CN-122024818-A - Method for optimizing traditional Chinese medicine compound based on network pharmacology and substance basis analysis

Abstract

The invention belongs to the field of modernization of traditional Chinese medicine and pharmaceutical preparations, and particularly relates to a method for optimizing a traditional Chinese medicine compound based on network pharmacology and substance basis analysis. The method comprises the steps of S1, obtaining medicinal material compositions, screening active ingredients and action targets, intersecting the medicinal material compositions with disease targets to obtain potential target point sets, constructing PPI network screening core targets, S2, analyzing compound extractum/preparations by adopting a separation technology, identifying main ingredients and source medicinal materials, S3, tracing the active ingredients and the source medicinal materials based on the core targets, evaluating contribution degree of the medicinal materials by combining high-abundance ingredients, and screening key medicinal material compositions to optimize a formula.

Inventors

• FAN GUORONG
• WANG LI
• WU ZHENGHUA

Assignees

• 上海交通大学

Dates

Publication Date

20260512

Application Date

20260122

Claims (10)

1. 1. The method for optimizing the traditional Chinese medicine compound based on network pharmacology and substance basis analysis is characterized by comprising the following steps of: S1, network pharmacology analysis, namely acquiring medicinal material composition of a target compound, screening potential active ingredients of the medicinal materials through a database, predicting action targets of the potential active ingredients, comparing disease targets related to a target disease, taking intersection of the action targets of the active ingredients and the disease targets to obtain a potential action target set, constructing a protein-protein interaction PPI network, and screening core targets based on topological parameters; S2, identifying a material basis, namely respectively preparing a total extract of the target traditional Chinese medicine compound and single extracts of all medicinal materials composing the target traditional Chinese medicine compound, adopting a separation identification technology to analyze chemical components of the total extract and the single extracts so as to identify main chemical components with relative abundance larger than a preset threshold value in a total ion flow diagram of the total extract, and determining source medicinal materials of the main chemical components according to analysis results of the single extracts; And S3, optimizing the formula, namely calculating the comprehensive contribution degree of each medicinal material, and screening out a preset number of key medicinal materials with the highest comprehensive contribution degree to form an optimized simplified formula.
2. 2. The method of claim 1, wherein the separation and identification technique comprises ultra performance liquid chromatography-mass spectrometry combined technique UPLC-MS analysis.
3. 3. The method of claim 2, wherein the UPLC-MS analysis uses electrospray positive and negative ion modes, the chromatographic column is a BEH C18 column, the mobile phase is acetonitrile solution containing 0.1% formic acid and aqueous solution containing 0.1% formic acid, and gradient elution is used.
4. 4. The method according to claim 1, wherein in step S1, the screening of the core targets is performed according to network topology parameters including node degree values, median centrality and near centrality.
5. 5. The method according to claim 1, wherein in step S3, the calculation of the comprehensive contribution degree comprises normalization and weighted summation of the total number of combined and de-duplicated targets hit by the compound from each medicinal material in the core targets and the relative abundance of the compound from each medicinal material in the mass spectrometry analysis result.
6. 6. The method of claim 1, wherein in step S1, the target compound is a compound for treating or preventing hyperlipidemia.
7. 7. A simplified formulation of traditional Chinese medicine obtained by the method according to any one of claims 1 to 6, characterized in that it comprises bighead atractylodes rhizome, pinellia ternate and lotus leaf.
8. 8. The simplified formulation of claim 7, wherein the formulation acts on the PTGS2, ADRB2 and/or ach targets and/or modulates PI3K-Akt signaling pathway and/or lipid and atherosclerosis pathway by containing flavonoids, terpenes and/or phenolic active ingredients, thereby exerting lipid regulating effect.
9. 9. The simplified formulation of traditional Chinese medicine according to claim 8, wherein the medicament is for lowering total cholesterol TC, triglyceride TG and low density lipoprotein cholesterol LDL-C levels in serum and/or liver, and/or for elevating high density lipoprotein cholesterol HDL-C levels.
10. 10. A pharmaceutical composition is characterized by comprising extracts prepared from three medicinal materials including bighead atractylodes rhizome, pinellia tuber and lotus leaf, and a pharmaceutically acceptable carrier or auxiliary material, wherein the pharmaceutical composition is used for treating or preventing hyperlipidemia.

Description

Method for optimizing traditional Chinese medicine compound based on network pharmacology and substance basis analysis Technical Field The invention relates to the field of modernization of traditional Chinese medicine and pharmaceutical preparations, in particular to a method for optimizing a traditional Chinese medicine compound based on network pharmacology and substance basis analysis. Background Lipid metabolism disorders refer to abnormal changes in lipid profile, including a variety of diseases associated with elevated Total Cholesterol (TC) and/or Triglycerides (TG), elevated Low Density Lipoproteins (LDL) and/or reduced High Density Lipoproteins (HDL). Studies have shown that hyperlipidemia, especially elevated LDL, is closely associated with diseases associated with abnormal lipid metabolism, such as atherosclerotic vascular disease, abnormal vasoconstrictor function and nonalcoholic fatty liver disease (NAFLD). Thus, modulation of abnormal lipid levels to the normal range is an effective strategy to reduce the incidence of these diseases. In clinical practice, drugs such as statin drugs, omega-3 polyunsaturated fatty acids (PUFA), bile acid binding resins, fibrates, nicotinic acid and proprotein convertase subtilisin/matrix metalloproteinase-like protein 9 (PCSK 9) inhibitors are widely used for the prevention and treatment of hyperlipidemia. However, in some cases, it is difficult for the patient to obtain the intended therapeutic effect due to side effects or high treatment costs. Treatment regimens combining two or more different mechanisms of action that are effective in ameliorating symptoms of a particular disease with fewer side effects are considered potential strategies for treating a variety of problematic complications. Traditional Chinese medicine is often used in combination with conventional therapies due to lower cost and fewer side effects. In view of the difference of cholesterol-lowering mechanisms between traditional Chinese medicine and western medicine, lipid-lowering combination therapy combining traditional Chinese medicine and western medicine has been widely reported. The lotus lipid-lowering oral liquid is an intracorporal preparation developed by the first people hospital in Shanghai in the 1980 s according to the national medicine master Zhang Jingren teachings of the deceased on the basis of the traditional theory of spleen deficiency, phlegm dampness generation, liver disease, liver transmission, spleen transmission and the like. The prescription takes stir-fried atractylodes macrocephala as a monarch, tonifies taiyin, promotes diuresis and excretes dampness, eliminates phlegm and regulates qi of pinellia tuber and dried orange peel, eliminates the stagnation of the Xuanming and rises Yang Mingmu to start new thought, the red sage root promotes blood circulation and regulates nutrient, the hawthorn eliminates phlegm and the stagnation, the pinellia tuber has the functions of clearing heat, nourishing yin, eliminating phlegm and reducing lipid, and the lotus leaf has the functions of ascending the clear, descending the turbid and eliminating phlegm without turbidity. The recipe (original name "Ning Zhifang") is used for treating diseases such as hyperlipidemia, obesity and the like, and has obvious curative effect. The study aims at discussing the pharmacological mechanism of the prescription for reducing blood fat and optimizing the prescription. On the premise of reducing the types of traditional Chinese medicines required by the prescription, the lipid-lowering effect of the prescription is not weakened or even possibly enhanced, and the adverse reaction is not increased or even possibly reduced. The effects of synergy, toxicity reduction and labor saving can be realized by optimizing the composition of the prescription. Disclosure of Invention In view of this, the invention provides a method for optimizing a traditional Chinese medicine compound based on network pharmacology and substance basis analysis. The invention aims to systematically analyze the pharmacodynamic substance foundation and key molecular targets thereof which exert the efficacy of reducing blood fat in the traditional Chinese medicine compound, and further clarify the integral action mechanism of the compound for synergistically regulating blood fat metabolism through multiple active ingredients, multiple action targets and multiple signal paths. On the basis, the prescription optimization strategy based on mechanism and network analysis maintains and even enhances the hypolipidemic drug effect while reducing the types of Chinese herbal medicines contained in the prescription, and ensures that the adverse reaction is not increased or even further reduced. The optimization path aims at realizing comprehensive improvement of the compound in the aspects of curative effect, safety and resource utilization efficiency, and achieves the modern preparation design targets of synergy, attenuation and mate