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1.
Article in Chinese | WPRIM | ID: wpr-906127

ABSTRACT

Objective:To explore the potential synergistic protective mechanism of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula compound by using the methods and tools of network pharmacology,and provide a basis for the modernization of traditional Chinese medicine(TCM) compounds and the discovery of new drugs. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the active components of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula and their corresponding targets. The obtained targets were input to the UniProt database to inquire the gene names corresponding to the targets. By searching the CTD database,Genecards database and OMIM database of disease-related websites,the anti-sunburn targets were obtained. The interaction of the active targets was analyzed with online STRING database to screen the predicted core targets. The gene ontolog(GO) gene function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis of the predictive targets were performed by using DAVID database. Cytoscape 3.6.1 software was used to make "drug-component-target" network diagram,"protein-protein interaction" network diagram and "component-target-pathway" network diagram. Online website Draw Venn Diagram was used to show the relationship between disease targets and drug predicted targets. R Studio software was used to draw the functional enrichment analysis diagram of GO gene and KEGG pathway. Molecular docking between the active ingredients and the core targets was performed using GOLD software. Result:The 16 active compounds were collected,such as liquiritin,glycyrrhizin,kaempferol and quercetin. The active components mainly acted on 5 core targets:protein kinase B1(AKT1),interleukin(IL)-6,vascular endothelial growth factor(VEGFA),tumor necrosis factor(TNF) and tumor suppressor gene (TP53) and played a role in anti-sunburn effect primarily through these pathways such as hepatitis B,pathways in cancer,toxoplasmosis,chagas disease(American trypanosomiasis),and TNF signaling pathway. Conclusion:Based on the method of network pharmacology,the present study has preliminarily explored the anti-sunburn targets and pathways of Glycyrrhizae Radix et Rhizoma-Granati Pericarpium formula,and further verified the characteristics of multi-component and multi-target treatment of diseases in TCM,so as to provide certain scientific ideas for the modernization research of Chinese herbal compound prescriptions.

2.
Article in Chinese | WPRIM | ID: wpr-872934

ABSTRACT

Objective:To predict the anti-inflammatory targets and relevant signaling pathways of Epimedii Folium in the treatment of depression by network pharmacology,in order to explore the potential mechanism of its anti-depression effect. Method:The active constituents of Epimedii Folium were collected and screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database. PharmMapper server and TCMSP database were used to predict and screen out protein targets. OMIM database,CTD database and GeneCards database were used to screen out relevant targets and anti-inflammatory targets of depression. Enrichment analysis of the gene ontology (GO) function and Kyoto Encyclopedia of genes and genomes(KEGG) signaling pathway for the key anti-inflammatory targets of Epimedii Folium were carried out by DAVID database. Cytoscape 3.6.0 was used to construct the network diagram of "active component-action target-signal pathway" of Epimedii Folium and analyze the topological structure of the network. GOLD molecular docking software was used to verify the results of active components and key anti-inflammatory targets. Result:A total of 12 active components,30 targets and 5 key anti-inflammatory targets of Epimedii Folium were screened out, 65 biological processes,4 cell components and 1 molecular function were enriched with GO function, and 41 KEGG pathways were enriched and analyzed,including 9 inflammation-related signaling pathways. Molecular docking verified that icariin and key anti-inflammatory targets could form the optimal binding structure. Conclusion:The study preliminarily reveals the molecular mechanism of Epimedii Folium on depression through its anti-inflammatory target and its relevant signaling pathway network,so as to provide a basis for further study on the antidepressant effect of Epimedii Folium.

3.
Article in Chinese | WPRIM | ID: wpr-790235

ABSTRACT

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate com-bination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM"Eighteen Incompatible Medicaments", are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphin-ganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of in-compatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM"Eighteen Incompatible Medicaments".

4.
Acta Pharmaceutica Sinica ; (12): 95-103, 2019.
Article in Chinese | WPRIM | ID: wpr-778672

ABSTRACT

The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg-1·d-1, CTL), high dose of CT group (0.078 g·kg-1·d-1, CTH), JF group (9.75 g·kg-1·d-1), low dose of CT combined with JF group (CT 0.039 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTH). On the 9th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.

5.
Article in Chinese | WPRIM | ID: wpr-777470

ABSTRACT

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae_ukn. The relative abundance of Desulfovibrio and Streptococcaceae_ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.


Subject(s)
Animals , Croton , Chemistry , Diuretics , Drug Interactions , Drugs, Chinese Herbal , Pharmacology , Gastrointestinal Microbiome , Glycyrrhiza , Chemistry , Intestines , Mice , Plant Roots , Chemistry , Seeds , Chemistry
6.
Article in Chinese | WPRIM | ID: wpr-771728

ABSTRACT

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.


Subject(s)
Animals , Drugs, Chinese Herbal , Pharmacology , Gastrointestinal Microbiome , Glycyrrhiza uralensis , Chemistry , Intestinal Mucosa , Pathology , Medicine, Chinese Traditional
7.
Chinese Pharmacological Bulletin ; (12): 1314-1320, 2018.
Article in Chinese | WPRIM | ID: wpr-705195

ABSTRACT

Aim To explore the antidepressant mecha-nism and laws of traditional Chinese formula Yueju Pill by taking drug pair as the breakthrough point. Meth-ods On the basis of anti-depressant activities of Yueju Pill, the combination of different herbs was obtained by the successively disassembling, and the key drug pair was obtained through the acute administration of Yueju Pill in mice. In addition, chronic unpredictable mild stress model was established to further verify the anti-depressant effect of key drug pair, and to explore its molecular mechanism. Results The drug pair of zhizi and chuanxiong was necessary to anti-depression effect of Yueju Pill, and the immobility time of TST and FST was significantly reduced. As expected, the expres-sions of IL-6 and TNF-a and p-NF-kBp65, P-IkBa were obviously lower than those in model group, but the expressions of BDNF and TrkB were up-regulated than those in model group. Conclusions The drug pair of zhizi and chuanxiong is necessary for traditional Chinese formula Yueju Pill for the antidepressant effect. It is assumed that the antidepressant effect and mechanism of zhizi and chuanxiong are connected with cytokine IL-6, TNF-a and protein expressions of p-NF-kBp65, P-IkBa, and BDNF.

8.
Acta Pharmaceutica Sinica ; (12): 222-228, 2017.
Article in Chinese | WPRIM | ID: wpr-779582

ABSTRACT

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).

9.
Article in Chinese | WPRIM | ID: wpr-231009

ABSTRACT

Abelmoschus manihot was rich in flavonoids, which has been reported the activity on protecting angiocarpy and improving renal function. This study aimed to explore the action mechanism of five flavonoids from A. manihot on how to ameliorating insulin resistance through the regulation of the glucose and expression of PPARγ, C/EBPα, SREBP-1, resistin, visfatin, adiponectin in 3T3-L1 adipocytes. After the 3T3-L1 preadipocytes were differentiated into mature adipocytes, insulin resistance model was built. Insulin resistance adipocytes were treated with 5, 100 μmol•L⁻¹ quercetin, isoquercitrin, hyperoside, quercitrin-3'-O-glucoside, gossypetin-8-O-β-glucoside. The glucose was indirectly determined by BCA kit. The mRNA expression levels of PPARγ, C/EBPα, SREBP-1, resistin, visfatin, adiponectin were detected by real-time quantitative PCR. Results showed that five flavonoids at 5 μmol•L⁻¹ could accelerate preadipocytes proliferation and inhibit that at 100 μmol•L⁻¹ Compared with the normal group, glucose uptake reduced significantly in model group (P<0.01). With the treatment of five flavonoids at 100 μmol•L⁻¹, glucose consumption increased significantly (P<0.01). The high expression of PPARγ, C/EBPα, adiponectin expression was significantly increased (P<0.01), and low expression of SREBP-1, resistin, visfatin after respective administration with five flavonoids at 100 μmol•L-1 promoted adipocyte differentiation. This study showed that, HY, JY, QT, QG, GG can control preadipocytes proliferation, promote adipocyte differentiation and regulate the expression of relative factors with lipid metabolism, such as PPARγ, C/EBPα, SREBP-1, adiponectin, resistin, visfatin, increasing glucose utilization and improving insulin resistance in 3T3-L1 adipocyte.

10.
Article in Chinese | WPRIM | ID: wpr-289883

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of postpartum depression (PPD) on adolescent depression of mice offspring.</p><p><b>METHODS</b>Totally 48 Balb/c female mice were equally randomized into control group and stress group. Control group was not given any stress, whereas stress group were given chronic stress: constraining (6 h/d) combined with light stimulation for 24 hours (twice a week). The stress group was divided into 3 groups to measue the animals' behaviors immediately after modeling, three weeks after modeling, and three weeks after delivery to test whether the PPD models were successfully constructed. The first generation (F1) of normal mothers and PPD-born F1 were as follows: control group (CTL-F1) and PPD offspring group (PPD-F1). The 3-4-week-old male CTL-F1 and PPD-F1 mice (n=8 each) were weighed, and received sucrose preference test, forced swimming test, and novelty-supressed feeding test to measure the depression-like behaviors.</p><p><b>RESULTS</b>The 3-and 4-week-old PPD-F1 had significantly lower body mass than CTL-F1 (P=0.000, P=0.002). Also, the sucrose preference significantly decreased (P=0.000), the forced swimming immobility time significantly increased (P=0.001), the latency to feed significantly increased (P=0.000), while food intake significantly decreased (P=0.005).</p><p><b>CONCLUSION</b>PPD offspring may be more susceptible to depression,with a possible eary onset in adolescence.</p>


Subject(s)
Animals , Depression , Depression, Postpartum , Female , Male , Mice , Mice, Inbred BALB C , Pregnancy , Risk Factors , Stress, Psychological
11.
Article in English | WPRIM | ID: wpr-812529

ABSTRACT

The present study aimed at exploring different roles of the same compound in different environment, using preparative HPLC, and the significance to investigating bio-active constituents in traditional Chinese medicine (TCM) on the basis of holism. In this study, the depletion of target component ferulic acid (FA) by using preparative HPLC followed by antioxidant activity testing was applied to investigate the roles of FA in Angelicae Sinensis Radix (DG), Chuanxiong Rhizoma (CX) and their combination (GX). The antioxidant activity was performed by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity testing. FA was successfully and exclusively depleted from DG, CX, and GX, respectively. By comparing the effects of the samples, it was found that FA was one of the main antioxidant constituents in DG, CX and GX, and the roles of FA were DG > CX > GX. Furthermore, the effects of FA varied at different doses in these herbs. This study provided a reliable and effective approach to clarifying the contribution of same compound in different TCMs to their bio-activities. The role of a constituent in different TCMs might be different, and a component with the same content might have different effects in different chemical environments. Furthermore, this study also suggested the potential utilization of preparative HPLC in the characterization of the roles of multi-ingredients in TCM.


Subject(s)
Angelica sinensis , Chemistry , Antioxidants , Chromatography, High Pressure Liquid , Coumaric Acids , Drugs, Chinese Herbal , Rhizome , Chemistry
12.
Article in Chinese | WPRIM | ID: wpr-854464

ABSTRACT

Objective: To investigate the theoretical basis of incompatibility of Euphorbiae pekinensis Radix (EPR) and Glycyrrhizae Radix et Rhizoma (GRR). Methods: In order to compare the effects of EPR used alone and combined with GRR, the diuretic effect was studied by weighing method to observe the urine output of normal mice, while the purgation effect was studied by observing the defecation time, feces pellets, and feces shape after drug administration. Results: In the equivalent dose range of China Pharmacopoeia 2010, the diuretic effect of EPR powder is stronger than its aqueous extract; GRR aqueous extract did not show any promoting or suppressing effect on the diuresis; Within 1 h after coadministration of EPR powder and GRR aqueous extract, urine output was significantly reduced, suggesting that GRR might inhibit the diuretic effect of EPR; The co-detection of EPR and GRR did not cause the obvious changes of urine output. There was no significant purgative effect of EPR powder alone and coadministered with GRR aqueous extract at the same dose level. Conclusion: The diuretic effect of EPR can be suppressed by GRR in the equivalent dose range of China Pharmacopoeia 2010, suggesting that the sweet and mitigation property of GRR relieving the effect of removing water retention by purgation is one of the incompatibility theoretical basis between EPR and GRR.

13.
Article in Chinese | WPRIM | ID: wpr-855273

ABSTRACT

Objective: To study the chemical constituents from the roots and rhizomes of Glycyrrhiza uralensis. Methods: The compounds were separated and purified by solvent and chromatographic methods. Their structures were identified by spectroscopic techniques. Results: Fourteen triterpenoid saponins isolated from 50% ethanol extract of the roots and rhizomes of G. uralensis were identified as uralsaponin C (1), uralsaponin D (2), licorice-saponin A3 (3), uralsaponin F (4), 22β-acetoxyl-glycyrrizin (5), 24-hydroxyl-licorice-saponin E2 (6), licorice-saponin E2 (7), licorice-saponin G2 (8), 22β-acetoxyl-glyrrhaldehyde (9), 3β-O-[β-D-glucuronopyranosyl-(1→2) - β-D-glucuronopyranosyl]-glycyrretol (10), araboglycyrrhizin (11), licorice-saponin J2 (12), glycyrrhizin (13), and glycyrrhetic acid monoglucuronide (14). Compounds 1-14 showed the cytotoxic activity against the human cancer cell lines MGC-803, SW620, and SMMC-7721 with IC50 > 100 μmol/L. The aglycones of compounds 2, 6-8, and 13 displayed the inhibition on the growth of cancer cells with IC50 at 18.3-41.6 μmol/L. Conclusion: Compound 14 is a new natural product, and compound 11 is isolated from the plant for the first time; Compounds 1-14 show no cytotoxic activity against the human cancer cell lines MGC-803, SW620, and SMMC-7721, and the aglycones of compounds 2, 6-8, and 13 could significantly increase the cytotoxic activity after hydrolysis.

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