(1) The research on the anti-tumor mechanism of the effective components of Pteris semipinnata L. was supported by the National Natural Science Foundation of China and the key science and technology projects of Guangdong Province. The extraction technology of the effective components of Pteris semipinnata L. applied for 1 national invention patents, and the medicinal uses of diterpenoids of Pteris semipinnata L. were granted national invention patents. The research results can provide a basis for applying for national new drugs.
There is no doubt that cancer is harmful to the whole world. Cancer is the second leading cause of death in China, and cancer control has become one of the focuses of China's health strategy. Under the auspices of Professor Liang Nianci, the research direction of this study began with 1990, screening anti-tumor drugs from traditional Chinese medicine. After years of arduous screening, it was found that the plant medicine Pteris semipinnata has obvious anticancer activity. Later, according to the research ideas of modern pharmacology, the research group carried out the research on the extraction of effective components from Pteris semipinnata, and further proved the pharmacological mechanism of these components. After nearly 10 years' efforts, the research group conducted a series of phytochemical, pharmaceutical, pharmacological and toxicological studies on the plant medicine Pteris semipinnata, and identified and confirmed that the components 5F, 6F and a (both diterpenoids) in Pteris semipinnata were anticancer active components. These constituents are diterpenoids with anticancer activity found from Pteris semipinnata for the first time in the world. Based on this, we applied for a national invention patent-Pteris semipinnata extract and its pharmaceutical composition (China PatentNo.: 95 1 19380.5) on 1995, and obtained the invention patent authorization in April 2002.
Since the establishment of this key laboratory, the anticancer mechanism of the anticancer active components 5F and 6F in the whole plant of Pteris semipinnata L. was mainly studied, and the new extraction technology of the active component 5F and several pharmaceutical preparations of 5F were studied, and the quality standards of two of them were initially established. At present, our laboratory is conducting pharmacodynamic research on the anticancer active components of Pteris semipinnata L.
Funding for this research direction includes the National Natural Science Foundation of China 1, the key research project of Guangdong Province 1, and a number of bureau-level scientific research projects. It has obtained 1 national invention patents, and newly applied for 1 national invention patents in 2002 (extraction method of diterpenoid effective components, application number: 02149680.3); Six graduate students have been trained successively. This study has obvious characteristics and advantages in the separation, extraction and identification of anticancer active components from Pteris semipinnata and the study of anticancer mechanism of anticancer active components from Pteris semipinnata. The research results are obviously innovative and practical, and have advantages in the research field of similar anti-cancer traditional Chinese medicines.
The main goal of this research direction is to develop new anticancer drugs with China characteristics and independent intellectual property rights. At present, the research direction is aimed at the systematic pharmacology and toxicology of the effective anticancer component of Pteris semipinnata L., and it is planned to develop this component into a national new drug with independent intellectual property rights in China.
In recent years, Professor Liang Nianci's research group has also carried out research on anti-tumor metastasis and anti-invasion drugs, screened a variety of flavonoids, terpenoids and anthraquinone compounds, and found many important signs. Quercetin, luteolin, apigenin, glycyrrhizic acid, cantharidin, 5F (the component of half-flag) and adenosine derivatives have obvious anti-tumor metastasis and anti-angiogenesis effects, and their mechanism has been preliminarily studied, which provides scientific basis for developing natural drugs for anti-tumor metastasis and anti-invasion.
(2) The research on the mechanism of apoptosis and the interference of apoptosis gene expression, as well as the research and development of many drugs to promote apoptosis, such as resveratrol and camptothecin, have accumulated a lot of experimental data in the research of using antisense nucleic acid and RNA interference technology to selectively block the apoptosis inhibitor gene bcl-xL to induce apoptosis of nasopharyngeal carcinoma cells and realize gene therapy of nasopharyngeal carcinoma, and obtained a lot of information on the molecular level of nasopharyngeal carcinoma, which provided a scientific basis for the prevention and treatment of nasopharyngeal carcinoma.
Nasopharyngeal carcinoma is a unique disease in southern China. According to statistics, the incidence rate in these areas is more than ten times that in other parts of the world. Under the auspices of Professor Zhou Keyuan, an academic leader, the research direction systematically studied the molecular biological characteristics such as enzymatic changes, DNA content and gene changes of nasopharyngeal carcinoma, an endemic disease in southern China. And recombinant genes promoting apoptosis were transfected into nasopharyngeal carcinoma cells to observe the effect on apoptosis.
This study starts with the mechanism and influencing factors of apoptosis, and observes the promoting effect of bcl-xS on apoptosis. After recombination, bcl-xS gene was transfected into cells to observe its promoting effect on cell apoptosis. The Bcl-xL gene was blocked by antisense oligonucleotide to observe the effect of bcl-xL gene on cell apoptosis. Explore the ways of mutual activation and regulation of Caspase, so as to understand the specific process of Caspase regulating cell apoptosis; In order to find new drugs to promote apoptosis, resveratrol, camptothecin and other drugs to promote apoptosis were discussed.
The research achievements in this field, "Molecular Biology Research of Nasopharyngeal Carcinoma" and "Study of Apoptosis Mechanism and Its Influencing Factors", won the first prize of Zhanjiang Science and Technology Progress in 2000 and 2003 respectively.
2. Study on the mechanism of anti-osteoporosis Chinese medicine and development of new Chinese medicine.
With the support of the key research project of Guangdong Science and Technology Plan and the provincial natural science fund, important progress has been made in the research of new Chinese medicine for osteoporosis. Four new national invention patents have been declared, three national invention patents have been obtained, three new Chinese medicines are under research, and two new Chinese medicines are 1 each, ranking at the advanced level in the research field of Chinese medicine for osteoporosis.
With the aging of the world population, the number of people suffering from osteoporosis is increasing year by year. According to statistics, the elderly population over 65 years old in China has reached 654.38+0.2 billion, of which about 90% are suffering from osteoporosis. In the next 654.38+00 years, the global number of hip fractures will reach 6 million, and the number of patients with hip fractures will reach 654.48+0 years. Therefore, the prevention and treatment of osteoporosis is a very urgent research topic to resist aging, prolong life and ensure people's quality of life. At present, the ideal drugs for the prevention and treatment of osteoporosis have not been found at home and abroad.
For a long time, the research on the prevention and treatment of osteoporosis by traditional Chinese medicine lacks strict experiments and mechanism discussion, so many foreign experts still don't know much about the prevention and treatment of osteoporosis by traditional Chinese medicine. The research direction is presided over by Professor Cui Liao, the academic leader. Starting from 199 1, the experimental method of studying anti-osteoporosis drugs by bone histomorphometry was established for the first time in China. Referring to the international research idea of establishing animal osteoporosis model by ovariectomy in rats, osteoporosis models of ovariectomized rats, testicles, steroids, hydroxyurea and cyclophosphamide were established successively to study the pharmacological action and mechanism of traditional Chinese medicine in preventing and treating osteoporosis. The research group also established the culture method of osteoblasts, screened the effective components of traditional Chinese medicine with positive effects on osteoblasts, and successively found the anti-osteoporosis active components of traditional Chinese medicine such as Fructus Cnidii, Herba Epimedii, Ginseng, Salvia miltiorrhiza, Polygonum Multiflori Radix and Glycyrrhiza Radix. We hope to find the effective components of traditional Chinese medicine with anti-osteoporosis activity and develop the components into new traditional Chinese medicine. On this basis, we selected some of them to study the animal model of anti-osteoporosis and made pharmacological observation by bone histomorphometry. Two active components of traditional Chinese medicine against osteoporosis with great development prospect were found.
Based on the latest research results of the pathogenesis of osteoporosis, our research group also discussed the pathogenesis and preventive measures of osteoporosis from the perspective of the regulation of bone marrow adipocytes. Taking the osteogenesis and adipogenic transformation of bone marrow stromal cells as the target, the effective components were extracted from traditional Chinese medicine with anti-aging effect, and the effective components that could act on bone marrow stromal cells to transform them into osteoblasts instead of adipocytes were found, thus fundamentally preventing the occurrence of osteoporosis. Through years of efforts, it was found that the water-soluble effective fraction of Salvia miltiorrhiza can promote the transformation of bone marrow stromal cells into osteoblasts and inhibit the transformation of bone marrow stromal cells into adipocytes. Based on this, the experiment of prevention and treatment of glucocorticoid-induced osteoporosis in rats by water-soluble effective fractions of Salvia miltiorrhiza was carried out. The results showed that Danshen Gubao, which is mainly composed of water-soluble effective parts of Danshen, has obvious preventive effect on glucocorticoid-induced osteoporosis in rats and also has preventive effect on osteoporosis in ovariectomized rats. In vitro experiments showed that Danshensu (a water-soluble effective component of Salvia Miltiorrhiza) inhibited the increase of lipoprotein esterase mRNA expression in bone marrow stromal cells induced by glucocorticoid, and increased the expression of type I collagen mRNA and osteoprotegerin mRNA induced by osteogenesis. The study of bone marrow cavity flow cytometry further proved that the number of fat cells in bone marrow decreased obviously, but the effect of alcohol extract of Salvia miltiorrhiza or pure tanshinone tablets was not as good as that of Salvia miltiorrhiza. Danshen Gubao is used to prevent and treat corticosteroid-induced osteoporosis and primary osteoporosis. Compared with the new traditional Chinese medicine developed in the market for the treatment of osteoporosis, this new medicine has obvious advantages: 1) According to the pharmacodynamic results of the effective components of traditional Chinese medicine, it is a modern Chinese medicine with simple formula and is not ancestral; 2) The mechanism of action is clear, that is, it promotes the bone formation of osteoblasts and inhibits the transformation of bone marrow stromal cells into adipocytes, especially the transformation of bone marrow adipocytes induced by corticosteroids; Bone morphometry shows that "Danshen Gubao" can significantly increase the bone mass of various animal models of osteoporosis, especially against the loss of bone mass induced by corticosteroids. 3) The side effects are extremely low, and the long-term effects also have protective effects on the brain and cardiovascular system.
We applied for a national invention patent (application number: 2003101162819; Name of the invention: A new medicine for preventing and treating osteoporosis is prepared from the water extract of Salvia miltiorrhiza or Danshensu. In order to clarify the anti-osteoporosis pharmacological effects of the effective parts of Salvia Miltiorrhiza, explore the best technology of the effective parts of Salvia Miltiorrhiza, and develop the pharmaceutical dosage forms of the effective parts of Salvia Miltiorrhiza into new anti-osteoporosis drugs, this study intends to complete the relevant research work according to the classification and application requirements of traditional Chinese medicines and natural medicines (effective parts extracted from traditional Chinese medicines and natural medicines and their preparations that have not yet been listed in China) stipulated in the National Measures for the Administration of Drug Registration.
The research direction was supported by the Provincial Natural Science Foundation, the provincial key scientific and technological research projects and Zhanjiang City, with about 6,543.8+0,000 yuan, over 654.38+0,000 papers published, 4 bureau-level and municipal-level scientific and technological progress awards and 3 national invention patents. Nine master students majoring in bone pharmacology have been trained, and another 10 is studying.
3. Research and development of bioactive drugs.
Progress has been made in screening broad-spectrum anti-inflammatory drugs in plants by fermentation engineering technology. The research team led by Professor Li Yanping made a new drug with high curative effect and little toxic and side effects by using the fermentation engineering technology of compound plant medicine. At present, the types and proportions of fermented plant drugs have been screened out according to the clinical efficacy. The fermentation process parameters such as culture medium, fermentation time, temperature, humidity, stirring times and ventilation were explored. Pharmacodynamic tests showed that the drug had therapeutic effect on passive Heymann nephritis rats, which could significantly reduce the contents of serum creatinine, urea nitrogen, triglyceride and total cholesterol, and had antibacterial effects on Staphylococcus aureus, Streptococcus and Candida albicans. Acute toxicity test shows that the drug is safe and reliable in clinical application. The project is funded by the Scientific Research Fund of the Provincial Department of Education, and the quality standard has been initially established. The screened prescription has applied for national patent (application number: 2004 10026970.5).