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The present study established the spectrum-effect relationship model of flavonoids in Citri Reticulatae Pericarpium(CRP) from 15 batches of Liujunzi Decoction and statistically analyzed the correlation between chemical peaks and efficacy to identify the main effective components. HPLC fingerprints of flavonoids in CRP from 15 batches of Liujunzi Decoction were established. HPLC analysis was carried out on the Venusil XBP C_(18)(L) column(4.6 mm×250 mm, 5 μm) at 30 ℃ with acetonitrile-water(containing 0.1% formic acid) as mobile phase for gradient elution, a flow rate of 1.0 mL·min~(-1), and detection wavelength of 300 nm to obtain chemical fingerprints. Additionally, the effects of flavonoids from CRP in 15 batches of Liujunzi Decoction on the content of GAS, MTL, and VIP, TFF3 mRNA expression, and percentage of CD3~+ T-cells of model rats with spleen deficiency were determined. The spectrum-effect relationship model was established by gray correlation analysis. The results showed that the main characteristic peaks with great contribution to the regulation of gastrointestinal tract were peak 16(vicenin-2), peak 63(sinensetin), peak 64(isosinensetin), peak 65(nobiletin), peak 67(3,5,6,7,8,3',4'-heptemthoxyflavone), peak 68(tangeretin), and peak 69(5-desmethylnobiletin). Therefore, there was a linear correlation between flavonoids from CRP in Liujunzi Decoction and the efficacy, and the medicinal effect was achieved by multi-component action. This study is expected to provide a new idea for exploring the material basis of the effect, i.e., regulating qi prior to replenishing qi, of CRP in Liujunzi Decoction.
Subject(s)
Animals , Rats , Citrus/chemistry , Drugs, Chinese Herbal , Flavonoids/pharmacology , Hormones , RNA, Messenger/genetics , SpleenABSTRACT
Objective::To discover a small molecule active ingredient of traditional Chinese medicine (TCM) with the inhibitory activity of histone deacetylase (HDAC) 3/8. Method::The molecular docking technique was performed by AutoDock 4.2.6 software. Trichostatin A (TSA) was used as a reference to screen 19 small molecular components from TCM, and the default docking conformation number was set to obtain the docking binding energy, active site amino acid residues and hydrogen bonds, and the biological activity was verified. Result::The binding energies of 19 small molecule components from TCM to HDAC3 and HDAC8 were different. Among them, ursolic acid, fangchinoline and tetrandrine have low binding energies to HDAC3 and HDAC8, and their binding activities were strong. The optimal binding energy of fangchinoline and HDAC3 at the site 1 was the lowest (-26.71 kJ·mol-1), and that of HDAC8 at the site 9 was the lowest (-26.84 kJ·mol-1). The optimal binding energy of tetrandrine and HDAC3 at the site 13 was the lowest (-26.38 kJ·mol-1), and that of HDAC8 at the site 12 was the lowest (-25.41 kJ·mol-1). In addition, the binding energy of ursolic acid and HDAC3 at the site 16 was the lowest (-25.83 kJ·mol-1), and that of HDAC8 at the site 8 was the lowest (-35.62 kJ·mol-1). Three kinds of amino acids at the docking site of small molecules were rendered by PyMOL 2.3.1.When ursolic acid was combined with HDAC3/8, the active sites produced two hydrogen bonds, and the interaction was strong, and many amino acids were connected at the active site. The fangchinoline formed two hydrogen bonds with the active site of HDAC3 and one hydrogen bond with the active site of HDAC8, and hydrophobic binding with some active site amino acids. There was no hydrogen bond between tetrandrine and HDAC3/8, and all docking sites were docked by 4 active amino acids. Three small molecules (ursolic acid, fangchinoline and tetrandrine) with the best docking effect had the inhibitory activity against HDAC3/8 at the concentration of 500 μmol·L-1 and 100 μmol·L-1, and the inhibitory activity was still optimal among the 10 selected small molecules. Conclusion::Among the screened 19 small molecules, ursolic acid, tetrandrine and fangchinoline may be the new anti-inflammatory drugs of HDAC3/8 inhibitory target, which provides a reference for further exploration and discovery of new anti-inflammatory drugs.
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Objective:The phase separation of Baihutang was carried out. The content of mangiferin，new mangiferin，calciumion，glycyrrhizin and ammonium glycyrrhizinate in the solution phase，the nano phase and the precipitated phase of Baihutang were measured，so as to define the effect of nanometer particles of Baihutang on the growth of active components，and explain the mechanisms of Baihutang in potent detoxification and heat removal. Method:The phase separation of Baihutang was performed by high-speed centrifugation and dialysis. The contents of mangiferin，new mangiferin，glycyrrhizin and ammonium glycyrrhizinate in Baihutang were determined by HPLC. Chromatographic column Diamonsil C18 (4.6 mm×250 mm，5 μm) was adopted, with acetonitrile-25 mmol·L-1 potassium dihydrogen phosphate solution as the mobile phase, and eluted in a gradient mode. The detection wavelength was 257 nm，the column temperature was 30 ℃，and the flow rate was 1.0 mL·min-1. EDTA-2Na solution was used to calibrate the calcium concentration in different phase states of Baihutang. Result:1 mL Baihutang nanoparticles contained 483.00 μg new mangiferin，1 068.88 μg mangiferin，219.93 μg glycyrrhizin and 187.10 μg ammonium glycyrrhizin，and the content of new mangiferin and mangiferin accounted for 89.4% and 89.9% respectively in 1 mL Baihutang. The new mangiferin and mangiferin in the nano phase were 230.0 and 23.3 times the true solution，and 8.5 and 14.4 times of the precipitation，respectively. The content of calcium ions in Baihutang in the nano phase was higher，accounting for 86.9% of Baihutang，and the content of calcium ions in Baihutang and Baihutang in the nano phase was higher than that in gypsum group. Conclusion:The content of main components in Baihutang in nanometer phase is significantly higher than that in other phases. The nanoparticles of Baihutang have a solubilizing effect on the main antipyretic components, such as mangiferin，mangiferin and calcium ions as well as the antitoxic components glycyrrhizic acid and glycyrrhizic acid. The mechanism of action of Baihutang is related to the formation of nanoparticles.
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Zixue was first recorded in detail in Qianjin Yifang, and practitioners of later generations renamed it as Zixuesan and Zixuedan, which is the representative prescription of antipyretic preparations and has high clinical application and research value. At present, there have been many studies on the pharmacological effect and clinical application of Zixue, but the medical books of the past dynasties have slightly different records on Zixue, which has brought some difficulties to the reasonable clinical application and research of this prescription. In addition to the introduction of Zixuesan, which is different from the ancient recipe, the researchers have questions about which development method can reasonably inherit and develop the classical preparation. The authors intend to summarize the historical evolution of "formula" and "preparation" of Zixue, in order to clarify its historical context, which can provide a reference for the modern research and development of this formula, and provide a new ideas for the in-depth exploration of other classic preparations.
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Breast cancer mainly occurs in woman's mammary epithelial tissues, with a complex and unclear pathogenesis. The mortality rate is high and increasing year by year, and the patients become younger and younger, which seriously threatens woman's health. Therefore, it's urgent to find high-efficiency and low-toxicity medicines against breast cancer. The breast is not an essential organ for life support, but the cancer cells can easily fall off and metastasize throughout the body with blood or lymph fluid. It's a main cause of death. Surgery, radiotherapy, chemotherapy, molecular targeting, endocrine therapy, immunity therapy have certain limitations due to serious toxicity and side effects and the difficulty in controlling the invasion and metastasis of the cancer cell. In recent years, traditional Chinese medicine（TCM）has been widely studied and valued by researchers at home and abroad due to its unique advantages, such as multiple pathways, multiple targets, low toxicity and fewer side effects, and a lot of TCMs and their active ingredients with the anti-breast cancer activity have been studied by the researchers. Based on flavonoids, polyphenols, alkaloids, terpenes and other TCM ingredients, the mechanism in inhibiting breast cancer cell proliferation, inducing it apoptosis, inhibiting it invasion and migration in vitro were taken as the main content, which was supplemented by the summary of main relevant signal pathways targeted by the ingredients. This study reviewed the mechanism of ingredients in suppressing breast cancer in vitro by viewing and screening relevant literature at home and abroad in the past 10 years. The in-depth study of effective ingredients of TCM is expected to provide a reference for the development of effective targeting preparations for treating breast cancer. On the basis of in-depth excavation of active ingredients of TCM, relevant studies in the future are suggested to apply the ingredients of TCM acting on the same or similar pathways, factors, proteins, and make use of the basic theory of TCM, so as to achieve the effect in against breast cancer.
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Objective:To prepare self-emulsifying carrier system which was suitable for three Chinese medicinal ingredients(baicalein,berberine and allicin),and investigate transdermal absorption effect in vitro of these three self-emulsifying preparations. Method:The optimum formulation and dosage were screened by the saturated solubility method,pseudo-ternary phase diagram method and orthogonal experiment.Transdermal absorption test in vitro was carried out with excised rats skin and Franz diffusion cell.The cumulative penetration amounts of baicalein,berberine and allicin in the identical self-emulsifying system were determined by HPLC and compared with baicalein powder,berberine powder and allicin powder,respectively. Result:The optimum formulation was ethyl oleate-cremophor RH40-polyethylene glycol(PEG)400.The self-emulsifying preparation had a suitable particle size with a relatively regular spherical shape.At 10 h of transdermal absorption,the transdermal rates of baicalein,berberine and allicin in identical self-emulsifying system were 6.898 6,7.600 4,190.040 μg·cm-2·h-1,the cumulative penetration amounts of them were 71.38,85.54,1 795.16 μg·cm-2,respectively. Conclusion:The self-emulsifying carrier system is prepared successfully,which can be used by different kinds of Chinese medicinal ingredients,and the transdermal absorption effect in vitro of these self-emulsifying preparations is good,which can provide experimental basis for the preparation and transdermal absorption of self-emulsifying preparation of Chinese herbal compound.
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The theory of medicinal properties of traditional Chinese medicine (TCM) is one of the core theories of TCM, which is an important basis for guiding the clinical application of TCM and the key supporting point for the modernization of TCM. How to study the modernization of TCM under the guidance of traditional Chinese medicine theory has become a great challenge for modern researchers. Currently, the researches in TCM mainly focus on chemical studies such as on active ingredients and effective components, lacking the guidance of traditional Chinese medicine theory, and losing the inherent characteristics of TCM. Therefore, the combination of the theory of TCM and the modernization of TCM and the establishment of research mode that is in line with the characteristics of modernization of traditional Chinese medicine under guidance by the theory of medicinal properties of TCM shall be the top priority in modern Chinese medicine research. The property and flavor of TCM are closely related to its chemical compositions, and also have certain regularity. The researches on the chemical components of TCM, systematic design of property and flavor, as well as the separation and combination of TCM property and flavor are beneficial to the overall analysis of the characteristics of TCM, showing great significance to inherit and carry forward TCM. The pharmacological effects about separation and combination methods based on TCM property and flavor were reviewed in this study, providing theoretical reference for the development of new drugs and the application of TCM.