Flash extraction of ulvan polysaccharides from marine green macroalga Ulva linza and evaluation of its antioxidant and gut microbiota modulation activities.

In this study, flash extraction was used to rapidly extract water-soluble polysaccharides from Ulva linza. The optimal extraction process for the flash extraction was determined by Box-Behnken design with extraction temperature 80 °C, extraction time 117 s, liquid-solid ratio 46:1 (mL/g) and a corresponding yield of 18.5 %. The crude Ulva linza polysaccharides (CULP) were subsequently isolated by chromatography technology to obtain purified Ulva linza polysaccharide (ULP) and characterized by monosaccharide composition and molecular weight determination analysis. Furthermore, the antioxidant bioactivity of ULP was studied and the results revealed that it had a good scavenging effect on DPPH, ABTS and OH, with IC50 values of 149.2 µg/mL, 252.5 µg/mL and 1073 µg/mL, respectively. After in vitro fermentation by human fecal microbiota, the pH value of fermentation culture significantly decreased to 5.06, suggesting that ULP could be hydrolyzed and utilized by gut microbiota. The abundance of beneficial bacteria including Bacteroides, Parabacteroides and Faecalibacterium was improved. Meanwhile, the relative abundance of Prevotella, Blautia and Ruminococcus was decreased, and the low ratio of these organisms might reveal positive effects on maintaining the balance of gut microbial biodiversity. These results suggested that the composition of the human gut microbiota could be modulated by ULP, and ULP might possess the potential to maintain gut homeostasis and improve human intestinal health.

Efficient dissolution of cellulose in slow-cooling alkaline systems and interacting modes between alkali and urea at the molecular level.

The dissolution of microcrystalline cellulose (MCC) in a urea-NaOH system is beneficial for its mechanical processing. The apparent MCC solubility was greatly improved to 14 wt% under a slow-cooling condition with a cooling rate of -0.3 °C/min. The cooling curve or thermal history played a crucial role in the dissolution process. An exotherm (-54.7 ± 3 J/g MCC) was detected by DSC only under the slow-cooling condition, and the cryogenic dissolution of MCC was attributed to the exothermic interaction between MCC and solvent. More importantly, the low cooling rate promoted the dissolution of MCC by providing enough time for the diffusion of OH- and urea into MCC granules at higher temperatures. The Raman spectral data showed that the intramolecularly and intermolecularly hydrogen bonds in cellulose were cleaved by NaOH and urea, respectively. XPS and solid-state 13C NMR results showed that hydrogen bonds were generated after dissolution, and a dual-hydrogen-bond binding mode between urea and cellulose was confirmed by DFT calculations. Both the decrease of enthalpy and increase of entropy dominated the spontaneity of MCC dissolution, and that is the reason for the indispensability of cryogenic environment. The high apparent solubility of MCC in the slow-cooling process and the dissolution mechanism are beneficial for the studies on cellulose modification and mechanical processing.

Water extract from Ligusticum chuanxiong delays the aging of Saccharomyces cerevisiae via improving antioxidant activity.

Ligusticum chuanxiong is a common traditional edible-medicinal herb that has various pharmacological activities. However, its effects on Saccharomyces cerevisiae (S. cerevisiae) remains unknown. In this study, we found that water extract of Ligusticum chuanxiong (abbreviated as WEL) exhibited excellent free radical scavenging ability in-vitro. Moreover, WEL treatment could delay the aging of S. cerevisiae, an important food microorganism sensitive to reactive oxygen species (ROS) stress. Biochemical analyses revealed that WEL significantly increased the activity of antioxidant enzymes in S. cerevisiae, including superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR), as well as their gene expression. As a result, ROS level was significantly decreased and accompanied with the decline of malondialdehyde (MDA), which represented a state of low oxidative stress. The reduction of oxidative stress could elevate S. cerevisiae's ethanol fermentation efficiency. Taken together, WEL plays a protective role against S. cerevisiae aging via improving antioxidant activity.

Fumigaclavine C ameliorates liver steatosis by attenuating hepatic de novo lipogenesis via modulation of the RhoA/ROCK signaling pathway.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been well defined as a common chronic liver metabolism disorder. Statins as a first-line therapeutic treatment had some side effects. Here, we found that Fumigaclavine C (FC) was collected from endophytic Aspergillus terreus via the root of Rhizophora stylosa (Rhizophoraceae), had potential anti-adipogenic and hepatoprotective effects both in vitro and in vivo without obvious adverse side effects. However, the mechanisms of the prevention and management of FC for hepatic steatosis are incompletely delineated. METHODS: The pharmacodynamic effects of FC were measured in high-fat diet (HFD)-induced obese mice. Liver index and blood biochemical were examined. Histopathological examination in the liver was performed by hematoxylin & eosin or oil red O. The levels of serum TG, TC, LDL-c, HDL-c, FFA, T-bili, ALT, AST, creatinine, and creatine kinase were estimated via diagnostic assay kits. The levels of hepatic lipid metabolism-related genes were detected via qRT-PCR. The expression levels of hepatic de novo lipogenesis were quantitated with Western blot analysis.  RESULTS: FC-treatment markedly reduced hepatic lipid accumulation in HFD-induced obese mice. FC significantly attenuated the hepatic lipid metabolism and ameliorated liver injury without obvious adverse side effects. Moreover, FC also could dose-dependently modulate the expressions of lipid metabolism-related transcription genes. Mechanically, FC notably suppressed sterol response element binding protein-1c mediated de novo lipogenesis via interfering with the RhoA/ROCK signaling pathway by decreasing the levels of geranylgeranyl diphosphate and farnesyl diphosphate. CONCLUSIONS: These findings suggested that FC could improve hepatic steatosis through inhibiting de novo lipogenesis via modulating the RhoA/ROCK signaling pathway.

Palladium-Catalyzed Tandem C(sp3)-H Insertion Cyclization of 2-(2-Vinylarene)acetonitriles with Isocyanides to Access Naphthalen-2-amines.

A Pd-catalyzed cyclization reaction of 2-(2-vinylarene)acetonitriles and isocyanides has been documented. Various naphthalen-2-amines were obtained in moderate to good yields under mild conditions. The in vitro cytotoxicity of all products was evaluated by MTT assay against seven human cancer cell lines. The results indicated that compounds 3ea, 3ma, and 3ob exhibited effective anticancer activities against the tested cancer cells.

Low-temperature aerobic carbonization and activation of cellulosic materials for Pb2+ removal in water source.

Targeting the removal of Pb2+ in wastewater, cellulosic materials were carbonized in an aerobic environment and activated via ion exchange. The maximum adsorption capacity reached 243.5 mg/g on an MCC-derived adsorbent activated with sodium acetate. The modified porous properties improved the adsorption capacity. The capacity could be completely recovered five times through elution with EDTA. Because of the negative effects of Ni, Mg, and Ca elements, the adsorption capacities of activated carbonized natural materials were lower than that of pure cellulose. N2 adsorption measurement showed that the adsorbent had a large specific surface area as well as abundant micropores and 4-nm-sized mesopores. FTIR and surface potential results proved that carboxyl group was generated in the aerobic carbonization, and was deprotonated during ion exchange. This adsorbent consisted of C-C bonds as the building blocks and hydrophilic groups on the surface. XPS results demonstrated that the Pb 4f binding energies were reduced by 0.7-0.8 eV due to the interaction between Pb2+ and the activated adsorbent, indicating that the carboxylate groups bonded with Pb2+ through coordination interactions. Pseudo-second-order and Elovich kinetic models were well fitted with the adsorption processes on the pristine and activated carbonized adsorbents, indicative of chemisorption on heterogeneous surfaces. The Freundlich expression agreed well with the data measured, and the pristine and activated adsorbents had weak and strong affinities for Pb2+, respectively. The Pb2+ adsorption process was exothermic and spontaneous, and heat release determined the spontaneity. The adsorption capacity is attributed to the carboxylate groups and pores generated in the aerobic oxidation and ion exchange procedures.

Fast and reversible adsorption for dibenzothiophene in fuel oils with metallic nano-copper supported on mesoporous silica.

Dibenzothiophene (DBT) in fuel oils causes the release of toxic sulfur oxide gases, and it is necessary to remove DBT in fuels. Herein, metallic copper was loaded on SBA-15 mesoporous silica through simple reduction reactions for the preparation of DBT adsorbents. On an adsorbent with a copper loading of 0.3 wt%, adsorption equilibrium was achieved within 5 min, and a DBT removal rate of 90.4% was achieved. The adsorption isotherm agreed with a linear Freundlich model and adsorption capacity was 12.1 mg sulfur/g. Nano-sized copper particles were observed by TEM, indicating the size effect of copper particles in DBT adsorption. A broad band, corresponding to copper-sulfur coordination bonds, was observed at 300-600 cm-1 in the Raman spectrum of DBT-doped adsorbent. Meanwhile, the band at 1233 cm-1 corresponding to C = C (-S) bonds in DBT was shifted to 1229 cm-1 in DBT adsorbed. XPS and Cu LMM XPS spectra proved that Cu(0) was oxidized by DBT sulfur during adsorption. Furthermore, Auger spectra verified that the adsorption of DBT on Cu(0) involved the formation of Cu(I) and Cu(II) species through coordination bonds. The adsorption capacity could be completely recovered via elution. This work sheds light on the removal of DBT in fuel oils with cost-effective efficient adsorbents.

Lead ion adsorption on functionalized sugarcane bagasse prepared by concerted oxidation and deprotonation.

Targeting the removal of Pb2+ in wastewater, sugarcane bagasse was treated with nitric acid and an alkaline solution to prepare adsorbents. On a typical adsorbent, the adsorption isotherms agreed well with the Langmuir expression, and the maximum adsorption capacity reached 200.3 mg/g. In the presence of 150 ppm Ca2+, a common cation in natural water, the Pb2+ adsorption capacity slightly declined. In contrast, Mg2+ obviously prohibited the adsorption for Pb2+. The spent adsorbent could be regenerated at least five times through elution with an EDTA solution. EDS and XPS results demonstrated that nitric acid functioned as an oxidant instead of nitrification agent in the treatment of bagasse. The adsorption process was consistent with quasi-second-order kinetics. Based on thermodynamic studies, the changes in enthalpy and Gibbs free energy were calculated to be - 33.3 and ca. - 18 kJ/mol, indicating that the adsorption process was exothermic and spontaneous. The equilibrium Pb2+ adsorption amounts were proportional to the numbers of carboxylate groups on different adsorbents. The binding energies of Pd 4f5/2 and Pd 4f7/2 XPS spectra of Pb2+ adsorbed were 0.6-0.7 eV lower than those of free Pb(NO3)2, indicating the transfer of electrons during adsorption. The conversion of hydroxymethyl groups in sugarcane bagasse into carboxylate groups, as well as the chelation between Pb2+ ions and carboxylate groups, was validated in this work, which is beneficial for the treatment of wastewater polluted by lead ions.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice.

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Fumigaclavine C exhibits anti-inflammatory effects by suppressing high mobility group box protein 1 relocation and release.

A previous study demonstrated that Fumigaclavine C (FC) had a potential immunosuppressive activity against concanavalin A-induced hepatitis in mice. However, the precise mechanisms of the anti-inflammatory and hepatoprotective effects of FC are incompletely delineated. This study further investigated the protective effects of FC on lipopolysaccharide (LPS)-induced murine RAW264.7 cells and the underlying molecular mechanism in liver kupffer cells. FC differentially attenuated the production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interferon gamma (IFN-γ), and high mobility group box protein 1 (HMGB-1). Intriguingly, FC significantly suppressed LPS-induced HMGB-1 nucleo-cytoplasmic shuttling relocation and release. FC notably decreased the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), protein kinase C beta II (PKCßII), and protein kinase C gamma (PKCγ). PKCßII/γ played an important part in this signaling pathway cascade. Furthermore, the docking simulation revealed that FC could directly bind to the HMGB-1 B box interfering with Lys90 and Leu145. All of these results indicated that FC exhibited anti-inflammatory and hepatoprotective effects through suppressing HMGB-1 relocation and release by interfering with Lys90 and Leu145.

Anti-photoageing and anti-melanogenesis activities of chrysin.

CONTEXT: Melanin plays an important role in preventing skin photoageing by blocking ultraviolet B (UVB). However, East Asian women prefer light and fair skin, therefore they want to keep their skin from photoageing and at the same time reduce the melanin in their skin. Chrysin is a kind of natural flavonoid with luxurious biological activities, which has a very promising effect on achieving this goal. OBJECTIVE: To elucidate the effects and mechanisms of chrysin on photoageing and melanogenesis. MATERIALS AND METHODS: Human dermal fibroblasts (HDF) and B16 murine melanoma cells were incubated with chrysin (0-25 µM) for 48 h. Anti-photoageing activity was examined in HDF by assessment of synthesis/degradation of collagen I, antioxidative and antisenescent activities through ELISA and colorimetric method. Anti-melanogenesis activity was tested by assessment of melanin, tyrosinase (TYR), melanogenic proteins inhibition activities in B16 cells using colorimetric and ELISA method. RESULTS: Chrysin increased collagen I secretion (50-121.54% at 6.25-25 µM) and chrysin showed anti-photoageing activity by decreasing the degradation of collagen I, repairing oxidation damage and reducing the rate of HDF senescence. Furthermore, chrysin exhibited inhibitory activities with 3.00-20.35% reduction of melanin content at 6.25-25 µM, and inhibited melanin synthesis through the inhibition of TYR activity and the suppression of melanogenic proteins (TYR, TYR-related protein-1/2 and microphthalmia-associated transcription factor) expressions. DISCUSSION AND CONCLUSION: Chrysin may have potential for developing a functional cosmetic agent because of its anti-photoageing and anti-melanogenesis activities.

Assessment of the Cytotoxic and Apoptotic Eἀects of Chaetominine in a Human Leukemia Cell Line.

Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

Multiple Comparisons of Glucokinase Activation Mechanisms of Five Mulberry Bioactive Ingredients in Hepatocyte.

Glucokinase (GK) activity, which is rapidly regulated by glucokinase regulatory protein (GKRP) in the liver, is crucial for blood glucose homeostasis. In this paper, the GK activation mechanisms of 1-deoxynojrimycin (DNJ), resveratrol (RES), oxyresveratrol (OXY), cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were compared. The results revealed that DNJ, RES, C3G, and C3R could differently improve glucose consumption and enhance intracellular GK activities. DNJ and RES significantly promoted GK translocation at 12.5 µM, whereas other ingredients showed moderate effects. DNJ, C3G, and C3R could rupture intramolecular hydrogen bonds of GK to accelerate its allosteric activation at early stage. RES and OXY could bind to a "hydrophobic pocket" on GK to stabilize the active GK at the final stage. Otherwise, RES, OXY, C3G, and C3R could interact with GKRP at the F1P binding site to promote GK dissociation and translocation. Enzymatic assay showed that RES (15-50 µM) and OXY (25-50 µM) could significantly enhance GK activities, which was caused by their binding properties with GK. Moreover, the most dramatic up-regulation effects on GK expression were observed in C3G and C3R groups. This work expounded the differences between GK activation mechanisms, and the new findings would help to develop new GK activators.

Dimethyl Cardamonin Exhibits Anti-inflammatory Effects via Interfering with the PI3K-PDK1-PKCα Signaling Pathway.

Consumption of herbal tea [flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae)] is associated with health beneficial effects against multiple diseases including diabetes, asthma, and inflammatory bowel disease. Emerging evidences have reported that High mobility group box 1 (HMGB1) is considered as a key "late" proinflammatory factor by its unique secretion pattern in aforementioned diseases. Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, DMC) is a major ingredient of C. operculatus flower buds. In this study, the anti-inflammatory effects of DMC and its underlying molecular mechanisms were investigated on lipopolysaccharide (LPS)-induced macrophages. DMC notably suppressed the mRNA expressions of TNF-α, IL-1ß, IL-6, and HMGB1, and also markedly decreased their productions in a time- and dose-dependent manner. Intriguingly, DMC could notably reduce LPS-stimulated HMGB1 secretion and its nucleo-cytoplasmic translocation. Furthermore, DMC dose-dependently inhibited the activation of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1), and protein kinase C alpha (PKCα). All these data demonstrated that DMC had anti-inflammatory effects through reducing both early (TNF-α, IL-1ß, and IL-6) and late (HMGB1) cytokines expressions via interfering with the PI3K-PDK1-PKCα signaling pathway.

Dual role of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone in inhibiting high-mobility group box 1 secretion and blocking its pro-inflammatory activity in hepatic inflammation.

A previous study reported that 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) had a potential hepatoprotective effect through preventing acute liver injury in mice. This study further evaluated the preventive effects of DMC on lipopolysaccharide (LPS)-stimulated hepatic inflammation and the underlying mechanism in liver macrophage. DMC significantly suppressed LPS-stimulated secretion and nucleocytoplasmic translocation of high-mobility group box 1 (HMGB1). DMC could dose-dependently reduce the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase C alpha (PKCα), and phosphoinositide-dependent kinase 1 (PDK1). Furthermore, HMGB1 phosphorylation, the interaction between PKC and HMGB1, and the expression of HMGB1-dependent inflammation-related molecules were dose-dependently inhibited by DMC. Finally, DMC could target binding to the B box of HMGB1 by molecular modeling studies. All of these results indicated that DMC exhibited a potential protective effect against hepatitis probably via inhibiting HMGB1 secretion and blocking HMGB1 pro-inflammatory activity.

Hepatoprotective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone on CCl4-induced acute liver injury in mice.

In this paper, the hepatoprotective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) on CCl(4)-induced acute liver injury in Kunming mice were investigated. DMC was administered intraperitoneally (ip) (5, 10, or 20 mg/kg of body weight) for 7 days prior to the administration of CCl(4) (0.1%, ip). Pretreatment with DMC significantly decreased activities of serum hepatic enzymes, namely alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, γ-glutamyl transferase, and total bilirubin, and decreased the elevation of lipid peroxidation, malondialdehyde, reactive oxygen species, and protein carbonyl content. Pretreatment with DMC markedly increased activities of enzymatic antioxidants such as superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase and increased levels of nonenzymatic antioxidant markers such as reduced glutathione, total sulfhydryl groups, vitamin C, and vitamin E in liver. These results combined with liver histopathology demonstrate that DMC has potential hepatoprotective effects, which may be related to the attenuation of oxidative stress, accelerating the antioxidant cascade and inhibition of lipid peroxidation.