Studies on Cordyceps sinensis showed that Astragalus membranaceus could significantly up-regulate the decrease of density of M-choline receptor and M 1 subtype receptor in cortex, hippocampus and striatum of naturally aging rats, and also regulate the content of cyclic nucleotide in plasma of aged rats. The density of β receptor and the contents of T3, T4 and cortisol in myocardium of aged rats decreased, while the contents of Astragalus membranaceus, Ginseng and Lycium barbarum increased. It can improve the abnormality of hypothalamic vasopressin system in cirrhotic rats; It can obviously improve the plasma albumin level, glomerular filtration rate and urinary sodium excretion in rats with nephrotic syndrome. It can significantly enhance the cytotoxicity of immunosuppressive mice induced by cyclophosphamide, and may enhance the immune and anti-tumor effects by regulating the secretion function of macrophage c1q. It was also found that both Radix Astragali decoction and mouse serum containing Radix Astragali could promote the proliferation of mouse spleen lymphocytes, the culture reaction of mixed lymphocytes and the production of IL-2. The aqueous extract of Cordyceps sinensis can reduce the intracellular Ca2+ concentration in normal myocardial cells, reduce the intracellular Ca2+ overload phenomenon during hypoxia and reoxygenation, and obviously reduce the intracellular lipid peroxidation during hypoxia and reoxygenation. Ginseng Rubra plays an important role in preventing hypertensive retinal arteriosclerosis. It can maintain the integrity of endothelial cell membrane, the structure of organelles and the normality of various vasodilators secreted by endothelial cells, inhibit the abnormal proliferation of smooth muscle cells, dilate blood vessels, reduce peripheral resistance and regulate blood pressure. Rehmannia glutinosa can obviously inhibit the high level expression of ia antigen in macrophages of corticosterone-induced "Yin deficiency" model mice, and reduce its antigen presenting ability, thus showing a certain immunosuppressive effect. Salvia Miltiorrhiza injection can obviously alleviate the brain edema caused by ischemia-reperfusion in rats, reduce the content of malondialdehyde in cerebral cortex and hippocampus, and increase the activities of catalase and superoxide dismutase and the contents of reduced glutathione and adenosine triphosphate. Compound prescription is the main form of Chinese medicine. Guided by the theory of traditional Chinese medicine and using modern scientific means, a multi-index systematic pharmacological study of ancient prescriptions and modern empirical prescriptions can reveal the therapeutic principle of prescriptions at a deeper level and effectively guide the research and innovation of clinical drugs and new products of traditional Chinese medicine. Good progress has been made in pharmacodynamics, pharmacokinetics and molecular pharmacology of traditional Chinese medicine.
There are dozens of pharmacological studies on ancient prescriptions, among which Guizhi decoction, Liuwei Dihuang decoction, Sijunzi decoction, Siwu decoction, Dachengqi decoction, Buzhong Yiqi decoction and Danggui Buxue decoction are more studied. In the study of ancient prescriptions, more attention is paid to the mechanism of prescription, and the traditional description of prescription efficacy has been given the content of modern pharmacology. For example, Guizhi decoction may regulate gastrointestinal movement by affecting gastrin, motilin and substance P, inhibiting somatostatin and vasoactive intestinal peptide in hypothalamus and gastrointestinal tract; Guizhi decoction can inhibit the cytopathic effect of 10 strain of respiratory infection-related virus to varying degrees, and its medicated serum can inhibit the proliferation of four strains of virus, such as herpes simplex virus, on Hep-2 cells. With the increase of dose, the colony number of hematopoietic progenitor cells increased significantly. Taking Liuwei Dihuang Decoction as a whole and under the guidance of activity evaluation, the active parts with immunomodulatory function were obtained from Liuwei Dihuang Decoction to regulate the functions of th and TC. These studies explain the action principle of prescription to some extent. The pharmacological research of empirical prescription is more extensive, and its research content is mostly combined with the relevant requirements of new drug research, focusing on efficacy and safety evaluation. Many prescriptions have been or will be developed into new drugs.
Compatibility is the characteristic and advantage of traditional Chinese medicine. It is still an important content of compound pharmacology to observe the relationship between prescription compatibility and pharmacological action changes by pharmacological research methods and explore the law of prescription compatibility. Although the methods of adding and subtracting herbs and orthogonal design are still the main methods, they have also been significantly improved in application. Some new methods were adopted to better analyze the compatibility of prescriptions. 1999, the basic research on the compatibility law of compound prescription was included in the key research project of National Natural Science Foundation, emphasizing the exploration of the material basis of prescription by high-tech means, comprehensively analyzing the relationship between compatibility, chemical composition changes and pharmacological effects, and clarifying the connotation of compatibility, which became a new exploration direction. The study on the relationship between chemical dynamic changes and pharmacodynamics of Shengmaisan compound shows that the changes of pharmacodynamics after compatibility of multiple drugs may be related to the production of new substances. Focusing on the study of material basis of prescription, focusing on the combination of prescription compatibility theory and modern pharmacological interaction theory, combining the analysis of material basis with the observation of pharmacological action, this paper discusses the relationship between prescription compatibility and material basis change from three aspects of single drug, chemical site and chemical composition of prescription, and discusses the relationship between prescription compatibility and pharmacological action, which has become the basic idea of compound compatibility research. The variety, origin, collection season, storage conditions, dosage, dosage form and route of administration of traditional Chinese medicine have great influence on the function of traditional Chinese medicine.
(1) The influence of Chinese medicine elements (original plants, animals, minerals)
The vast majority of Chinese herbal medicines are produced in China, and a few are transplanted or imported. In terms of varieties, herbal works in past dynasties have also increased frequently. Many cursive scripts point out the confusion of traditional Chinese medicine varieties in history. Therefore, it is very important to carry out serious textual research, analysis and appraisal. For example, the traditional Chinese medicines used in China, such as Rhizoma Dryopteris, Radix Angelicae Pubescentis and Cortex Magnolia Officinalis, come from more than 20 different species and genera. The same Chinese medicine Isatidis Folium is used in different places, such as Polygonum of Polygonaceae, Pinus of Cruciferae, Malan of Acanthaceae, Isatidis Folium of Verbenaceae, etc. The medicinal parts are also different from leaves and stems with leaves. Moreover, the phenomenon that foreign bodies have the same name is also very common. Because the variety is unclear, the chemical composition content and pharmacological action are different.
(2) The influence of origin and harvest time of Chinese herbal medicines.
Ginseng a) The origin of traditional Chinese medicine: The origin of medicinal materials has a direct relationship with the quality and curative effect of drugs, which has been attached great importance by doctors in past dynasties, and there has been a saying of "authentic medicinal materials" since ancient times. Traditional Chinese medicine is mostly plant medicine, and its natural growth environment is regional. Natural conditions such as soil, water quality, climate and rainfall in different regions can affect a series of ecological processes such as the growth, flowering and fruiting of medicinal plants, especially the soil composition can affect the quality and quantity of internal components of traditional Chinese medicine. According to Shennong's Herbal Classic, "When it is made, when it is cooked and when it comes out, it is true or not, and Xin Chen has its own laws" and "Newly revised Materia Medica" say: "If you leave its original soil, the quality will be the same but the effect will be different; Being good at picking is a specious thing. " Both emphasize the place of origin. Different habitats and the same plant contain different effective components, which leads to different pharmacological effects and unstable clinical efficacy. For example, wild ginseng in Changbai Mountain, garden ginseng in northeast provinces, and garden ginseng in Korea and Japan have different total saponin content and saponin monomer. For example, the content of ginsenoside in the stems and leaves of ginseng from seven producing areas in Jilin Province is quite different. Different producing areas and different processing methods have different yields of ginseng extract.
B) Harvest time: The roots, leaves, flowers, fruits, seeds or whole grass of different plants all grow and mature to a certain extent, so the harvest time and method vary with the varieties and medicinal parts of traditional Chinese medicine. China has a vast territory, from the cold zone to the subtropical zone, and the climate is very different. Therefore, the time of drug collection should be adapted to local conditions, but medicinal plants should be harvested when the interaction effect is the highest. The content of effective components varies with different growing seasons and different medicinal parts. For example, the content of ginsenoside is the highest after August, the content of ephedra alkaloids is the highest in autumn, the content of rutin in Sophora japonica is the highest in bud stage, and the content of artemisinin in Artemisia annua reaches its peak from mid-July to mid-August before bud appears, so it should be harvested before flowering. When some plants begin to sprout, the content of volatile oil is high. The ancients collected herbs entirely by experience. The Preface to Notes on Materia Medica said: "When collecting herbs, the root material was collected in February and August, which means that the body fluid began to sprout in early spring, and the branches and leaves were not washed, so it was strong; In autumn, branches and leaves dry up, and body fluids flow down ... "Compendium of Materia Medica says:" Cooked and pure in taste; Ye Caixin is powerful. " Take the hypotensive effect of Prunus persica as an example. Leaves picked before flowering in May have a strong antihypertensive effect on animals, while leaves collected after flowering have a weak antihypertensive effect. Taking ginseng as an example, seasonal changes have a significant impact on the contents of saponins and sugars in the roots of garden ginseng, so the harvest should be in June-September, not in winter.
(3) Influence of medicinal parts: The quality and quantity of chemical components contained in different medicinal parts may be different, so their pharmacological effects are also different. The content of ginsenoside in different parts of white ginseng and red ginseng from different habitats was compared and studied, and it was found that there was a great difference. Another example is the content of alkaloids in ephedra, which is the highest in the stem pith, less in the nodes and no alkaloids in the roots.
(4) Influence of storage conditions: The Classic of Materia Medica says: "All medicines should be guarded against. If it is not completely dehumidified by drying in the shade, it will rot and rot, which is bound to be a disaster. " Improper storage will lead to mildew, deterioration, oil loss and moth-eaten, which will directly affect pharmacological action and medical quality. Therefore, it is necessary to choose suitable stacking places, strengthen warehouse management, and pay attention to the storage of special medicinal materials (such as precious medicinal materials, aromatic and colloidal medicinal materials, etc.). ), and regular inspection, pest control. Improper storage will also lead to the oxidation, decomposition or natural volatilization of medicinal materials containing volatile oil (such as camphor, borneol and musk), thus reducing the efficacy. Due to the long storage time, some components will be decomposed by enzymes.
(5) Influence of processing: Before and after processing, the composition and quantity of medicinal materials will change, and the pharmacological effects and clinical effects will be different. From the clinical experience, Compendium of Materia Medica once pointed out: "Wine is on the rise; Ginger diverges; Go into salt to soften the kidney; Inject vinegar into the liver to relieve pain; The milk system moistens dryness and produces blood; Honey is sweet and slow ... "
The processing of traditional Chinese medicine in mice affects pharmacological effects from the following aspects:
(1) Attenuate and detoxify. For example, Pinellia ternata "makes people vomit, but it makes people cook." Pinellia ternata has a strong stimulating effect on gastric mucosa, so it causes vomiting; Jiang Banxia showed antiemetic effect.
(2) Synergism, for example, Eucommia ulmoides contains a lot of gutta-percha, while raw Eucommia ulmoides contains few effective components; The colloid is destroyed after processing, so the fried Eucommia ulmoides decoction has a stronger antihypertensive effect than the raw one.
(3) changing the ingredients of medicinal materials to strengthen or highlight a certain function. For example, raw rhubarb mainly has purgative effect, but processed rhubarb has strong antibacterial effect.
(4) Improve the cutting process and increase the efficacy. The processing process of medicinal materials can affect its internal components, which is directly related to the nature and intensity of its pharmacological reaction.
(6) Influence of dosage forms and preparations: Different dosage forms of the same traditional Chinese medicine often affect drug absorption and blood drug concentration due to different manufacturing processes and routes of administration, which is directly related to the strength of pharmacological action. Shennong's Classic of Materia Medica points out that "medicinal properties include pills, powder, boiled water, wine stains, ointment and soup, which are suitable for both, and some can't be boiled and drunk, and can't be contrary to medicinal properties." It shows that the ancients have long noticed the influence of dosage forms on drug efficacy: for example, the decoction of Fructus Aurantii Immaturus or Pericarpium Citri Reticulatae Viride is taken orally, and there is no record of hypertension, but when it is made into injection, it has a strong antihypertensive effect.
The "method of mixing medicines" recorded in Compendium of Materia Medica has certain regulations on the balance of medicines, cutting requirements, dosage forms, pharmaceutical methods, and even wax and honey. Modern pharmacy has higher requirements. Even the same traditional Chinese medicine or compound prescription has the same dosage and dosage form, but different pharmaceutical factories produce different preparations, and their curative effects and toxicity are often different. Even different batches of products from the same factory are different. In order to ensure the same curative effect of products with the same name produced by different pharmaceutical factories, certain measures should be taken to strengthen quality control. The preparation shall be implemented according to the provisions of People's Republic of China (PRC) Pharmacopoeia or the drug standards approved by provincial and municipal health bureaus. It has played a good guiding role in standardizing Chinese patent medicine preparations and unifying products. Body factor are also important factors that affect pharmacological action, include physiological conditions, pathological state and so on.
(1) Influence of physiological conditions: constitution, age, gender, mood, etc. It has a great influence on the function of drugs. Traditional Chinese medicine emphasizes the influence of different endowments on drug efficacy. It means that genetic factors and physical fitness have great differences in disease resistance and drug response. There is also a phenomenon in clinic, that is, the therapeutic dose of a drug varies many times between different races or individuals. This difference between species or races is called species or race difference; Differences between individuals are called individual differences. Different ages have different reactions to drugs. Children and the elderly react differently to drugs than ordinary adults. Childhood is in the developmental stage, many organs and systems are underdeveloped, and the liver and kidney functions of the elderly generally decline, which will affect the metabolism and excretion function of drugs in the body, so the dosage should be reduced appropriately. Traditional Chinese medicine believes that the elderly are weak and have weak tolerance to drugs, so they should reduce the use of drugs to attack diseases; Children's Yang Can can't be seriously supplemented, so children shouldn't use ginseng and pilose antler to supplement suddenly. There are also obvious differences in the responses of different sexes to drugs. On the one hand, women have different sensitivities to certain drugs because of the weight difference, on the other hand, because of the influence of hormones. For example, Ding Kundan, Tiaojing Pill and Wuji Baifeng Pill are suitable for gynecology; While emetics and laxatives are forbidden for pregnant women. Emotion and mental state also have an influence on the effect of drugs. The so-called seven emotions, such as joy, anger, worry, thinking, sadness, fear and surprise, have obvious influence on the function of drugs.
Scutellaria baicalensis Georgi In addition, there are two individual differences in drugs, quantitative and qualitative. Pharmacology has so-called high sensitivity and tolerance; There are also very few patients who have allergic reactions to certain drugs. Such as oral ginseng syrup, intravenous drip of Shengmai liquid, etc. There are reports of allergic reactions.
(2) Influence of pathological state: Pathological state will also affect the effect of drugs, such as Scutellaria baicalensis Georgi and Andrographis paniculata, which have no effect on lowering normal body temperature, and only patients with fever can have antipyretic effect after taking them. Another example is Wuling powder, which has no diuretic effect on dogs and mice in experiments, but has diuretic effect on patients with edema and dysuria in clinic. Liver and kidney diseases, weakened function, can affect the metabolic process of drugs in the body, often prolonging the action time of drugs. There are also traditional Chinese medicines with antipyretic effect screened from artificial fever animal models, which are not ideal for patients in clinic, such as andrographis paniculata; There are also some antipyretics that are very effective for patients, but the experimental results are not necessarily ideal, such as Baihu Decoction. This also shows that there are some differences between animal models and human diseases. The influence of environment on drugs is also well known. For example, geographical conditions, cold and warm climate, diet and daily life, family environment, and place of residence all have great influence on people's health. When people are depressed by the environment, it can directly affect the therapeutic effect of drugs. Generally, when limbs move, the blood flow of abdominal organs decreases, which is not conducive to the recovery of some abdominal diseases. In addition, when the lungs are inflamed, if you are forced to overwork, the inflammation will spread to the surrounding tissues and the condition will worsen.
According to the circadian rhythm of biological activities, the circadian rhythm fluctuation of body temperature, adrenaline and corticosteroid secretion is often related to the circadian rhythm change of the external environment. This circadian rhythm is common in the action of drugs, such as aconite and aconite. By measuring the content of aconitine and the acute toxicity of Shenfu injection, it is confirmed that there is a circadian rhythm in the sensitivity of animals. The toxicity of aconitine was the highest at noon (13) (66.7%). The lowest (13.3%), the difference between the two groups was significant. LD50 of Shenfu injection was 9.8629/kg at noon and 8.308/kg at noon after intravenous injection. Another example is the ethyl acetate extract of tripterygium wilfordii, which is a drug for treating rheumatoid arthritis. Mice were divided into groups at different times every 4 hours for 24 hours. The mortality rate within one week after administration was observed, and it was found that its toxicity had obvious time rhythm. The death rate of people given at noon 12 is the highest, and the death rate of people given from 20: 00 to 8: 00 the next morning is the lowest.