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Objective: To construct the “active components-inflammatory target-anti-inflammatory pathway” network of Zanthoxylum nitidum intervened in inflammation, and predict the target of Z. nitidum intervened in inflammation and its anti-inflammatory mechanism. Methods: Using domestic and foreign literatures, TCMSP database, Pharmmapper server, oral availability (OB), and pharmacodynamics (DL) as the limiting conditions, the components of Z. nitidum were screened and the relative targets were predicted and collected. OMIM database was used to screen inflammation-related genes and protein targets; The STRING database was used to construct the interactive network between inflammatory targets; The network file of “active ingredient-predictive target-inflammatory target” was obtained by PPI analysis and imported into Cytoscape 3.5.1 software to construct the network of “active ingredient- inflammatory target”, so as to obtain the targets directly related to the anti-inflammatory effects of Z. nitidum. DAVID database was used to enrich the KEGG pathway of the selected targets, and then ClueGO plug-in was used to analyze the biological function of the target involved. Finally, the “active component-inflammatory target-anti-inflammatory pathway” network was constructed by combining the above relationships. Results: Twenty-three active ingredients were screened, and nine core anti-inflammatory targets were identified as COX-2, iNOS, PPARG, COX1, MAPK-14, JUN, NR3C1 and so on; The most critical pathways included TNF TRLs signaling pathways. Conclusion: It is preliminarily revealed that the anti-inflammatory effect of Z. nitidum is achieved through the interaction of multiple components and multiple targets, regulating the joint intervention of multiple pathways. However, the key targets and specific regulatory mechanisms need to be explored and verified by further experimental studies.
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Objective To study the pharmacokinetics of nitidine chloride (NC) in rat plasma after intragastrical (i.g.) administration. Methods A liquid chromatography-electrospray ionization-mass/mass sprectrometry (LC-ESI-MS/MS) was used and carbamazepine was used as an intermal standard (I.S.). The rat plasma samples were deproteinized with acetonitrile and the resultant supernatant was assayed on an analytical Diamonsil™ ODS C18 column (2.1 mm × 150 mm) equipped with a C18 guard column (4 mm × 20 mm) with a mobile phase of acetonitrile–10 mM ammonium acetate buffer–formic acid (35: 65: 0.2, v/v/v) at the flow rate of 0.25 mL/min. The LC–MS was carried out on a triple-quadrupole mass spectrometry equipped with an ESI and positive selected-ion monitoring. Target ions were monitored at [M-Cl]+ m/z 348.2 for NC and [M + H]+ m/z 237.2 for I.S., respectively. Results The simple one step deproteinize and rapid analysis method were successfully used in pharmacokinetic study on NC after i.g. administration. The linear relationship was good over the range of 2.5 – 1000.0 ng/ml (r2 = 0.999 2) in rat plasma. The lower limit of quantification and detection were 2.5 and 1.6 ng/ml, respectively. The extraction recovery was in the range of 86.54 – 98.60%. The intra- and inter-day precisions (relative standard deviation) were less than 6.00%, with accuracies deviation between 89.40 to 95.57%. A two-compartment pharmacokinetic open model was proposed and validated to explain the apparent biphasic disposition of NC in rat plasma after i.g. administration. Conclusion This study was successfully applied to a pharmacokinetic study of NC in rats plasma following i.g. administration and could be used for preclinical and clinical pharmacokinetic evaluation of NC.
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Objective: To investigate the pollen morphological and physiological characteristics of Zanthoxylum nitidum. Methods: The pollen grain viability was studied using an in vitro method and the optimal concentration of sucrose, H3BO3, and CaCl2 on pollen germination were investigated by 3414 test. At the same time it contrasted with the I2-KI and TTC methods to find the proper determination method for Z. nitidum pollen vitality. And then It was further studied that different storage time and methods had an effect on pollen grain viability by having established method. Pollen morphology was studied by scanning electron microscopy (SEM). Results: The I2-KI and TTC methods were not fit for determining the mature pollen vitality of Z. nitidum. The optimal medium was 10% sucrose + 0.1 mg/mL H3BO3 + 0.1 mg/mL CaCl2 on pollen germination in vitro and the pollen germination ratio was up to 66.67%. Pollen viability was the highest in 24 h and it could keep about 15 d in 4 ℃ environments. The pollen grains were 3-colpate prolate, with reticulate ornamentation. Conclusion: The determination and storage of pollen grain viability is established preliminarily to provide reliable basis of knowing physiological characteristics, breeding and taxonomy.
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Objective: To isolate and identify the antibacterial constituents from the roots of Zanthoxylum nitidum. Methods: Bioassay-guided fractionation led to the isolation of compounds from the roots of Z. nitidum by using various chromatographic techniques such as silica gel, alumina, preparative TLC, and HPLC, and their chemical structures were then elucidated on the basis of spectroscopic data, including NMR, MS analysis, and their physicochemical properties. Results: Eleven compounds were isolated from the bioactive extracts in the roots of Z. nitidum and then were identified as skimmianine (1), oxychelerythrine (2), 8-methoxy-dihydrochelerythrine (3), β-sitosterol (4), L-sesamin (5), 8-methoxy-9-demethoxyldihydrochelerythrine (6), 4-hydroxy-N- methylproline (7), liriodenine (8), avicine (9), nitidine (10), and isobutyl benzoate (11), respectively. Compounds 1, 3, 6, 8, and 10 showed the potential inhibition on Staphylococcus aureus. Compound 8 showed the most potential inhibitory activity with MIC value of 31.3 μg/mL; Further studies demonstrated that compound 8 inhibited the clinical multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) activity with MIC value of 93.8 μg/mL, significantly. Conclusion: A series of bioactive alkaloids with the anti-staphylococcal activities were identified from the roots of Z. nitidum. Compounds 7, 9, and 11 are obtained from this plant for the first time, and the potential anti-staphylococcal activity of compound 8 against MRSA has been demonstrated, which has provided the chemical template as a new anti-bacterial agent against clinical multidrug-resistant MRSA infection.
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OBJECTIVE: To develop a RP-HPLC method for simultaneous determination of magnoflorine, hesperidin, nitidine chloride, ethoxychelerythrine and toddaloactone in Zanthozylum nitidum (Roxb) DC.f. fastuosum How ex Huang. METHODS: The RP-HPLC system consisted of a Diamonsil C18 column (4.6 mm×250 mm, 5μm) with the mobile phase of acetonitrile solution-water solution (containing 0.2% phosphoric acid and 0.2% triethylamine) for gradient elution. DAD detector was used and the detection wave lengths were 273, 283 and 328 nm. The flow rate was 1.0 mL·min-1 and the column temperature was 30°C. For different constituents, external standard method was used with the peak area at the maximum absorption wavelength as the quantitative index. RESULTS: The liner ranges of magnoflorine, hesperidin, nitidine chloride, ethoxychelerythrine and toddaloactone were 0.0957-1.3391 μg (r=0.9995), 0.3189-2.1260 μg(r=0.9998),0.0397-0.2648 μg (r=0.9995), 0.1004-1.0040 μg(r=0.9999), and 0.1080-2.1600 μg (r=0.9999), respectively. The average recoveries (n=6) were 100.2%, 99.8%, 97.1%, 98.8% and 101.6% (n=6) Respectively. CONCLUSION: The method is accurate, simple, rapid, and reproducible for the determination of magnoflorine, hesperidin, nitidine chloride, ethoxychelerythrine and toddaloactone in Zanthoxylum nitidum (Roxb) DC.f. fastuosum How ex Huang. The determination result can be used as a reference for the reasonable medication, quality control and further study of Zanthoxylum nitidum (Roxb) DC.f. fastuosum How ex Huang.
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Aim To investigate the anti-tumor effect of nitidine chloride(NC)on human HepG2 hepatocellular transplanted tumor in nude mice and its effect on topoisomerase.Methods The subcutaneous transplantable tumor model of human liver cancer in nude mice was established and the anti-tumor effect of NC was calculated.The effects of NC on TopoⅠ/Ⅱ mediated-pBR322 DNA relaxation were measured by using agarose gel electrophoresis.Results NC inhibited significantly the growth of hepatoma,The inhibitory rate at the dose of 2.5,5,10 mg·kg~(-1) was 12.06%,35.63% and 60.91% respectively.At the concentration of 6.25 μmol·L~(-1),NC completely inhibited the pBR322 DNA cleavage mediated by TopoⅠ;at the concentration of 25 μmol·L~(-1),NC completely inhibited the pBR322 DNA cleavage mediated by Topo Ⅱ.Conclusion Nitidine Chloride can inhibit hepatic carcinoma growth in nude mice,The anti-tumor mechanism is probably related to the inhibitory effect on Topo.
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Objective To study the chemical constituents from the roots of Zanthoxylum nitidum.Methods The constituents were isolated and purified by column chromatography.Their structures were identified on the basis of physiochemical properties and spectral data.Results Two benzophenanthridine alkaloids,1,3-bis(8-dihydronitidinyl)-acetone(1)and 8-acetonyldihydrofagaridine(2),have been iso-lated from the roots of Z.nitidum.Conclusion Compounds 1 and 2 are new compounds named nitidumtone A and nitidumtone B.