Fish oil extracted from Coregonus peled improves obese phenotype and changes gut microbiota in a high-fat diet-induced mouse model of recurrent obesity.

Recurrent obesity is rapidly emerging as a public health problem. Previous studies have confirmed that fish oil supplementation can alleviate obesity in mice; however, the effect of fish oil on recurrent obesity remains unclear. In the present study, the modulatory effects of fish oil extracted from Coregonus peled on the phenotypes and gut microbiota of recurrent obese mice were evaluated by MRI, OGTT, and bioinformatics analysis. We found that fish oil supplementation could significantly reduce the body weight gain, net weight gain, body fat distribution, and glucose tolerance. In addition, the composition and structure of gut microbiota were significantly shifted toward those of the control group by fish oil treatment. Moreover, the relative abundance of gut microbiota, such as Bacteroidetes, Bacteroidia, Lachnospiraceae, and Bifidobacterium, was markedly responding to the rapid dietary changes between fish oil and high-fat diet. Overall, our results confirmed that the alleviation of recurrent obesity using fish oil supplementation might be modulated by altering the hysteretic behavior and memory-like function of gut microbiota. We proposed that further studies are needed to elucidate the modulation mechanism.

Dehydrodiconiferyl alcohol from Silybum marianum (L.) Gaertn accelerates wound healing via inactivating NF-κB pathways in macrophages.

OBJECTIVES: The aim of this study was to investigate the molecular mechanisms of the efficacy of lignin compound dehydrodiconiferyl alcohol (DHCA) isolated from Silybum marianum (L.) Gaertn in improving wound healing. These findings preliminarily brought to light the promising therapeutic potential of DHCA in skin wound healing. METHODS: First, the effect of DHCA on healing in vivo was studied using a full-thickness scalp wound model of mice by topical administration. Histopathological examinations were then conducted by haematoxylin and eosin (H&E), Masson's trichrome staining and the immunofluorescence assay. Second, we further examined the anti-inflammatory mechanism of DHCA in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages by immunofluorescence assay and Western blot analysis. KEY FINDINGS: DHCA could promote scalp wound healing in mice by enhancing epithelial cell proliferation and collagen formation and reducing inflammatory cells infiltration. Moreover, the NF-κB nuclear translocation was suppressed remarkably by DHCA administration in connective tissue of healing area. DHCA was also shown to inhibit production of nitric oxide (NO) and interleukin (IL)-1ß with downregulated inducible nitric oxide synthase (iNOS) expression in LPS-induced RAW 246.7 cells. More importantly, DHCA administration upregulated p-IκBα expression and induced nuclear translocation of NF-κB without affecting its expression. CONCLUSIONS: Our study indicated that DHCA exerted anti-inflammatory activity through inactivation of NF-κB pathways in macrophages and subsequently improved wound healing.

Zinc-Chelating Mechanism of Sea Cucumber (Stichopus japonicus)-Derived Synthetic Peptides.

In this study, three synthetic zinc-chelating peptides (ZCPs) derived from sea cucumber hydrolysates with limited or none of the common metal-chelating amino-acid residues were analyzed by flame atomic absorption spectroscopy, circular dichroism spectroscopy, size exclusion chromatography, zeta-potential, Fourier transform infrared spectroscopy, Raman spectroscopy and nuclear magnetic resonance spectroscopy. The amount of zinc bound to the ZCPs reached maximum values with ZCP:zinc at 1:1, and it was not further increased by additional zinc presence. The secondary structures of ZCPs were slightly altered, whereas no formation of multimers was observed. Furthermore, zinc increased the zeta-potential value by neutralizing the negatively charged residues. Only free carboxyl in C-terminus of ZCPs was identified as the primary binding site of zinc. These results provide the theoretical foundation to understand the mechanism of zinc chelation by peptides.

Identification of flavonolignans from Silybum marianum seeds as allosteric protein tyrosine phosphatase 1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) is an attractive molecular target for anti-diabetes, anti-obesity, and anti-cancer drug development. From the seeds of Silybum marianum, nine flavonolignans, namely, silybins A, B (1, 2), isosilybins A, B (3, 4), silychristins A, B (5, 6), isosilychristin A (7), dehydrosilychristin A (8), and silydianin (11) were identified as a novel class of natural PTP1B inhibitors (IC50 1.3 7-23.87 µM). Analysis of structure-activity relationship suggested that the absolute configurations at C-7" and C-8" greatly affected the PTP1B inhibitory activity. Compounds 1-5 were demonstrated to be non-competitive inhibitors of PTP1B based on kinetic analyses. Molecular docking simulations resulted that 1-5 docked into the allosteric site, including α3, α6, and α7 helix of PTP1B. At a concentration inhibiting PTP1B completely, compounds 1-5 moderately inhibited VHR and SHP-2, and weakly inhibited TCPTP and SHP-1. These results suggested the potentiality of these PTP1B inhibitors as lead compounds for further drug developments.

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala.

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5-8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC50 value of 15.41 µM.