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In this paper， the name， origin， quality evaluation， producing area and processing methods of Platycodonis Radix used in the famous classical formulas are researched by consulting related materia medicas， prescription books and medical books of the past dynasties. It was found that Platycodonis Radix was the correct name in the materia medicas of the past dynasties， which was named for its "roots are strong but the stems are straight". Its dominant base of the past dynasties was Platycodon grandiflorus， and since the Ming and Qing dynasties， Hexian county of Anhui has been respected as the representative authentic producing area. In modern times， it has been concluded that the quality of Platycodonis Radix is best if the body is dry， thick and uniform， solid， white in color， and bitter in taste. In ancient times， the processing methods of Platycodonis Radix were mainly removing the reed head and floating skin， rice simmering and drying， and slicing and micro-frying. In modern times， its processing methods have been mainly simplified to peeling and cutting into thick slices. Therefore， it is recommended to use the dry roots of P. grandiflorus and its raw products in the famous classical formulas.
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To investigate the potential molecular mechanism of the combination of Platycodonis Radix and Lilii Bulbus with the homology of medicine and food in the treatment of pneumonia by means of network pharmacology and in vitro verification experiment. Under the condition of bioavailability(OB)≥30% and drug-like(DL)≥0.18, the active components of Platycodonis Radix and Lilii Bulbus were screened in TCMSP database; the prediction targets of active components were searched from TCMSP, DrugBank and other databases, and the potential targets of pneumonia were obtained through GeneCards and OMIM database. The common targets were obtained by the intersection of drug and disease targets. The PPI network of common targets was constructed by STRING 11.0, and the core targets were obtained by topological analysis. Then the core targets received GO and KEGG analysis with use of WebGestalt and Metascape. The "component-target-pathway" network was constructed with the help of Cytoscape 3.7.1 software, and the component-target molecular docking verification was carried out with Discovery Studio 2016 software. Finally, the core targets and pathways were preliminarily verified in vitro. In this study, 12 active components were screened, 225 drug prediction targets and 420 potential diseases targets were obtained based on data mining method, and 14 core targets were obtained by topological analysis, including TNF, MMP9, AKT1, IL4 and IL2. The enrichment results of GO and KEGG showed that "Platycodonis Radix and Lilii Bulbus" drug pair may regulate inflammation, cell growth and metabolism by acting on 20 key signaling pathways such as TNF and IL-17, thereby exerting anti-pneumonia effects. The results of molecular docking showed that 12 active components had good binding ability with 14 core targets. In vitro experiment results showed that the core components of "Platycodonis Radix and Lilii Bulbus" drug pair could inhibit the expression of MMP9 and TNF-α by regulating TNF signal pathway. This study confirmed the scientificity and reliability of the prediction results of network pharmacology, and preliminarily revealed the potential molecular mechanism of the compatibility of Platycodonis Radix and Lilii Bulbus in the treatment of pneumonia. It provides a novel insight on systematically exploring the mechanism of the compatible use of Platycodonis Radix and Lilii Bulbus, and has a certain reference value for the research, development and application of new drugs.
Subject(s)
Humans , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Molecular Docking Simulation , Pneumonia/drug therapy , Reproducibility of ResultsABSTRACT
Objective:To screen out the active components of Platycodonis Radix-Armeniacae Semen Amarum, predict the targets and signaling pathways, construct the "multi-components, multi-targets and multi-pathways" interaction network and further investigate their molecular mechanism for the treatment of lung carcinoma based on network pharmacology. Method:Active components and corresponding targets of Platycodonis Radix-Armeniacae Semen Amarum were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature consultation. Therapeutic targeted genes of Platycodonis Radix-Armeniacae Semen Amarum in the treatment of lung carcinoma were obtained from UniProt database and Genecards database. The "components-targets" network was constructed by using Cytoscape 3.6.0 software, and the protein-protein interactions network was constructed by String database and "Generate Style From Statistics" tool in Cytoscape software. Its molecular docking with active components of Platycodonis Radix-Armeniacae Semen Amarum was carried out by using Systems Dock Web Site network server. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis on the therapeutic targets of Platycodonis Radix-Armeniacae Semen Amarum were performed with the Database for Annotation, Visualization Andintegrated Discovery (DAVID). Result:Fourteen active components of Platycodonis Radix-Armeniacae Semen Amarum were screened out, including acacetin, cis-dihydroquercetin, spinasterol, licochalcone B, and luteolin, et al. One hundred and three therapeutic targets were screened out, including nitric oxide synthase 2 (NOS2), prostaglandin endoperoxide synthase 1 (PTGS1), androgen receptor (AR), prostaglandin endoperoxide synthase 2 (PTGS2), and dipeptidyl peptidase 4 (DPP4), et al. Identified signaling pathways mainly involved prostate cancer signaling pathway, small cell lung cancer signaling pathway, hepatitis B signaling pathway and T cell receptor signaling pathway. Conclusion:The possible molecular mechanism of Platycodonis Radix-Armeniacae Semen Amarum for the treatment of lung carcinoma was explored in this study based on network pharmacology, providing the direction for subsequent research.
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Platycodonis Radix, which was first recorded in the Agriculture God's Canon of Materia Medica. It is a multi-functional drug with a wide range of applications. The processing of Platycodonis Radix has been recorded as early as in the Jin dynasty, and has a long history of processing. Today, in addition to the washing, cutting and stir-frying with honey, there have also been more than 20 kinds of processing methods, such as stir-frying with wine, stir-frying with bran, stir-frying with Lilii Bulbus juice and so on. The ancients believed that Platycodonis Radix could enhance the effect of diffusing the lung, promoting pharynx and relieving cough by processing. In terms of the chemical compositions in Platycodonis Radix, more than 100 compositions, like triterpenoid saponins, flavonoids, phenols, sterols, polysaccharides and polyacetylenes, have been isolated and identified from it. Among them, triterpenoid saponins are the essential compositions. In addition, Platycodonis Radix has the pharmacological effects of expectorant, antitussive, anti-inflammatory, anti-tumor, etc. The medicinal ingredients of Platycodonis Radix are mainly triterpenoid saponins and polysaccharides. Among them, triterpenoid saponins have diverse biological activities, which lead it to be one of the hotspots of current researches. Platycodonis Radix has a good role in promoting lung and removing phlegm. After being processed, its medicinal effects are enhanced. It is complex and diverse in compositions of Platycodonis Radix so that has rich pharmacological activities. On the basis of sorting out the literature, this paper discusses the processing history, chemical composition and pharmacological effect of Platycodonis Radix, in order to provide reference for the special processing and modern research of Platycodonis Radix. Furtherly, it provides a theoretical basis for the research of its processing mechanism and quality control.
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To reveal the medication patterns of Chinese patent medicine in the treatment of cough based on the analysis of the patent status of Chinese materia medica (CMM) in the field of cough control in nearly 20 years. Patents of Chinese patent medicine in the treatment of cough were systematically searched in SIPO Platform and CNKI, association analysis and network analysis of high-frequency medicines were used to reveal the medication patterns of Chinese patent medicine in the treatment of cough with software Clementine 12.0. The results showed that Chinese medicine with highest frequency in 316 formulas was Glycyrrhizae Radix et Rhizoma, the other Chinese herbs with higher frequency were Platycodonis Radix, Ephedrae Herba, Citri Reticulatae Pericarpium, Pinelliae Rhizoma, etc. The main categories were the medicines used to treat cough and asthma, as well as to reduce phlegm. The commonly used herbal pairs were Glycyrrhizae Radix et Rhizoma-Platycodonis Radix, Glycyrrhizae Radix et Rhizoma-Citri Reticulatae Pericarpium, Pinelliae Rhizoma-Glycyrrhizae Radix et Rhizoma, Ephedrae Herba-Glycyrrhizae Radix et Rhizoma, etc. It was concluded that the medication patterns of Chinese patent medicine in the treatment of cough can be revealed based on the analysis of the herbal frequency, herbal pairs, association rules, and the network of high-frequency medicines and the theory of traditional Chinese medicine, so as to provide reference evidences for clinical medication.
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Objective To compare the pharmacokinetic effect of Platycodonis Radix in Painong Powder on naringin and paeoniflorin in rats, and study the compatibility effects of Platycodonis Radix. Methods A total of 12 healthy male SD rats were randomly divided into the Painong Powders full formula group and Painong Powder without Platycodonis Radix group; The solution of Painong Powders full formula and Painong Powder without Platycodi Radix was ig administrated to rats at dose of 16 g/kg. The blood was collected from theretinal vein plexus of rats at predetermined time and pre-prepared with liquiritin as internal standard (IS). UPLC-MS/MS was adopted to determine the contents of naringin and paeoniflorin. The chromatography was eluted with mobile phase consisted of 0.1% formic acid and methyl alcohol at a flow rate of 0.2 μL/min. ESI sources were adopted to scan in a negative ion scanning mode. Results After ig administration Painong Powder and Painong Powder without Platycodonis Radix, the main pharmacokinetic parameters of naringin were as follow: AUC0-t = (2 643.22 ± 277.75), (1 934.01 ± 371.98) μg∙h/L; Cmax = (597.57 ± 22.46), (477.13 ± 25.67) μg/L; CL = (821.96 ± 175.64), (542.21 ± 100.97) L/(h∙kg); Paeoniflorin showed AUC 0-t = (3 178.25 ± 235.97), (1 384.11 ± 320.11) μg∙h/L; Cmax = (816 ± 28.88), (402.67 ± 58.22) μg/L; CL = (1 102.27 ± 341.17), (482.59 ± 39.74) L/(h∙kg) (P<0.05). Conclusion Compared Painong Powders without Platycodonis Radix, the naringin and paeoniflorin in rat plasma showed similar pharmacokinetic changes after oral :201 administration Painong Powders full formula, such as the peak time was shortened, the rate of absorption, peak concentration, and the clearance were accelerated. This study proved scientific compatibility of Platycodonis Radix in Painong Powder and provided a reference for further study of the prescription compatibility regularity in Painong Powders.
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Objective To establish the quality standard for Baibu Zhike syrup .Methods TLC method was used for qualitative identification of Stemonae Radix and Platycodonis Radix .The content of hesperidin in Citri Exocarpium Rubrum was determined by HPLC method on C18 column with mobile phase of acetonitrile-water (18:82) .The detection wavelength was 284 nm .Results The clear spots on TLC indicated a good separation with no interference to negative control .The linear range of hesperidin was 0 .0669-1 .6725μg (r=0 .9999) .The average recovery was 96 .6％ .Conclusion This method is sim-ple ,rapid and reproducible .It can be used for the quality control of Baibu Zhike syrup .
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Objective To observe the lung injury of rats caused by PM2.5 and the intervention effect of Platycodonis Radix total saponins (PGS); To discuss the repair mechanism of PGS for lung injury caused by PM2.5. Methods The model of lung injury caused by PM2.5 was induced by tracheal instillation. The rats were randomly divided into blank group, model group and PGS high-, medium- and low-dose groups, with 10 rats in each group. After medication for 14 d, BALF and left lung and right lung tissue of rats were collected. HE staining was used to observe the pathological changes of lung tissue. The contents of TNF-α, IL-6, IL-10 and IL-13 in BALF were detected by ELISA. RT-PCR was used to detect the expression of TGF-β mRNA in lung tissues. The expression of TGF-β protein in lung tissue was detected by Western blot. Results Compared with model group, TNF-α and IL-6 decreased significantly while IL-10 and IL-13 increased significantly in BALF in high- and medium-dose group of PGS. Degree of pulmonary interstitial edema and fibroplasia alleviated in PGS groups. Expressions of TGF-βmRNA and protein in lung tissue was reduced in PGS groups. Conclusion PGS can alleviate inflammatory injury caused by PM2.5 via regulating the balance of cytokine and down-regulating the expression of TGF-β and inhibiting the development of fibrosis, which results in the protection and repair on the lung injury of rats caused by PM2.5.
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Objective: To establish the quality standard for Zhike Qutan oral liquid.Methods: A TLC method was used for the qualitative identification of Platycodonis Radix and Glycyrrhizae Radix et Rhizoma;the content of belamcandin in Belamcandae Rhizoma was determined by an HPLC method on a Waters Symmetry C 18 column(150 mm× 4.6 mm , 3.5 μm)with the mobile phase consisting of acetonitrile-water (14∶86), the flow rate was 1.0 ml·min-1 , the column temperature was 35℃ and the detection wavelength was 265 nm.Results: The TLC spots were clear without interference from the negative control.The linear range of belamcandin was 0.115-2.880 μg (r=0.999 9),and the average recovery was 92.44% (RSD=1.83% , n =6).Conclusion: The method is simple and rapid with good reproducibility, which can be used for the quality control of Zhike Qutan oral liquid.