Chemical composition and therapeutic mechanism of Xuanbai Chengqi Decoction in the treatment of COVID-19 by network pharmacology, molecular docking and molecular dynamic analysis.

Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.

Application of HPLC Fingerprint Combined with Chemical Pattern Recognition and Multi-Component Determination in Quality Evaluation of Echinacea purpurea (L.) Moench.

Echinacea purpurea (EP) is a common medicinal material for extracting anti-RSV components. However, up to now, there has been no effective and simple method to comprehensively reflect the quality of EP. In our current study, the quality of Echinacea purpurea (L.) Moench samples from six different cultivation locations in China was evaluated by establishing a high-performance liquid chromatography (HPLC) fingerprint, combining chemical pattern recognition and multi-component determination. In this study, the chemical fingerprints of 15 common peaks were obtained using the similarity evaluation system of the chromatographic fingerprints of traditional Chinese medicine (2012A Edition). Among the 15 components, three phenolic acids (caftaric acid, chlorogenic acid and cichoric acid) were identified and determined. The similarity of fingerprints of 16 batches of Echinacea purpurea (L.) Moench samples ranged from 0.905 to 0.998. The similarity between fingerprints of five batches of commercially available Echinacea pupurea (L.) Moench and the standard fingerprint "R" ranged from 0.980 to 0.997, which proved the successful establishment of the fingerprint. PCA and HCA were performed with the relative peak areas of 15 common peaks (peak 3 as the reference peak) as variables. Anhui and Shaanxi can be successfully distinguished from the other four cultivation areas. In addition, the index components of caftaric acid, chlorogenic acid and cichoric acid were in the range of 1.77-8.60 mg/g, 0.02-0.20 mg/g and 2.27-15.87 mg/g. The results of multi-component index content determination show that the contents of the Shandong cultivation area were higher, followed by Gansu, Henan and Hebei, and the lowest were Anhui and Shaanxi. The results are consistent with PCA and HCA, which proved that the quality of Echinacea purpurea (L.) Moench from different origins was different. HPLC fingerprint combined with chemical pattern recognition and multi-component content determination was a reliable, comprehensive and prospective method for evaluating the quality of Echinacea purpurea (L.) Moench. This method provides a scientific basis for the quality control and evaluation of Echinacea purpurea (L.) Moench.

Visualizing the spatial distribution of functional metabolites in Forsythia suspensa at different harvest stages by MALDI mass spectrometry imaging.

As a traditional Chinese medicine, Forsythia suspensa (F. suspensa) has attracted much attention due to its significant pharmacological activity. Revealing the spatial distribution of metabolites during F. suspensa development is important for understanding its biosynthesis rules and improving the quality of medicinal materials. However, there is currently a lack of information on the spatial distribution of F. suspensa metabolites. In this work, the spatial distribution and growth metabolism patterns of important metabolites of F. suspensa were studied for the first time using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Using 2,5-dimethylnaphthalene (DAN) as the matrix and detecting in negative ion mode, the spatial distribution and growth patterns of 11 metabolites obtained from longitudinal sections of F. suspensa included pinoresinol, phillygenin, forsythoside A, forsythoside E, rutin, caffeic acid, malic acid, citric acid, stearic acid, oleic acid, and linoleic acid. These results showed the mesocarp and endosperm tissues of F. suspensa were important for storing important functional metabolites. Changes in mesocarp and endosperm growth and development tissues caused large changes in the content of important functional metabolites in F. suspensa. These results provide a basis for understanding the spatial distribution of metabolites in F. suspensa tissues and the significant changes that occur during growth and development, exploring the mechanism of important synthesis of metabolites, regulating the harvest of F. suspensa, and improving the quality of medicinal herbs.

Chicoric Acid: Natural Occurrence, Chemical Synthesis, Biosynthesis, and Their Bioactive Effects.

Chicoric acid has been widely used in food, medicine, animal husbandry, and other commercial products because of its significant pharmacological activities. However, the shortage of chicoric acid limits its further development and utilization. Currently, Echinacea purpurea (L.) Moench serves as the primary natural resource of chicoric acid, while other sources of it are poorly known. Extracting chicoric acid from plants is the most common approach. Meanwhile, chicoric acid levels vary in different plants as well as in the same plant from different areas and different medicinal parts, and different extraction methods. We comprehensively reviewed the information regarding the sources of chicoric acid from plant extracts, its chemical synthesis, biosynthesis, and bioactive effects.

Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis.

Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein-protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson-Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

Exploring the potential therapeutic effect of Eucommia ulmoides-Dipsaci Radix herbal pair on osteoporosis based on network pharmacology and molecular docking technology.

Eucommia ulmoides-Dipsaci Radix (EU-DR) is a commonly used herbal pair for the treatment of osteoporosis (OP) in China. The purpose of this study was to investigate the potential mechanism of EU-DR on OP through network pharmacology and molecular docking approaches. Combining data from multiple open-source databases and literature mining, the active compounds and potential targets of EU-DR were screened out. The OP related targets were identified from the interactive web tool GEO2R. The shared targets were obtained by intersecting the targets of EU-DR and OP. The protein-protein interaction (PPI) network was constructed via the STRING database and Cytoscape 3.7.2 software. GO and KEGG enrichment analysis were conducted using R 3.6.3 software with adjusted p-value < 0.05. Sybyl-x 2.1.1 and Autodock Vina 1.1.2 software were used to cross validate the affinity between active compounds and target proteins. Our results showed that a total of 50 active compounds were screened, corresponding to 895 EU-DR targets, 2202 OP targets and 144 shared targets. The flavonoids in EU-DR played an important role in anti-OP. The enrichment analysis of GO and KEGG suggested EU-DR exerted a therapeutic effect on OP mainly by regulating the osteoclast differentiation related signaling pathway. Meanwhile, molecular docking results showed that most active compounds in EU-DR had strong binding efficiency to the target proteins. In conclusion, this study elaborated the multi-component, multi-target, and multi-pathway interaction mechanism of the EU-DR herbal pair in the treatment of OP for the first time, which also provided a pharmacological basis for treating OP.

Preparation of a new component group of Ginkgo biloba leaves and investigation of the antihypertensive effects in spontaneously hypertensive rats.

Ginkgo (Ginkgo biloba L.) is a traditional economic tree species in China. Ginkgo biloba extract (GBE) is widely used in combination to treat hypertension and complications in clinical practice. However, the antihypertensive effect of GBE alone is weak and it is also difficult to study the mechanism because of its complex composition. This study was to prepare a new component group of Ginkgo biloba leaves (GBLCG) with clear chemical structures, and to investigate its effect on reducing blood pressure and improving myocardial hypertrophy in spontaneously hypertensive rats with GBE and amlodipine as positive controls. The results showed that total flavonoid aglycones (TFAs) of GBLCG was mainly composed of quercetin (QCT), kaempferol (KMF) and isorhamnetin (ISR); Total terpenoid lactones (TTLs) of GBLCG might be a novel cocrystal composed of Ginkgolide A (GA), Ginkgolide B (GB) Ginkgolide C (GC), Ginkgolide J (GJ) and bilobalide (BB). The hypotensive activity of GBLCG (4.4 mg/kg) group was better than that of GBE group (p < 0.05), and the effect of improving myocardial hypertrophy was better than that of amlodipine besylate group (p < 0.01). GBLCG might reduce blood pressure and improve myocardial hypertrophy by promoting the synthesis and release of NO in endothelial cells, reducing oxidative stress, inhibiting platelet aggregation and promoting lesion circulation. Eventually, we hope to introduce GBLCG as a new drug for hypertension.

The mechanism of Bushen Huoxue decoction in treating intervertebral disc degeneration based on network pharmacology.

BACKGROUND: This study aimed to explore the mechanism of Bushen Huoxue decoction (BHD) in treating intervertebral disc degeneration using the network pharmacology method. METHODS: Using of oral bioavailability >30% and drug-likeness >0.18 as the screening standards, the effective components and targets of BHD were retrieved from the TCMSP database and the BATMAN-TCM database. The disease targets of intervertebral disc degeneration were retrieved from the GeneCards database. The Wayne map of the interaction targets of the effective components of BHD and intervertebral disc degeneration were drawn using R software. The protein-protein interaction (PPI) network of common targets was constructed using STRING software. The network map of the interaction targets of the effective components of BHD-intervertebral disc degeneration was drawn using Cytoscape3.7.2 software. The GO and KEGG enrichment analysis of the common targets of BHD and intervertebral disc degeneration was performed using R software and the related plug-ins to screen the potential pathways and analyze its mechanism. RESULTS: This study screened 164 effective components of BHD, 131 interaction targets, 626 targets for degenerative disc disease, and 31 common interaction targets. IL6, VEGFA, CASP3, EGFR, ESR1, and MAPK8 appeared more frequently. These were mainly enriched in the AGE-RAGE, TNF, PI3K Akt, and MAPK signaling pathways. CONCLUSIONS: BHD mainly intervenes in intervertebral disc degeneration through IL6, VEGFA, CASP3, EGFR, ESR1, and MAPK8. The mechanism of the intervention of BHD on intervertebral disc degeneration may be related to AGE-RAGE, TNF, PI3K Akt, MAPK, and other signal pathways.

Traditional Chinese medicine compound, Bu Sheng Hui Yang Fang, promotes the proliferation of lymphocytes in the immunosuppressed mice potentially by upregulating IL-4 signaling.

The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immunosuppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4+ and CD8+ lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.

[Biodegradation Coefficients of Typical Pollutants in the Plain Rivers Network].

Biodegradation is a significant part of pollutant integrated degradation, the process rate of which is represented by the biodegradation coefficient. To investigate the biodegradation law of typical pollutants in the plain rivers network located in the upstream of the Lake Taihu, experiments were conducted in site in September 2015, one order kinetics model was used to measure the biodegradation coefficients for permanganate index, ammonia, total nitrogen and total phosphorus, and influencing factors of the biodegradation coefficients were also analyzed. The results showed that the biodegradation coefficients for permanganate index, ammonia, total nitrogen and total phosphorus were 0.008 3-0.126 4 d⁻¹, 0.002 1-0.213 8 d⁻¹, 0.002 1-0.090 5 d⁻¹ and 0.011 0- 0.152 8 d⁻¹, respectively. The influencing factors of the biodegradation coefficients for permanganate index were permanganate index and pH; those for ammonia were ammonia concentration and pH; those for total nitrogen were inorganic nitrogen concentration, total dissolved solid concentration and nitrite concentration; and those for total phosphorus were background concentration and pH. The research results were of important guiding significance for pollutants removal and ecological restoration of the plain rivers network located in the unstream of the Lake Taihu.