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A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.
Subject(s)
Animals , Mice , Anti-Inflammatory Agents/pharmacology , Cyclooxygenase 2/chemistry , Dinoprostone , Interleukin-6/metabolism , Iridoid Glucosides , Molecular Docking Simulation , PyridinolcarbamateABSTRACT
Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.
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Danggui Buxue Decoction is a classic prescription of Qi and blood tonification, which is mainly applied in treating fatigue, internal damage Qi weakness, blood deficiency, and outward going of floating Yang. Modern pharmacology shows that it can promote hematopoiesis, regulate immunity, and protect heart and cerebral vessels. The prescription, often used for the treatment of anemia and other diseases in clinic, is composed of Astragali Radix and Angelicae Sinensis Radix at a dosage ratio of 5∶1. It is a modern compound prescription for invigorating Qi and generating blood. Based on the review of the chemical constituents, pharmacological effects, and clinical applications of Danggui Buxue Decoction, its Q-marker was predicted and analyzed according to the "five principles" of Chinese medicine Q-marker--quality transmissibility and traceability, ingredient specificity, component validity, component measurabi-lity, and formula compatibility environment. The results suggested that calycosin, calycosin-7-O-β-D-glucoside, formononetin, ononin, astragaloside A, ferulic acid, and ligustilide could be used as Q-markers of Danggui Buxue Decoction, which provides reference for establishing the quality system of Danggui Buxue Decoction.
Subject(s)
Astragalus Plant , Drugs, Chinese Herbal/pharmacology , Plant RootsABSTRACT
The energy adjustment models in nutritional epidemiological studies could substantially reduce the confounding effect of total energy intake from the intake of dietary components, and it could explore the real relationship between the intake of dietary component and research outcomes. Four energy adjustment models were introduced in this article, including the standard multivariate model, multivariate nutrient residual model, energy partition model, and multivariate nutrient density model. The four energy adjustment models were applied to analyze the association between the intake of saturated fatty acids and the risk of all-cause mortality based on the data of the US National Health and Nutrition Examination Survey. The consistent results of different energy adjustment models could indicate that the four models could better control the confounding effect of total energy intake.
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Suanzaoren Decoction is a classic prescription for nourishing the heart and liver, nourishing blood and tranquilizing the mind. It has the functions of sedation and hypnosis, anti-anxiety, anti-depression, anti-convulsion and so on. Modern clinic is mostly used to treat different types of insomnia, depression, neurasthenia, tension headache and vertigo. In this paper, the chemical consti-tuents, pharmacological effects and clinical application of Suanzaoren Decoction are reviewed. Based on this, the quality marker(Q-marker) of Suanzaoren Decoction was predicted and analyzed according to the "five principles" of Q-marker of traditional Chinese medicine--transmission and traceability, specificity, effectiveness, measurability and compatibility environment of compound prescriptions. The results indicated that jujuboside, spinosin, ferulic acid, senkyunolide Ⅰ, sarsasapogenin, mangiferin, liquiritoside and glycyrrhizic acid were predicted and analyzed, and those can be used as Q-markers of Suanzaoren Decoction. Subsequently, the above components can be selected as indicators to control and evaluate the quality of Suanzaoren Decoction and its preparations, and establish a quality traceability system.
Subject(s)
Humans , Biomarkers , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Sleep Initiation and Maintenance DisordersABSTRACT
<b>Objective::To observe the effect of Youguiwan on the levels of cartilage transducers and activators of transcription 3 (STAT3) and interleukin-6 (IL-6) in rats with knee osteoarthritis (KOA). <b>Method::Sixty SD rats were randomly divided into six groups: sham control group, model group, glucosamine sulfate group and Youguiwan (high, middle and low-dose) groups. The modified Hulth method was used to prepare KOA models for 6 weeks. The shame control group and the model group were treated with normal saline, Youguiwan high, middle, low-dose groups received Youguiwan 4.8, 2.4, 1.2 g·kg<sup>-1</sup> by gavage respectively, and the glucosamine sulfate group was treated with glucosamine sulfate 0.17 g·kg<sup>-1</sup>. The rats were administrated for 8 weeks according to the dose. After intervention, each group was put to death by femoral artery blood collection, and the keen cartilages of the rats were collected. The pathological changes were observed by htoxylin eosin (HE) staining method, and Mankin score was evaluated. The expressions of STAT3, superoxide dismutase3(SOD3) and Wnt inhibitory factor 1(WIF1) in articular cartilage were detected by immunohistochemistry. The expressions of IL-6 mRNA in articular cartilage were detected by quantitative real-time fluorescence polymerase chain reaction (Real-time PCR). The expression of WIF1 in articular cartilage was detected by Western blot. <b>Result::Compared with the sham control group, the Makin score was obviously increased in the model group, the protein expression of STAT3 was increased significantly, the mRNA of IL-6 was raised significantly, but the protein expression of WIF1 was decreased significantly (<italic>P</italic><0.01), articular cartilage was seriously damaged, and chondrocytes were arranged in disorder. Compared with the model group, the Makin score was declined obviously in the high-dose Youguiwan group, the protein expression of STAT3 was significantly reduced, the mRNA expression of IL-6 was significantly reduced in Youguiwan treatment group, while the protein expression of WIF1 was significantly increased (<italic>P</italic><0.05, <italic>P</italic><0.01), the cartilage structure returned to be normal, the chondrocytes distribution was uneven, and articular cartilage surface was not smooth. <b>Conclusion::Youguiwan could significantly improve the articular cartilage degeneration of KOA rats, and inhibit the inflammation of chondrocytes, which may be related to the suppression of STAT3 and IL-6 expression.
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The chemical components (groups) contained in traditional Chinese medicine(TCM) and its compound preparations are the material basis for its curative effect, because of the integrity of the action of TCM and the complexity of its compositions and mechanism. The separation and analysis of chemical constituents in TCM and its compound prescriptions by various methods is always a key problem to be solved in the research of disease prevention and treatment of TCM. The binding of drug molecules to receptors at the cellular level was explored to provide a new idea for the screening of active components of TCM or its compound preparations. Traditional methods have some drawbacks, such as cumbersome operation, time-consuming, waste of solvents and irreversible adsorption of samples. The basic information of pharmacological parameters cannot be given in the separation process, and the active ingredients cannot be efficiently and accurately located. At present, cell membrane chromatography (CMC), one of the methods, is used to study the interaction between drug molecules and receptors, and can combine the existing chromatography and mass spectrometry technology, cell biology and receptor pharmacology, and correctly reflect the interaction between active parts, active components and cell membrane and membrane receptors, so it has unique advantages in screening effective parts, separation of active components and high-throughput screening from complex TCM system. The principles and characteristics of CMC, the cell membrane model in the field of active ingredient selection of TCM and its research status in combination with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were reviewed, and its development prospects and future research methods were discussed, which provides theoretical basis and practical guidance for the research and utilization of CMC in the field of TCM.
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Objective: To investigate the correlation between the quality and climatic factors for Gentiana officinalis H. Smith from different producing area in Gansu province, China by grey correlation degree analysis combined with CRITIC-AHP weight ed evaluation. Methods: Contents of the total secoiridoid glycosides, total alcohol extracts and the metallic elements Ca, Fe and Zn were determined for the medicinal herb G. officinalis samples from 10 producing areas in Gansu, and their quality was estimated by the CRITIC-AHP weighted evaluation. The relationship between the quality and related climatic factors was then investigated by the grey correlation degree analysis. The climatic factors included the altitude, annual mean temperature, monthly mean temperature of Janu ary and July, annual mean relative humidity and the annual mean rainfall precipitation. Results : The content of the determined com ponents showed variation in the G. officinalis samples from the 10 different producing area. The altitude, annual mean temperature, monthly mean temperature of January and July, annual mean relative humidity and the annual mean rainfall all showed certain influ ence on the G. officinalis quality, and the biggest influence was the monthly mean temperature of July. Conclusion: The present re sults of the grey correlation degree analysis identifies the main climatic factors influencing the G. officinalis quality, which provides an experimental basis for the proper area selection and planting standardization for the G. officinalis production.
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OBJECTIVES@#To observe the effects of Yougui pill (Traditional Chinese Medicine) on the related factors of Wnt signal pathway of rats with knee osteoarthritis (KOA), and explore its protective mechanism.@*METHODS@#Sixty SPF SD rats were randomly divided into the sham-operative group, model group, glucosamine sulfate group, high-dose, middle-dose, low-dose of Yougui pill treated group (=10). KOA model was established by modified Hulth method for six weeks. The rats in the high, middle and low-dose of Yougui pill group were treated with Yougui pills at the doses of 20,10 and 5 g/kg respectively by gastrogavage once a day for 8 weeks, while equal volume of normal saline was given to those in the sham and model control group and an equal volume of glucosamine sulfate (1.7 g/kg·d) was given to those in glucosamine sulfate group for 8 weeks. The knee joint was removed after the last dose of drug. The pathological changes of cartilaginous tissues were observed under a microscope. The mRNA levels of Dickkopf homolog 1(DKK1), Wnt induced secreted protein 1(WISP1), Wnt1, low density lipoprotein receptor related protein 5(LRP5) and beta -catenin in rats cartilaginous tissues were analyzed by using RT-PCR method, and the protein contents of DKK1, WISP1, Wnt1, LRP5 and beta-catenin in cartilaginous tissues were detected by Western blot.@*RESULTS@#Compared with the sham group, the articular cartilage was severely damaged, the Mankin score was increased significantly (<0. 05), the mRNA and protein expression levels of DKK1 in cartilaginous tissue were markedly decreased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were increased significantly in model group(<0.05). Compared with model group, the articular cartilage lesions was light (<0.05), the Mankin Score was decreased significantly(<0.05), and the mRNA and protein levels of DKK1 in cartilaginous tissue were increased(<0.05), while those of WISP, Wnt1, LRP5 and beta-catenin were decreased in Yougui pill high-dose group and glucosamine sulfate group (<0.05).@*CONCLUSIONS@#Yougui pill has protective effects on the KOA by inhibiting the expressions of WISP, Wnt1, LRP5, beta-catenin and increasing the expression of DKK1 cytokine in the Wnt signaling pathway.
Subject(s)
Animals , Rats , CCN Intercellular Signaling Proteins , Metabolism , Drugs, Chinese Herbal , Pharmacology , Glucosamine , Pharmacology , Intercellular Signaling Peptides and Proteins , Metabolism , Osteoarthritis, Knee , Drug Therapy , Proto-Oncogene Proteins , Metabolism , Random Allocation , Rats, Sprague-Dawley , Wnt Signaling Pathway , Wnt1 Protein , Metabolism , beta Catenin , MetabolismABSTRACT
Objective To optimize prescription of gentiopicroside nanoemulsion; To evaluate its quality and security. Methods According to the basic properties of gentiopicroside, single-factor test and pseudo-ternary phase diagram were adopted to optimize prescription of gentiopicroside nanoemulsion. The physicochemical property was investigated, and the content was evaluated by HPLC. Results Optimal prescription was obtained as gentiopicroside/ethyl acetate/ EL-35/ absolute ethyl alcohol/ ultrapure water (1.77:7.66:5.94:11.91:72.71); the particle size of nanoemulsion was 23.08 nm; the content of gentiopicroside was determined by HPLC; the specificity of the method was good with a linear range of 0.004 28–0.214 mg/mL; stability of prepared gentiopicroside nanoemulsion was good in the state of different temperatures, illumination intensity and humidity conditions, without significant changes. Conclusion The optimized preparation technology of gentiopicroside nanoemulsion is simple, repeatable and stable, which can provide references for improving the bioavailability of gentiopicroside.
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Objective To optimize extraction technology of Compound Danggui Buxue Decoction. Methods On the basis of single factor test, factorial design, and fastest rise test, yield and weight sum of extraction efficiency of ferulic acid, paeoniflorin and ligustilide were set as response, and central composite design-response surface method was used to optimize the extraction technology of Danggui Buxue Decoction. Results The optimum conditions consisted of ultrasonic-wave extraction for 60 min, ethyl alcohol concentration 36％ and the ratio of material to solvent = 1:94. Conclusion This method has high extraction efficiency, easy operation and good predictability.
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The paper is to report the establishment of three methods for determination of methyl salicylate-2-O-beta-D-galactopyranoside (1-4)-beta-D-glucopyranoside (MSG) by HPLC, UV or potentiometric titration. The results determined by the three methods turned out to be of no significant difference (P>0.05). The method was chosen according to MSG difference test demands.
Subject(s)
Anti-Inflammatory Agents , Chemistry , Chromatography, High Pressure Liquid , Methods , Glycosides , Chemistry , Molecular Structure , Potentiometry , Methods , Reproducibility of Results , Salicylates , Chemistry , Sensitivity and Specificity , Spectrophotometry, Ultraviolet , MethodsABSTRACT
<p><b>OBJECTIVE</b>To study the chemical constituents from the flowers of Carthamus tinctorius.</p><p><b>METHOD</b>Compounds were isolated by chromatographic techniques. Their structures were elucidated by spectral methods.</p><p><b>RESULT</b>Ten compounds were identified as 7,8-dimethylpyrazino [2,3-g] quinazolin-2, 4-(1H, 3H) -dione (1), adenosine (2), adenine (3), uridine (4), thymine (5), uracil (6), roseoside (7), 4'-O-dihydrophaseic acid-beta-D-glucopyranoside methylester (8), 4-O-beta-D-glucopyranosyloxy-benzoic acid (9) and p-hydroxybenzoic acid (10).</p><p><b>CONCLUSION</b>Compounds 1 and 8 were isolated from natural plants for the first time, and compounds 7, 9 and 10 were isolated from this plant for the first time.</p>
Subject(s)
Carthamus tinctorius , Chemistry , Drugs, Chinese Herbal , Chemistry , Flowers , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To prepare sustained-release microsphere containing extract of Sanguis Draconis and to measure its dissolution in vitro.</p><p><b>METHOD</b>Sustained-release microsphere was prepared with polylactic acid (PLA) as carriers using the oil-in-water (O/W) emulsion solvent evaporation method. The powder particle's characteristics of sustainded-release microsphere were evaluated comprehensively, and its dissolution characteristics in vitro were studied.</p><p><b>RESULT</b>The microsphere was round and its surface was smooth, drug-loading rate was 21.97% and the entrapment rate was 55.76%, the accumulative release percentage was 76. 71% in 16 hours.</p><p><b>CONCLUSION</b>The sustained release effect of Sanguis Draconis microspheres was formed with potentially wide applications.</p>