The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion(I/R)is little known.The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chroma...The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion(I/R)is little known.The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chromatography.The molecular mechanism of D.odorifera leaves on cerebral I/R was investigated.Methods:Serial affinity chromatography based on D.odorifera leaves extract(DLE)affinity matrices were applied to find specific binding proteins in the brain tissues implemented on C57BL/6 mice by intraluminal middle cerebral artery occlusion for 1 h and reperfusion for 24 h.Specific binding proteins were subjected to mass-spectrometry to search for the differentially expressed proteins between control and DLE-affinity matrices.The hub genes were screened based on weighted gene co-expression network analysis(WGCNA).Then,predictive biology and potential experimental verification were performed for the candidate genes.The protective role of DLE in blood-brain barrier damage in cerebral I/R mice was evaluated by the leakage of Evans blue,western blotting,immunohistochemistry,and immunofluorescent staining.Results:952 differentially expressed proteins were classified into seven modules based on WGCNA under soft threshold 6.Based on WGCNA,AKT1,PIK3CA,NOS3,SMAD3,SMAD1,IL6,MAPK1,TGFBR2,TGFBR1,MAPK3,IGF1R,LRG1,mTOR,ROCK1,TGFB1,IL1B,SMAD2,and SMAD518 candidate hub proteins were involved in turquoise module.TGF-β,MAPK,focal adhesion,and adherens junction signaling pathway were associated with candidate hub proteins.Gene ontology analysis demonstrated that candidate hub proteins were related to the TGF-βreceptor signaling pathway,common-partner SMAD protein phosphorylation,etc.DLE could significantly reduce the leakage of Evans blue in mice with cerebral I/R,while attenuating the expression of occludin,claudin-5,and zonula occludens-1.Western blotting demonstrated that regulation of TGF-β/SMAD signaling pathway played an essential role in the protective effect of DLE.Conclusion:Thus,a number of candidate hub proteins were identified based on DLE affinity chromatography through WGCNA.DLE could attenuate the dysfunction of bloodbrain barrier in the TGF-β/SMAD signaling pathway induced by cerebral I/R.展开更多
[Objectives]To develop a paeonol bead popping gum with hypoglycemic effect.[Methods]The paeonol bead popping gum was prepared by the"two-step method",that is,the pill core was prepared by the guttate pill me...[Objectives]To develop a paeonol bead popping gum with hypoglycemic effect.[Methods]The paeonol bead popping gum was prepared by the"two-step method",that is,the pill core was prepared by the guttate pill method,and then the coating was cured by sodium alginate solution and CaCl_(2) solution.The single factor method was used to determine the effects of PEG-4000:paeonol dosage ratio,dropper diameter,condensation time,dropping distance,melting temperature on the comprehensive score of paeonol guttate pill,and the effects of sodium alginate solution concentration,CaCl_(2) solution concentration,number of coating layers,drying time on the comprehensive score of popping gum.Finally,the optimal process was determined and verified by orthogonal experiment method.[Results]When the dosage ratio of PEG-4000:paeonol was 4∶1,the dropper diameter was 4 mm,the condensation time was 5 min,the dropping distance was 6 cm,and the melting temperature was 90℃,the quality of the prepared guttate pill was the optimal.When the concentration of sodium alginate solution was 0.02 g/mL,the concentration of CaCl_(2) solution was 0.25 g/mL,the number of coating layers was 3,and the drying time was 25 min,the appearance and comprehensive score of the obtained popping beads were the optimal.[Conclusions]This study is expected to provide some reference and basis for the development and utilization of hypoglycemic products of traditional Chinese medicine.展开更多
AIM To verify whether curcumin(Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches(PPs) in...AIM To verify whether curcumin(Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches(PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin(IL)-10, interferon(IFN)-γ and transforming growth factor(TGF)-β1 in spleen and colonic mucosa were determined by ELISA.RESULTS The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex Ⅱ, CD205, CD40, CD40 L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis.CONCLUSION Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.展开更多
The quality standards for Fructus Comi have been established based on the effects of the manufacturing processes.Three critical process parameters(CPPs)of extraction,filtration,and concentration to prepare Fructus Com...The quality standards for Fructus Comi have been established based on the effects of the manufacturing processes.Three critical process parameters(CPPs)of extraction,filtration,and concentration to prepare Fructus Comi concentrate were identified by Plackett-Burman design with a single batch of Fructus Corni,which were heating medium temperature,extraction time,and water addition.Morroniside yield,loganin yield,and dry matter yield were process critical quality attributes(CQAs).CPPs arranged with a Box-Behnken design were applied to treat different batches of Fructus Comi After constructing a model that included CPPs,material propertie s,and process CQAs,loganin content was found to be the critical material attribute(CMA).The design space was calculated with a probability method.According to the limits of process CQAs,the minimum content of loganin in Fructus Corni was calculated with an error propagation method,which was 6.92 mg·g^(-1).When the content of loganin in Fructus Corni reaches up to 6.92 mg·g^(-1),the material is considered high-quality and is most suitable for the process.High-quality material can be used for production of Fructus Comi concentrate.This method can also be used to set material quality standards for other Chinese medicines.展开更多
Enhancement of the surface hydrophilicity of biodegradable poly （D,L-lactic acid）（PLA） films is studied. The PLA films were treated by nitrogen plasma （PLA-N2） and nitrogen/hydrogen plasma （PLA-N2/H2）, respect...Enhancement of the surface hydrophilicity of biodegradable poly （D,L-lactic acid）（PLA） films is studied. The PLA films were treated by nitrogen plasma （PLA-N2） and nitrogen/hydrogen plasma （PLA-N2/H2）, respectively. The surface properties and microstructure ofPLA-N2 and PLA-N2/H2 were studied by static contact angle measurement, surface free energycalculation, X-ray photoelectron spectroscopy （XPS） and atomic force microscopy （AFM）. It isconfirmed that the surface hydrophilicity of PLA-N2 and PLA-N2/H2 was higher than that of pristinePLA, and the surface hydrophilicity of PLA-N2 films was better than that of PLA-N2/H2.展开更多
[Objectives]To explore the effects of injection of oregano oil submicron emulsion on lipopolysaccharide-induced pneumonia in rats.[Methods]Rats induced by lipopolysaccharide were used as animal models of acute pneumon...[Objectives]To explore the effects of injection of oregano oil submicron emulsion on lipopolysaccharide-induced pneumonia in rats.[Methods]Rats induced by lipopolysaccharide were used as animal models of acute pneumonia.The experiment was divided into blank group,model group,administration group and positive drug control group.The morphology of lung tissue and the changes of cells and inflammatory factors in each group were observed,and the anti-inflammatory effects of injection of oregano oil submicron emulsion.[Results]The injection of oregano oil submicron emulsion can improve the pathological injury of rat lung tissue,inhibit the release of IL-6,IL-10,TNF-αcytokines induced by lipopolysaccharide,and significantly reduce the value of CRP.[Conclusions]Oregano oil submicron emulsion has a certain therapeutic effect on lipopolysaccharide-induced pneumonia in rats,and its mechanism may be related to reducing the release of cytoinflammatory factor IL-6,IL-10,and TNF-αand alleviating the injury to tissues and organs.展开更多
Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In t...Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.展开更多
Macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential tar...Macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential targets for treating inflammatory diseases.Andrographolide(AND)is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB/MAPK pathway in activated macrophages.Although AND has many medicinal properties,its lower water solubility and first-pass effect in the liver have hindered its clinical application.In this context,by using a metal phenolic network as a stabilizer,we designed and prepared highly stabilized AND nanocrystals(AND-MPN Ns)with high drug loading capacity to facilitate the clinical application of AND.Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization,reducing proinflammatory cytokines IL-6 and TNF-α,and suppressing the NF-κB signaling pathway activation.The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.展开更多
Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indom...Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vector”of rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial cells.The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%SOD.Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine model.Particularly,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect.In vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial cells.In vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the lungs.In conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation.The study offers a promising approach to combat pulmonary endothelium-associated diseases.展开更多
The magnetism of nanographene is dominated by the structure of its carbon skeleton.However,the magnetism engineering of nanographene is hindered due to finite precursors.Here,we demonstrate an ingenious synthetic stra...The magnetism of nanographene is dominated by the structure of its carbon skeleton.However,the magnetism engineering of nanographene is hindered due to finite precursors.Here,we demonstrate an ingenious synthetic strategy to engineer the magnetism of nanographene through hetero-coupling two precursors on Au(111)surface.Bond-resolved scanning tunneling microscopy and spectroscopy results show that two homo-coupled products host a closed-shell structure,while the products with five membered ring defects perform as an open-shell one with the total spin number of 1/2,confirmed by spin-polarized density functional theory calculations.While two hetero precursors on Au(111)substrate,the heterocoupled products both perform as the magnetic structure with total spin quantum numbers of 1/2 and 1,resulting from carbon skeleton transformations.Our work provides an effective way to engineer the magnetism of nanographene by enriching the magnetic products simultaneous,which could be extended into other controllable magnetic nanographene instruction.展开更多
Background:Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff.The attenuation function of biochanin A on blood-brain barrier(BBB)damage induced by cerebral ...Background:Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff.The attenuation function of biochanin A on blood-brain barrier(BBB)damage induced by cerebral ischemia-reperfusion remains unclear.Methods:C57BL/6 mice were subjected to 1 h middle cerebral artery occlusion(MCAO)followed by 24 h reperfusion.The infarct volume of the brain was stained by TTC,while leakage of the brain was quantitatively stained by Evans blue,and the neurologic deficit score was measured.Microglial-induced morphologic changes were observed via immunofluorescence staining,and rolling and adhering leukocytes in venules were observed via two-photon imaging,while the inner fluorescein isothiocyanate-albumin of venules were compared with those of surrounding interstitial area through venular albumin leakage.Results:The attenuation effect of biochanin A on tight junction injury was compared in ischemia-reperfusion mice or conventional knockdown of leucine-richα2-glycoprotein 1(Lrg1)mice.Biochanin A could ameliorate BBB injury in mice with cerebral ischemiareperfusion in a dose-dependent manner by strengthening the immunostaining volume of occludin,claudin-5,and zonula occludens-1.The amoeba morphologic changes of microglial combined with the elevated expression of Lrg1 could be relieved under the treatment of biochanin A.Biochanin A played a countervailing role on the rolling leukocytes in the vessel,while the leakage of blood vessels was reduced.Biochanin A diminished its functions to further improved attenuation for tight junction injury on conventional Lrg1-knockout mice,as well as the inhibition effects on TGF-β1,and the phosphorylation of suppressor of mothers against decapentaplegic 2(Smad2)/Smad2 via western blot assay.Conclusion:Biochanin A could alleviate tight junction injury induced by cerebral ischemiareperfusion and blocked the Lrg1/TGF-β/Smad2 pathway to modulate leukocyte migration patterns.展开更多
AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide(APS) against experimental colitis.METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colit...AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide(APS) against experimental colitis.METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid(TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T(Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-gt(ROR-gt), IL-23 and STAT-5a was measured by Western blot.RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin(IL)-2, IL-6, IL-17, IL-23 and ROR-gt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-β and STAT5 a in the colonic tissues were up-regulated.CONCLUSION: APS effectively ameliorates TNBSinduced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches.展开更多
Objective To study the flavonoids from the heartwood of Dalbergia cochinchinensis. Methods The chemical constituents were isolated and purified by combination of silica gel, macroporous resin, Sephadex LH-20, and ODS ...Objective To study the flavonoids from the heartwood of Dalbergia cochinchinensis. Methods The chemical constituents were isolated and purified by combination of silica gel, macroporous resin, Sephadex LH-20, and ODS column chromatography. Their structures were identified by means of spectral analysis. Results Fifteen flavonoids were isolated and identified as pinocembrin(1), liquiritigenin(2), galangin(3), 7-hydroxy-6-methoxyflavone(4), naringenin(5), alpinetin(6), 2,3-dimethoxyxanthone(7), 6,4′-dihydroxy-7-methoxy-flavan(8), mucronulatol(9), 7,8-dihydroxyflavanone(10), 5,7,3′,5′-tetrahydroxyflavanone(11), 4,2′,5′-trihydroxy-4′-methoxychalcone(12), isoliquiritigenin(13), butein(14), and 3′,5′,5,7-tetrahydroxy-6-C-β-D-glucopyranosylflavanone(15), respectively. Conclusion Compounds 7, 8, 10, and 15 are isolated from the plants of Dalbergia L. f. for the first time, and compounds 1, 3, 5, 6, 9, 11, 12, and 14 are isolated from this plant for the first time.展开更多
Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated ...Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations o200 μmol/L, the effect of peimine concentration, p H, temperature, efflux transport protein inhibitors and EDTA-Na_2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at p H 6.0 and 7.4, the P_(app(AP-BL))of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL)and P_(app(BL-AP))at 4 1C are significantly higher than their corresponding values at 37 1C; that the P-glycoprotein(P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary,the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.展开更多
Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been a...Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile γ-cyclodextrin(γ-CD) metal-organic framework(CD-MOF) large molecular cages in which azilsartan(AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague–Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering(SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy(SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the γ-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.展开更多
A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin ...A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin plate was used to determine the fibrinolytic activity. For the first time fibrinolytic enzyme was found during the fermentation of SSP and the fibrinolytic activities of samples were shown to increase significantly over time. In the "yellow cladding" stage, the fibrinolytic activity was 619.75 IU/g. On day 6, 12 and 15 of the "secondary fermentation" stage, the fibrinolytic activity was 711.49 IU/g, 866.67 IU/g, 1 022.31 IU/g, respectively. The results indicate that fibrinolytic enzyme was generated during the fermentation of SSP and it displayed increasing activity which peaked at the "secondary fermentation" stage. The fibrinolytic enzyme was found to not only degrades fibrin directly, but also activate plasminogen to do so.展开更多
Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obviou...Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.展开更多
Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery o...Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.展开更多
Cyclodextrin metal-organic framework(CD-MOF)as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol(STV).The solubility of STV was lower than20.00 ng/mL at pH 1.0 and ...Cyclodextrin metal-organic framework(CD-MOF)as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol(STV).The solubility of STV was lower than20.00 ng/mL at pH 1.0 and pH 4.5,whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and129.58 ng/mL in water with a significant pH-dependence.The in vitro release profiles of STV from STV@CD-MOF(0.5:1)were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF(1:1)owing to nanoclusters formation.The bioavailability of STV@CD-MOF(1:1)in rats was 8.67-fold higher than that of STV,and was1.32-and 1.27-fold higher than that of STV@CD and STV@CD-MOF(0.5:1).Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio,while the increasement in bioavailability at a high loading ratio,which was attributed to the nanocluster mechanism.This was confirmed by molecular simulation.In conclusion,CD-MOF is a promising system for STV loading,overcoming the insolubility and to improve the bioavailability of this natural compound.展开更多
Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vin...Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vincristine through the membrane of MDCK-MDR1 cells was used as an indicator of the effect of bergapten on vincristine transport.Molecular docking was employed to predict the binding force between bergapten and P-glycoprotein(Pgp). The effects of bergapten on P-gp function and P-gp ATPase activity were determined by rhodamine123(Rho123) accumulation and activity analysis, respectively. 1,6-Diphenyl-1,3,5-hexatriene(DPH) was used to study the effects of bergapten on membrane fluidity, and Western blotting and quantitative realtime PCR assays were performed to analyze the effect of bergapten on the protein and mRNA expression of P-gp, respectively. These experiments clarified the effects of bergapten on the transport of vincristine and allowed exploration of the possible mechanism underlying the effects of bergapten.Results: The results showed that bergapten could inhibit the transport of vincristine in MDCK-MDR1 cells,and the binding force between bergapten and P-gp was weaker. Bergapten could reduce the accumulation of Rh123 in MDCK-MDR1 cells, increase the membrane fluidity, and upregulate P-gp protein and mRNA expression but it had no effect on P-gp ATPase activity.Conclusions: Overall, we concluded that the possible mechanism through which bergapten inhibits vincristine transport was related to the bergapten-mediated upregulation of P-gp protein and mRNA expression, membrane fluidity or P-gp enzyme activity.展开更多
基金supported by National Natural Science Foundation of China(Nos.82100417,81760094,81760724)The Foundation of Jiangxi Provincial Department of Science and Technology Project(Nos.20202ACBL206001,20212BAB206022,20181BAB205026)+1 种基金Youth Project of Jiangxi Education Department(No.GJJ200217)Open Project of Key Laboratory of Modern of TCM,Ministry of Education Jiangxi University of Traditional Chinese Medicine(TCM-2019010).
文摘The attenuation function of Dalbergia odorifera leaves on cerebral ischemia-reperfusion(I/R)is little known.The candidate targets for the Chinese herb were extracted from brain tissues through the high-affinity chromatography.The molecular mechanism of D.odorifera leaves on cerebral I/R was investigated.Methods:Serial affinity chromatography based on D.odorifera leaves extract(DLE)affinity matrices were applied to find specific binding proteins in the brain tissues implemented on C57BL/6 mice by intraluminal middle cerebral artery occlusion for 1 h and reperfusion for 24 h.Specific binding proteins were subjected to mass-spectrometry to search for the differentially expressed proteins between control and DLE-affinity matrices.The hub genes were screened based on weighted gene co-expression network analysis(WGCNA).Then,predictive biology and potential experimental verification were performed for the candidate genes.The protective role of DLE in blood-brain barrier damage in cerebral I/R mice was evaluated by the leakage of Evans blue,western blotting,immunohistochemistry,and immunofluorescent staining.Results:952 differentially expressed proteins were classified into seven modules based on WGCNA under soft threshold 6.Based on WGCNA,AKT1,PIK3CA,NOS3,SMAD3,SMAD1,IL6,MAPK1,TGFBR2,TGFBR1,MAPK3,IGF1R,LRG1,mTOR,ROCK1,TGFB1,IL1B,SMAD2,and SMAD518 candidate hub proteins were involved in turquoise module.TGF-β,MAPK,focal adhesion,and adherens junction signaling pathway were associated with candidate hub proteins.Gene ontology analysis demonstrated that candidate hub proteins were related to the TGF-βreceptor signaling pathway,common-partner SMAD protein phosphorylation,etc.DLE could significantly reduce the leakage of Evans blue in mice with cerebral I/R,while attenuating the expression of occludin,claudin-5,and zonula occludens-1.Western blotting demonstrated that regulation of TGF-β/SMAD signaling pathway played an essential role in the protective effect of DLE.Conclusion:Thus,a number of candidate hub proteins were identified based on DLE affinity chromatography through WGCNA.DLE could attenuate the dysfunction of bloodbrain barrier in the TGF-β/SMAD signaling pathway induced by cerebral I/R.
基金Supported by National Natural Science Foundation of China(81560659&81860771)Science and Technology Project of the Education Department of Jiangxi Province(GJJ201219)+1 种基金Students’Innovative Entrepreneurial Training Plan Program of Jiangxi University of Traditional Chinese Medicine(S202110412003,202010412025,202110412028)Doctoral Research Startup Fund of Jiangxi University of Traditional Chinese Medicine(2018WBZR011)。
文摘[Objectives]To develop a paeonol bead popping gum with hypoglycemic effect.[Methods]The paeonol bead popping gum was prepared by the"two-step method",that is,the pill core was prepared by the guttate pill method,and then the coating was cured by sodium alginate solution and CaCl_(2) solution.The single factor method was used to determine the effects of PEG-4000:paeonol dosage ratio,dropper diameter,condensation time,dropping distance,melting temperature on the comprehensive score of paeonol guttate pill,and the effects of sodium alginate solution concentration,CaCl_(2) solution concentration,number of coating layers,drying time on the comprehensive score of popping gum.Finally,the optimal process was determined and verified by orthogonal experiment method.[Results]When the dosage ratio of PEG-4000:paeonol was 4∶1,the dropper diameter was 4 mm,the condensation time was 5 min,the dropping distance was 6 cm,and the melting temperature was 90℃,the quality of the prepared guttate pill was the optimal.When the concentration of sodium alginate solution was 0.02 g/mL,the concentration of CaCl_(2) solution was 0.25 g/mL,the number of coating layers was 3,and the drying time was 25 min,the appearance and comprehensive score of the obtained popping beads were the optimal.[Conclusions]This study is expected to provide some reference and basis for the development and utilization of hypoglycemic products of traditional Chinese medicine.
基金Supported by the National Natural Science Foundation of China,No.81260595 and No.81460679Chinese Scholar-ship Council and Jiangxi Province as visiting scholar,No.201408360106 and No.201408360110+1 种基金the Traditional Chinese Medicine Project of Health Department of Jiangxi Province,No.2015B049Jiangxi University of Traditional Chinese Medicine,No.JZYC15S13
文摘AIM To verify whether curcumin(Cur) can treat inflammatory bowel disease by regulating CD8+CD11c+ cells. METHODS We evaluated the suppressive effect of Cur on CD8+CD11c+ cells in spleen and Peyer's patches(PPs) in colitis induced by trinitrobenzene sulfonic acid. Mice with colitis were treated by 200 mg/kg Cur for 7 d. On day 8, the therapeutic effect of Cur was evaluated by visual assessment and histological examination, while co-stimulatory molecules of CD8+CD11c+ cells in the spleen and PPs were measured by flow cytometry. The levels of interleukin(IL)-10, interferon(IFN)-γ and transforming growth factor(TGF)-β1 in spleen and colonic mucosa were determined by ELISA.RESULTS The disease activity index, colon weight, weight index of colon and histological score of experimental colitis were obviously decreased after Cur treatment, while the body weight and colon length recovered. After treatment with Cur, CD8+CD11c+ cells were decreased in the spleen and PPs, and the expression of major histocompatibility complex Ⅱ, CD205, CD40, CD40 L and intercellular adhesion molecule-1 was inhibited. IL-10, IFN-γ and TGF-β1 levels were increased compared with those in mice with untreated colitis.CONCLUSION Cur can effectively treat experimental colitis, which is realized by inhibiting CD8+CD11c+ cells.
基金Supported by the Open Fund of Key Laboratory of Modern Chinese Medicine Preparations,Ministry of Education,Jiangxi University of Traditional Chinese Medicine and First-class Discipline Construction Project of Jiangxi Province(JXSYLXK-ZHYAO009,JXSYLXK-ZHYAO010)。
文摘The quality standards for Fructus Comi have been established based on the effects of the manufacturing processes.Three critical process parameters(CPPs)of extraction,filtration,and concentration to prepare Fructus Comi concentrate were identified by Plackett-Burman design with a single batch of Fructus Corni,which were heating medium temperature,extraction time,and water addition.Morroniside yield,loganin yield,and dry matter yield were process critical quality attributes(CQAs).CPPs arranged with a Box-Behnken design were applied to treat different batches of Fructus Comi After constructing a model that included CPPs,material propertie s,and process CQAs,loganin content was found to be the critical material attribute(CMA).The design space was calculated with a probability method.According to the limits of process CQAs,the minimum content of loganin in Fructus Corni was calculated with an error propagation method,which was 6.92 mg·g^(-1).When the content of loganin in Fructus Corni reaches up to 6.92 mg·g^(-1),the material is considered high-quality and is most suitable for the process.High-quality material can be used for production of Fructus Comi concentrate.This method can also be used to set material quality standards for other Chinese medicines.
基金supported by the Fundamental Research Funds for the Central Universities (Nos. GK200901023, GK201004001)
文摘Enhancement of the surface hydrophilicity of biodegradable poly （D,L-lactic acid）（PLA） films is studied. The PLA films were treated by nitrogen plasma （PLA-N2） and nitrogen/hydrogen plasma （PLA-N2/H2）, respectively. The surface properties and microstructure ofPLA-N2 and PLA-N2/H2 were studied by static contact angle measurement, surface free energycalculation, X-ray photoelectron spectroscopy （XPS） and atomic force microscopy （AFM）. It isconfirmed that the surface hydrophilicity of PLA-N2 and PLA-N2/H2 was higher than that of pristinePLA, and the surface hydrophilicity of PLA-N2 films was better than that of PLA-N2/H2.
基金Supported by National Natural Science Foundation of China(81860771)Science and Technology Project of the Education Department of Jiangxi Province(GJJ201219,GJJ170722)+2 种基金Students Innovative Entrepreneurial Training Plan Program of Jiangxi University of Traditional Chinese Medicine(202010412006,202010412143)Program of Key Discipline Training of Young Teachers of Jiangxi University of Traditional Chinese Medicine(2017jzzdxk001)Scientific Research Foundation of Jiangxi University of Traditional Chinese Medicine(2018WBZR011).
文摘[Objectives]To explore the effects of injection of oregano oil submicron emulsion on lipopolysaccharide-induced pneumonia in rats.[Methods]Rats induced by lipopolysaccharide were used as animal models of acute pneumonia.The experiment was divided into blank group,model group,administration group and positive drug control group.The morphology of lung tissue and the changes of cells and inflammatory factors in each group were observed,and the anti-inflammatory effects of injection of oregano oil submicron emulsion.[Results]The injection of oregano oil submicron emulsion can improve the pathological injury of rat lung tissue,inhibit the release of IL-6,IL-10,TNF-αcytokines induced by lipopolysaccharide,and significantly reduce the value of CRP.[Conclusions]Oregano oil submicron emulsion has a certain therapeutic effect on lipopolysaccharide-induced pneumonia in rats,and its mechanism may be related to reducing the release of cytoinflammatory factor IL-6,IL-10,and TNF-αand alleviating the injury to tissues and organs.
基金This research was funded by the Key Program for International Science and Technology Cooperation Projects of China(No.2020YFE0201700)the Innovation Leading Talents Short-term Program of Jiangxi Province,China(No.1262000102)Shanghai Science and Technology Plan(No.21DZ2260400,China).
文摘Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 82073782)the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine,China(No.zdsys-202103)。
文摘Macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential targets for treating inflammatory diseases.Andrographolide(AND)is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB/MAPK pathway in activated macrophages.Although AND has many medicinal properties,its lower water solubility and first-pass effect in the liver have hindered its clinical application.In this context,by using a metal phenolic network as a stabilizer,we designed and prepared highly stabilized AND nanocrystals(AND-MPN Ns)with high drug loading capacity to facilitate the clinical application of AND.Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization,reducing proinflammatory cytokines IL-6 and TNF-α,and suppressing the NF-κB signaling pathway activation.The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.
基金supported by the National Natural Science Foundation of China,China (Nos.81872823,82073782 and 82241002)the Shanghai Science and Technology Committee,China (No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine,China (zdsys202103)。
文摘Lung inflammation is an essential inducer of various diseases and is closely related to pulmonary-endothelium dysfunction.Herein,we propose a pulmonary endothelium-targeted codelivery system of anti-inflammatory indomethacin(IND)and antioxidant superoxide dismutase(SOD)by assembling the biopharmaceutical SOD onto the“vector”of rod-like pure IND crystals,followed by coating with anti-ICAM-1 antibody(Ab)for targeting endothelial cells.The codelivery system has a 237 nm diameter in length and extremely high drug loading of 39%IND and 2.3%SOD.Pharmacokinetics and biodistribution studies demonstrate the extended blood circulation and the strong pulmonary accumulation of the system after intravenous injection in the lipopolysaccharide(LPS)-induced inflammatory murine model.Particularly,the system allows a robust capacity to target pulmonary endothelium mostly due to the rod-shape and Ab coating effect.In vitro,the preparation shows the synergistic antiinflammatory and antioxidant effects in LPS-activated endothelial cells.In vivo,the preparation exhibits superior pharmacodynamic efficacy revealed by significantly downregulating the inflammatory/oxidative stress markers,such as TNF-a,IL-6,COX-2,and reactive oxygen species(ROS),in the lungs.In conclusion,the codelivery system based on rod-like pure crystals could well target the pulmonary endothelium and effectively alleviate lung inflammation.The study offers a promising approach to combat pulmonary endothelium-associated diseases.
基金supported by the National Natural Science Foundation of China(No.61901200)the National Recruitment Program for Young Professionals(No.132310976002)+2 种基金the Yunnan Fundamental Research Projects(Nos.2019FD041,202101AV070008,202101AW070010 and 202101AU070043)the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB30000000)the Dongguan Innovation Research Team Program。
文摘The magnetism of nanographene is dominated by the structure of its carbon skeleton.However,the magnetism engineering of nanographene is hindered due to finite precursors.Here,we demonstrate an ingenious synthetic strategy to engineer the magnetism of nanographene through hetero-coupling two precursors on Au(111)surface.Bond-resolved scanning tunneling microscopy and spectroscopy results show that two homo-coupled products host a closed-shell structure,while the products with five membered ring defects perform as an open-shell one with the total spin number of 1/2,confirmed by spin-polarized density functional theory calculations.While two hetero precursors on Au(111)substrate,the heterocoupled products both perform as the magnetic structure with total spin quantum numbers of 1/2 and 1,resulting from carbon skeleton transformations.Our work provides an effective way to engineer the magnetism of nanographene by enriching the magnetic products simultaneous,which could be extended into other controllable magnetic nanographene instruction.
基金supported by a Foundation Project:National Natural Science Foundation of China(Nos.82100417,81760094),ChinaThe Foundation of Jiangxi Provincial Department of Science and Technology Project(Nos.20202ACBL206001,20212BAB206022,20181BAB205026).
文摘Background:Biochanin A is an excellent dietary isoflavone that has the concomitant function of both medicine and foodstuff.The attenuation function of biochanin A on blood-brain barrier(BBB)damage induced by cerebral ischemia-reperfusion remains unclear.Methods:C57BL/6 mice were subjected to 1 h middle cerebral artery occlusion(MCAO)followed by 24 h reperfusion.The infarct volume of the brain was stained by TTC,while leakage of the brain was quantitatively stained by Evans blue,and the neurologic deficit score was measured.Microglial-induced morphologic changes were observed via immunofluorescence staining,and rolling and adhering leukocytes in venules were observed via two-photon imaging,while the inner fluorescein isothiocyanate-albumin of venules were compared with those of surrounding interstitial area through venular albumin leakage.Results:The attenuation effect of biochanin A on tight junction injury was compared in ischemia-reperfusion mice or conventional knockdown of leucine-richα2-glycoprotein 1(Lrg1)mice.Biochanin A could ameliorate BBB injury in mice with cerebral ischemiareperfusion in a dose-dependent manner by strengthening the immunostaining volume of occludin,claudin-5,and zonula occludens-1.The amoeba morphologic changes of microglial combined with the elevated expression of Lrg1 could be relieved under the treatment of biochanin A.Biochanin A played a countervailing role on the rolling leukocytes in the vessel,while the leakage of blood vessels was reduced.Biochanin A diminished its functions to further improved attenuation for tight junction injury on conventional Lrg1-knockout mice,as well as the inhibition effects on TGF-β1,and the phosphorylation of suppressor of mothers against decapentaplegic 2(Smad2)/Smad2 via western blot assay.Conclusion:Biochanin A could alleviate tight junction injury induced by cerebral ischemiareperfusion and blocked the Lrg1/TGF-β/Smad2 pathway to modulate leukocyte migration patterns.
基金Supported by National Natural Science Foundation of ChinaNo.81260595 and No.81460679+5 种基金Natural Science Foundation of Jiangxi ProvinceNo.20122BAB215046Chinese Scholarship Council and Jiangxi Province as visiting scholar(CSC:No.201408360106No.201408360110)the Science and Technology project of TCM from the Department of Health of Jiangxi ProvinceNo.2012A017
文摘AIM: To explore probable mechanism underlying the therapeutic effect of Astragalus polysaccharide(APS) against experimental colitis.METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups. Colitis was induced with 2, 4, 6-trinitrobenzene sulfonic acid(TNBS). The rats with colitis were treated with 400 mg/kg of APS for 7 d. The therapeutic effect was evaluated by colonic weight, weight index of the colon, colonic length, and macroscopic and histological scores. The levels of regulatory T(Treg) cells in Peyer's patches were measured by flow cytometry, and cytokines in colonic tissue homogenates were analyzed using enzyme-linked immunosorbent assay. The expression of related orphan receptor-gt(ROR-gt), IL-23 and STAT-5a was measured by Western blot.RESULTS: After 7-d treatment with APS, the weight index of the colon, colonic weight, macroscopical and histological scores were decreased, while the colonic length was increased compared with the model group. The expression of interleukin(IL)-2, IL-6, IL-17, IL-23 and ROR-gt in the colonic tissues was down-regulated, but Treg cells in Peyer's patches, TGF-β and STAT5 a in the colonic tissues were up-regulated.CONCLUSION: APS effectively ameliorates TNBSinduced experimental colitis in rats, probably through restoring the number of Treg cells, and inhibiting IL-17 levels in Peyer's patches.
基金National Natural Science Foundation of China(81360629)
文摘Objective To study the flavonoids from the heartwood of Dalbergia cochinchinensis. Methods The chemical constituents were isolated and purified by combination of silica gel, macroporous resin, Sephadex LH-20, and ODS column chromatography. Their structures were identified by means of spectral analysis. Results Fifteen flavonoids were isolated and identified as pinocembrin(1), liquiritigenin(2), galangin(3), 7-hydroxy-6-methoxyflavone(4), naringenin(5), alpinetin(6), 2,3-dimethoxyxanthone(7), 6,4′-dihydroxy-7-methoxy-flavan(8), mucronulatol(9), 7,8-dihydroxyflavanone(10), 5,7,3′,5′-tetrahydroxyflavanone(11), 4,2′,5′-trihydroxy-4′-methoxychalcone(12), isoliquiritigenin(13), butein(14), and 3′,5′,5,7-tetrahydroxy-6-C-β-D-glucopyranosylflavanone(15), respectively. Conclusion Compounds 7, 8, 10, and 15 are isolated from the plants of Dalbergia L. f. for the first time, and compounds 1, 3, 5, 6, 9, 11, 12, and 14 are isolated from this plant for the first time.
基金supported by a grant from the Natural Science Foundation of Jiangxi Province (Grant No. 2008GZY0115)financially supported by the National Natural Science Foundation of China (Grant No. 81060346)
文摘Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations o200 μmol/L, the effect of peimine concentration, p H, temperature, efflux transport protein inhibitors and EDTA-Na_2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at p H 6.0 and 7.4, the P_(app(AP-BL))of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL)and P_(app(BL-AP))at 4 1C are significantly higher than their corresponding values at 37 1C; that the P-glycoprotein(P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary,the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.
基金financial support from the Project funded by the National Science and Technology Major Projects for the Major New Drugs Innovation and Development (2018ZX09721002-009, China)Strategic Priority Research Program of Chinese Academy of Sciences (XDA12050307)+1 种基金National Natural Science Foundation of China (81430087)China Postdoctoral Science Foundation (2017M610284)
文摘Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile γ-cyclodextrin(γ-CD) metal-organic framework(CD-MOF) large molecular cages in which azilsartan(AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague–Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering(SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy(SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the γ-CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six γ-CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.
基金Supported by the National Natural Science Foundation of China(81660664)the Natural Science Foundation of Jiangxi Province(20192ACBL21032,20192BBGL70051,20192BAB205098,20171BAB21 5061,GJJ150844,GJJ160858)+1 种基金Jiangxi Provincial Health and Family Planning Commission(2017Z016)the Natural Science Foundation of Jiangxi University of Traditional Chinese Medicine(2014BS013).
文摘A strong fibrinolytic activity was demonstrated in the Semen Sojae Praeparatum(SSP), which is a famous traditional Chinese medicine. To study the activities and dynamic changes of fibrinolytic enzyme, standard fibrin plate was used to determine the fibrinolytic activity. For the first time fibrinolytic enzyme was found during the fermentation of SSP and the fibrinolytic activities of samples were shown to increase significantly over time. In the "yellow cladding" stage, the fibrinolytic activity was 619.75 IU/g. On day 6, 12 and 15 of the "secondary fermentation" stage, the fibrinolytic activity was 711.49 IU/g, 866.67 IU/g, 1 022.31 IU/g, respectively. The results indicate that fibrinolytic enzyme was generated during the fermentation of SSP and it displayed increasing activity which peaked at the "secondary fermentation" stage. The fibrinolytic enzyme was found to not only degrades fibrin directly, but also activate plasminogen to do so.
基金supported by National Nature Science Fundation of China(Nos.81274026 and 81403115)
文摘Aconite is a valuable drug and also a toxic material, which can be used only after detoxification processing. Although traditional processing methods can achieve detoxification effect as desired, there are some obvious drawbacks, including a significant loss of alkaloids and poor quality consistency. It is thus necessary to develop a new detoxification approach. In the present study, we designed a novel one-step detoxification approach by quickly drying fresh-cut aconite particles. In order to evaluate the technical advantages, the contents of mesaconitine, aconitine, hypaconitine, benzoylmesaconine, benzoylaconine, benzoylhypaconine, neoline, fuziline, songorine, and talatisamine were determined using HPLC and UHPLC/Q-TOF-MS. Multivariate analysis methods, such as Clustering analysis and Principle component analysis, were applied to determine the quality differences between samples. Our results showed that traditional processes could reduce toxicity as desired, but also led to more than 85.2% alkaloids loss. However, our novel one-step method was capable of achieving virtually the same detoxification effect, with only an approximately 30% alkaloids loss. Cluster analysis and Principal component analysis analyses suggested that Shengfupian and the novel products were significantly different from various traditional products. Acute toxicity testing showed that the novel products achieved a good detoxification effect, with its maximum tolerated dose being equivalent to 20 times of adult dosage. And cardiac effect testing also showed that the activity of the novel products was stronger than that of traditional products. Moreover, particles specification greatly improved the quality consistency of the novel products, which was immensely superior to the traditional products. These results would help guide the rational optimization of aconite processing technologies, providing better drugs for clinical treatment.
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 81773826)the Double First-Class(CPU2018PZQ13,China)of the China Pharmeutical University+2 种基金the Ministry of Science and Technology of China(2018ZX09711001)the Shanghai Science and Technology Committee(19430741500,China)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of traditional Chinese Medicine(TCM201905,China)
文摘Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
基金financial support from the National Science Foundation for Young Scientists of China(No.81803441)the National Science and Technology Major Projects for the Major New Drugs Innovation and Development(No.2018ZX09721002-009,China)+1 种基金the National Natural Science Foundation of China(No.81873019)the University Synergy Innovation Program of Anhui Province(GXXT-2020-025)
文摘Cyclodextrin metal-organic framework(CD-MOF)as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol(STV).The solubility of STV was lower than20.00 ng/mL at pH 1.0 and pH 4.5,whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and129.58 ng/mL in water with a significant pH-dependence.The in vitro release profiles of STV from STV@CD-MOF(0.5:1)were pH-independent in distinct pH media and closed to be thoroughly released but no such release profiles were observed for STV@CD-MOF(1:1)owing to nanoclusters formation.The bioavailability of STV@CD-MOF(1:1)in rats was 8.67-fold higher than that of STV,and was1.32-and 1.27-fold higher than that of STV@CD and STV@CD-MOF(0.5:1).Our results indicated that the inclusion mechanism played a primary role when STV in CD-MOF was at a low loading ratio,while the increasement in bioavailability at a high loading ratio,which was attributed to the nanocluster mechanism.This was confirmed by molecular simulation.In conclusion,CD-MOF is a promising system for STV loading,overcoming the insolubility and to improve the bioavailability of this natural compound.
基金supported by a project of the National Natural Science Foundation of China(Grant No.81303237)the Training Project of Young Scientists in Jiangxi Province(No.20153BCB23019)+1 种基金China Postdoctoral Science Foundation(2016M590606)the National Natural Science Foundation of Jiangxi Province(20161ACB21020)
文摘Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism.Methods: The apparent permeability coefficient(Papp) for the transport of vincristine through the membrane of MDCK-MDR1 cells was used as an indicator of the effect of bergapten on vincristine transport.Molecular docking was employed to predict the binding force between bergapten and P-glycoprotein(Pgp). The effects of bergapten on P-gp function and P-gp ATPase activity were determined by rhodamine123(Rho123) accumulation and activity analysis, respectively. 1,6-Diphenyl-1,3,5-hexatriene(DPH) was used to study the effects of bergapten on membrane fluidity, and Western blotting and quantitative realtime PCR assays were performed to analyze the effect of bergapten on the protein and mRNA expression of P-gp, respectively. These experiments clarified the effects of bergapten on the transport of vincristine and allowed exploration of the possible mechanism underlying the effects of bergapten.Results: The results showed that bergapten could inhibit the transport of vincristine in MDCK-MDR1 cells,and the binding force between bergapten and P-gp was weaker. Bergapten could reduce the accumulation of Rh123 in MDCK-MDR1 cells, increase the membrane fluidity, and upregulate P-gp protein and mRNA expression but it had no effect on P-gp ATPase activity.Conclusions: Overall, we concluded that the possible mechanism through which bergapten inhibits vincristine transport was related to the bergapten-mediated upregulation of P-gp protein and mRNA expression, membrane fluidity or P-gp enzyme activity.
