Synthesis, light-controlled antibacterial and anti-tumor activities of Ginkgo biloba leaves polyprenols-based polypyridine metal complexes.

In this study, Ginkgo biloba leave polyprenols (GBP) and polypyridine metal complex were individually utilized as functional ligand and main ligand, four kinds of novel GBP-based polypyridine metal complexes were successfully synthesized and their cell absorption capacity, light-dark stability, photodissociation efficiency, ROS production capacity, light-controlled antibacterial and anti-tumor activities as well as mechanisms were systematically investigated by ultraviolet visible spectrophotometer (UV-vis), confocal laser scanning microscope (CLSM), gel electrophoresis (GE), scanning electron microscope (SEM), oxford cup method, MTT method etc. The lipid water distribution coefficients of complex 1, 2 and 4 were all within the range of 0∼3, demonstrating their better cell absorption capacity and more competitive bioavailability potentiality compared with GBP. All of the synthesized complexes possessed excellent stability in a dark environment, and could conduct ligand dissociation under the condition of visible light irradiation except complex 1. In which, complex 2 and complex 4 were able to achieve degradation rates of 37.9 % and 54.4 % within 5 min, separately. In addition, complex 2 and complex 4 exhibited superior inhibitory activities on the HN-3 tumor cells on account of their stronger ROS production capacity. Moreover, the constricted expression of BCL-2 and NF-kB p-p65, especially the promoted expression of BAX may be one of the root cause. The four synthesized complexes had preferable inhibition effects against S. aureus under the condition of visible light irradiation in contrast to darkness, in which complex 4 was the best and its MIC and MBC values were 6.25 and 12.5 µg/mL, respectively. The antibacterial mechanism of the complex 4 may be in relation to the synergistic effect of multiple factors, including leakage of bacterial inclusion, change of cell membrane permeability and disruption of cell wall etc. All of the above generalized researches will pave a way for the high-value development and application of GBP-based functional products.

Lutein-Based pH and Photo Dual-Responsive Novel Liposomes Coated with Ce6 and PTX for Tumor Therapy.

Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from -45.45 to -28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.

Design, Synthesis, and Biological Evaluation of New Urushiol Derivatives as Potent Class I Histone Deacetylase Inhibitors.

In the present study, a novel series of 11 urushiol-based hydroxamic acid histone deacetylase (HDAC) inhibitors was designed, synthesized, and biologically evaluated. Compounds 1-11 exhibited good to excellent inhibitory activities against HDAC1/2/3 (IC50 : 42.09-240.17 nM) and HDAC8 (IC50 : 16.11-41.15 nM) in vitro, with negligible activity against HDAC6 (>1409.59 nM). Considering HDAC8, docking experiments revealed some important features contributing to inhibitory activity. According to Western blot analysis, select compounds could notably enhance the acetylation of histone H3 and SMC3 but not-tubulin, indicating their privileged structure is appropriate for targeting class I HDACs. Furthermore, antiproliferation assays revealed that six compounds exerted greater in vitro antiproliferative activity against four human cancer cell lines (A2780, HT-29, MDA-MB-231, and HepG2, with IC50 values ranging from 2.31-5.13 µM) than suberoylanilide hydroxamic acid; administration of these compounds induced marked apoptosis in MDA-MB-231 cells, with cell cycle arrest in the G2/M phase. Collectively, specific synthesized compounds could be further optimized and biologically explored as antitumor agents.

Characterization and antibacterial activity of ruthenium-based shikimate cross-linked chitosan composites.

The unsustainable antibacterial activity of ruthenium antibacterial agents is an important factor limiting their applications. This present work attempts to prepare ruthenium (Ru) coordination polymer composites with chitosan quaternary ammonium polymers (CQ) and shikimic acid (SA) through the interaction of ionic bonds and covalent bonds by microwave-assisted high-pressure homogenization methods. The prepared CQ@Ru-SA was characterized by size distribution, zeta potential, TEM, UV-vis, FTIR, XPS and XRD analyses. The coordination structure and morphology of Bridge-CQ-NH-Ru-SA were verified. The CQ@Ru-SA was well-dispersed in both the aqueous or anhydrous states. MIC and MBC, time-killing curves, biofilm formation inhibition assay, mature biofilm disruption assay, SEM, Ca2+ mobilization assay and Ca2+-Mg2+-ATPase activity studies revealed that CQ@Ru-SA had a stronger inhibitory effect against S. aureus than CQ and showed sustained antibacterial properties in the dynamic time-killing curves. Meanwhile, CQ@Ru-SA had good antibacterial effects against S. aureus and inhibited their biofilm forming ability in a dose-dependent manner. Further studies on antibacterial mechanisms revealed that CQ@Ru-SA influenced cell membrane integrity, Ca2+-Mg2+-ATPase activity on the cell membrane and intracellular Ca2+ levels of S. aureus. This study will provide the necessary data for the further design and development of ruthenium-based photosensitive antibacterial agents.

Development and physicochemical characterization of nanoliposomes with incorporated oleocanthal, oleacein, oleuropein and hydroxytyrosol.

Oleocanthal, oleacein, oleuropein and hydroxytyrosol comprise characteristic polyphenols of olive with high biological value. However, stability problems hinder their further investigation. Thus, in the present study they were incorporated in nanoliposomes by thin film hydration method. The particles sizes, PDI, zeta-potential and physicochemical stabilities of nanoliposomes were evaluated by light scattering methods while FTIR, XRD, TGA and DSC methods were carried out for further physicochemical characterization. Their micromorphology was illustrated by negative-staining TEM and Cryo-TEM, revealing well-dispersed round-shaped vesicles. According to in vitro release studies, oleocanthal and oleacein were rapidly released in a higher percentage than oleuropein and hydroxytyrosol and compatible with the Ritger-Peppas model release mechanism while only oleuropein liposomes were governed by anomalous diffusion of non-Fickian diffusion. Antioxidant assays showed that nanoliposomes presented comparable activity with pure compounds enabling them as suitable carriers for the delivery of olive active biophenols in the human organism.

Effect of Variety and Maturity Index on the Physicochemical Parameters Related to Virgin Olive Oil from Wudu (China).

Physical parameters (i.e., extraction yield, oil content), chemicals (i.e., fatty acids, phenolics) and oxidative stability associated with virgin olive oil (VOO) from ten varieties in Wudu, China, were analyzed as a function of maturity index and variety by multivariate analysis models. Most of the analytical parameters were significantly affected by the variety and maturity index, and the former was more influential than the latter. Phenolics were the principal factor dividing the ten varieties into four groups. High phenolic levels were observed in the 'Koroneiki' group and 'Manzanilla' group, but the oil extractability index differentiated between them, being the highest and lowest, respectively. The 'Koroneiki' group demonstrated high oil productivity and oil quality, which was worthy of promotion in large-scale cultivation. High amounts of linoleic enhanced the VOO health benefits of 'Ascolana tenera, Arbequina and Zhongshan24' group, but brought the risk of shortening the shelf-life. The 'Ulliri Bardhe, Empeltre, Ezhi8, Yuntai14 and Picual' group clustered for the higher relative value of oleic acid. The maturity index had significant negative effects on the content of total phenolics, oleacein, oleocanthal, and oleic acid, but had a positive effect on the extractability index, which suggested that varieties with low phenolics and oleic acid levels should be harvested early.

Dietary Fiber Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Function Damage in Piglets by Modulation of Intestinal Microbiome.

Weaning of piglets is accompanied by intestinal inflammation, impaired intestinal barrier function, and intestinal microflora disorder. Regulating intestinal microflora structure can directly or indirectly affect intestinal health and host growth and development. However, whether dietary fiber (DF) affects the inflammatory response and barrier function by affecting the intestinal microflora and its metabolites is unclear. In this study, we investigated the role of intestinal microflora in relieving immune stress and maintaining homeostasis using piglets with lipopolysaccharide (LPS)-induced intestinal injury as a model. DF improved intestinal morphology and barrier function, inhibited the expression of inflammatory signal pathways (Toll-like receptor 2 [TLR2], TLR4, and NF-κB) and proinflammatory cytokines (interleukin 1ß [IL-1ß], IL-6, and tumor necrosis factor alpha [TNF-α]), and upregulated the expression of barrier-related genes (encoding claudin-1, occludin, and ZO-1). The contents of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and the activity of diamine oxidase in plasma were decreased. Meanwhile, DF had a strong effect on the composition and function of intestinal microflora at different taxonomic levels, the relative abundances of cellulolytic bacteria and anti-inflammatory bacteria were increased, and the concentrations of propionate, butyrate, and total short-chain fatty acids (SCFAs) in intestinal contents were increased. In addition, the correlation analysis also revealed the potential relationship between metabolites and certain intestinal microflora, as well as the relationship between metabolites and intestinal morphology, intestinal gene expression, and plasma cytokine levels. These results indicate that DF improves intestinal barrier function, in part, by altering intestinal microbiota composition and increasing the synthesis of SCFAs, which subsequently alleviate local and systemic inflammation.IMPORTANCE Adding DF to the diet of LPS-challenged piglets alleviated intestinal and systemic inflammation, improved intestinal barrier function, and ultimately alleviated the growth retardation of piglets. In addition, the addition of DF significantly increased the relative abundance of SCFA-producing bacteria and the production of SCFAs. We believe that the improvement of growth performance of piglets with LPS-induced injury can be attributed to the beneficial effects of DF on intestinal microflora and SCFAs, which reduced the inflammatory response in piglets, improving intestinal barrier function and enhancing body health. These research results provide a theoretical basis and guidance for the use of specific fiber sources in the diet to improve intestinal health and growth performance of piglets and thus alleviate weaning stress. Our data also provide insights for studying the role of DF in regulating gastrointestinal function in human infants.

Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein.

Ursolic acid (UA) is an accessible triterpenoid, widely applied in the design and synthesis of antitumor compounds. However, the mechanism of its anti-tumor effect is still unclear. To verify the molecular mechanism of its biological activity, based on the bifunctional activity of ubiquitination and subsequent proteasomal degradation of the target protein of the proteolysis-targeting chimeras (PROTACs) strategy, here we report the design, synthesis and cellular activity of six UA PROTAC hydrochloride compounds 1A-1F, in which UA acts as the binding ligand of the PROTAC and is linked to thalidomide (E3 ligand) through a series of synthetic linkers. The results revealed that compound 1B, connected with a POE-3 (3-Polyoxyether) possessed remarkable in vitro antitumor activity (with the IC50 value of 0.23 ~ 0.39 µM against A549, Huh7, HepG2). WB results demonstrated that the administration of compound 1B induced significant degradation of MDM2 (only 25% to that of SM1), and promoted the expression of P21 and PUMA proteins, and thus inhibited the proliferation (77.67% of 1B vs 60.37% of CON in G1 phase) and promoted the apoptosis (26.74% of 1B vs 3.35% of CON) of A549 cells. This work demonstrated proof of designing the efficient target protein degradation by UA PROTACs with the POE linkers. In addition, we confirmed that UA possess the characteristic of targeted-binding the protein of murine double minute-2 protein (MDM2). This will lay a foundation for the comprehensive utilization of forest natural compound UA.

Consumption of Dietary Fiber from Different Sources during Pregnancy Alters Sow Gut Microbiota and Improves Performance and Reduces Inflammation in Sows and Piglets.

In pregnant and lactating sows, metabolism and immunity undergo drastic changes, which can lead to constipation, abortion, and intrauterine growth restriction (IUGR) and reduce production performance. Dietary fiber can regulate animal gut microbiota, alleviate inflammatory responses, and improve performance. Here, 48 sows (Large × Landrace) were randomly allocated to groups including, control, and with alfalfa meal (AM), beet pulp, and soybean skin dietary supplementation for 60 days of gestation. The AM diet decreased IUGR, increased food intake during lactation, and promoted the reproductive performance and physical condition of sows. Further, the AM diet significantly reduced markers of intestinal permeability (reactive oxygen species and endotoxin) in sow serum, and of systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor alpha) in sow feces and serum, as well as piglet serum, while it increased the anti-inflammatory marker, IL-10, in sow serum and feces. The AM diet also significantly affected gut microbiota by increasing the relative abundance of proinflammatory bacteria, while decreasing anti-inflammatory bacteria. Moreover, the total short-chain fatty acid (SCFA) content was higher in feces from sows fed an AM diet, with butyric acid content significantly higher during lactation, than in controls. Sow performance was correlated with intestinal permeability, inflammation, and gut microbiota, which were also vertically transmitted to piglets. Our results are significant for guiding feed management in the pig breeding industry. Further, the "sows to piglets" model provides a reference for the effect of dietary fiber on the gastrointestinal function of human mothers and infants.IMPORTANCE Although the direct effects of dietary fiber on gut microbiota composition have been studied extensively, systematic evaluation of different fiber sources on gut health and inflammatory responses of sows and their offspring has rarely been conducted. Excessive reactive oxygen species produced by overactive metabolic processes during late pregnancy and lactation of sows leads to increased endotoxin levels, disordered gut microbiota, decreased SCFA production, and secretion of proinflammatory factors, which in turn causes local inflammation of the gut, potential damage of the gut microbial barrier, increased gut permeability, increased blood endotoxin levels (resulting in systemic inflammation), and ultimately decreased sow and piglet performance. Our results showed that supplementation of the diet with alfalfa meal in mid and late pregnancy can reverse this process. Our findings lay a foundation for improving the gut health of sows and piglets and provide insights into the study of the gastrointestinal tract function in human mothers and infants.

Protective effects of alfalfa saponins on oxidative stress-induced apoptotic cells.

As is known, alfalfa saponins can be used as a feed additive in a pig's diet and the addition of alfalfa saponins to a pig's diet could improve its antioxidant capacity. However, the mechanism by which alfalfa saponins exert their antioxidant effects has not been studied. To address this issue, H2O2-induced rat intestinal epithelial cells were used to establish an oxidative stress model to explore the protective mechanism of alfalfa saponins in this study. The results demonstrated that alfalfa saponins could rescue the cell proliferation activity, elevate the amount of antioxidant enzymes and downregulate the release of MDA and LDH in H2O2-induced cells. The antioxidant activity of alfalfa saponins was achieved by restoring GSH homeostasis. Further results demonstrated that alfalfa saponins could inhibit cell apoptosis through activating the MAPK signaling pathway. These results elucidated the mechanism by which alfalfa saponins exert their antioxidant effects and provided a potential strategy for alleviating oxidative stress in monogastric animals.

Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity.

PURPOSE: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(ß-amino ester) (mPEG-PBAE). MATERIALS AND METHODS: We synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo. RESULTS: The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation. CONCLUSION: The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.

Synthesis and cytotoxicity of hybrids of 1,3,4- or 1,2,5-oxadiazoles tethered from ursane and lupane core with 1,2,3-triazole.

Ursane and lupane type (1-((5-aryl-1,3,4-oxadiazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl and (1-((4-methyl-2-oxido-1,2,5-oxadiazol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl hybrids were prepared by 1,3-cycloaddition reactions of azole-derived azides with alkyne esters connected to positions C-3 and C-28 of triterpene core and tested for cytotoxicity. Hybrid compounds of 1,3,4-oxadiazoles attached at positions 3- and 28- of triterpenoid frame via triazole spacer and combinations of 1,2,5-oxadiazole or 1,3,4-oxadiazole, tethered with succinate linker and 1,2,3-triazole at the position 3- of the ursane backbone, were inactive in relation to all the cancer cells tested. Eventually, combinations of furoxan fragment and 1,2,3-triazole linked to C-28 position of triterpene backbone demonstrated marked cytotoxic activity towards MCF-7 and HepG2 cells. The most active ester of ursolic acid with (1-((4-methyl-2-oxido-1,2,5-oxadiazol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl substituent and 3-O-acetyl group was superior in activity and selectivity over doxorubicin and ursolic acid on MCF-7 cells. The length of the carbon spacer group may be of crucial importance for cytotoxicity. The introduction of the additional ester linker between the C-28 of triterpenoid and triazole or changing triazole spacer between furoxan moiety and triterpenoid core resulted in activity decrease against all the tested cells. In accordance with molecular modeling results, the activity of new derivatives may be explained in terms of the interaction of the new hybrid molecules and Mdm2 binding sites.

Characterization and Cytotoxicity of Polyprenol Lipid and Vitamin E-TPGS Hybrid Nanoparticles for Betulinic Acid and Low-Substituted Hydroxyl Fullerenol in MHCC97H and L02 Cells.

BACKGROUND: This study demonstrated an innovative formulation including the polyprenol (GBP) lipid and vitamin E-TPGS hybrid nanoparticles (NPs) which was aimed to control the transfer of betulinic acid (BA) and low-substituted hydroxyl fullerenol (C60(OH)n). Additionally, it developed BA-C60(OH)n-GBP-TPGS-NPs delivery system and researched the anti-hepatocellular carcinoma (HCC) effects. MATERIALS AND METHODS: The NPs were prepared by nanoprecipitation with ultrasonic-assisted emulsification (UAE) method. It was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), FTIR spectrum, size distribution and zeta potential. Physical and chemical properties were evaluated through measurement of drug release, stability studies, drug loading efficiency (DE) and encapsulation efficiency (EE). Biological activities were evaluated through measurement of MTT assay, lactate dehydrogenase leakage assay (LDH), cell proliferation assays, cell apoptosis analysis, comet assay, wound healing assay, cell invasion and Western blot analysis. RESULTS AND CONCLUSIONS: The NPs exhibited clear distribution characteristics, improved solubility and stability. BA and C60(OH)n for the NPs displayed a biphasic release pattern with sustained drug release properties. The mixture of C60(OH)n with different hydroxyl groups may have a certain effect on the stability of the NPs system itself. The NPs could effectively inhibit MHCC97H cell proliferation, migration and invasion in vitro. Combined use of C60(OH)n and BA in GBP lipids may improve the inhibit effect of C60(OH)n or BA against HCC cells and reduce cytotoxicity and genotoxicity of C60(OH)n for normal cells. We concluded that one of the important mechanisms of BA-C60(OH)n-GBP-TPGS-NPs inhibiting MHCC97H cells is achieved by up-regulating the expression of Caspase-3, Caspase-8 and Caspase-9.

Isolation of polyphenol compounds from olive waste and inhibition of their derivatives for α-glucosidase and α-amylase.

Olive waste was used as a sustainable resource because it contained a variety of valuable compounds. The polyphenols active fraction from enrichment by microporous resin and extraction with ethyl acetate were analysed by different chromatographic methods. A total of 14 polyphenolic compounds were isolated and identified by structure elucidation. Based on the above obtained compounds, tyrosol was selected as a characteristic polyphenol and participated in transesterification reaction to synthesise ß-ketoester using Yb(OTf)3. Then the Biginelli reaction with benzaldehyde, urea and ketoester (1:1.2:1.2) was performed at 90 °C for 3.0 h under the acidic condition. In addition, the ß-ketoester prepared using tyrosol with benzyl had a greater inhibitory effect on α-glucosidase and α-amylase, and the inhibition of enzyme activity for 3, 4-dihydropyrimidinone derivatives prepared using abovementioned ß-ketoester was improved significantly. Meanwhile, fluorine-containing dihydropyrimidinone derivatives were considerable inhibitors for both enzymes.

Synthesis of cytotoxic urs-12-ene- and 28-norurs-12-ene- type conjugates with amino- and mercapto-1,3,4-oxadiazoles and mercapto-1,2,4-triazoles.

A small library of 2-mercapto-1,3,4-oxadiazoles, 2-amino-1,3,4-oxadiazoles, and 3-mercapto-1,2,4-triazoles attached to the urs-12-ene- and 28-nor-urs-12-ene skeleton has been obtained. Ursolic acid derived hydrazides have been identified as useful starting materials for the developed synthesis. Ursolic acid hydrazide provided access to oxadiazoles attached directly to C-17 of the ursane core, but synthesis of structurally related 3-mercapto-1,2,4-triazoles was not possible in this way due to steric hindrance of the triterpenoid. Ester- and amide-linked hydrazides arising from ethoxycarbonylmethyl ursolate and ursolic acid amide with methyl ß-alaninate served as key starting materials for the remotely connected mercapto-and amino-azoles. Antioxidant activities (DPPH method) of the newly obtained compounds are mediocre. However, excellent cytotoxicity and selectivity against MCF7 cell line were found for 28-nor-urs-12-ene 2-amino-1,3,4-oxadiazole conjugate. Also some other library members exceeded the cytotoxicity values of natural ursolic acid. The novel hybrid heterocycles with amino and mercapto substituents possess a great potential for further derivatization and are prospective scaffolds for the synthesis of triterpenoid analogs with chemopreventive and cytotoxic properties.

Characterization, Cytotoxicity and Genotoxicity of Graphene Oxide and Folate Coupled Chitosan Nanocomposites Loading Polyprenol and Fullerene Based Nanoemulsion Against MHCC97H Cells.

Hepatocellular carcinoma (HCC) is one of the most lethal diseases worldwide. Ginkgo Biloba Leaves polyprenol (GBP) is considered potential efficacy in the treatment of HCC. This study involved oil-in-water type nanoemulsion (NE) loading GBP and Fullerene C60 (C60F) were prepared by dissolving GBP and C60F in NE using inversed phase emulsification (EIP) with ultrasonic-assisted emulsification (UAE) method. Folic acid (FA) coupled Chitosan (CS) and Graphene oxide (GO) nanocomposites (NCs): FA-CS-GO-NCs were fabricated by ionic cross-linking of positively charged FA-CS-GO solution conjugates and negative charged NE with TPP. We combined these materials for preparing NCs loading GBP and C60F (GBP-C60F-FA-CS-GO-NCs) based GBP-C60F-NE. GBP-C60F-FA-CS-GO-NCs in the NE were the mean size was 44.9 nm, PdI was 0.267 and the mean zeta potential was 47.8 mV. And they had good drug loading efficiency, encapsulation efficiency, drug release property and storage stability. In this cytotoxic study, it demonstrated the GBP-C60F-FA-CS-GO-NCs were greater inhibition capacity on MHCC97H cells compared with GBP-NE, C60F-NE, GBP-C60F-NE, GBP-FA-CS-GO-NCs and C60F-FA-CS-GO-NCs. In this genotoxic study, GBP-C60F-FA-CS-GO-NCs at low C60F concentration showed low genotoxicity on MHCC97H and L02 cells. By comparison, GBP-C60F-FA-CS-GO-NCs had higher cytotoxicity on MHCC97H than L02 cells. By the cell apoptosis analysis, the results revealed that GBP-C60F-NE and GBP-C60F-FA-CS-GO-NCs could obviously induce MHCC97H cell apoptosis, especially high concentration GBP-C60F-FA-CS-GO-NCs had the strongest apoptosis inducing ability. The treatment against MHCC97H cells with moderate C60F concentrations of GBP-C60F-FA-CS-GO-NCs effectively inhibited the overexpressions of Akt1 and Akt2, and significantly increased the expression of PTEN. Our results suggest that PTEN, Akt1 and Akt2 might play an important role in the aspect of GBP-C60F-FA-CS-GO-NCs inhibiting against HCC cells. It provides further evidence to speculation that up-regulated PTEN expression and down-regulated Akt1 and Akt2 expression might be one of the important mechanisms for GBP-C60F-FA-CS-GO-NCs inhibiting HCC cells. All these results suggest that GBP-C60F-FA-CS-GO-NCs effectively inhibited the HCC malignant development and has potentially important value in the HCC treatment.

Separation of polyprenols from Ginkgo biloba leaves by a nano silica-based adsorbent containing silver ions.

Polyprenols extracted from Ginkgo biloba leaves is a kinds of unsaturated compound containing double bonds. Traditionally, the separation methods for the polyprenols are lack of selectivity and their separation efficiency are low. We synthesized two kinds of functional nano-silica containing silver ions materials (AgTCM and AgTCN) which have selectivity for unsaturated compounds to separate Ginkgo biloba leaves polyprenols for the first time. AgTCN displays exceptionally high selectivity for polyprenols and high stability under extended heat and light exposure, while silver is virtually immobile during solvent elution. Importantly, the exceptional stability of AgTCN gives rise to much higher polyprenols recovery than conventional silica gel during the chromatographic elution. In addition, we found that the adsorption of polyprenols onto the AgTCN conforms to pseudo-second-order kinetic model and AgTCN has strong affinity with polyprenols by analyzing Langmuir, Freundlich, Temkin-Pyzhev, and Dubinin-Radushkevich isotherms. The calculation results of thermodynamic parameters demonstrate that decrease of temperature in favor of increasing the adsorbing capacity of polyprenols onto the AgTCN, and the adsorption process of which is exothermic reaction. Our results pave the way for the novel separation methods of polyprenols from Ginkgo biloba leaves.

Synergies of urushiol and its pechmann derivative compatible with paclitaxel anti-HepG2 activity.

The paper investigated the synergistic inhibitory effects of 1 (triene urushiol), 2 (monoene urushiol), 3 (urushiol pechmann derivative) and paclitaxel on proliferation of human hepatocellular carcinoma cell line HepG2. The inhibitory rate of cell proliferation was detected by MTT assay after HepG2 cells were separately treated with compounds 1, 2 and 3 combined with paclitaxel at different concentrations for 72 h. The joint index analysis was used to examine whether those compatible drugs had synergistic effect. The results showed that compounds 1, 2 and 3 had significant inhibitory effect on the proliferation of HepG2 cells in a dose-dependent manner, and their half inhibitory concentrations IC50 were 29.3, 55.5 and 27.1 µM respectively. The synergistic effect of compounds 1, 2 and 3 combined with paclitaxel significantly inhibited the proliferation of HepG2 cells in vitro.

Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study.

A series of novel C15 urushiol derivatives were designed by introducing a pechmann structure and F-, Cl-, and Br-nitro substituents with different electronic properties into its alkyl side chain, as well as a triazolyl functional group in its aromatic oxide. Their chemical structures were determined based on the analysis of the NMR (nuclear magnetic resonance) spectroscopic and mass spectrometric data. The results showed that compound 4 exhibited a strong inhibition of the HepG2 cell proliferation (half maximal inhibitory concentration (IC50): 2.833 µM to human hepatocellular carcinoma (HepG2), and 80.905 µM to human normal hepatocytes (LO2)). Furthermore, it had an excellent synergistic effect with levopimaric acid. The nitrogen atom of the triazole ring formed a hydrogen-bonding interaction with Gly103, Gly154, and Tyr308, which made compound 4 bind to histone deacetylase (HDAC)2 more tightly. One triazole ring and His33 formed a π⁻π stacking effect; the other, whose branches were deep into the pocket, further enhanced the interaction with HDAC2. Meanwhile, compound 4 involved a hydrophobic interaction with the residues Phe210 and Leu276. The hydrophobic interaction and π⁻π stacking provided powerful van der Waals forces for the compounds.

Identification of Volatile Oxidation Compounds as Potential Markers of Walnut Oil Quality.

In this study, a 10-day accelerated storage at 60 °C was carried out to investigate the evolution of volatile profiles of walnut oils from three cultivars (cvs. Santai, Xiangling, Qingxiang). Eighteen volatile oxidation compounds, including three alcohols, 11 aldehydes, one furan, one ketone, and two acids, were identified in all oil samples. Data from the three cultivars were combined and the analysis showed that 2-heptenal and 1-octen-3-ol exhibited the strongest linear correlations with peroxide value (PV), p-anisidine value (p-AnV), and the residual content of total tocopherols (Rtocos ). The contents of both compounds were also proved to be significant variables for PV, p-AnV, and Rtocos , according to the jack-knife uncertainty test applied in partial least squares analysis. Hence, 2-heptenal and 1-octen-3-ol could be used as potential markers of walnut oil quality. Besides, the oleic-derived compounds such as octanal and nonanal were suggested to be used to indicate notable decrease of PUFAs during walnut oil oxidation, since they showed the strongest negative correlations with the residual content of PUFAs (RPUFAs ). PRACTICAL APPLICATION: Nowadays a large-scale planting of walnut has taken place in China. Since walnut contains more than 60% of oil, the development of walnut oil is of great significance. Volatiles such as aldehydes are secondary oxidation products. Study on the dynamic changes of their types and contents could be helpful to understand the process of walnut oil oxidation. The measurement of walnut oil quality could also be more convenient and predictable with the use of volatile markers. Hence, this research provides insights for the future development of online quality control system for walnut oil.