Phillygenin Attenuated Colon Inflammation and Improved Intestinal Mucosal Barrier in DSS-induced Colitis Mice via TLR4/Src Mediated MAPK and NF-κB Signaling Pathways.

Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory bowel disease (IBD). Phillygenin (PHI), a natural bioactive ingredient, isolated from Forsythiae Fructus, exhibits anti-inflammatory, anti-oxidative, and hepatoprotective activities. However, few reports provide direct evidence on the efficacy of PHI in improving colitis mice. The present study elucidated that the symptoms of DSS-induced colitis mice were alleviated after PHI administration, including body weight loss, the disease activity index, colon length shortening, colonic pathological damage, splenomegaly, and hepatomegaly. PHI treatment improved the intestinal mucosal barrier by protecting goblet cells, promoting gene expressions of Clca1, Slc26a3, and Aqp8, increasing tight junction proteins (TJs), and reducing epithelial cell apoptosis. In addition, the levels of oxidative stress (MPO, SOD, and MDA) and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10) were reversed by PHI in colitis mice. According to transcriptome and network pharmacology analysis, inflammatory pathway might be an important mechanism for PHI to improve colitis. Western blotting displayed that the PHI inhibited the activation of tyrosine kinase Src mediated by TLR4, and then reduced the phosphorylation of downstream proteins p38, JNK, and NF-κB in colitis mice. In summary, our results suggested that PHI might be an appropriate and effective drug candidate to protect colitis.

Dietary phillygenin supplementation ameliorates aflatoxin B1-induced oxidative stress, inflammation, and apoptosis in chicken liver.

Aflatoxin B1 (AFB1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB1 in the liver of chickens. Chickens were administered with AFB1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB1-induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI.

Characterization of Composition and Antifungal Properties of Leaf Secondary Metabolites from Thirteen Cultivars of Chrysanthemum morifolium Ramat.

Chrysanthemum morifolium Ramat is an ornamental plant of worldwide cultivation. Like many other species in the family Asteraceae, C. morifolium is a rich producer of secondary metabolites. There are two objectives in this study: (I) to determine and compare the diversity of apolar secondary metabolites among different cultivars of C. morifolium and (II) to compare their properties as antifungal agents. To attain these objectives, we selected 13 cultivars of C. morifolium that are commonly used for making chrysanthemum tea as experimental materials. Leaves at the same developmental stage were collected from respective mature plants and subjected to organic extraction. The extracts were analyzed using gas chromatography-mass spectrometry. A total of 37 apolar secondary metabolites including 26 terpenoids were detected from the 13 cultivars. These 13 cultivars can be largely divided into three chemotypes based on chemical principal components analysis. Next, the extracts from the 13 cultivars were examined in in vitro assays for their antifungal properties against three species of pathogenic fungi: Fusarium oxysporum, Magnaporthe oryzae, and Verticillium dahliae. Significant variability in antifungal activity of the leaf extracts among different cultivars was observed. The 13 cultivars can be divided into four groups based on their antifungal activities, which could be partly correlated to the contents of terpenoids. In short, this study reveals large variations in chemical composition, particularly of terpenoids, of leaf secondary metabolites among different cultivars of C. morifolium and their different abilities in functioning as antifungal agents.

What dictates which ion, I- or Br-, mediates the growth of cubic Pd nanocrystals?

Cubic Pd nanocrystals (CPNCs) as one of typical nanostructures are generally fabricated using I- or Br- as capping ions. However, which ion, I- or Br-, exclusively mediates the growth of CPNCs in a given reaction system is not well understood. Herein, regardless of I- or Br- as the capping ion, we successfully achieved CPNCs in the same reaction system simply by adjusting the pH. Based on the Finke-Watzky kinetic model, an increase in pH accelerates the overall reduction rate of Pd2+, and the formation of CPNCs only occurs over the range of specific solution reduction rate constants (k1). This kinetically illuminates that the reduction rate of Pd2+ is the physicochemical parameter that determines which ion, I- or Br-, dictates the growth of CPNCs. Also, density functional theory (DFT) calculations further elucidate the dependence of the reduction rate of Pd2+ on pH and the configuration of the activated Pd2+ complex.

Multiple constituents co-assembly of ordered mesoporous Al2O3-SiO2-carbon nanocomposites.

Ordered mesoporous Al2O3-SiO2-carbon nanocomposites have been synthesized via the direct triblock-copolymer self-assembly route using soluble phenolic resols as polymer precursors, aluminium chloride hexahydrate as an aluminum precursor, tetraethoxysilane as a silica precursor, and Pluronic F127 as a template. Characterization of XRD, N2 sorption isotherms, TEM, solid-state NMR, TG, and NH3-TPD techniques is used to investigate the mesostructure, pore properties, phase composition, metal incorporation state, and acidic properties. Ordered mesoporous nanocomposites have "reinforced concrete"-structured frameworks, in which the oxide and carbon components are microphase separated and homogenously dispersed inside pore walls. Al species are tetrahedrally incorporated into silica frameworks to compose the inorganic oxide compounds which provides acidic center. The nanocomposites have the ordered 2-D hexagonal mesostructure, high surface areas (291-360 m2/g), large pore volumes (0.25-0.42 cm3/g), large pore diameters (- 5 nm) and accessible acidic sites.

Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota.

Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called "Qingqiao" and "Laoqiao" referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.

Scattering of Magnetoacoustic Waves and Dynamic Stress Concentration around Double Openings in Piezomagnetic Composites.

Based on the magnetoacoustic coupled dynamics theory, the wave function expansion method is used to solve the problem of acoustic wave scattering and dynamic stress concentration around the two openings in e-type piezomagnetic composites. To deal with the multiple scattering between openings, the local coordinate method is introduced. The general analytical solution to the problem and the expression of the dynamic stress concentration are derived. As an example, the numerical results of the dynamic stress distribution around two openings with equal diameters are given. The effects of the parameters, such as the incident wave number and the spacing between the openings, on the dynamic stress concentration factor are analyzed.

Multi-omics reveals the mechanisms of antidepressant-like effects of the low polarity fraction of Bupleuri Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri (Bupleurum chinense DC.) is a traditional Chinese medicine that has the effect of soothing the liver and relieving depression, and widely used in the field of antidepression. AIM OF THE STUDY: The low polarity fraction of Bupleuri Radix (PBR) has proved to be effective for the treatment of depression based on the results of our previous study. However, mechanisms of definite antidepressant-like effects remained unclear. The purpose of this study is to reveal mechanisms of antidepressant-like effects of PBR with multi-dimensional omics. MATERIALS AND METHODS: LC-MS metabolomics combined with 16S rRNA gene sequencing were used to investigate the effects of PBR on gut microbiota and metabolites in CUMS-induced depression, and Pearson correlation analysis was carried out on gut microbiota and metabolites. RESULTS: PBR significantly improved depression-like behaviors in the CUMS model rats. Moreover, PBR significantly increased the levels of BDNF in the hippocampus. Cecum contents metabolomics revealed that 16 biomarkers associated with PBR antidepressant effect were screened, which were involved 3 metabolic pathways including primary bile acid biosynthesis, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism. Gut microbiota further analysis demonstrated that PBR increased the diversity of gut microbiota, and significantly inhibited the growth of [Prevotella] and Ochrobactrum. Furthermore, Pearson analysis revealed there was a strong correlation between cecum contents of metabolites and gut microbiota. CONCLUSIONS: PBR improved depression-like behavior by regulating metabolic profiles and gut microbiota, and contributing to further understand the entailed antidepressant-like mechanisms of PBR.

Self-Microemulsifying Drug Delivery System of Phillygenin: Formulation Development, Characterization and Pharmacokinetic Evaluation.

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.

Occurrence and distribution of perfluoroalkyl substances (PFASs) in sediments of the Dalian Bay, China.

In the present study, the spatial distributions and vertical variations of PFASs in the sediments of the Dalian Bay were investigated. The total concentrations of PFASs (∑PFASs) in surface sediments of Dalian Bay ranged from 1.49 to 2.66ngg-1 dw. The predominant PFASs in surface sediments were PFOA, PFBS and PFBA with the concentration ranges of 0.50 to 0.95, 0.21 to 0.94, and 0.035 to 0.32ngg-1 dw, respectively. For the two sediment cores, ∑PFASs ranged from 1.20 to 2.00 and from 1.37 to 2.06ngg-1 dw, respectively. There was a maximum ∑PFASs concentration value near the surface. In general, ∑PFASs gradually decreased with increasing sampling depth after reaching the maximum. PFOA, PFBS and PFBA were also the predominant PFASs in the two sediment cores. It is recommended that the monitoring and risk assessment of short-chain PFAS should be taken into consideration, and further researches are needed to understand the transportation and fate of these chemicals in the aquatic environment.

Isolation and Structural Characterization of Antioxidant Peptides from Degreased Apricot Seed Kernels.

BACKGROUND: The composition and sequence of amino acids have a prominent influence on the antioxidant activities of peptides. OBJECTIVE: A series of isolation and purification experiments was conducted to explore the amino acid sequence of antioxidant peptides, which led to its antioxidation causes. METHODS: The degreased apricot seed kernels were hydrolyzed by compound proteases of alkaline protease and flavor protease (3:2, u/u) to prepare apricot seed kernel hydrolysates (ASKH). ASKH were separated into ASKH-A and ASKH-B by dialysis bag. ASKH-B (MW < 3.5 kDa) was further separated into fractions by Sephadex G-25 and G-15 gel-filtration chromatography. Reversed-phase HPLC (RP-HPLC) was performed to separate fraction B4b into two antioxidant peptides (peptide B4b-4 and B4b-6). RESULTS: The amino acid sequences were Val-Leu-Tyr-Ile-Trp and Ser-Val-Pro-Tyr-Glu, respectively. CONCLUSIONS: The results suggested that ASKH antioxidant peptides may have potential utility as healthy ingredients and as food preservatives due to their antioxidant activity. HIGHLIGHTS: Materials with regional characteristics were selected to explore, and hydrolysates were identified by RP-HPLC and matrix-assisted laser desorption ionization-time-of-flight-MS to obtain amino acid sequences.

Composition, Distribution, and Antioxidant Activity of Phenolic Compounds in 18 Soybean Cultivars.

Natural phenols are an important functional compound widely distributed in plants with benefits that promote human health. The content of total phenols, flavonoids, and anthocyanins and their composition distribution in 18 soybean cultivars was investigated. There are four phenolic acid distribution forms in these soybean cultivars, namely free, esterified, glycosided, and insoluble-bound. Total phenols, flavonoids, and anthocyanins from 6 black soybean cultivars were found in higher numbers than those from 12 other yellow soybean cultivars. Free and esterified phenolic acids were the main phenolic acid form in all 18 soybean samples. Chlorogenic acid and caffeic acid were the dominant phenolic acids in eight detected phenolic acids, and daidzin and genistin were the abundant isoflavones in five detected isoflavones. Furthermore, the antioxidant activities of total phenols from the 6 black soybean cultivars were greater than those from the 12 yellow soybean cultivars, and there was a significant positive correlation between antioxidant activity and total phenolic content. Black soybeans could be a potential resource for developing natural antioxidants that may play a crucial role in human health protection.

Asymmetrical etching of Ag nanoparticles into symmetry-reduced bi-metallic nanocups at the single-nanoparticle level.

Asymmetrical etching of nanoparticles was achieved by employing interface-confined galvanic replacement reactions. Interfacial Ag nanocubes, nanowires and nanospheres were fabricated into symmetry-reduced cubic, trough-like and spherical nanocups, respectively. The formation of nanocups is attributed to in situ local nanomasking and selective etching of interfacial nanoparticles at the single-nanoparticle level.

Occurrence and distribution of perfluoroalkyl substances (PFASs) in the water dissolved phase and suspended particulate matter of the Dalian Bay, China.

In the present study, the contamination level and spatial distribution of PFASs in the water dissolved phase and suspended particulate matter (SPM) phase of the Dalian Bay, and the SPM-water partition behavior were investigated. The total concentrations of PFASs (∑PFASs) in the water dissolved phase ranged from 6.9 to 17.1 ng L-1, with perfluorooctanoic acid (PFOA), perfluorobutanoic acid, and perfluorobutane sulfonate (PFBS) as the predominant PFASs, while ∑PFASs in SPM ranged from 1.7 to 27.5 ng g-1 dw with higher contributions from PFBS, perfluorooctane sulfonic acid and PFOA. As for the pollution distribution, the concentrations of PFASs inside the Dalian Bay were higher than those outside the bay. For perfluoroalkyl carboxylic acid (PFCAs) and perfluoroalkane sulfonic acids (PFSAs), the suspended particulate matter-water partition coefficient (log Kd) values ranged from 2.62 to 3.76, and from 3.39 to 3.56, respectively. The log Kd values of PFASs generally increased with the increasing perfluorinated carbon chain length. Short-chain PFCAs were mostly detected in the water dissolved phase, while long-chain PFCAs and PFSAs appeared to bind more strongly to SPM phase. The contamination level of long-chain PFCAs and PFSAs could be underestimated if only the water dissolved phase were measured. Therefore, further investigations should consider the role of SPM on the environmental behavior and fate of PFASs in the aquatic environment.

Occurrence and distribution of perfluoroalkyl substances (PFASs) in surface water and bottom water of the Shuangtaizi Estuary, China.

Perfluoroalkyl substances (PFASs) have been recognized as emerging environmental pollutants. However, there is limited information on the contamination level and spatial distribution of PFASs in the Shuangtaizi Estuary, where the Shuangtaizi Hekou Nature Reserve is located. In the present study, the contamination level and spatial distribution of PFASs in surface water (approximately 0.5 m below the surface) and bottom water (about 0.5 m above the bottom) of the Shuangtaizi Estuary were investigated. The data indicated that the Shuangtaizi Estuary was commonly contaminated by PFASs. The total concentration of PFASs in surface and bottom water of the Shuangtaizi Estuary ranged from 66.2 to 185 ng L(-1) and from 44.8 to 209 ng L(-1), respectively. The predominant PFASs were perfluorobutanoic acid (PFBA), perfluoropentanoic acid, perfluorooctanoic acid, perfluorohexanoic acid and perfluorobutane sulfonate (PFBS). In general, PFAS concentrations in surface water samples were lower than those in bottom water samples. The spatial distribution of PFASs in the Shuangtaizi Estuary was mainly affected by particular landform, tide and residual currents in Liaodong Bay. The total mass flux of 15 PFASs from the Shuangtaizi River to Liaodong Bay was estimated to be 352 kg year(-1), which was lower than the total flux from the Daling River and the Daliao River. As short-chain PFASs, such as PFBS and PFBA, have been the prevalent compounds in some places and are continuously produced and used, long-term monitoring and effective pollution controls are suggested.