CN112107662B - Traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer and medicament and application thereof - Google Patents

Traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer and medicament and application thereof Download PDF

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CN112107662B
CN112107662B CN202010996982.XA CN202010996982A CN112107662B CN 112107662 B CN112107662 B CN 112107662B CN 202010996982 A CN202010996982 A CN 202010996982A CN 112107662 B CN112107662 B CN 112107662B
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traditional chinese
chinese medicine
chronic gastritis
precancerous lesions
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李佃贵
杨倩
刘建平
刘启泉
白海燕
霍永利
郎晓猛
李博林
徐伟超
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Hebei Province Hospital Of Cm
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Abstract

The invention relates to a traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the following raw materials: herba Agastaches, Coptidis rhizoma, Atractylodis rhizoma parched with bran, fructus Amomi rotundus, herba Scutellariae Barbatae, herba Hedyotidis Diffusae, radix Angelicae sinensis, rhizoma Ligustici Chuanxiong, Notoginseng radix, Poria, radix Paeoniae alba preparata, Bulbus Lilii, fructus Aurantii Immaturus parched with bran, rhizoma Cyperi processed with vinegar, radix aucklandiae, fructus Amomi, Scorpio, and rhizoma corydalis processed with vinegar. Adding pharmaceutically conventional adjuvants into the composition according to pharmaceutically conventional process, and making into pharmaceutically acceptable dosage forms. The traditional Chinese medicine composition has definite curative effects on chronic gastritis, chronic atrophic gastritis and precancerous lesions of gastric cancer (such as intestinal metaplasia and intraepithelial neoplasia) in clinical symptoms, histopathology and molecular level, is convenient to take, carry and store, and has low cost.

Description

Traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer and medicament and application thereof
Technical Field
The invention relates to the technical field of traditional Chinese medicines for treating diseases, relates to a traditional Chinese medicine composition, and particularly relates to a traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer, and a medicament and application thereof.
Background
The data in 2018 show that the incidence rate of gastric cancer in east Asia is 2 times of that in east Europe, which is the highest in the world. The marked mortality rate of gastric cancer in Hebei province, which is the main malignant tumor with life-threatening, is 22.30/10 ten thousand.
Gastric Precancerous Lesions (GPL) refer to pathological histological changes of Gastric mucosa which are easy to become cancerous, mainly comprise intermediate and severe intestinal metaplasia and intraepithelial neoplasia of the Gastric mucosa, the annual canceration rate of the Gastric mucosa reaches 0.25% -6%, and the Gastric Precancerous Lesions are mostly accompanied by chronic atrophic gastritis and are a transitional stage of the development of the Gastric benign Lesions to the malignant Lesions. Modern medicine aims at the problem that GPL is lack of corresponding medicines so far, and takes symptomatic treatment and regular follow-up as main strategies. The traditional Chinese medicine has unique characteristics in the aspects of improving symptoms of GPL related diseases, delaying pathological progress and even reversing pathological changes. Researches prove that the individualized traditional Chinese medicine treatment scheme based on syndrome differentiation can obviously delay the GPL progress and has good safety. In addition, the GPL treatment based on syndrome differentiation can relieve the uncomfortable symptoms of patients, and further improve the life quality. The GPL treatment effect of the traditional Chinese medicine is definite, but different insights are still provided for syndrome differentiation and typing, etiology and pathogenesis understanding and prescription and medicine application. In 2017, the "consensus opinion on the combined diagnosis and treatment of the traditional Chinese medicine and the western medicine for chronic atrophic gastritis" issued 6 main types of syndrome differentiation and classification (such as blood stasis, damp-heat, liver depression and the like) in traditional Chinese medicine. In addition, there are different etiological and differentiating ideas such as collateral diseases, turbid toxin and deficiency of the origin for GPL related diseases.
Most chronic gastritis patients have no symptoms, so accurate and definite epidemiological data are difficult to obtain, the prevalence rate of the current chronic gastritis based on endoscopic diagnosis in China is close to 90%, and hundreds of millions of patients are presumed. The chronic gastritis has certain canceration risk, and the morbidity of gastric cancer, intestinal tumor and pancreatic cancer of patients with the chronic gastritis is higher than that of general people. The chronic gastritis with intraepithelial neoplasia is a typical representative, and the cancer rate reaching 0.25% -6% is regarded as a key transition stage of the malignant lesion development of the stomach, and becomes one of the main chronic diseases which harm the health of people in China and reduce the quality of life. Modern medicine mainly adopts symptomatic treatment and regular follow-up as intervention strategies for the disease, and traditional Chinese medicine treatment has unique characteristics in the aspects of improving symptoms of diseases related to chronic gastritis, delaying pathological progress and even reversing pathological changes. The researchers have guiding significance for the research of the non-controllable inflammation of the chronic gastritis based on the theory of the collateral disease, and the researchers discuss the action and the mechanism of the reversal of the inflammation-cancer transformation from the tumor toxicity mechanism, and the researchers also differentiate and treat the chronic gastritis by the syndrome differentiation of spleen deficiency, cold and heat and blood stasis and toxin. Therefore, the diagnosis and treatment of chronic gastritis by traditional Chinese medicine form a plurality of syndrome differentiation treatment schemes with theoretical, regional and genre as main representative characteristics, and become an important academic innovation source in 'inheriting essence, keeping right and creating innovation'.
In recent years, with the development of endoscope technology, the detection rate of chronic atrophic gastritis in China is in a rising trend, and the incidence rate accounts for about 20% of the total population to be detected. At present, many medicines for treating chronic gastritis at home and abroad exist, but few medicines for treating chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia are available. Most western medicines are symptomatic treatments, but the number of Chinese patent medicines is small, and the effect is more and less definite. The number of chronic gastritis out-patient visits is 10 ten thousand, and the number of chronic atrophic gastritis out-patient visits is about 2 ten thousand.
With the change of human disease spectrum and the continuous change of survival and working environment, the original treatment method and prescription can not meet the diagnosis and treatment of diseases at present, and the traditional treatment method is also found in clinic, so that some patients can not be obviously improved. At present, the existing therapeutic drugs only aim at a specific stomach disease, such as chronic gastritis, and few drugs which can simultaneously have effects on chronic gastritis, chronic atrophic gastritis and gastric precancerous lesions (such as chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia) are available, so that the research and development of a therapeutic drug which is effective on various stomach diseases becomes an urgent need at present. Because the decoction pieces of traditional Chinese medicine are convenient to decoct, take, carry and store, and the cost is relatively high, the patient also urgently expects a treatment medicine which is convenient to take, carry and store and has low cost.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer, a medicament and application thereof. The traditional Chinese medicine composition is guided by the innovative traditional Chinese medicine turbidity toxicity theory, and results of clinical tests, animal experiments, network pharmacology experiments, data mining and the like prove that the traditional Chinese medicine composition has definite curative effects on various stomach diseases.
The invention provides a traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the following raw materials in parts by weight: 8-12 parts of agastache rugosus, 3-9 parts of coptis chinensis, 9-15 parts of bran-fried bighead atractylodes rhizome, 3-9 parts of cardamom, 12-18 parts of sculellaria barbata and 12-18 parts of oldenlandia diffusa; wherein herba Agastaches and Coptidis rhizoma are principal drugs, and Atractylodis rhizoma parched with bran, fructus Amomi rotundus, herba Scutellariae Barbatae, and herba Hedyotidis Diffusae are ministerial drugs.
The invention also provides a traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the following raw materials in parts by weight: 8-12 parts of wrinkled gianthyssop herb, 3-9 parts of coptis chinensis, 9-15 parts of bran-fried bighead atractylodes rhizome, 3-9 parts of round cardamom, 12-18 parts of barbed skullcap herb, 12-18 parts of spreading hedyotis herb, 9-15 parts of Chinese angelica, 6-12 parts of szechuan lovage rhizome, 4-8 parts of pseudo-ginseng, 12-18 parts of poria cocos, 12-18 parts of fried white paeony root, 9-15 parts of lily, 8-12 parts of bran-fried immature bitter orange, 6-12 parts of vinegar nutgrass galingale rhizome, 3-9 parts of costustoot, 3-9 parts of villous amomum fruit, 3-6 parts of scorpion and 8-12 parts of vinegar corydalis tuber.
Preferably, the traditional Chinese medicine composition for treating chronic gastritis and gastric precancerous lesions comprises the following raw materials in parts by weight: 10 parts of wrinkled gianthyssop herb, 6 parts of coptis chinensis, 12 parts of bran-fried bighead atractylodes rhizome, 6 parts of round cardamom, 15 parts of barbed skullcap herb and 15 parts of spreading hedyotis herb; wherein herba Agastaches and Coptidis rhizoma are principal drugs, and Atractylodis rhizoma parched with bran, fructus Amomi rotundus, herba Scutellariae Barbatae, and herba Hedyotidis Diffusae are ministerial drugs.
Preferably, the traditional Chinese medicine composition for treating chronic gastritis and gastric precancerous lesions comprises the following raw materials in parts by weight: 10 parts of wrinkled gianthyssop herb, 6 parts of coptis chinensis, 12 parts of white atractylodes rhizome fried with bran, 6 parts of round cardamom, 15 parts of barbed skullcap herb, 15 parts of spreading hedyotis herb, 12 parts of Chinese angelica, 9 parts of szechuan lovage rhizome, 6 parts of sanchi, 15 parts of tuckahoe, 15 parts of fried white paeony root, 12 parts of lily, 10 parts of immature bitter orange fried with bran, 9 parts of rhizoma cyperi with vinegar, 6 parts of costustoot, 6 parts of fructus amomi, 3 parts of scorpion and 10 parts of rhizoma corydalis fried with vinegar.
The agastache rugosus in the traditional Chinese medicine composition is fragrant and turbid, has the effects of harmonizing stomach and lowering adverse qi, has the effects of clearing away heat and toxic materials, thickening intestines and stomach, and clearing turbid toxin, and is a monarch drug in total; the white atractylodes rhizome and the round cardamom which are stir-fried with bran have the functions of strengthening spleen, eliminating turbid pathogen and harmonizing stomach, and the barbed skullcap herb and the oldenlandia have the functions of clearing away heat and toxic materials and are used as ministerial drugs; angelica, rhizoma ligustici wallichii and pseudo-ginseng activate blood and relieve pain, poria cocos invigorates spleen and excretes dampness, fried white peony root nourishes blood and relieves middle energizer, lily nourishes yin and calms nerves, bran-fried immature bitter orange, vinegar-fried rhizoma cyperi and elecampane promote qi circulation and harmonize stomach, relieve distension and remove stuffiness, fructus amomi dissolves turbidity and stimulates appetite, scorpion detoxifies and dissipates nodulation, and vinegar-fried rhizoma corydalis promotes qi circulation and activates blood and relieves pain.
Wherein, the proportion of the monarch drug wrinkled gianthyssop herb and the golden thread is crucial, and the effect on chronic gastritis, chronic atrophic gastritis, gastric precancerous lesion, chronic atrophic gastritis with intestinal metaplasia can not be achieved simultaneously by changing the proportion. In addition, the bran-fried bighead atractylodes rhizome and the round cardamom in the ministerial drugs have the effects of tonifying spleen, eliminating turbid pathogen and harmonizing stomach, and have great contribution to the curative effect of the whole traditional Chinese medicine composition.
The invention also provides granules for treating chronic gastritis and gastric precancerous lesions, which comprise the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary materials are one or more of filling agent, adhesive, wetting agent, disintegrating agent, lubricant and film coating material.
The invention also provides an oral liquid for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation adjuvants are one or more of solvent, aromatic, correctant, clarifier and antiseptic.
The invention also provides a tablet for treating chronic gastritis and gastric precancerous lesions, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary materials are one or more of diluent, adhesive, lubricant and disintegrant.
The invention also provides a capsule for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary material is a hard capsule shell or a soft capsule shell.
The invention also provides powder for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition.
The pharmaceutical composition provided by the invention can be prepared into granules, oral liquid, tablets, capsules and powder, and is more convenient to take, carry and store.
The invention also provides application of the traditional Chinese medicine composition in preparing medicines for treating chronic gastritis, chronic atrophic gastritis, precancerous lesion of gastric cancer, chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia.
In summary, compared with the prior art, the invention achieves the following technical effects:
1. the traditional Chinese medicine composition has definite curative effects on chronic gastritis, chronic atrophic gastritis and precancerous lesions of gastric cancer (such as chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia) in clinical symptoms, histopathology and molecular level.
2. The traditional Chinese medicine composition can be prepared into powder, oral liquid, granules, tablets or extracts, and is more convenient to take, carry and store compared with the traditional Chinese medicine decoction.
3. The medicinal composition of the invention has no very rare and expensive medicinal materials, has low preparation cost and is convenient for large-scale popularization.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a hidden structure model of medicine with the number of 5 or more for patients with atrophic gastritis in Jingjin Ji area;
FIG. 2 is a target point Wien diagram of coincidence of the traditional Chinese medicine composition of the invention and chronic gastritis;
fig. 3 is a diagram of an active ingredient-target site of the Chinese medicinal composition of the present invention;
FIG. 4 is a diagram of the interaction core network of the Chinese medicinal composition of the present invention and the protein of chronic gastritis;
FIG. 5 is a BP histogram and a bubble chart of the main action targets of the Chinese medicinal composition of the present invention;
FIG. 6 is a CC histogram and a bleb chart of the major action targets of the Chinese medicinal composition of the present invention;
FIG. 7 is a MF bar graph and a bubble graph showing the main action targets of the Chinese medicinal composition of the present invention;
FIG. 8 is a diagram of the action target-pathway of the Chinese medicinal composition of the present invention.
Detailed Description
In order to make the technical solutions of the present invention better understood, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, shall fall within the scope of protection of the present invention.
The pharmaceutical composition is prepared based on turbid toxicity theory of tsukudani research team of third-stage medical university teacher, namely tsukudani, and by combining the research foundation of a hidden structure model at the early stage of a subject group, as shown in figure 1, and the characteristics and clinical characteristics of the current-stage chronic gastritis case. The former prescription mostly treats by strengthening the spleen, clearing heat and promoting diuresis, and the difference of the recipe is resolving turbidity and detoxifying. The composition consists of agastache rugosus, coptis chinensis, bighead atractylodes rhizome, round cardamom, barbed skullcap herb, spreading hedyotis herb, Chinese angelica, szechuan lovage rhizome, pseudo-ginseng, poria cocos, white paeony root, lily, immature bitter orange, nutgrass galingale rhizome, costustoot, villous amomum fruit, scorpion and corydalis tuber, has the functions of eliminating turbid pathogen and detoxifying, harmonizing stomach and lowering adverse qi, and is used for treating epigastric fullness and oppression, pain, belching, anorexia, dry mouth and bitter taste, sticky stool and uncomfortable stool and the like. Clinical experiments prove that the formula has good clinical curative effects on patients with the symptoms of chronic gastritis, chronic atrophic gastritis, gastric precancerous lesion and chronic atrophic gastritis with intestinal metaplasia, and specific clinical examples are shown in the following text.
The traditional Chinese medicine composition mainly comprises the following components in parts by weight: 8-12 parts of agastache rugosus, 3-9 parts of coptis chinensis, 9-15 parts of bran-fried bighead atractylodes rhizome, 3-9 parts of cardamom, 12-18 parts of sculellaria barbata and 12-18 parts of oldenlandia diffusa.
Further preferably, the traditional Chinese medicine composition of the invention can comprise the following components in parts by weight: 8-12 parts of wrinkled gianthyssop herb, 3-9 parts of coptis chinensis, 9-15 parts of bran-fried bighead atractylodes rhizome, 3-9 parts of round cardamom, 12-18 parts of barbed skullcap herb, 12-18 parts of spreading hedyotis herb, 9-15 parts of Chinese angelica, 6-12 parts of szechuan lovage rhizome, 4-8 parts of pseudo-ginseng, 12-18 parts of poria cocos, 12-18 parts of fried white paeony root, 9-15 parts of lily, 8-12 parts of bran-fried immature bitter orange, 6-12 parts of vinegar nutgrass galingale rhizome, 3-9 parts of costustoot, 3-9 parts of villous amomum fruit, 3-6 parts of scorpion and 8-12 parts of vinegar corydalis tuber.
The agastache rugosus in the traditional Chinese medicine composition is fragrant and turbid, has the effects of harmonizing stomach and lowering adverse qi, has the effects of clearing away heat and toxic materials, thickening intestines and stomach and clearing turbid and toxic materials, and is a monarch drug in total. Monarch drugs are indispensable for the main treatment of the principal symptoms in the prescription, and have less medicinal taste and larger dosage according to the potency; the white atractylodes rhizome and the round cardamom which are stir-fried with bran strengthen the spleen and resolve turbidity and harmonize the stomach, and the barbed skullcap herb and the oldenlandia which are used as ministerial drugs for clearing away heat and toxic materials. Ministerial drugs assist monarch drugs to enhance the therapeutic effect; angelica, rhizoma ligustici wallichii and pseudo-ginseng activate blood and relieve pain, poria cocos invigorates spleen and excretes dampness, fried white peony root nourishes blood and relieves middle energizer, lily nourishes yin and calms nerves, bran-fried immature bitter orange, vinegar-fried rhizoma cyperi and elecampane promote qi circulation and harmonize stomach, relieve distension and remove stuffiness, fructus amomi dissolves turbidity and stimulates appetite, scorpion detoxifies and dissipates binds, vinegar-fried rhizoma corydalis promotes qi circulation and activates blood and relieves pain, and the traditional Chinese medicines are used together as adjuvant medicines. Adjuvant drugs assist the monarch drugs in treating concurrent symptoms or secondary symptoms, or inhibit the toxicity and the severity of the monarch and ministerial drugs, or act as an anti-adjuvant.
Wherein, the proportion of the monarch drug wrinkled gianthyssop herb and the golden thread is crucial, and the effect on chronic gastritis, chronic atrophic gastritis, gastric precancerous lesion, chronic atrophic gastritis with intestinal metaplasia can not be achieved simultaneously by changing the proportion. In addition, the bran-fried bighead atractylodes rhizome and the round cardamom in the ministerial drugs have the effects of tonifying spleen, eliminating turbid pathogen and harmonizing stomach, and have great contribution to the curative effect of the whole traditional Chinese medicine composition.
The meaning of turbid toxicity is divided into broad sense and narrow sense, and the broad sense of turbid toxicity refers to all dirty substances harmful to human body, while the narrow sense of turbid toxicity is both pathogenic factors and pathological products. Turbid toxin is a pathogenic factor causing serious damage to human body and is a pathological product generated by accumulation in vivo.
The turbid virus pathogenic factor is cemented and acted on the human body, which causes the turbid transformation of cells, tissues and organs of the human body, namely the pathogenic process; the result of opacification is opacification of cells, tissues and organs, i.e., changes in morphological structure including hypertrophy, hyperplasia, atrophy, metaplasia and canceration in modern pathologies, as well as changes in inflammation, degeneration, apoptosis and necrosis. The result of turbidity changes is toxic to cells, tissues and organs, causing their metabolism and malfunction, and even failure.
Turbid toxin is one of pathological products and also a pathogenic factor, and is closely related to spleen and stomach diseases. Pathogenic damp-turbidity is classified into interior and exterior, exogenous damp-turbidity is caused by exogenous damp-turbidity, endogenous damp-turbidity is caused by hypofunction or disorder of spleen and stomach, and the endogenous damp-turbidity cannot be normally transported and transformed to cause the damp-turbidity to grow from the interior. The pathogenic dampness in and out of the body is related to each other, and the exogenous dampness encumbers the spleen, which inevitably leads to dysfunction of the spleen in transportation and stomach in descending; stagnation of endogenous damp-turbidity often causes invasion of exogenous damp-turbidity. Stomach pertains to yang earth, stomach diseases are easy to be transformed into heat and fire, namely yang is full; or, the initial stage of the disease is damp-heat, the damp-heat will accumulate turbid, the heat will be transformed into damp-heat, the damp-turbidity will transform into heat-toxin, and the toxin will grow from damp-turbidity, i.e. the heat will gradually transform into toxin, the toxin will become the extreme heat, the toxin will be contained in heat, and the heat will transform into toxin. Therefore, turbid toxin is considered to be one of the main pathogenesis of the spleen and stomach diseases, and a set of strict treatment rules and treatment methods for treating the spleen and stomach diseases by mainly dissolving turbid and detoxifying are established on the basis of the theory.
The pattern of turbid-toxin refers to one or several groups of syndromes that the body is in a turbid-toxin state due to the pathogenic factor of turbid-toxin, and thus the specific clinical manifestations are produced. Turbid nature refers to turbid nature, toxicity refers to toxicity. Turbid pathogenic factors are usually caused by sticky and greasy turbidity, and tend to stagnate in the meridians, block qi movement, linger and consume qi. The glue is not adhered and is easy to brew toxicity; while the toxic pathogen damages the body, its nature is vigorous and changeable, damaging qi, blood, ying and wei. When they are combined, the toxicity is caused by the turbid and the turbid with the toxicity, which often damages the zang-fu organs and meridians. While turbid toxins invade the upper, middle and lower triple energizers, they are most common in the middle energizer, and the spleen and stomach are most common in the middle energizer.
The technical route of the invention is as follows:
(1) screening a traditional Chinese medicine formula with the functions of dissolving turbidity and detoxifying through the theory of turbidity and toxicity;
(2) a disease-active ingredient-target-drug multilayer biological information network is constructed through network pharmacology, and a disease-drug recessive relation is disclosed;
(3) carrying out animal experiments by taking a rat as a material, and detecting the expression changes of Hippo/TAZ signal channel related protein transcription co-activator PDZ binding motif (TAZ), tumor suppressor kinase (LATS2) and mammal sterile line 20-like kinase (MST1) in the stomach tissue of the rat with chronic atrophic gastritis;
(4) the curative effect of the pharmaceutical composition on the chronic atrophic gastritis is verified by a human body test.
The network pharmacology integrates the integration, the dynamics and the analysis into a whole, is an emerging interdiscipline integrating system biology, pharmacology, traditional Chinese medicine pharmacology, molecular biology and computer science, can construct a disease-active component-target-medicine multilayer biological information network, and reveals a disease-medicine recessive relation. The compound traditional Chinese medicine formula can provide a research visual angle of multilayer, multi-component and multi-target, and a new method and a new paradigm are provided for the visual and data research of traditional Chinese medicine empirical medicine. The invention adopts a network pharmacology technology to search the compound and the target protein of the pharmaceutical composition, construct and analyze a target network, screen a core target, perform function enrichment, discuss the potential molecular mechanism of the pharmaceutical composition for preventing and treating chronic gastritis, and provide partial visual data support for clinical practice of the medicine prepared from the pharmaceutical composition.
Example 1A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials comprise the following components in parts by weight: 8 parts of wrinkled gianthyssop herb, 3 parts of coptis chinensis, 9 parts of bran-fried bighead atractylodes rhizome, 3 parts of round cardamom, 12 parts of barbed skullcap herb and 12 parts of spreading hedyotis herb; wherein herba Agastaches and Coptidis rhizoma are principal drugs, and Atractylodis rhizoma parched with bran, fructus Amomi rotundus, herba Scutellariae Barbatae, and herba Hedyotidis Diffusae are ministerial drugs.
Example 2A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials comprise the following components in parts by weight: 12 parts of wrinkled gianthyssop herb, 9 parts of coptis chinensis, 15 parts of bran-fried bighead atractylodes rhizome, 9 parts of round cardamom, 18 parts of barbed skullcap herb and 18 parts of spreading hedyotis herb; wherein herba Agastaches and Coptidis rhizoma are principal drugs, and Atractylodis rhizoma parched with bran, fructus Amomi rotundus, herba Scutellariae Barbatae, and herba Hedyotidis Diffusae are ministerial drugs.
Example 3A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials comprise the following components in parts by weight: 10 parts of wrinkled gianthyssop herb, 6 parts of coptis chinensis, 12 parts of bran-fried bighead atractylodes rhizome, 6 parts of round cardamom, 15 parts of barbed skullcap herb and 15 parts of spreading hedyotis herb.
Example 4A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials of the material comprise the following components in parts by weight: 8 parts of wrinkled gianthyssop herb, 3 parts of coptis chinensis, 9 parts of bran-fried bighead atractylodes rhizome, 3 parts of round cardamom, 12 parts of barbed skullcap herb, 12 parts of spreading hedyotis herb, 9 parts of Chinese angelica, 6 parts of szechuan lovage rhizome, 4 parts of pseudo-ginseng, 12 parts of poria cocos, 12 parts of fried white paeony root, 9 parts of lily, 8 parts of bran-fried immature bitter orange, 6 parts of vinegar-processed rhizoma cyperi, 3 parts of costustoot, 3 parts of villous amomum fruit, 3 parts of scorpion and 8 parts of vinegar-processed rhizoma corydalis.
Example 5A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials of the material comprise the following components in parts by weight: 12 parts of wrinkled gianthyssop herb, 9 parts of coptis chinensis, 15 parts of white atractylodes rhizome fried with bran, 9 parts of round cardamom, 18 parts of barbed skullcap herb, 18 parts of spreading hedyotis herb, 15 parts of Chinese angelica, 12 parts of szechuan lovage rhizome, 8 parts of pseudo-ginseng, 18 parts of tuckahoe, 18 parts of fried white paeony root, 15 parts of lily, 12 parts of immature bitter orange fried with bran, 12 parts of rhizoma cyperi with vinegar, 9 parts of costustoot, 9 parts of fructus amomi, 6 parts of scorpion and 12 parts of rhizoma corydalis with vinegar.
Example 6A Chinese medicinal composition for treating chronic gastritis and gastric precancerous lesions
The raw materials of the material comprise the following components in parts by weight: 10 parts of wrinkled gianthyssop herb, 6 parts of coptis chinensis, 12 parts of white atractylodes rhizome fried with bran, 6 parts of round cardamom, 15 parts of barbed skullcap herb, 15 parts of spreading hedyotis herb, 12 parts of Chinese angelica, 9 parts of szechuan lovage rhizome, 6 parts of sanchi, 15 parts of tuckahoe, 15 parts of fried white paeony root, 12 parts of lily, 10 parts of immature bitter orange fried with bran, 9 parts of rhizoma cyperi with vinegar, 6 parts of costustoot, 6 parts of fructus amomi, 3 parts of scorpion and 10 parts of rhizoma corydalis fried with vinegar.
Example 7 Collection and screening of major Compounds in pharmaceutical compositions of the invention
According to the prescription composition of the pharmaceutical composition and the pharmaceutical specification name of the 'Chinese pharmacopoeia' 2015 edition, the pharmaceutical composition comprises agastache rugosa (Pogostemonis HERBA), coptis chinensis (Coptis RHIZOMA), bighead atractylodes rhizome (Atractylodis macrophylla), cardamom (Amomum fruticosus Rotund.), barbat skullcap (Scutellaria barbata), oldenlandia DIFFUSA (HEDYOTIS difusas wild), angelica sinensis (ANGELICAE SINENSIS RADIX), Ligusticum wallichii (Chuanxinong rhizome), NOTOGINSENG (Notholing RADIX rhizome), tuckahoe (PORIA), white peony root (Paeonia ALBA), lily (LILII BULBUS), immature bitter orange (AURANTII FRUCTUS frutus IMMATURUS), cyperus (Cyperzoma), aucklia root (aucuba), aucuba root (olea villus), lily (BULBUS), and CORYDALIS tuber (CORYDALIS tuber). Searching TCMSP (traditional Chinese Medicine Systems pharmaceutical Database and Analysis platform) Database (http:// ibts. hkbu. edu. hk/LSP/tcmsp. php) Database to collect the main chemical components of the pharmaceutical composition of the invention, and screening the components with higher activity and possible blood entering from the Database according to the conditions of Oral Bioavailability (OB) ≥ 30%, Drug-like property (DL) ≥ 0.18 and Half-Life (Half-Life, HL) ≥ 8 (lily and amomum fruit ≥ 6).
Based on the conditions of OB more than or equal to 30 percent, DL more than or equal to 0.18 and HL more than or equal to 8 (HL more than or equal to 6 is used for lily and fructus amomi), the active ingredients of the Chinese medicaments are screened (related results are not searched by scorpion and angelica or searched results do not meet the conditions), and 59 active ingredients are obtained.
Example 8 predictive screening of target of the pharmaceutical composition of the invention and construction of the active ingredient-target network of Chinese herbs
The analyzed and screened active blood components are subjected to one-by-one pairing of potential targets of the active pharmaceutical ingredients by utilizing TCMSP database compound correlation targets, and no data of 2 medicinal materials including angelica and scorpion are available; predicting component-Related Targets by using Related Targets in the TCMSP database; preprocessing the target point name through a UniProt database (https:// www.uniprot.org /) to obtain the final target point related to the active ingredients of the traditional Chinese medicine; screening related targets of the chronic gastritis by using a GeneCards database (https:// www.genecards.org /), mapping the related targets of diseases and the related targets of active ingredients of the medicine, wherein the neutralization target is the target of the active ingredients of the medicine composition acting on the chronic gastritis.
232 component-Related Targets are predicted from Related Targets in a TCMSP database, and 1139 disease-Related Targets are obtained by searching a 'chronic gastritis' Related target from a Genecards database. Then, 232 component targets and 1139 chronic gastritis targets are subjected to Wien graph drawing, and the drawing is shown in a figure 2; and (4) counting 101 neutralizing target points, which are shown in figure 3.
Example 9 target protein interaction network construction and Key target screening
Analyzing Protein Interaction (PPI) of a target by using a String online database (https:// String-db.org /), inputting target information into the database, selecting Homosapiens from species, screening Protein Interaction comprehensive score > 0.4 as screening conditions to obtain PPI information, and introducing the information into Cytoscape software to obtain a PPI visual network diagram.
According to the active ingredients screened from the medicine and the relevant targets acting on diseases, a medicine active ingredient-target network is constructed by using Cytoscape software, which is shown in figure 3. The values of the Degree in the active ingredients of the medicine in the first 7 are respectively: quercetin (Quercetin, MOL00098), Luteolin (Luteolin, MOL000006), Kaempferol (MOL 000422), Wogonin (MOL 000173), Baicalein (Baicalein, MOL002714), Nobiletin (MOL 005828), and Naringenin (Naringenin, MOL 004328).
Example 10 target Gene ontology (Gene ontology, GO) and KEGG pathway enrichment analysis
The Cytoscape software Clue GO plug-in is used for carrying out GO and KEGG enrichment analysis on a neutralization target, a result that P is less than or equal to 0.05 is reserved, a visual picture is obtained, a target-signal path network diagram is constructed by using the Cytoscape software, and a possible action mechanism of the pharmaceutical composition for treating chronic gastritis based on the target and the signal path is further explained.
Based on the disease-prescription 101 neutralization targets input on the STRING online data platform, PPI network diagram is obtained after analysis, as shown in FIG. 4, the diagram contains 101 target proteins and 1783 interaction edges.
Go (gene integration) enrichment analysis of the target site comprises Biological Processes (BP), Cell Composition (CC), Molecular Function (MF). Performing GO biological function annotation on 101 coactive target proteins by using a ClueGO plug-in Cytoscape software, and performing visual analysis on the first 20 data according to the result that the reserved P is less than or equal to 0.01 to obtain a (BP, CC, MF) histogram and a bubble diagram, wherein the ordinate represents enrichment items, and the abscissa represents the enrichment number, which is shown in FIGS. 5, 6 and 7. FIG. 5 shows that disease-prescription co-acting targets are in BP, and the main enrichment items are response to metal ions (stress to metal), response to oxidative stress (stress to oxidative stress), lipopolysaccharide response (stress to lipopolysaccharide), response to bacteria-derived molecules (stress to molecular of bacterial origin), and response to antibiotics (stress to antibiotic), among others. FIG. 6 shows disease-prescription co-acting targets in CC, with the main enrichment items being cystic space (vesicular cavity), secretory granule cavity (secretory granule cavity), cytoplasmic cystic space (cytoplasmic vesicular cavity), membrane rafts (membrane raft), membrane microdomains (membrane microdomains), etc. FIG. 7 shows that the disease-prescription co-action targets are in MF, and the main enrichment items are phosphatase binding (phosphatase binding), protein phosphatase binding (protein phosphatase binding), ubiquitin-like protein ligase binding (ubiquitin-like protein ligase binding), antioxidant activity (antioxidant activity), scaffold protein binding (scaffold protein binding), and the like.
And importing the obtained channel items and target point information into Cytoscape software, and drawing to obtain a target point-channel diagram, wherein a triangle represents a channel, a square represents a target point, and the larger the shape is, the more remarkable the enrichment is represented, as shown in FIG. 8. The medicinal composition has the comprehensive treatment effect on the chronic gastritis by multiple components, multiple targets and multiple channels.
Example 11 animal experiments to verify the efficacy of the pharmaceutical compositions of the present invention
First, experiment method
(1) Healthy and clean SD rat, male, weight 250-: SCXK (Ji) 2018-1-003, which was fed in an animal house of Hebei medical university, freely fed with water, and adaptively fed for 7 days before the start of the experiment.
(2) The experimental medicine is purchased from a traditional Chinese medicine room of a traditional Chinese medicine institute in Hebei province, decocted by a decoction room of the traditional Chinese medicine institute in Hebei province, decocted by 4 times of distilled water, and decocted liquid is uniformly mixed and concentrated to the crude drug content of 2.8g/mL for later use after 2 times of 50 min.
(3) Main drugs, reagents and instruments:
MLV reverse transcription kit: U.S. Fementas, lot number: k1622;
trizol, usa Invitrogen, lot number: 15596018, respectively;
PCR primer synthesis: U.S. Invitrogen, lot number: a13838;
an optical microscope: Olympus-BX63, Japan;
image-pro plus: media Cybernetics, usa;
real-time fluorescent quantitative PCR instrument: model ABI7500, Life Tech corporation, usa.
(4) Grouping, modeling, drug delivery and material collection
Rats were randomly divided into 4 groups: normal group, model group, turbid pathogen removing and detoxifying group and vitamine group. The atrophic gastritis rat model was induced by a combined modeling method. The normal group and the model group are infused with 10mL/kg/d distilled water, the turbid removing and detoxifying group is infused with 28g/kg decoction of the traditional Chinese medicine composition of the embodiment 6, 10mL/kg decoction, and the vitamin group is infused with 0.06g/kg suspension solution, and the treatment course is 12 weeks. 48 hours after the last gastric lavage, the 10% chloral hydrate 3.5mL/kg is killed after intraperitoneal injection for anesthesia and the materials are taken.
Second, experimental results
(1) Western blot detection result of LATS2 and MST1 proteins in gastric mucosal tissue
Western blot is used for detecting the expression changes of Hippo/TAZ signal channel related protein transcription coactivator PDZ binding motif (TAZ), tumor suppressor kinase (LATS2) and mammal sterile line 20-like kinase (MST1) in rat stomach tissue with chronic atrophic gastritis.
The expression levels of LATS2, MST1 were reduced in the model group compared to the normal group. Compared with the model group, the turbid pathogen removing and detoxifying group and the vitamin group can improve the LATS2 and MST1 contents of rat gastric mucosal tissues, and the turbid pathogen removing and detoxifying group has the most obvious effect. See table 1.
TABLE 1 expression levels of LATS2, MST1 proteins in atrophic gastritis rat gastric mucosal tissue
Figure GDA0003465496000000111
(2) TAZ protein and gene expression result of gastric mucosa tissue
The level of TAZ expression was increased in the model group compared to the normal group. Compared with the model group, the turbid pathogen removing and detoxifying group and the vitamine group can reduce the TAZ protein and gene expression level of the rat gastric mucosa tissue, and the turbid pathogen removing and detoxifying group has the most obvious effect. See table 2.
TABLE 2 TAZ protein and Gene expression in atrophic gastritis rat gastric mucosal tissue
Figure GDA0003465496000000121
In conclusion, the traditional Chinese medicine composition disclosed by the invention can play a role in a rat model by reducing the expression level of TAZ protein and genes in gastric mucosa tissues and increasing the expression level of LATS2 and MST1 protein and genes, the 28g/kg turbidity-dissolving and detoxifying group can obviously improve the pathological condition of the gastric mucosa, the TAZ protein and genes are reduced in the regulation process of a Hippo/TAZ signal channel, and the LATS2 and MST1 are increased to be better than the vitamine group.
Example 12 human experiments demonstrate the efficacy of the pharmaceutical composition of the present invention on chronic atrophic gastritis
Materials and methods
(1) General data
86 patients with chronic atrophic gastritis with low-grade intraepithelial neoplasia or intestinal metaplasia in outpatient service of department of spleen and stomach and ward of traditional Chinese medicine in Hebei province in 2019 and 1 month 2020 are collected and are in accordance with informed consent and voluntary principle, and the patients are divided into an observation group and a control group by adopting a random digital table method, wherein each group comprises 43 patients. Wherein 23 men and 20 women in the observation group are aged 45-68 years, the average (56.5 +/-6.2) years and the course of disease is 6 months-13 years; the age of the control group is 43-67 years, the average (55.0 +/-5.7) years and the disease course is 5 months-12 years. The difference between the general data, disease degree and disease duration of two groups of patients is not statistically significant (P > 0.05).
(2) Inclusion criteria
Western medicine diagnosis of chronic atrophic gastritis with low-grade intraepithelial neoplasia meets relevant diagnosis and treatment standards in Chinese consensus of chronic gastritis (2017, Shanghai); ② 35-70 years old; thirdly, obeying experimental arrangement; signing an informed consent by the patient and the family members.
(3) Exclusion criteria
(ii) those less than 35 years old or more than 70 years old; ② patients suffering from basic diseases such as severe center of gravity, brain, liver, kidney and the like or mental disorder; ③ patients taking anticoagulant drugs for a long time or allergic to the drugs used in the experiment; fourthly, pregnant women or lactating women; poor compliance and incapability of maintaining. The invention meets the requirements of the ethical committee of hospitals and approves the passing.
(4) Method of treatment
The control group administered Chinese patent medicine stomach rejuvenation tablet (Hangzhou Chongyutang pharmaceutical industry Co., Ltd., national Standard Z20040003, 0.36 g/tablet, 4 tablets/time, 3 times/day), the observation group administered the Chinese medicinal composition of example 6 of the present invention, the prescription: 10g of wrinkled gianthyssop herb, 6g of coptis chinensis, 12g of bran-fried bighead atractylodes rhizome, 6g of round cardamom, 15g of barbed skullcap herb, 15g of spreading hedyotis herb, 12g of Chinese angelica, 9g of szechuan lovage rhizome, 6g of pseudo-ginseng, 15g of poria cocos, 15g of fried white paeony root, 12g of lily, 10g of bran-fried immature bitter orange, 9g of vinegar-processed nutgrass galingale rhizome, 6g of costustoot, 6g of villous amomum fruit, 3g of scorpion and 10g of vinegar-processed rhizoma corydalis. Modified according to the syndrome. 3 months is 1 course of treatment, and 2 courses of treatment are continued.
(5) Observation index
a) Evaluating the curative effect of the traditional Chinese medicine syndrome: observing traditional Chinese medicine syndrome integrals before and after treatment of two groups of patients, scoring 4 main symptoms of epigastric pain, fullness, stuffiness and warm air, fatigue, poor sleep, gastric upset and acid regurgitation of the patients according to the 'consensus opinion of traditional Chinese and western medicine combined diagnosis and treatment of chronic atrophic gastritis' (2017), wherein the main symptoms are divided into four grades of no, light, medium and heavy, the main symptoms are divided into 0, 2, 4 and 6, and the secondary symptoms are divided into 0, 1, 2 and 3. The traditional Chinese medicine syndrome curative effect judgment standard is as follows: the recovery is realized (the curative effect index is improved by more than or equal to 95 percent); ② the medicine has obvious effect (the curative effect index is improved by 70-95%); effect (curative effect index is improved by 30-70%); (iv) no effect (improvement in efficacy index < 30%).
Efficacy index ═ (pre-treatment score post-treatment score)/pre-treatment score × 100%.
Total effective rate (number of cure cases + number of significant cases + number of effective cases)/total number of cases × 100%.
b) Evaluation of histopathological curative effect of gastric mucosa: according to pathological results, the atrophy degree of the chronic atrophic gastritis is classified according to the non, light, medium and heavy grades and respectively marked as 0, 1, 2 and 3, and the atrophy degree is calculated by the reduction of the inherent glands of the gastric mucosa, namely 1/3, and is mild: intrinsic glandular reduction < 1/3; medium: the number of the inherent glands is reduced from 1/3 to 2/3; and (3) severe degree: intrinsic gland reduction > 2/3. The low grade intraepithelial neoplasia is marked with non-mild dysplasia and moderate dysplasia by 0, 2 and 4 points respectively.
c) And (6) evaluating safety. Before treatment and after two treatment courses, the liver and kidney functions and the blood coagulation function are checked, and the adverse drug reactions of nausea, vomiting, abdominal pain, diarrhea, rash and the like of the patient are recorded.
d) The processing is performed by SPSS15.0 statistical software, and the data is measured by (
Figure GDA0003465496000000131
) Expressing that the comparison between the sample mean numbers conforming to normal distribution adopts t test, the counting data is expressed by rate, the comparison between groups adopts chi-square test and P test<A difference of 0.05 is statistically significant.
Second, experimental results
(1) Integral comparison of Chinese medicine syndrome before and after treatment of two groups of patients
The results are shown in Table 3, and the difference of the integral of the TCM syndromes (major symptoms and minor symptoms) in the two groups of patients before treatment has no statistical significance (P > 0.05). Compared with the traditional Chinese medicine before treatment, the traditional Chinese medicine syndrome integrals of the two groups of patients are obviously reduced after treatment (P <0.05), and the traditional Chinese medicine syndrome integrals of the observation group are obviously lower than those of the control group (P < 0.05).
Table 3 the integral comparison of the syndrome of traditional Chinese medicine before and after treatment of two groups of patients (score,
Figure GDA0003465496000000141
n＝43)
Figure GDA0003465496000000142
note: compared with the group before treatment,*P<0.05; compared with the control group after the treatment,#P<0.05
(2) comparison of histopathological efficacy before and after treatment of two groups of patients
Results are shown in table 4, with no statistical significance for the histopathological score differences between the two groups of patients prior to treatment (P > 0.05). The histological score was significantly reduced in both groups of patients after treatment (P <0.05) compared to before treatment, and the histopathological score was significantly lower in the observed group than in the control group (P < 0.05).
TABLE 4 comparison of histopathological treatment of gastric mucosa in two groups (minutes)
Figure GDA0003465496000000143
Note: compared with the group before treatment,*P<0.05; compared with the control group after the treatment,#P<0.05
(3) comparison of SF-36 quality of Life Scale scores before and after treatment in two groups of patients
The results are shown in Table 5, and the difference of the scores of the SF-36 quality of life scale in the two groups of patients before treatment is not statistically significant (P is more than 0.05). Compared with the pre-treatment group, the scores of each index of the SF-36 quality of life scale of the two groups of patients are obviously increased after the treatment (P is less than 0.05), and the scores of each index of the SF-36 quality of life scale of the observation group are obviously higher than those of the control group (P is less than 0.05).
TABLE 5 twoComparison of SF-36 quality of Life Scale scores before and after treatment in groups of patients: (
Figure GDA0003465496000000144
n＝43)
Figure GDA0003465496000000151
Note: compared with the group before treatment,*P<0.05; compared with the control group after the treatment,#P<0.05
(4) adverse reaction comparison of two groups of patients
After treatment, two groups of patients do not have liver and kidney function and blood coagulation function abnormality through reexamination, 1 nausea and vomiting, 2 diarrhea and 1 rash appear in an observation group, and the incidence rate of adverse reactions is 9.30%: the control group had 1 nausea and vomiting, 2 abdominal pain, 2 diarrhea, 2 rash and 16.28% adverse reaction. The difference of the incidence rate of the adverse reactions in the two groups is not statistically significant (P is more than 0.05).
In the study, the observation group patients used the traditional Chinese medicine composition of the invention, and the control group patients treated with the patent drug, namely, the stomach rejuvenation, by comparison, it can be found that the difference of adverse reactions in the treatment process of the two groups has no statistical significance, which indicates that the safety of the treatment methods of the two groups is consistent, the two groups of patients treated by the treatment have the trend of improving clinical symptoms, but the improvement degree of the patients in the observation group is significantly higher than that in the control group (P < 0.05).
The traditional Chinese medicine has unique effect on treating chronic gastritis, and has unique characteristics in the aspects of improving inflammation-cancer related disease symptoms, delaying pathological progress and even reversing pathological changes. Researchers argue from the treatment of tumor toxicity, and think that the traditional Chinese medicine can effectively inhibit the atrophy of mucosal glands; it is also found that the erosion and atrophy symptoms of gastric mucosa under endoscope can be obviously improved after the treatment of strengthening spleen, removing blood stasis and detoxifying. Partial drug effective substance basis of the medicine is to be determined, the innovation and development of the traditional Chinese medicine are restricted, how to quickly and effectively determine the drug effective substance basis of the traditional Chinese medicine for treating the chronic gastritis, and the medicine becomes one of the urgent scientific problems to be solved for the traditional Chinese medicine to effectively treat the chronic gastritis. Network pharmacology, as a cross discipline in pharmacology, computer science, traditional Chinese medicine and molecular biology, can partially solve the problem and becomes one of methodologies for analyzing possible targets of drugs. Part of clinical laboratory tests and medicines are subjected to network pharmacology or molecular docking prediction research by medical researchers, and a plurality of possible targets and signal paths are found, so that the medicine effect material basis of the medicine is determined. In recent years, the application of information science means to carry out diagnosis and treatment experience analysis and learning of famous families is one of important research directions for modern Chinese medicine, related data analysis methods are widely applied to the field of research of legal medicines, and the mining of implicit rules and hidden features in data is regarded as a brand new effective means for researching the traditional Chinese medicine syndrome rules. The medicine prepared from the medicine composition is used as a chronic gastritis proved recipe summarized based on machine learning and famous and old traditional Chinese medicine experiences, and related research reports are not found at present.
In the early-stage research, the invention discovers that the traditional Chinese medicine syndrome curative effect of chronic gastritis can be improved by applying a turbid-removing detoxification method, the life quality of a patient is improved, the serum tumor specific growth factor and gastric cancer monoclonal antibody MG7 related antigen are influenced, the serum inflammatory factor level is reduced, and on the basis, a hidden structure model is applied and the experience of famous and old traditional Chinese medicine is combined, so that the traditional Chinese medicine composition is summarized, the action mechanism of the traditional Chinese medicine composition is subjected to exploratory research by means of network pharmacology, and the conclusion is as follows:
screening 59 main active ingredients and 101 ingredient targets. The most important active ingredients are Quercetin (Quercetin, QT), Luteolin (Luteolin, Lut), Kaempferol (Kaempferol, Kae), Wogonin (Wogonin), Baicalein (Baicalein), Nobiletin (Nobiletin), and Naringenin (Naringenin). QT as a natural dietary flavonoid is rich in most plant traditional Chinese medicines and has obvious antioxidant and anti-inflammatory effects. The researchers find that QT can enhance the induction activity of 5-fluorouracil on the apoptosis of the mitochondrial pathway of gastric cancer cells through the c-Jun/ATF2/Bcl-x L pathway; in addition, researchers find that QT possibly has a certain inhibiting effect on proliferation and invasion of gastric cancer cells through reduction of Cav-1 expression. Lut is a natural flavonoid compound mainly existing in traditional Chinese medicines, and has certain immunoregulation, anticancer and antioxidant effects. The learner finds that the Lut can induce the gastric cancer cell MGC803 to generate G2 stage block and apoptosis through a mitochondrial pathway; kae is a flavonoid compound rich in dampness-resolving traditional Chinese medicines, and has the effects of resisting oxidation, inflammation and virus. Researchers find that Kae can promote the apoptosis of gastric cancer cells and inhibit the malignant proliferation of the cancer cells; also, it was found that Kae was effective in relaxing rat longitudinal colon muscle.
Through PPI network analysis of target spots and screening of key target spots, the target spots with higher values are MAPK3, MAPK1, AKT1, BAL, IL, BAD, IKB, NFKBIA, JUN, CASP9 and the like, have a certain relation with inflammatory reaction from different aspects, and are consistent with the key target spots of other reported traditional Chinese medicine compound for treating chronic gastritis. Researches show that the Akt/MAPK pathway is an important potential mechanism for protecting gastric mucosa and is important for the development of digestive tract inflammation-cancer transformation. The current evidence proves that MAPK3, MAPK1 and MAPK14 can cause cell variation through pro-inflammatory reaction, AKT1 is a target gene of PI3K, the active ingredients can enhance the in-vitro proliferation and invasiveness of gastric cancer cells through an Akt1 pathway, and the potential role of AKT1 in the generation and development process of gastric cancer is further proved. It can be predicted that: QT, Lut, Kae, Wogonin and the like in the medicine prepared from the pharmaceutical composition can act on MAPK, AKT1, BAL and IL to play pharmacological actions, and a new idea is provided for continuously researching and discussing the effect of the traditional Chinese medicine composition on treating gastric precancerous lesions of chronic gastritis chickens and delaying inflammatory cancer transformation.
By the enrichment analysis of the GO and KEGG target points of the medicine prepared from the medicine composition for treating chronic gastritis, the result mainly focuses on the aspects of inflammatory reaction and the like, mainly relates to the biological processes of regulating immunity, oxidation reduction and the like, and can deduce the treatment effect of the traditional Chinese medicine composition and the regulation and control mechanism of inflammation, proteoglycan, transcription and choline metabolism disorder pathways related target points on chronic gastritis. According to the analysis and prediction results, combined analysis is found with previous-team animal experiments, the formula plays a role by reducing the expression level of TAZ protein and gene in the gastric mucosa tissue of a rat model with chronic gastritis and up-regulating the expression levels of LATS2 and MST1 protein and gene, the genes and the proteins are closely related to inflammation, proteoglycan, transcription and choline metabolism, and the medicine prepared by the medicine composition is proved to be possible to improve the related symptoms of chronic gastritis and delay and block inflammation-cancer transformation by regulating the protein expression of the key genes or regulating the signal transduction pathways.
In conclusion, the pharmaceutical composition is analyzed based on a hidden structure model and network pharmacology, and preliminary beneficial exploration is made by combining animal experiment prediction and verification on potential relation and action mechanism of an active compound, an action target, a signal path and a disease for treating chronic gastritis.
The invention also provides granules for treating chronic gastritis and gastric precancerous lesions, which comprise the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary materials are one or more of filling agent, adhesive, wetting agent, disintegrating agent, lubricant and film coating material. The traditional Chinese medicine is extracted, concentrated and prepared into powder, and the sustained-release auxiliary agent is added for kneading and granulating, so that the obtained traditional Chinese medicine granules can release the traditional Chinese medicine components with high efficiency and high quality, and the efficacy and the treatment effect are improved.
The invention also provides an oral liquid for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation adjuvants are one or more of solvent, aromatic, correctant, clarifier and antiseptic.
The invention also provides a tablet for treating chronic gastritis and gastric precancerous lesions, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary materials are one or more of diluent, adhesive, lubricant and disintegrant.
The invention also provides a capsule for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition and preparation auxiliary materials; the preparation auxiliary material is a hard capsule shell or a soft capsule shell.
The invention also provides powder for treating chronic gastritis and precancerous lesions of gastric cancer, which comprises the traditional Chinese medicine composition.
The pharmaceutical composition provided by the invention can be prepared into granules, oral liquid, tablets, capsules and powder, and is more convenient to take, carry and store.
From the above results, the Chinese medicinal composition of the present invention shows a definite therapeutic effect on chronic gastritis, chronic atrophic gastritis, and gastric precancerous lesions (chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia) at clinical symptoms, histopathology and molecular level. Wherein, the proportion of the monarch drug wrinkled gianthyssop herb and the golden thread is crucial, and the effect on chronic gastritis, chronic atrophic gastritis and precancerous lesion of stomach (chronic atrophic gastritis with intestinal metaplasia and intraepithelial neoplasia) can not be achieved simultaneously by changing the proportion. In addition, the bran-fried bighead atractylodes rhizome and the round cardamom in the ministerial drugs have the effects of tonifying spleen, eliminating turbid pathogen and harmonizing stomach, and have great contribution to the curative effect of the whole traditional Chinese medicine composition. The traditional Chinese medicine composition is added with pharmaceutically conventional auxiliary materials according to a pharmaceutically conventional process to prepare pharmaceutically acceptable dosage forms, such as granules, oral liquid, tablets, capsules, powder and the like, and is convenient to take, carry and store and low in cost.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims (7)

1. A traditional Chinese medicine composition for treating chronic gastritis and precancerous lesions of gastric cancer is characterized by being prepared from the following raw materials in parts by weight: 10 parts of wrinkled gianthyssop herb, 6 parts of coptis chinensis, 12 parts of white atractylodes rhizome fried with bran, 6 parts of round cardamom, 15 parts of barbed skullcap herb, 15 parts of spreading hedyotis herb, 12 parts of Chinese angelica, 9 parts of szechuan lovage rhizome, 6 parts of sanchi, 15 parts of tuckahoe, 15 parts of fried white paeony root, 12 parts of lily, 10 parts of immature bitter orange fried with bran, 9 parts of rhizoma cyperi with vinegar, 6 parts of costustoot, 6 parts of fructus amomi, 3 parts of scorpion and 10 parts of rhizoma corydalis fried with vinegar.
2. A granule for treating chronic gastritis and gastric precancerous lesions, which is prepared from the traditional Chinese medicine composition of claim 1 and preparation auxiliary materials.
3. An oral liquid for treating chronic gastritis and precancerous lesions of gastric cancer, which is prepared from the traditional Chinese medicine composition of claim 1 and preparation auxiliary materials.
4. A tablet for treating chronic gastritis and gastric precancerous lesions, which is prepared from the traditional Chinese medicine composition of claim 1 and preparation auxiliary materials.
5. A capsule for treating chronic gastritis and gastric precancerous lesions, which is prepared from the traditional Chinese medicine composition of claim 1 and preparation auxiliary materials.
6. A powder for treating chronic gastritis and precancerous lesions of gastric cancer, which is prepared from the Chinese medicinal composition of claim 1.
7. The use of the Chinese medicinal composition of claim 1 in the preparation of medicaments for treating chronic gastritis and gastric precancerous lesions.
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