novel coronavirus pneumonia (coronavirus disease 2019, COVID-19), H1N1 influenza A, infectious atypical pneumonia (severe acute respiratory syndrome, SARS) have caused serious harm to human society. These diseases belong to the category of "epidemic diseases" in traditional Chinese medicine, and strengthening the prevention and treatment of this type of viral epidemic. In the treatment of viral epidemics, traditional Chinese medicine has significant efficacy in reducing disease symptoms and delaying the development of the disease. It also has the effects of improving the body's immunity and restoring the body's positive energy, and has extremely high promotion and application value. The "Diagnosis and Treatment Plan for the New Coronavirus Pneumonia (Trial Ninth Edition)" shows that the current epidemic mutant strain Omicron has stronger transmission, weakened its pathogenicity, and mild symptoms, mainly fever, dry cough, and fatigue [1]. As the product of traditional Chinese medicine culture and health, it has a significant advantage in preventing and treating modern viral epidemics, especially diseases characterized by mild symptoms and asymptomatic diseases. Therefore, it is of great practical significance to study the application of chemotherapy and food traditional Chinese medicines to prevent and treat modern epidemics.
1 Current status of Chinese medicine and medicine in the prevention and treatment of modern viral diseases
Chinese medicine and medicine have a long history of development in my country. Its initial germination can be traced back to Warring States period , and its theoretical basis first appeared in the "Huangdi Neijing". " Huangdi Neijing Taisu " records that Chinese medicine is of the same origin as medicine and food "eating on an empty stomach is food, and patients eat it as medicine." With the development of food, medical and other fields, the theory of homologous medicine and food has been continuously enriched and improved, and a large number of classic works of homologous medicine and food have emerged, such as "Qianjin Yao Prescriptions and Food Treatment" [2], "Diet Therapy of Materia Medica" [3], " Liquor and Food " [4], etc. At present, my country has announced that "according to tradition, both food and Chinese medicinal materials" has a total of 110 kinds of Chinese medicines, and medicine and food are both food and health. Their theory and practice have played an important role in maintaining human health, improving the body's immunity and disease resistance.
"Healthy China Action (2019-2030)" and "National Nutrition Plan 2017-2030" [5-6] and national policies vigorously encourage the promotion of the research and development of products of medicine and food. With the development and popularization of health cultures such as "preventing diseases" in traditional Chinese medicine, the concept of medicine and food and food has also been widely recognized. In-depth research and development of traditional Chinese medicines of the same origin as medicine and food is of great significance to promoting the culture of traditional Chinese medicine, implementing the concept of "adhering to the truth and innovation", promoting the diversification of the traditional Chinese medicine industry, promoting the development process of a healthy China, and adapting to the development trend of social aging.
Modern epidemic diseases COVID-19, H1N1 influenza, SARS, etc. belong to the category of "epidemic diseases" in traditional Chinese medicine. In the practice of preventing and treating COVID-19, Chinese medicine scholars have carried out more detailed academic research and thinking. For example, the team of Academician Wang Yongyan and believe that it belongs to the "cold and damp epidemic" [7], Academician Tong Xiaolin's team believes that it belongs to the "cold and damp epidemic" [8], and Academician Zhang Boli and believe that it belongs to the "wet and toxin epidemic" [9]. Chinese medicines with the same origin as medicine and food have unique advantages in preventing and treating modern viral diseases due to their wide application and high safety characteristics. For example, during the COVID-19 epidemic, Zhejiang University was based on the Qing Dynasty's prescription Yinqiao Powder (from "Warm Disease Breaking") recommended in the "Diagnosis and Treatment Plan for Pneumonia Infected by the New Coronavirus Infection (Trial Third Edition)" announced by the National Health Commission, and developed it into "Qingmao Soup", which uses fresh reed roots, dandelions, honeysuckle, Houttuynia cordata, Poria, coix seed , Chen The 12 Chinese herbal medicines and 12 kinds of medicines, platycodon, mint, , aquamarine, ginger, and jujube are cut into Chinese herbal medicines, which is more suitable for the public's prevention needs. The combination of all medicines can clear , heat toxin , remove dampness, and relieve lung qi, and relieve fever, cough, chest tightness, and hold back breath. It has the functions of clearing heat and detoxifying, clearing lungs and relieving phlegm and relieving cough, and strengthening the spleen and removing dampness and warding.
Changchun University of Traditional Chinese Medicine "Aquarius Platycodon Ginseng Peptide (Q/HCHR0087S-2020)" solid beverage developed by the "Aquarius Platycodon Ginseng Peptide (Q/HCHR0087S-2020)" developed by the solid beverage of "Aquarius Platycodon Ginseng Peptide (Q/HCHR0087S-2020)" for COVID-19 cold and dampness epidemics is successfully launched. The prescription has the functions of aromatic dampness and stagnation, clearing the lungs and relieving phlegm and relieving cough. Guangxi University of Traditional Chinese Medicine uses 11 Chinese herbal medicines, including Agastache, honeysuckle, coix seed, perilla, amomum villossia, platycodon, Five-fingered peach , White lentil flower , reed root, Luohan fruit, and licorice to make Qingyi fragrant flower bags for tea. It has the function of aromatic dampness and strengthening the spleen and relieving stagnation. It can provide people with qi deficiency, dampness and heavy constitution, asymptomatic infection but asymptomatic, and susceptible to weak body as preventive tea drinks, thereby effectively responding to the "time epidemic".
In addition, Chinese medicines such as licorice, platycodon, honeysuckle, and aquamarine have certain antiviral activities and have great application promotion value in the prevention and control of modern viral epidemics. In the COVID-19 diagnosis and treatment plan, traditional Chinese medicine treatment focuses on removing dampness and detoxifying and supporting positive energy. Given the high safety and long-term application of Chinese medicines, both medicine and food, have great development potential and application value in people's daily prevention of viral diseases, and are especially suitable for high-risk patients with direct or indirect contact with the source of infection. For example, during the COVID-19 epidemic, Huoxiang Zhengqi Capsules , Jinhua Qinggan Granules , etc. were recognized as recommended drugs for patients during the medical observation period. These drugs play an important role in preventing viral epidemics and controlling the development of the disease course. Among them, patchouli , perilla, angelica , tangerine peel, ginger, and honeysuckle, mint and other medicines in Jinhua Qinggan Granules have contributed great strength. These medicines and food homologous Chinese medicines can effectively prevent viral epidemics by enhancing the body's immune function and enhancing antiviral ability.
Medicinal and food homologous traditional Chinese medicine has great practical value in preventing and treating modern viral epidemics due to its safety, effectiveness, and health. Studying the prescription matching rules for preventing and treating viral epidemics by drug and food homologous traditional Chinese medicine is of great significance to the prevention and control of viral epidemics, new drug development, etc. Especially at present, COVID-19 patients are mostly characterized by mild symptoms and asymptomatic symptoms, so the development of traditional Chinese medicine preparations based on the same cognate of medicine and food reflects great practical significance.
This study takes the nationally published Chinese medicine and homologous Chinese medicine as the analysis object. Through literature mining, the prescriptions used to treat modern viral diseases are clustered, modeled and other treatments, and the combination of drugs for the prevention and treatment of modern viral diseases is determined. The network pharmacology is used to analyze the relevant mechanisms of antiviral active ingredients in these drugs, providing a certain reference for the subsequent drug prescriptions for the prevention and treatment of modern viral diseases, as well as the development of new Chinese medicine and health products for medicine and food.
2 Methods and results
2.1 Prescription collection for modern viral diseases and analysis of Chinese medicine and medicine homologous Chinese medicine
2.1.1 Traditional Chinese medicine prescription collection
set keywords as "Traditional medicine", "disease", "prescription", and "anti-viral", and in China National Knowledge Infrastructure (CNKI), Weipu Chinese Science and Technology Journal Database (VIP), Wanfang Database (Wangfang) (Wangfang Database (Wangfang) Data), Duxiu Database, Chinese Biomedical Literature Database and other databases and related ancient books on epidemic diseases are searched. The search time limit is March 2012 to March 2022. The prescriptions collected include classic prescriptions, expert experience prescriptions, and verification prescriptions with reasonable efficacy. The composition and dosage of relevant prescription drugs are complete. Repeated literature, reviews, and no pharmacodynamic verification are excluded. The collected modern antiviral Chinese medicine prescriptions and ancient prescriptions for prevention and treatment of epidemics were combined.Then the collected prescriptions are processed and analyzed. First, the name of the Chinese medicine is unified and standardized in reference to the 2020 edition of the Chinese Pharmacopoeia [10] and the 2020 edition of the Chinese Pharmacopoeia [11]. For example, the broad peel in the collected prescription is replaced with tangerine peel, Ophiopogon japonicus is replaced with Ophiopogon japonicus, reed roots are replaced with reed roots, honeysuckle is replaced with honeysuckle, etc., and then the subsequent association rules and cluster analysis are used to use Excel, SPSS, R language, etc.
2.1.2 Analysis of the rules of Chinese medicine for medicines for medicines
(1) High-frequency Chinese medicine and medicine pair analysis: According to relevant inclusion standards, a total of 264 prescriptions were collected, involving 255 Chinese medicines. Among these prescriptions, there are many Chinese medicines for replenishing deficiency, relieving exteriors, and clearing heat. Among them, Chinese medicines for high-frequency Chinese medicines are licorice, poria, platycodon, honeysuckle, aquamarine, almond, astragalus, dried ginger, ginseng, perilla, pueraria, ginger, etc., indicating that these Chinese medicines for medicines and food have great development potential in preventing and treating modern viral epidemics. High-frequency core drugs and their properties are shown in Table 1. The application of drug combinations is also the advantage of traditional Chinese medicine treatment. SPSS analysis of high-frequency medicine and food homologous traditional Chinese medicines was obtained to obtain high-frequency prevention and treatment of viral diseases. The pair of Chinese medicines with drug combinations of platycodon, poria, almond, aquamarine, honeysuckle, ginseng, astragalus-honivorous, aquamarine-honivorous, tangerine peel-perus, astragalus-aquamarine, astragalus-aquamarine, astragalus-aquamarine, astragalus-aquamarine, astragalus-aquamarine, astragalus-platycodon, etc. (Table 2).
(2) Analysis of the core compatibility association rules of : In order to further determine the core compatibility relationship of the homologous prescriptions of medicine and food, high-frequency drugs were associated with Apriori in the R language pack. According to the conditions of support of ≥10% and confidence of ≥80%, a complex correlation network diagram as shown in Figure 1 was obtained, among which 14 core drug combinations of medicine and food were 14 (Table 3). Among these combinations, " licorice- Platycodon" had the highest support, at 17.53%, and "licorice-tangerine peel and poria" had the highest confidence, at 98.714%.
(3) prescription system clustering analysis: In order to further analyze the clustering application of Chinese medicines with medicine and food homologous, the R language intergroup clustering algorithm was first used to cluster the collected prescriptions, among which the clustering of high-frequency Chinese medicines is shown in Figure 2; then, using Chinese medicine and food homologous Chinese medicines as the analysis subject, six combinations of drug clustering with good clustering were determined based on Rhs comprehensive clustering similarity >1.5, namely honeysuckle-astragalus-aquamarine-aquaticus, licorice-almond-poria-platycodon-tangerine peel, dried ginger-ginseng, perilla-puerarium-puerarium, reed root- mulberry leaf , ginger-jujube. These new drug combinations can provide new ideas for the compatibility application of Chinese medicines with medicine and food homologous Chinese medicines for prevention and treatment of viral epidemics and the treatment of traditional Chinese medicines with traditional Chinese medicines.
2.2 High-frequency medicine and food homologous Chinese medicine for prevention and treatment of modern viral epidemics
Through the above analysis, the medicine and food homologous Chinese medicine for prevention and treatment of viral epidemics was obtained. In order to further determine its antiviral active ingredients, this study used the method of literature mining to determine the characteristic antiviral active ingredients in these Chinese medicines that have been clearly recorded in the literature (Table 4), including glycyrrhizic acid , glycyrrhizin, licorice chaltone A in licorice peel, hesperidin in tangerine peel, poric acid in poric acid, platycodon saponin D in platycodon, chlorogenic acid in honeysuckle, patchouli alcohol in agastache, astragalus mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic mesogenic meso immunodeficiency virus 4, HIV), SARS coronavirus (severe acute respiratory syndrome coronavirus, SARS-CoV), herpes simplex virus-I, HSV-Ⅰ), human cytomegalovirus AD169, novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), enterovirus A71, rotavirus (rota virus, RV), flow A virus H1N1/H3N2/H2N2/H5N3, respiratory syncytial virus (respiratory syncytial) virus, RSV), coxsackie virus B3 (CVB3), adeno virus type 3 (ad-3), avian influenza virus H5N1, hepatitis B, herpes simplex virus-II, HSV-II, murine herpes virus 68, MHV-68.The above analysis shows that Chinese medicines with homologous medicines have a certain medicinal substance basis in preventing and treating modern viral diseases, which also proves the rationality of Chinese medicines with homologous medicines with homologous medicines in antiviral applications.
2.3 Analysis of modern viral pathogenesis mechanisms for the prevention and treatment of high-frequency medicine and food homologous traditional Chinese medicines
In order to clarify the mechanism of action of these high-frequency medicine and food homologous traditional Chinese medicines for the prevention and treatment of viral diseases, combined with the above excavation and analysis of characteristic active ingredients, it is planned to adopt the network pharmacology method to comprehensively analyze these active ingredients that have clearly defined antiviral effects, so as to achieve a specific investigation of the mechanisms for the prevention and treatment of viral pathogenesis of medicine and food homologous traditional Chinese medicines. The virus targets are derived from the modern pandemic viruses SARS-CoV-2, H1N1, and SARS-CoV.
2.3.1 Determination of the action of the active ingredient of on the virus target
First, the targets of glycyrrhizic acid, glycyrrhizone, glycyrrhizone A, hesperidin, poric acid, platycodon saponin D, chlorogenic acid, patchouli alcohol, astragalus membranacetin and ginseng saponin Rb1, Rb3, Rg1, Rg3, Rh1, Re were obtained from the TCMSP platform. After correcting and deduplication, 229 targets of these antiviral active ingredients were obtained. The targets of SARS-CoV-2, H1N1, and SARS-CoV were obtained from the Genecards and OMIM databases. After correcting and deduplication, 1,538 virus targets were obtained. After the active ingredients and the viral targets were collected, 44 effective targets of the active ingredients were obtained (Figure 3).
2.3.2 active ingredient antiviral target protein interactions (PPI) analysis
The effective targets obtained from the above analysis were introduced into the String platform for PPI analysis. The minimum interaction threshold was set to medium (0.4), and the species was limited to "homo sapiens". The topological parameter information obtained is shown in Table 5. The PPI-related information was imported into Cytoscape software for visual processing (Figure 4). The node degree value in the figure is an important evaluation index. The larger the shape and darker the color of the height targets such as signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), and JUN are, and the darker the color, which is more meaningful in the overall biological function evaluation.
2.3.3 Analysis of biological functions and pathways of active ingredients of Chinese medicine and food homologous Chinese medicine
To investigate the biological function regulation of active ingredients of Chinese medicine and food homologous Chinese medicine, the David database and the Metascape database were used for analysis of biological processes (BP), cell components (CC), and molecular function (MF). The analysis results were visualized using the R language pack (Figure 5). The BP enrichment analysis showed that the positive regulation of protein phosphorylation , the positive regulation of cell migration, the cell response to chemical stress, the positive regulation of external stimulation response, the response to heterologous stimulation, the transmembrane receptor protein tyrosine kinase signaling pathway , the circulatory system process, and the positive regulation of hydrolase activity are more serious in the prevention and treatment of epidemics of active ingredient. CC enrichment analysis shows that the target products may mainly be in membrane rafts, cystic cavity, extracellular matrix, cell apical ends, receptor complexes, and lateral side of plasma membrane ; MF enrichment analysis shows that the target may play a corresponding role by binding to kinase , growth factor receptors, and glycosaminoglycans to regulate endopeptidase, protein kinase , and protein homodimerization activities.The mechanism analysis results of
are shown in Figure 6. The mechanism of action of active ingredients of Chinese medicines and food homologous Chinese medicines involves Kaposi's sarcoma -related herpes virus infection, human cytomegalovirus infection, coronavirus disease-COVID-19, influenza A, human immunodeficiency virus type 1 infection, Epstein-Bar virus infection, virus carcinogenic, human T cell leukemia virus 1 infection and other diseases. The pathways of action mainly involve PI3K-Akt signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, JAK-STAT signaling pathway, tumor necrosis factor signaling pathway, and vascular endothelial growth factor (vascular endothelial growth factor) factor, VEGF) signaling pathways suggest that these mechanisms of action play an important role in preventing and treating epidemics of active ingredients of Chinese medicine and food homologous Chinese medicine. The functions and related action pathways of core action targets such as disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), EGFR, JAK, STAT3, MAPK, TLR4, etc. can effectively inhibit the "cytokine storm" effect in COVID-19, and intend to analyze the impact of drug-food-homologous Chinese medicine active ingredients on the COVID-19 pathway (Figure 7). From the analysis, it can be seen that the structural protein S in SARS-Cov-2 can cause subsequent inflammatory effects by directly regulating TLR4 and indirectly regulating MAPK. These target proteins produce inflammatory cytokines such as IL-6 through a series of interactions, which in turn induces the "cytokine storm" effect. Macrophages and neutrophils will also respond to this effect, causing symptoms such as " stroke ", acute lung injury, acute renal injury, macrophage activation syndrome, and severe acute respiratory distress syndrome. Therefore, the active ingredients of Chinese medicine homologous to medicine and food can effectively regulate the core factors in the "cytokine storm" and thus inhibit their development process.
3 Discussion
3.1 Licorice : Medicinal and food homologous traditional Chinese medicine to prevent and treat viral epidemics
Licorice is a typical Chinese medicine with high safety and high safety. It is at the core position in the prescription combination of Chinese medicine and food homologous traditional Chinese medicine. It tastes sweet and flat, and can show the effect of detoxifying and alleviating the medicinal properties of other compatibilizing drugs while nourishing the body. Licorice can rely on its own strong theoretical basis of nature and taste and its characteristics of "supplementing", "relieving" and "harmony" and "harmony" to be widely used in the compatibility [42], and its own characteristic active ingredients, glycyrrhizic acid, glycyrrhizin, and licorice chalone, have also been proven to be able to fight against a variety of viruses. Therefore, the prescription of medicine and food homologous compatibility with licorice as the core has a certain foundation in traditional Chinese medicine and pharmacodynamics for the prevention and treatment of epidemics.
The multiple medicines and prescriptions derived from licorice as the core can effectively deal with various syndromes in epidemic diseases. For example, the "licorice-platycodon" medicine pairs are combined. Licorice is powerful in clearing heat, while Platycodon is biased towards catharsis. After the two are combined, they all play the role of detoxification and salivating throat, promoting lungs and eliminating phlegm. There is a folk proverb that "licorice platycodon is specialized in treating the throat". Zhang Zhongjing once said, "If the throat is sore, it can be combined with licorice soup. If it is not cured, it is combined with Platycodon Decoction." Later generations combined the two methods into one, and changed the name to "Ganju Decoction", which is used to treat throat, mouth and tongue diseases.
In other traditional Chinese medicine monographs, Ganji Decoction is used to treat sore throat and unfavorable throat. Therefore, licorice with platycodon can effectively prevent and improve the symptoms of itchy throat and sore throat in epidemics; in the combination of "licorice-almond", almonds are good at reducing lung qi, and licorice can regulate its effect of reducing lung qi, which is effective in targeting symptoms such as cough and poor lung qi caused by epidemics; in the combination of "licorice-honeysuckle", honeysuckle can not only disperse wind and heat, but also clear and relieve blood toxins, and can be used for heat toxins, sores, carbuncles, sore throat, etc. For those with strong heat toxins, it is difficult to achieve the ideal effect due to insufficient medicinal power alone. , and adding licorice can significantly enhance its effect of clearing heat and detoxifying. In addition, based on the effect of licorice and sweet to relieve the stomach, it can reduce the bitter cold of honeysuckle and attack the spleen and stomach qi, so as not to harm the stomach, and can effectively target fever, sore throat and other symptoms caused by epidemics; for example, Sijunzi Decoction, combination of "Licorice-Poria-Ginseng", among which Poria has the function of replenishing the spleen and replenishing qi, ginseng has the function of replenishing vital energy, replenishing the pulse and solidifying the loss. Licorice can enhance the tonic effect of both. This prescription can regulate the stomach and intestines, improve the body's immunity, and effectively improve the symptoms of sallow complexion, , less eating, loose stools, pale tongue and white coating.
3.2 Combination of Chinese medicine and food homologous for different syndrome viral diseases
cluster analysis results have obtained 6 types of medicine and food homologous prescriptions, which also provides a reference for Chinese medicine syndrome differentiation treatment.
Category 1 prescription "Horubicum - Honeysuckle - Astragalus". Huoxiang is spicy and warm in nature. It is an important medicine for aromatic and turbidity. It can both eliminate dampness and relieve exterior symptoms. It is good at relieving exterior symptoms and stomach. The "Bencao Tujing" records it as an important medicine for treating vomiting and reversal of the spleen and stomach. Honeysuckle is powerful in detoxification. "Bencao Zheng" says that it is "good at transforming poison, so it is the key medicine for treating carbuncles, swelling, tinea, and rheumatism poisons"; "Bencao Huiyan" records: " Astragalus is a medicine that nourishes the lungs and strengthens the spleen, strengthens the body and astrings sweat, and drives away wind and poisons." Astragalus has the reputation of "the most important medicine for replenishing qi", and there is also a saying among the people that "drinking Astragalus soup often prevents diseases and maintains health". Astragalus decoction or using Astragalus soaks in water instead of tea has a good anti-disease and health effect; combined with 3 medicines, it can achieve the integrated effect of removing dampness, , harmonizing the middle, detoxifying, and replenishing qi, and can effectively prevent and treat cold, vomiting, diarrhea and other symptoms in modern viral diseases.
Category 2 prescription "Licorice-Poria cocos-Platinum-Almond-Tanut peel", which is a combination of flavors of Poria cocos almond licorice soup. Among them, Platycodon's nature powder is ascending, which eliminates phlegm and relieves cough and relieves throat, and has a strong effect of discharge pus. It can also be used as a boat agent and carries medicine to move upward. Almonds are good at reducing lung qi, relieving cough and asthma, and moistening the intestines and promoting bowel movements. Platycodon and almonds can act on the upper burner to achieve the effect of pursuing the water in the chest and lowering the reverse qi of the lungs, and also have the effect of opening the chest and dispersing the nodules. Poria cocos are mainly used to promote diuresis and reduce swelling, calm the heart and strengthen the spleen. They can act on , middle burner , achieving the effect of tracing the water in the middle burner and leveling the qi of the upper burner; tangerine peel can also resolve the dampness in the spleen and stomach of the middle burner. Licorice can relieve the middle and strengthen the spleen, and remove water and relieve lung qi. All medicines are used in combination, which can effectively prevent and treat sore throat, cough, poor breathing, vomiting and other symptoms in modern viral diseases.
The third prescription "Dried Ginger-Ginseng" is a combination of Zhang Zhongjing's famous prescription "Dried Ginger and Rengan Banxia Decoction". Both dried ginger and ginseng can enter the spleen and stomach of the middle burner. Dried ginger and ginseng can enter the spleen and stomach in the middle burner. Dried ginger is spicy and sweet, and is good at warming the spleen and stomach and removing cold. Ginseng is sweet and slightly warm, and is good at nourishing qi and strengthening the spleen and strengthening the body. For the symptoms of chronic cold in the stomach, using ginseng alone will not have enough warming power and can easily cause replenishment without relieving it; using dried ginger alone will have strong ability to remove cold, but it is easy to dissipate due to its weak replenishment power. The two medicines are used to nourish each other, and the effect of dry ginger is used to warm the middle burner and ginseng to nourish the spleen and stomach, and to nourish the yang, so that ginseng can be used to nourish the stomach and can flow, and the atmosphere can flow; dry ginger can be used to treat ginseng but not to be used to, and the effect of smooth middle qi can effectively prevent and treat stomach cold and physical deficiency in modern viral epidemics.
The fourth prescription "Perilla-Kudzu" is a combination of the prescriptions for treating cold epidemics in "Si Shengshu". Perilla is a combination of the prescriptions for the treatment of cold epidemics in "Si Sheng Xuanshu". Perilla is spicy and warm in nature, has strong dispersal and expels, and has the effect of detoxifying and relieving pain; Puerilla is cool in nature, sweet and spicy in taste, and is good at relieving exterior and reducing fever, raising yang and stopping diarrhea, and going out. The two medicines are incompatible with each other. The dosage of Chinese medicine can be increased according to the syndrome type. The combination of the two medicines plays the role of detoxifying, relieving fever and removing cold, which can effectively prevent and treat cold, fever, and headaches in modern viral epidemics.
Category 5 prescription " Reed Root- Mulberry Leaf". Reed Root and Mulberry Leaf are both sweet and cold products. Reed Root is good at clearing heat and promoting salivation, stopping vomiting and eliminating restlessness. Mulberry Leaf is good at dispersing wind and heat, clearing lungs and moistening dryness. The combination of the two is more in treating wind and heat cough, and can be used to prevent and treat hot cough, dry mouth, vomiting and other symptoms in modern viral diseases.
Category 6 prescription "Ginger-Japans", ginger is spicy and warm in nature, and is good at sweating and relieving exteriors, warming the stomach and dispelling cold. It is fragrant and unobstructed, and it gets jujube without being too dispersed and consuming qi; jujube is sweet and warm in nature, and is good at replenishing the middle and replenishing qi and calming the heart and spleen. It is sticky and greasy and sweet insisting the stomach and dispersing the stomach. It gets ginger is spicy and dispersed without being too dispersed and hindering the spleen. The combination of the two medicines is used to combine hardness and softness, making the effect of spicy and sweetness to transform yang even more effective, and can effectively target the symptoms of cold body and vomiting in modern viral diseases.
3.3 Mechanism of action of Chinese medicine for treating viral diseases
By analyzing the antiviral active ingredients of Chinese medicine for drug and food homologous Chinese medicine for high-frequency prevention and treatment of viral diseases, it was found that there are 44 effective targets for their role in modern representative epidemic viruses, including EGFR, cysteine protease-3 (Caspase-3, CASP3), vascular endothelial growth factor A (VEGFA), STAT3, matrix metalloproteinase 9 (MMP9), heat shock protein 90 alpha family class A member 1, HSP90AA1), mammalian target of rapamycin (MTOR), cyclooxygenase 2 (PTGS2), MMP2, TLR4, MAPK14 and other core targets. The mechanism of action is closely related to Kaposi's sarcoma-related herpes virus infection, human cytomegalovirus infection, coronavirus disease-COVID-19, influenza A, human immunodeficiency virus type 1 infection, Epstein-Bar virus infection, viral carcinogenic, human T cell leukemia virus 1 infection, and other diseases. The main regulatory mechanisms are related to PI3K-Akt signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, JAK-STAT signaling pathway, tumor necrosis factor signaling pathway, VEGF signaling pathway, etc.
These active ingredients of medicinal and food homologous Chinese medicines show strong inhibitory effects on the modern epidemic viruses SARS-Cov, SARS-CoV-2, and H1N1. The mechanism of action is mainly to inhibit viral replication. The specific mechanisms vary. For example, glycyrrhizic acid can indirectly inhibit the activity of SARS-Cov virus by inducing NO synthesis; chlorogenic acid can affect H1N1 virus mRNA transcription and protein translation by inhibiting neuraminidase activity; patchouli alcohol can exert anti-H1N1 virus by inhibiting viral replication, regulating the level of inflammatory cytokines in serum, enhancing the host of host intensification of the RLH signaling pathway, and regulating the RLH signaling pathway; Platycodon saponin D can prevent the host of SARS-CoV-2 from entering and preventing membrane fusion by redistributing membrane cholesterol. When the virus continues to invade the body, the immune system is continuously activated, and the immune response produces an overreaction state, leading to a homeostasis imbalance and a large number of inflammatory factors are released, thereby inducing the cascade amplification effect of cytokine , and creating a "cytokine storm".
In the new crown epidemic, the "cytokine storm" effect is considered a major trigger for the worsening of COVID-19 patients. Since this effect is dominated by inflammatory factors, controlling the development of inflammation is very important in preventing and treating epidemics. The results of network pharmacological analysis show that EGFR is an effective antiviral target of licorice chaltone A. Studies have confirmed that hesperidin can reduce the expression of EGFR mRNA level [43], and the strong expression of EGFR is closely related to inflammatory factors such as TNF-α, IL-1, and IL-6. The EGFR pathway can induce inflammatory responses in epithelial cells [44-45].
JAK2 is an effective antiviral target of licorice chalkone A, STAT6 is an effective antiviral target of licorice chalkone A, and STAT3 is an effective antiviral target of ginsenoside Rb1, Rg1, Rg3, and Rh1. Studies have shown that ginsenoside Re can effectively activate the JAK2/STAT3 pathway [46], and the JAK/STAT signaling pathway is an important pathway for multiple cytokines to play a role, which is closely related to the occurrence of "cytokine storm", which plays an important role in immunomodulation and various inflammation processes [47].
VEGFA is an effective antiviral target of ginseng saponins Rb1, Rg1, Rg3, Rh1 and Astragalus membranaceus. Astragalus membranaceus can promote the secretion of VEGFA by human endothelial progenitor cells [48]. VEGFA can activate the PI3K pathway through the phosphorylation process. It is also closely related to the expression of inflammation. It can significantly increase the permeability of blood vessels and play an important regulatory role in the formation and development of inflammation [49-51].
MMP2 is an effective target for glycyrrhizic acid and chlorogenic acid antivirals, and MMP9 is an effective target for glycyrrhizalone A antiviral. MMPs can regulate the activity of inflammatory factors and related proteases, and play an important regulatory role in bronchial inflammation [52-53]. Studies have confirmed that glycyrrhizic acid can control inflammation development by regulating MMPs [54].
PTGS2 is an effective antiviral target of licorice chaltone A and poric acid. PTGS2 is an important inflammatory mediator and can also cause related inflammatory reactions [55-56]. TLR4 is an effective antiviral target of Platycodon saponin D. TLR4 can also activate nuclear factor-κB (NF-κB) and mitogen-activated protein kinase signaling pathways, promoting the activation of gene expression of various inflammatory cytokines. Studies have confirmed that chlorogenic acid can activate autophagy by inhibiting the TLR4/MAPK/NF-κB pathway, thereby inhibiting inflammation and oxidative stress [57].
MAPK14 is an effective antiviral target of licorice chaltone A and ginsenoside Rh1. MAPK can participate in the regulation of cell proliferation and differentiation and other processes through phosphorylation of nuclear transcription factors and related enzymes, and is closely related to inflammation [58-59]. Studies have also shown that licorice chaltone A can promote the expression of phosphorylation of MAPK pathway-related proteins and inhibit the expression of inflammatory factors, thereby exerting the role of inhibiting the proliferation of fibroblast-like synovial cells in rheumatoid arthritis and inducing their apoptosis [60]. Poric acid can inhibit the inflammatory response and apoptosis of the rat pneumonia model by regulating the MAPK pathway and regulate the MAPK pathway [61], and patchouli alcohol can also exert inhibitory effects on influenza viruses by targeting the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway [62].
4 Conclusion
Traditional medicine has demonstrated great advantages and value in assisting in cutting off the transmission pathway and alleviating the pressure of epidemic prevention and control. It can effectively deal with viral epidemics by improving patient symptoms, delaying disease progression, and improving body immunity [63]. As a characteristic component of traditional Chinese medicine, Chinese medicine is highly safe and widely used, and has more advantages in dealing with mild and asymptomatic viral diseases. The above analysis also shows that these Chinese medicine active ingredients can directly inhibit viruses, regulate immunity, and anti-inflammatory. Among them, the regulation of the "cascade effect" of inflammation plays a core role in the development of the epidemic.
This study takes medicine and food homologous traditional Chinese medicine as the main body, systematically analyzes its application rules for preventing and treating modern viral diseases, and determines high-frequency and high-confidence pharmaceutical and food homologous combination prescriptions. At the same time, based on the antiviral active ingredients of these high-frequency medicine and food homologous traditional Chinese medicine, the mechanism of its effect on modern viral diseases is analyzed, in order to provide a certain reference for the research on the prevention and treatment of viral diseases by the prescription of medicine and food homologous traditional Chinese medicine and the development of new drugs and health products, and at the same time provide reference for the prevention and treatment of viral diseases under the concept of big health of traditional Chinese medicine.
Conflict of interest All authors declare that there is no conflict of interest
References (omitted)
Source: Li Zeyu, Hao Erwei, Cao Rui, Lin Si, Wan Wanruo, Li Siwei, Chen Jingmei, Wang Xingyuan, Hou Xiaotao, Deng Jiagang. Analysis of the application rules and mechanisms of traditional Chinese medicine for the prevention and treatment of modern viral diseases by the same origin of medicine and food [J]. Chinese Herbal Medicine, 2022, 53(15): 4781-4794.
