Design, semisynthesis, α-glucosidase inhibitory, cytotoxic, and antibacterial activities of p-terphenyl derivatives.

Terphenyllin (1), a naturally abundant p-terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2-5. To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α-glucosidase inhibitory, cytotoxic, and antibacterial activities. Compounds 1, 3, 4, 7, 8, 10, 11, 14, 15, 21, 23, 24, 29, 39, and 40 showed significant α-glucosidase inhibitory activity with IC50 values of 4.79-15 µM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC50 = 192.0 µM) and acarbose (IC50 = 707.9 µM). Compounds 7 and 10 have relatively higher therapeutic indices (CC50/IC50 = 17 and 10, respectively), representing potential promising leads. The enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α-glucosidase with Ki values of 1.50 and 3.45 µM, respectively. Additionally, compounds 14, 21, 26, 29, 32, 35, and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC50 values ranging from 0.15 to 5.26 µM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression.

Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.

[Comparison of structural characteristics and anticoagulation activity of enoxaparin sodium with different degree of 1,6-anhydro derivatives].

The fine structure of enoxaparin sodium samples with different degree of 1,6-anhydro derivatives were analyzed with polyacrylamide gel electrophoresis, high performance liquid chromatography, ultraviolet spectroscopy, infrared spectroscopy and nuclear magnetic resonance spectroscopy. A further study of anticoagulation activity of enoxaparins was performed, including those on their inhibition activities of coagulation factor Xa (FXa) and thrombin (FIIa). The results showed that the anti-FXa and -FIIa activities of enoxaparins with different degree of 1,6-anhydro derivatives (20.0%-39.7%) with similar structure characteristics, had decreasing tendency when the degree of 1,6-anhydro derivatives increased. Especially, the anti-FXa activity was sensitive to the change of the degree of 1,6-anhydro derivatives.

Activated AMPK explains hypolipidemic effects of sulfated low molecular weight guluronate on HepG2 cells.

Low molecular weight and sulfated low molecular weight guluronate (LMG and SLMG) were prepared and hypolipidemic effects were studied in a human hepatocellular carcinoma HepG2 cell line. Both compounds decreased total cholesterol (TC) and triglycerides (TG) and inhibited 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) activity in HepG2 cells. In general, SLMG had greater effects than LMG. Activation of sterol regulatory element-binding protein 2 (SREBP-2), low density lipoprotein receptor (LDLR), AMP-activated protein kinase (AMPK), and AMPK's downstream targets were evidenced by increased phosphorylation of AMPK, HMGCR, and acetyl-CoA-carboxylase (ACC), which decreased HMGRC and ACC activity. We further demonstrated that activated AMPK was linked to down-regulated SREBP-1 and up-regulated cholesterol 7α-hydroxylase (CYP7A1).

Involvement of lignocellulolytic enzymes in the decomposition of leaf litter in a subtropical forest.

The involvement of ligninolytic and cellulolytic enzymes, such as laccase, lignin peroxidase, manganese peroxidase, carboxymethylcellulase (CMCase), and filter paper activity (FPA), in the decomposition process of leaf litter driven by 6 soil-inhabiting fungi imperfecti was studied under solid-state fermentations. All the tested fungi exhibited varied production profiles of lignocellulolytic enzymes and each caused different losses in total organic matter (TOM) during decomposition. Based on the results, the 6 fungi could be divided into 2 functional groups: Group 1 includes Alternaria sp., Penicillium sp., Acremonium sp., and Trichoderma sp., and Group 2 includes Pestalotiopsis sp. and Aspergillus fumigatus. Group 1, with higher CMCase and FPA activities, showed a higher decomposition rate than the fungi of Group 2 over the first 16 d, and thereafter the cellulolytic activities and decomposition rate slowed down. Group 2 showed the maximum and significantly higher CMCase and FPA activities than those of the Group 1 fungi during the later days. This, combined with the much higher laccase activity, produced a synergistic reaction that led to a much faster average mass loss rate. These results suggest that the fungi of Group 1 are efficient decomposers of cellulose and that the fungi of Group 2 are efficient decomposers of lignocellulose. During cultivation, Pestalotiopsis sp. produced an appreciable amount of laccase activity (0.56+/-0.09 U/ml) without the addition of inducers and caused a loss in TOM of 38.2%+/-3.0%, suggesting that it has high potential to be a new efficient laccase-producing fungus.