Tatarinan T, an α-asarone-derived lignin, attenuates osteoclastogenesis induced by RANKL via the inhibition of NFATc1/c-Fos expression.

We have previously reported that the lignin-like compounds, Tatarinan O (TO) and Tatarinan N (TN), extracted from the roots of Acorus tatarinowii Schott, inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. In the present study, the potential function of the α-asarone-derived lignins, Tatarinan T (TT) and Tatarinan A (TA), to regulate RANKL-induced osteoclastogenesis was investigated, and it was found that only early treatment with TT may inhibit RANKL-triggered formation of osteoclasts and resorption. The results revealed repressed expression levels of several osteoclast marker genes, including ATPase H+ -transporting V0 subunit d2 (Atp6v0d2), αvß3 integrin, and osteoclast-associated receptor (OSCAR), following TT treatment during osteoclastogenesis. Moreover, TT reduced the expression levels of the core transcription elements, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and c-Fos. However, western blotting analysis showed that TT treatment did not alter nuclear factor-κΒ (NF-κB) activation or mitogen-activated protein kinase (MAPK) or Syk/Btk/phospholipase Cγ2 (PLCγ2) phosphorylation. Taken together, these results suggest the potential of TT in the treatment of diseases of increased bone resorption.

Calycosin Suppresses RANKL-Mediated Osteoclastogenesis through Inhibition of MAPKs and NF-κB.

Calycosin, an isoflavonoid phytoestrogen, isolated from Radix Astragali, was reported to possess anti-tumor, anti-inflammation, and osteogenic properties, but its impact on osteoclast differentiation remains unclear. In this study, we examined the effects of calycosin on osteoclastogenesis induced by RANKL. The results showed that calycosin significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). Calycosin also dose-dependently suppressed the formation of bone resorption pits by mature osteoclasts. In addition, the expression of osteoclatogenesis-related genes, including cathepsin K (CtsK), tartrate-resistant acid phosphatase (TRAP), and MMP-9, was significantly inhibited by calycosin. Furthermore, the results indicated that calycosin down-regulated the expression levels of NFATc1 and c-Fos through suppressing the activation of NF-κB and MAPKs. Our results indicate that calycosin has an inhibitory role in the bone loss by preventing osteoclast formation, as well as its bone resorptive activity. Therefore, calycosin may be useful as a therapeutic reagent for bone loss-associated diseases.

Proteomics Analysis of Cellular Proteins Co-Immunoprecipitated with Nucleoprotein of Influenza A Virus (H7N9).

Avian influenza A viruses are serious veterinary pathogens that normally circulate among avian populations, causing substantial economic impacts. Some strains of avian influenza A viruses, such as H5N1, H9N2, and recently reported H7N9, have been occasionally found to adapt to humans from other species. In order to replicate efficiently in the new host, influenza viruses have to interact with a variety of host factors. In the present study, H7N9 nucleoprotein was transfected into human HEK293T cells, followed by immunoprecipitated and analyzed by proteomics approaches. A series of host proteins co-immunoprecipitated were identified with high confidence, some of which were found to be acetylated at their lysine residues. Bioinformatics analysis revealed that spliceosome might be the most relevant pathway involved in host response to nucleoprotein expression, increasing our emerging knowledge of host proteins that might be involved in influenza virus replication activities.

Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.

Anti-allergic flavones from Arthraxon hispidus.

Bioactivity-guided fractionation for an EtOAc-soluble fraction of methanolic extract of Arthraxon hispidus, using primary cell assay with bone marrow-derived mast cells (BMMC), led to an isolation of six new flavones and nine known compounds. The structures of the new compounds were established by one dimensional (1D)- and 2D-NMR spectroscopic data, as luteolin 8-C-ß-kerriopyranoside (1), luteolin 8-acetic acid methyl ester (2), 7-methyl-luteolin 8-C-ß-(6-deoxyxylo-3-uloside) (3), apigenin 8-C-α-fucopyranoside (4), apigenin 8-C-ß-fucopyranoside (5) and luteolin 8-C-ß-fucopyranoside (6). All the isolates were evaluated for inhibitory activities on interleukin-6 release in the primary cultures using BMMC. Of the tested compounds, compounds 2, 3 and 10 were found to inhibit interleukin-6 release. Furthermore, compound 2 displayed inhibitory activity against prostaglandin D2, leukotriene C4, and ß-hexosaminidase releases.

Xanthone constituents of the fruits of Garcinia mangostana with anticomplement activity.

Phytochemical investigation of a chloroform-soluble fraction of the freeze-dried fruits of Garcinia mangostana (Clusiaceace) with anticomplement activity in the classical pathway led to the identification of five known xanthones. The structures of these compounds were confirmed by interpretation of NMR and MS spectroscopic data. Of the isolates obtained, 1-isomangostin and garcinone E were found to be active constituents in the anticomplement assay used.

Dioscin Inhibits Virulence Factors of Candida albicans.

Candida albicans infections present a heavy burden upon public health, with only a few drugs available, while biofilms formed by C. albicans worsen this situation. Dioscin has antitumor, anti-inflammatory, and hepatoprotective effects, and this study was conducted to evaluate the effects of dioscin on the biofilm formation and development, as well as other virulence factors of C. albicans such as morphological transition, adhesion, and extracellular secreted phospholipase. Our results showed dioscin inhibits these virulence factors and has low cytotoxicity against mammalian cells. Considering protective effects of dioscin against damage on liver and kidney, dioscin may be used as a potential candidate for antifungal development.