Anti-inflammatory action of physalin A by blocking the activation of NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis Calyx seu Fructus is typically used to treat inflammatory diseases such as upper respiratory tract infection and acute tonsillitis in clinical practice of China. Physalin A, a main active ingredient of this traditional Chinese medicine (TCM), has been reported for its significant anti-tumor activity. However, most reports focused on the studies of its anti-tumor activity, the anti-inflammatory activity of physalin A and its molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study was to investigate the anti-inflammatory activities both in vitro and in vivo and molecular mechanism of physalin A. MATERIALS AND METHODS: The potential anti-inflammatory properties of physalin A were evaluated in vitro by lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells, and in vivo via two typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by enzyme-linked immuno sorbent assay (ELISA) and Western blotting. RESULTS: The results showed that physalin A inhibited carrageenan-induced paw edema of rats and capillary permeability of mice induced by acetic acid in vivo. Furthermore, physalin A also significantly reduced the release of inflammatory mediators nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW 264.7 in vitro. Further investigations indicated that physalin A can down-regulate the high expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Physalin A remarkably blocked the degradation of inhibitor of nuclear factor kappa B alpha (IκB-α) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 induced by LPS in RAW 264.7 cells. However, physalin A did not significantly inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) family proteins c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) or p38. CONCLUSIONS: All the results clearly illustrated that the anti-inflammatory action of physalin A is due to the inactivation of NF-κB signal pathway, but is irrelevant to the MAPKs pathway.

(3R, 7R)-7-Acetoxyl-9-Oxo-de-O-Methyllasiodiplodin, a Secondary Metabolite of Penicillium Sp., Inhibits LPS-Mediated Inflammation in RAW 264.7 Macrophages through Blocking ERK/MAPKs and NF-κB Signaling Pathways.

Twelve polyketones were isolated from the fermentation broth of Penicillium sp., including six new compounds (supplementary material). Penicillium sp. is widely used in clinic as a highly effective and low toxic antibiotic. Among these compounds, (3R, 7R)-7-acetoxyl-9-oxo-de-O-methyllasiodiplodin named PS-2 showed significant anti-inflammatory activity. So, the anti-inflammatory mechanism of PS-2 was investigated by using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The results showed that PS-2 can significantly inhibit the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6), whereas it showed no inhibition on the release of pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Cell-free colorimetric method demonstrated that PS-2 could obviously inhibit the enzymatic activity of cyclooxygenase-2 (COX-2). Western blot results indicated that PS-2 could significantly inhibit high expression of iNOS and COX-2 proteins. Further investigations on the anti-inflammatory mechanism showed that PS-2 could suppress the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but did not exhibit obvious inhibition on the phosphorylation of c-JunN-terminal kinase (JNK) and phosphorylated 38 (p38). In addition, PS-2 inhibited the degradation of inhibitor of kappa-B alpha (IκB-α) and translocation to nucleus of nuclear factor kappa-B (NF-κB) p65 in RAW 264.7 macrophages. These results suggested that PS-2 might be an effective intervention against inflammatory diseases.

Environment-dependent distribution of the sediment nifH-harboring microbiota in the Northern South China Sea.

The South China Sea (SCS), the largest marginal sea in the Western Pacific Ocean, is a huge oligotrophic water body with very limited influx of nitrogenous nutrients. This suggests that sediment microbial N(2) fixation plays an important role in the production of bioavailable nitrogen. To test the molecular underpinning of this hypothesis, the diversity, abundance, biogeographical distribution, and community structure of the sediment diazotrophic microbiota were investigated at 12 sampling sites, including estuarine, coastal, offshore, deep-sea, and methane hydrate reservoirs or their prospective areas by targeting nifH and some other functional biomarker genes. Diverse and novel nifH sequences were obtained, significantly extending the evolutionary complexity of extant nifH genes. Statistical analyses indicate that sediment in situ temperature is the most significant environmental factor influencing the abundance, community structure, and spatial distribution of the sediment nifH-harboring microbial assemblages in the northern SCS (nSCS). The significantly positive correlation of the sediment pore water NH(4)(+) concentration with the nifH gene abundance suggests that the nSCS sediment nifH-harboring microbiota is active in N(2) fixation and NH(4)(+) production. Several other environmental factors, including sediment pore water PO(4)(3-) concentration, sediment organic carbon, nitrogen and phosphorus levels, etc., are also important in influencing the community structure, spatial distribution, or abundance of the nifH-harboring microbial assemblages. We also confirmed that the nifH genes encoded by archaeal diazotrophs in the ANME-2c subgroup occur exclusively in the deep-sea methane seep areas, providing for the possibility to develop ANME-2c nifH genes as a diagnostic tool for deep-sea methane hydrate reservoir discovery.