Recent advances in the pharmacology of Chinese medicines

The pharmacological study of commonly used single-flavored Chinese medicines is an important part of the pharmacological study of Chinese medicines. It still focuses on the observation of the pharmacological effects on the whole animal and the effects on organs, tissues and cells, etc. Modern biotechnology, such as molecular biology, has also received extensive attention and application. The research is relatively concentrated on medicinal flavors, with the majority of tonic drugs, blood circulation and blood stasis medicines, and the new pharmacological mechanism of many commonly used traditional Chinese medicines has been revealed.

Cordyceps Sinensis It was found that Astragalus had a significant up-regulating effect on the reduced density of M cholinergic receptors and M1 subtype receptors in three brain regions of cortex, hippocampus, and striatum of naturally aging rats, and it could also regulate the content of plasma cyclic nucleotides in aged rats; the density of β-receptor in the myocardium and the content of T3, T4, and cortisol of aging rats were all lowered, which could be elevated by Astragalus, ginseng, and Lycium barbarum; and it could also have a positive effect on the existence of hypothalamic vasopressin in cirrhotic rats, which was also found in the presence of ginseng and wolfberry. 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 cytotoxicity in immunosuppressed rats caused by cyclophosphamide, and it can also enhance the immunity and anti-tumor effect by regulating the secretion function of macrophage C1q; it is also found that Astragalus decoction and serum of Astragalus-containing rats have a significant impact on the proliferation of splenic lymphocytes in mice. It was also found that both the decoction of Astragalus and the serum of mice containing Astragalus promoted the proliferation of mouse splenic lymphocytes, the reaction of mixed lymphocyte culture and the production of IL-2. The aqueous extract of Cordyceps sinensis can reduce the concentration of Ca2+ in normal cardiomyocytes, alleviate the phenomenon of intracellular Ca2+ overload during hypoxia and reoxygenation, and significantly reduce intracellular lipid peroxidation during hypoxia and reoxygenation. Red ginseng plays an important role in the prevention of hypertensive retinal atherosclerosis, which can make the endothelial cell membrane of the optical rectification, the structure of the organelle and the endothelial cell secretion of a variety of vasodilatory substances to maintain normal, and inhibit the abnormal proliferation of smooth muscle cells, as well as dilate the blood vessels, reduce the peripheral resistance and regulate the role of blood pressure. Radix Rehmanniae Praeparata can obviously inhibit the high level expression of macrophage Ia antigen in mice modeled as "Yin deficiency" caused by corticosterone, and reduce its ability of presenting antigen, thus showing certain immunosuppressive effect. Salvia divinorum injection can significantly reduce cerebral edema induced by ischemia-reperfusion in rats, reduce malondialdehyde content in cerebral cortex and hippocampus, and increase catalase, superoxide dismutase activity and reduced glutathione and adenosine triphosphate content. Compounding is the main form of traditional Chinese medicine. With the guidance of the theory of traditional Chinese medicine and the use of modern scientific means, the systematic pharmacological study of ancient and modern empirical prescriptions with multiple indicators can reveal the therapeutic principle of prescriptions at a deeper level, and effectively guide the clinical use of medication and the research and creation of new products of traditional Chinese medicine. Good progress has been made in the pharmacodynamics, pharmacokinetics and molecular pharmacology of Chinese medicine compounding.

Pharmacological experiments There are dozens of pharmacological studies on ancient formulas, among which Gui Zhi Tang, Liu Wei Di Huang Tang, Si Jun Zi Tang, Si Wu Tang, Da Cheng Qi Tang, Zhong Zhong Yi Qi Tang, and Angelica Sinensis Blood Replenishing Tang have been studied more. The mechanism of action of formulas has been more frequently explored in the study of ancient formulas, giving modern pharmacological content to the traditional efficacy descriptions of formulas. For example, Gui Zhi Tang may regulate gastrointestinal motility by affecting the content of gastrin, gastric motility, substance P, which excites gastrointestinal motility, as well as the content of growth inhibitory hormone and vasoactive intestinal peptide, which inhibits gastrointestinal motility, in the hypothalamus and the gastrointestinal tract; Gui Zhi Tang inhibits cytopathic lesions of 10 strains of viruses related to respiratory infections with varying degrees of severity, and its drug-containing serum inhibits the proliferation of Hep-2 cells by 4 strains of herpes simplex virus, and so forth. The serum containing the drug inhibited the proliferation of Hep-2 cells by four strains of viruses including herpes simplex virus. The serum contained in Angelica sinensis blood tonic soup increased the number of hematopoietic progenitor cell colonies with the increase of the administered dose. Considering the formula of Liu Wei Di Huang Tang as a whole and oriented to the evaluation of activity, the active site with immunomodulatory function was obtained by directional tracking and isolation from Liu Wei Di Huang Tang, which had a modulating effect on the function of TH and TC. All these studies illustrate to some extent the principle of action of the formula. Pharmacological research on empirical formulas has been carried out more widely, and its research content is mostly combined with the relevant requirements of new drug research, focusing on the evaluation of drug efficacy and safety, and many formulas have been or will be developed into new drugs.

Preparation is the characteristic and advantage of Chinese medicine, and it is still an important part of the pharmacological research of compound prescription to observe the relationship between the preparation of prescription and the change of pharmacological effect, and to explore the law of preparation of prescription. Although the methods such as addition and subtraction of prescription flavors and orthogonal design are still the main methods, there are obvious improvements in the application and some new methods are adopted to better analyze the compounding of prescriptions. The basic research on the law of compound formulae compounding was incorporated into the key research project of the National Natural Science Foundation of China in 1999, which emphasized the use of high and new technology to explore the material basis of the formulae, comprehensively analyze the connection between compounding - chemical composition changes - pharmacological effects, and clarify the connotation of compounding, and became a new direction of exploration. The study on the relationship between chemical dynamic change and pharmacological effect of Shengmusan formula shows that the change of pharmacological effect after compounding may be related to the generation of new substances. Taking the material basis of formula as the core, focusing on the combination of the theory of formula compounding and modern pharmacological interaction theory, combining the analysis of material basis with the observation of pharmacological effect, exploring the relationship between the compounding of formula and the change of material basis from the three levels of the single drug, the chemical part and the chemical constituents, and discussing the compounding and the change of material basis of the formula at the level of the whole animal, organs and tissues, subcellular cells and molecular biology. It has become the basic idea of compound prescription research to explore the relationship between compounding, change of material basis and pharmacological effect at four levels: whole animal, organ tissue, cell subcellular and molecular biology. The variety, origin, season of collection, storage conditions, dose, dosage form, and route of administration of traditional Chinese medicines all have a significant impact on the effects of traditional Chinese medicines.

(1) Influence of Chinese medicine matrix (original plants, animals and minerals)

The vast majority of Chinese herbal medicines are homegrown in China, and a few are transplanted or imported. In terms of varieties, there have been repeated additions in the works on materia medica through the ages. Many materia medica books point out the confusion of the varieties of Chinese medicines in history. Therefore, it is very important to carry out the work of careful examination, analysis and identification. For example, China with the Guanzhong, Dushu, Houpu and other traditional Chinese medicines, from more than 20 different species of plants; the same Chinese medicine Daqing Ye, used in various parts of the herb is different, there are Polygonum Polygonum, Cruciferae Pine orchid, Jurassicaceae Malan, Verbenaceae, etc., the medicinal part of the leaves and leaves and stems and branches of the different. Moreover, the phenomenon of the same name is also very common. Because of the unclear species, the content of its chemical constituents and pharmacological effects are different.

(2) The influence of the origin of traditional Chinese medicine and the collection season

Ginseng a) The origin of traditional Chinese medicine: the origin of herbs has a direct relationship with the quality and efficacy of the drug, which has been emphasized by the medical doctors from the ancient times, that is, there is a "Taoist medicinal materials". Most of the traditional Chinese medicine for plant medicine, natural growth environment has a certain regional, each region of the soil, water quality, climate, rainfall and other natural conditions can affect the growth of medicinal plants, flowering, fruiting and a series of ecological processes, especially the soil composition can affect the quality and quantity of the intrinsic components of traditional Chinese medicine. Shennong's Classic of the Materia Medica" recorded in the records of "the time and month of harvesting, raw and ripe, the land out of the authenticity of the new, old and new, and have their own method" and "new revision of the Materia Medica" said: "away from its native, the quality of the same and different effects; behavior in the picking, it is the thing is not the real". Both emphasize the origin. Different places of origin, the same plant does not contain the same active ingredient, so that the pharmacological effect is different, clinical efficacy is not stable. Such as Changbai Mountain wild ginseng, Northeastern provinces and North Korea, Japan's garden ginseng, not only the amount of ginsenosides is different, and the content of different saponin monomers are not the same. Ginseng stem and leaves saponin content in the Jilin Province, seven origin samples, the difference in content is quite different. Different origins and different processing methods to ginseng extracts of different amounts.

b) Harvesting season: different plants, roots, leaves, flowers, fruits, seeds or grass have a certain period of growth and maturity, so the harvesting time of the harvesting method with the varieties of traditional Chinese medicine and the parts of the medicine and there are different. China's vast territory, from the frigid zone to the subtropical, the climate varies greatly, so the time of harvesting in accordance with local customary local conditions, but to choose the medicinal plants have the highest content of cross-effective points when harvesting. The content of active ingredients with different growing seasons and different parts of the medicine and different, such as ginseng saponins in August after the highest content, ephedra alkaloids in the fall of the highest content, acacia flowers in the buds when the highest content of rutin, Artemisia artemisiae artemisinin content in July to August in the buds appeared in front of the peak, should be harvested before the blossoming of the peppermint in the beginning of the part of the plant when there are buds, the volatile oil content is large. Ancient people harvested all based on experience, the "Materia Medica Classic Annotated" preface said: "Where to pick medicine when the month ...... of its root material to February, August pickers, said that the beginning of the spring fluid began to buds, did not punch the branches and leaves, the power of Chunzhong also; to the fall branches and leaves dry up, the fluid returns to the flow of the next... ..." "Materia Medica Monchuan" said: "the real has been ripe, pure flavor; leaf picking new, double the force." Taking the hypotensive effect of stinking sycamore as an example, leaves picked in May before flowering have a strong hypotensive effect on animals, and leaves collected after flowering have a weakened hypotensive effect. Then take ginseng as an example, seasonal changes in the garden ginseng root saponins and sugar content has a significant impact, so the harvest should be in June to September, and should not be in the winter.

(3) the 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. There has been a comparative study of the ginsenoside content of different parts of white ginseng and red ginseng produced in different places, and found that there is a big difference. Another example is the content of ephedra alkaloids, ephedra stems of the pith of the highest content of ephedra, ephedra nodes in the content of less, while the root does not contain alkaloids.

(4) the effect of storage conditions: "the herb mon chyuan" said: "where the drug storage, it is appropriate to always be on guard, if the shade drying drying drying drying not exhaustive dehumidification, then the moth moth decay mold decay, not inevitable for the disaster." Improper storage, to mold and deterioration, oil, insect, will directly affect the pharmacological effect and medical quality. Therefore, we must choose the appropriate place to stack, strengthen the warehouse management, pay attention to the custody of special herbs (such as precious herbs, aromatic and gelatinous herbs, etc.), but also regular inspection, prevention and control of insect pests. Improper storage can also make the volatile oil-containing herbs oxidized, decomposed or naturally volatile (such as camphor, ice chips, musk) and reduce the efficacy. Some ingredients will be stored for a long time and be decomposed by enzymes and so on.

(5) the effect of concoction: before and after the concoction, the quality and quantity of the components of the herbs will change, pharmacological effects and clinical efficacy can be different. "The Materia Medica Monchuan" has pointed out from clinical experience: "Wine system ascension; ginger system dispersal; into the salt to go to the kidneys and soft; with vinegar injection of the liver and live pain; milk system to run wither blood; honey system sweet slow benefit yuan ......."

Mice Chinese medicine concoction from the following aspects affect the pharmacological effect:

① Reduce toxicity, de-toxicity. For example, half-summer "raw people vomit, cooked people down." Raw half-summer has a powerful stimulating effect on the gastric mucosa, so it causes vomiting; ginger half-summer shows antiemetic effect.

②Enhancement, such as eucommia contains a large number of eucommia gum, raw eucommia decoction of the active ingredient is very little; after the shelling of eucommia gum destruction, so the fried eucommia decoction to lower the blood pressure is stronger than the raw.

③Change the composition of the components of the herbs, to strengthen or highlight a role. For example, the raw rhubarb mainly has a laxative effect, but the concocted rhubarb has a strong antibacterial effect.

④Improve the cutting process, increase the efficacy. The concoction and processing of herbs can affect their intrinsic composition, which is directly related to the nature and intensity of their pharmacological reactions.

(6) the influence of dosage form and preparation: the same kind of Chinese medicine made of different dosage forms, due to the manufacturing process and the different routes of administration, often affecting the absorption of the drug and the blood concentration, which is directly related to the strength of the pharmacological effect. Shennong Ben Cao Jing" pointed out that "the nature of the medicine is suitable for the pill, suitable for the dispersion, suitable for the boiled, suitable for the wine impregnated, suitable for the paste decoction, there is a thing both suitable for those who also can not be into the soup and wine, and with the nature of the medicine, shall not be violated." That the ancients have long been aware of the impact of the dosage form on the efficacy of the drug: such as Citrus aurantium or green peel decoction orally, did not see elevated blood pressure records, but made into injections intravenously, but there is a powerful effect of elevated blood pressure.

The "Materia Medica Jing Jiezhu" records the "combined medicine and dose law", on the balance of the drug, cutting requirements, dosage form, pharmaceutical methods, up to the use of wax with honey, etc., there are certain provisions. Modern pharmaceutical, more demanding, the same Chinese medicine or compound, even if the dose is equal, the same dosage form, but lying in the production of preparations in different pharmaceutical factories of different processes, efficacy and toxicity are often different. Even different batch numbers of products from the same factory are not the same. In order to ensure that not wait for the batch number of different pharmaceutical companies with the same name have the same therapeutic effect, certain measures should be taken to strengthen quality control. Preparations are in accordance with the provisions of the Chinese People's *** and State Pharmacopoeia or the provincial and municipal health bureaus to approve the implementation of drug standards. It plays a good role in guiding the preparation of proprietary Chinese medicines and standardizing the specifications of the products. Organismal factors are also important factors affecting pharmacological effects, which include physiological conditions, pathological states and so on.

(1) the influence of physiological conditions: constitution, age, gender, emotions, etc., on the role of drugs play a great influence. Chinese medicine emphasizes the influence of different endowments on the efficacy of medicines. Means that genetic factors, physical quality of disease resistance and drug response, there are large differences. Clinically, there are also different races or different individuals, the therapeutic dosage of a drug differs many times the phenomenon. This kind of difference exists in the species or race, called species or race differences; exists in the individual differences, called individual differences. The response to drugs varies with age. Pediatrics and the elderly respond differently to medications than do adults in general. Children are in the developmental stage, many organs and systems are not yet perfect, the elderly liver and kidney function is generally reduced, will affect the metabolism and excretion of drugs in the body, so the dosage should be appropriately reduced. Chinese medicine believes that the elderly body is weak, the tolerance of drugs is weak, so it is appropriate to reduce the amount of drugs used to attack the disease; young children's body of young yang can not be a severe tonic, so it is not appropriate to use ginseng, antler sudden tonic for children. Different genders, there are obvious differences in the response to drugs, women on the one hand, due to differences in body weight, on the one hand, due to the influence of hormones, the sensitivity of certain drugs is quite different. Such as Dingkundan, menstruation pills, Wuji Baifeng Pills for gynecology; and emetic drugs, diarrhea drugs are prohibited for pregnant women. Emotions, mental state on the role of drugs also have an impact. The so-called joy, anger, worry, thoughts, sadness, fear, shock and other seven emotions on the role of drugs, obviously have an impact.

Scutellaria baicalensis In addition, the individual differences in drugs, there are quantitative and qualitative manifestations of both. Both the pharmacology of the so-called hypersensitivity, tolerance; there are very few patients on a drug allergic reaction. Such as oral ginseng syrup, intravenous drip of raw vein solution, etc., there are reports of allergic reactions.

(2) the effect of pathological state: pathological state can also affect the role of drugs, for example, Scutellaria baicalensis, andrographis paniculata and other medicines, the normal body temperature does not reduce the role of only feverish patients with the use of fever, appeared to have the effect of antipyretic. Another example is that Wu Ling San does not show diuretic effect on dogs and mice in the experiment, but it has diuretic effect on patients suffering from edema and unfavorable urination in the clinic. Liver and kidney disease, weakened function, can affect the metabolic process of the drug in vivo, often make the drug's action time is prolonged. There are also artificial fever animal models screened out with antipyretic effect of traditional Chinese medicine, clinically used for patients are not satisfied, such as Andrographis paniculata; there are also some clearing drugs on the patient is very effective, and the experimental results are not necessarily ideal, such as Baihu Tang. This also indicates that there are some differences between animal models and human diseases. The influence of the environment on drugs is also well known. For example, geographic conditions, climate warmth and cold, diet, home environment, living area, all have a greater impact on human health. When a person is mentally upset by the environment, it can directly affect the therapeutic effect of the drug. Generally when the limbs are in motion, the blood flow to the abdominal viscera is reduced, which is detrimental to the recovery of some abdominal disorders. In addition, in the case of inflammation of the lungs, such as forced to work too much, can make the inflammation to the surrounding tissues spread, the condition worsened.

According to the circadian rhythm of biological activity, the diurnal fluctuation of body temperature, adrenaline, corticosteroid secretion, etc., is often related to the diurnal changes of the external environment. Drugs also often appear such circadian rhythms, such as aconite, aconite, through the determination of the amount of aconite contained in the aconite and the acute toxicity of ginseng and aconite injections, confirmed that the animal's sensitivity to the existence of circadian rhythms. The toxicity of aconitine was highest (66.7%) at noon (13:00); lowest (13.3%) at 11:00, with a significant difference between the two groups. The LD50 value of ginseng injection was 9.8629/kg at noon, and 8.308/kg at noon, and the ethyl acetate extract of Lei Gongteng, a drug for the treatment of rheumatoid arthritis, was administered to mice in groups at different times of the day and every 4 hours for a period of 24 hours to observe the mortality rate within a week of the administration of the drug, and it was found that its toxicity had a clear hourly rhythm, with the highest mortality rate being found in the group administered at 12 noon, and the highest mortality rate being found in the group administered from 20:00 to the next morning. It was found that the toxicity of the drug had a clear hourly rhythm, with the highest mortality rate in those who were given the drug at 12:00 noon, and the lowest mortality rate in those who were given the drug from 20:00 to 8:00 the next morning.