad for reference. This is a difficult problem for Liu. Clinically, we know that the activities of serum aldolase and phosphocreatine kinase (CPK) in patients with polymyositis often increase, and we are inspired by the phenomenon of inflammatory reaction in muscle biopsy. Can we simulate these pathological and biochemical changes in clinic to replicate the animal model of immune myositis similar to it, and see if Myosheng injection has preventive and therapeutic effects? In addition, it is known from the literature that when the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is poisoned by humans and animals, muscle rigidity may occur due to the damage of the structure and function of muscle cell membrane. He also assumed that injecting 2,4-D into animals may cause the increase of serum aldolase and CPK enzyme activities, which can be used as an animal model to judge the curative effect of Jiansheng injection. Based on the above ideas, he injected the homogenate of guinea pig thigh muscle with Freund's adjuvant into the soles of rats once a week for 4 weeks. Results Immune myositis model was successfully reproduced, and the leg muscles of rats showed inflammatory reaction, and the levels of serum aldolase and CPK enzyme increased. Injecting 2,4-D into mice also successfully caused the increase of serum aldolase and CPK enzyme. By using these two models, it is proved that Myosheng injection has obvious preventive and therapeutic effects, and the mechanism of Myosheng injection protecting muscles from injury is studied, and meaningful results are obtained, which provides scientific experimental basis for the clinical application of Myosheng injection. Unfortunately, what is the really effective material basis of Ganoderma lucidum and Ganoderma lucidum spore powder so far has not been clearly studied. If you want to uncover the mystery of Ganoderma lucidum as a "fairy grass", you need to continue to do a lot of research. At present, the pharmacological action and clinical use of ganoderma lucidum spore powder, especially the broken spore powder, have been heated up in China, and how good the anti-cancer effect is has been covered with a "mysterious" veil. The scientific attitude should be honest comparative study, and come up with convincing experimental data, so that Ganoderma lucidum can better serve human health.