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Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.
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【Objective】 To clarify the composition of essential oil extracted from Chimonanthus praecox flowers in Shiyan area and to explore its anti-inflammatory effects to provide support for further development of the resources of Chimonanthus praecox flowers. 【Methods】 SD rats were randomly divided into blank control group, model group, positive control group (aspirin 200 mg/kg), and low-, medium- and high-dose essential oil groups (0.1, 0.3 and 0.8g/kg). The blank control group and the model group were treated with distilled water by intragastric administration. The positive control group was treated with aspirin by intragastric administration. The low, medium, and high doses of the essential oil extracted from Chimonanthus praecox flowers were given 10, 30 and 80 mL/L at 10 mL/kg once a day. On day 5 of the experiment, 30 minutes after intragastric administration, 0.1 mL of Freund’s complete adjuvant was injected subcutaneously into the right foot plantar of each group of rats, and the blank control group was subcutaneously injected with 0.1 mL of normal saline. We observed and measured the toe’s volume of the rats before and 1, 2, 3, 5, 24, 48, and 72 h after injection by using drainage method. We then calculated the toe’s swelling rate in each group of rats at each time point, and used ELISA kit to measure the content of inflammatory factors in swollen foot tissue. 【Results】 In the medium- and high-dose essential oil groups, we observed significant inhibitory effects on the toe’s swelling rate in rats at 1, 2, 3, 5, 24, and 48 h after inflammation with Freund’s complete adjuvant (P<0.05). The essential oil extracted from Chimonanthus praecox flowers could significantly decrease the contents of TNF-α and IL-1β in the swollen foot tissue, and its anti-inflammatory effect was dose-dependent. 【Conclusion】 The essential oil extracted from Chimonanthus praecox flowers has obvious inhibitory effects on the rate of the toe’s swelling induced by Freund’s complete adjuvant. The anti-inflammatory effect may be related to the inhibition of TNF-α and IL-1β, but its anti-inflammatory effect is weaker than that of aspirin.
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OBJECTIVE:To systematically review the efficacy and safety of insulin glargine versus premixed insulin in treat-ment of type 2 diabetes,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,CJFD, Wanfang Database and VIP Database,the randomized controlled trials(RCT)about the efficacy and safety of premixed insulin ver-sus insulin glargine in the treatment of type 2 diabetes were collected. Meta-analysis was performed by using Rev Man 5.0 statistics software after extracting data and evaluating quality by modified Jadad. RESULTS:A total of 10 RCTs were enrolled,involving 1 655 patients. Results of Meta-analysis showed that insulin glargine was better than premixed insulin on reducing glycated hemoglobin [M=-0.41,95% CI(-0.64,-0.18),P<0.001] and fasting blood glucose [MD=-0.51,95% CI(-0.99,-0.02),P=0.04], there were significantly differences between 2 groups,and there were no significantly differences in reducing 2 h postprandial blood glucose [MD=-0.56,95% CI(-1.21,0.09),P=0.09] and body mass index [MD=-0.52,95% CI(-1.52,0.48),P=0.31];the incidence of hypoglycemia in insulin glargine group was significantly lower than premixed insulin,there were significantly differ-ences between 2 groups [RR=0.65,95%CI(0.46,0.90),P=0.01]. CONCLUSIONS:The efficacy and safety of insulin glargine are better than premixed insulin in the treatment of type 2 diabetes.