Study on the mechanism of Gualou Xiebai Guizhi decoction (GLXBGZD) in the treatment of coronary heart disease based on network pharmacology.

BACKGROUND: This study aims to analyze the mechanism of Gualou Xiebai Guizhi decoction (GLXBGZD) in treating coronary heart disease (CHD) utilizing network pharmacology. METHODS: The GLXBGZD effective components were searched on the pharmacological database platform of the Traditional Chinese Medicine Systems Pharmacol, and its potential target was predicted. The Online Mendelian Inheritance obtained CHD disease target in Man and GeneCards database. The Venn map of the intersection target for GLXBGZD and CHD was constructed by using Venn online website. The "drug-component-target-disease" network map was constructed by Cytoscape 3.7.2 software. The DAVID online platform was used to analyze the function of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) at the intersection of targets of drugs and diseases. RESULTS: A total of 27 articles were searched for GLXBGZD, including 111 potential targets, 5521 disease targets, 100 drug and disease intersection targets. The core target network map shows that Interleukin (IL)-6, TNF, vascular endothelial growth factor (VEGFA), TP53, EGF, JUN, MAPK1, Catalase (CAT), and prostaglandin-endoperoxide synthase 2 (PTGS2) may be the key targets in CHD therapy. GO functional enrichment analysis revealed that the biological functions of GLXBGZD involved biological processes such as response to drugs, positive regulation of nitric oxide biosynthesis process, and response to hypoxia. KEGG pathway enrichment analysis showed that GLXBGZD might participate in CHD treatment through Hypoxia-inducible factor-1 (HIF-1), Tumor necrosis factor (TNF), PhosphoInositide-3 Kinase--Threonine protein kinase (PI3K-Akt), and the calcium signal pathway. CONCLUSIONS: This study reveals that the GLXBGZD mechanism in CHD treatment has the characteristics of multi-components, multi-targets, and multi-pathways, which provides a theoretical basis for its clinical application and subsequent experimental verification.

An "all-in-one" strategy based on the organic molecule DCN-4CQA for effective NIR-fluorescence-imaging-guided dual phototherapy.

Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an "all-in-one" functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.

[Detection of free amino acids in tea using ultra-high performance liquid chromatography-tandem mass spectrometry].

To efficiently and quickly detect free amino acid components in tea, a method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. With the optimization of mass spectrometry, chromatographic conditions, and amino-acid extraction conditions, a total of 20 free amino acids were identified using 5 mmol/L ammonium acetate aqueous solution containing 0.2% (v/v) formic acid and methanol as mobile phases for gradient elution and detected by electrospray ionization (ESI) and positive-ion scanning. The results showed that all calibration curves expressed good linearities. Theanine (Thea), Arg, Asn, and Asp were in the range of 50-500 µg/L. The other amino acids were in the range of 10-250 µg/L with all correlation coefficients ≥ 0.99. The average recoveries were between 92.3% and 109.2%. The relative standard deviation (RSDs) were between 2.00% and 9.88%. The limits of detection (LODs) were 0.001-0.011 mg/L, and the limits of quantification (LOQs) were 0.010-0.053 mg/L. The method is sensitive, accurate, and has good repeatability and stability. The method can effectively detect 20 types of amino acids and amino components in tea leaves from the samples of green tea, white tea, and black tea.

[Determination of glyphosate, glufosinate, and main metabolite aminomethylphosphonic acid residues in dry tea using ultra-high performance liquid chromatography-tandem mass spectrometry].

A method has been developed for the determination of glyphosate (GLY), glufosinate (GLUF), and the main metabolite aminomethylphosphonic acid (AMPA) residues in dry tea based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with pre-column derivatization. A systematic study of the effects of pretreatment methods including extraction and purification procedures was designed and carried out for the determination of GLY, GLUF, and AMPA. The results indicated that the optimal pretreatment method was as follows:the tea sample was first extracted by water in vortex, and then purified by a cation exchange solid-phase extraction column with the elution of 0.5% (v/v) formic acid aqueous solution. Finally, the eluant was derivatized by 9-fluorenylmethyl chloroformate, and the target compounds were separated on a C18 chromatographic column and analysed by UPLC-MS/MS (ESI+). GLY, GLUF, and AMPA showed good linearity in the range of 1-100 µ g/L, with correlation coefficients above 0.991. The limits of detection and limits of quantification were found to be 0.0160-0.0300 mg/kg and 0.0530-0.100 mg/kg, respectively. The average spiked recoveries of GLY, GLUF, and AMPA varied from 78.3% to 108% at three spiked levels (0.0500, 0.400, and 1.20 mg/kg), while the relative standard deviations ranged from 5.46% to 9.63%. The proposed method was utilized to detect 837 batches of tea samples. The detection ratios of GLY, GLUF, and AMPA were 3.46%, 0.24%, and 4.42%, respectively, while 0.24% of the investigated tea samples had values above maximum residue limits. The developed method is simple, rapid, sensitive, and accurate for the determination of GLY, GLUF, and AMPA in dry tea and may be used for routine analysis.

Degradation of phytosterols in tobacco waste extract by a novel Paenibacillus sp.

Phytosterols have been demonstrated to be precursors of polycyclic aromatic hydrocarbons (PAHs) formed during biomass pyrolysis. Here, a novel Paenibacillus sp. was evaluated for its ability to degrade phytosterols in tobacco waste extract (TWE). The optimal conditions for cell growth and stigmasterol (a representative of phytosterols) degradation were 37 °C, pH 7.0, 1.0 g/L yeast extract, and 6.0 g/L glucose. Paenibacillus sp. could degrade stigmasterol under high concentrations of glucose (up to 130 g/L) and tolerate wide pH (5.0-9.0) and temperature (25-42 °C) ranges. The new strain could degrade stigmasterol completely into CO2 and H2 O, and no intermediate steroids were detected during the degradation process. Phytosterol degradation in TWE was demonstrated by high-performance liquid chromatography-tandem mass spectrometry. Under optimal conditions (37 °C, pH 7.0, with the exponential-phase cells), the total degradation ratio of phytosterols reached 38.5% in TWE, including 45.2% of stigmasterol, 37.4% of ß-sitosterol, 27.3% of campesterol, and 28.7% of cholesterol. These results showed that Paenibacillus sp. is a candidate for phytosterol degradation in TWE and other biomass and is potentially useful in reducing the PAHs generated from biomass pyrolysis.

Effects of tetramethylpyrazine on nitric oxide/cGMP signaling after cerebral vasospasm in rabbits.

Tetramethylpyrazine (TMP), an ingredient of Chinese herbal Szechwan lovage rhizome, shows vasorelaxant effect. Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. Here, we evaluated the effect of TMP in a model of CVS and sought to identify the underlying mechanisms of action. A rabbit SAH model was established by injection of the autoblood via cisterna magna. Cerebral blood flow and arterial diameter were measured by Transcranial Doppler (TCD) and Computed Tomography Angiography (CTA). Expression of eNOS and PDE-V in basilar artery (BA) was assessed by western blots. Levels of nitric oxide (NO) in plasma and cerebral spinal fluid, and of intra-endothelium Ca(2+) were measured. Significantly reduced diameter and accelerated blood flow velocity were detected in BAs of SAH animals (P<0.05 vs. sham group). Expression of eNOS and NO was increased, and PDE-V expression was reduced by TMP.TMP ameliorated cerebral vasospasm (P<0.05 vs. SAH group), and L-NAME (a NOS inhibitor) partly abrogated the effects of TMP. TMP induced a dose-dependent increase of intra-endothelium Ca(2+). The current results demonstrated that the vasorelaxant effect of TMP was at least in part via regulation of NO/cGMP signaling.