Cellular Anti-Inflammatory and Antioxidant Activities of Bamboo Sasa albomarginata Leaf Extract and Its Constituent Coumaric Acid Methyl Ester.

Background: Hot water extract of Sasa albomarginata (Kumazasa) leaves is commercially available and used as a dietary supplement or skincare cream. The extract possesses anti-inflammatory activity on the mouse atopic dermatitis model. To elucidate the mechanism of in vivo activity, we have studied the cellular anti-inflammatory and antioxidant activities of the extract and its constituents. Methods: Secretion of mouse and human IL-6 was measured by ELISA. ROS production was measured by a fluorescent reagent. Ultrahigh performance liquid chromatography (UHPLC)/MS was used for the ingredient analysis. Results: The Sasa albomarginata extract inhibited inflammatory mediators such as LPS-induced NO, IL-6, and ROS production in mouse monocyte leukemia RAW264.7 cells. It also inhibited iNOS, IL-6, and IL-1ß expressions. Moreover, it inhibited LPS-induced IL-6 expression and production in human monocyte leukemia THP-1 cells differentiated into macrophages. The HPLC analysis of the extract revealed the existence of coumaric acid, ferulic acid, and coumaric acid methyl ester. Coumaric acid methyl ester but not coumaric acid or ferulic acid inhibited LPS-induced NO, IL-6, and ROS production in RAW264.7 cells and IL-6 production in differentiated THP-1 cells. Conclusion: The hot water extract of Sasa albomarginata leaves and one of its constituents possess cellular anti-inflammatory and antioxidant activities.

NF­κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle­induced interleukin­1ß production: Inhibition of the PM2.5­induced inflammation model.

PM2.5 is a particle with a diameter <2.5 µm that is often involved in air pollution. Nanoparticles <100 nm are thought to invade the trachea and lungs to cause inflammation, possibly through the activation of macrophages. On the other hand, titanium dioxide (TiO2) particles can be used in models of nano­micro­sized particles, as one can prepare the particles with such sizes. TiO2 particles are classified into Rutile, Anatase, and Brookite types by their crystal structure. Among them, Anatase­type TiO2 particles with a primary diameter of 50 nm (A50) were reported to induce interleukin (IL)­1ß production and secretion effectively in phorbol 12­myristate 13­acetate­treated human monocytic leukemia THP­1 cells (THP­1 macrophages). We previously designed and synthesized dehydroxymethyl­epoxyqinomicin (DHMEQ) as an inhibitor of NF­κB. The present study investigated whether the NF­κB inhibitor DHMEQ inhibits TiO2 nanoparticle­induced IL­1ß production in THP­1 macrophages, and determined the mechanism. As a result, DHMEQ inhibited A50­induced IL­1ß secretion in ELISA assays at nontoxic concentrations. It decreased the expression of IL­1ß mRNA, which was dependent on NF­κB. Although NLR family pyrin domain containing 3 (NLRP3)­inflammasome­caspase­1 activation is required for the maturation of IL­1ß, and DHMEQ reduced the NLRP3 mRNA expression and caspase­1 activity; a caspase­1 inhibitor did not influence the A50­induced IL­1ß production. Therefore, it is likely that inhibition of pro­IL­1ß expression by DHMEQ may be sufficient to inhibit mature IL­1ß production. Thus, DHMEQ may be useful for the amelioration of inflammation in the trachea and lungs caused by inhalation of PM2.5.

Therapeutic activity of plant-derived alkaloid conophylline on metabolic syndrome and neurodegenerative disease models.

Increasing metabolic syndromes including type-2 diabetes mellitus, obesity, and steatohepatitis are serious problems in most countries in the world. Neurodegenerative diseases such as Alzheimer, Parkinson's, and Huntington's diseases are increasing in many countries. However, therapy for these diseases is not sufficient yet. Thus, effective chemotherapy for these diseases is being expected. Conophylline is an alkaloid isolated from the leaves of Ervatamia microphylla and related plants. It was found to induce beta-cell differentiation in the precursor pancreatic cells. Oral administration of this compound ameliorated type-2 diabetes mellitus model in mice and rats. Later, fibrosis of the pancreatic islets was found to be greatly reduced by conophylline in the pancreatic islets. It also inhibited chemically induced liver cirrhosis. Further study indicated that conophylline inhibited non-alcoholic steatohepatitis in the model mice. On the one hand, loss of autophagy often causes protein aggregation to give neural cell death. Conophylline was found to activate autophagy in cultured neural cells. Activation of autophagy ameliorated cellular models of Parkinson's and Huntington's diseases. Thus, conophylline is likely to be useful for the development of chemotherapy for metabolic and neurodegenerative diseases.

Titanium Dioxide Particle Type and Concentration Influence the Inflammatory Response in Caco-2 Cells.

Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreens, biomedicine, and food products. When used as a food additive, TiO2 nanoparticles are used in significant amounts as white food-coloring agents. However, the effects of TiO2 nanoparticles on the gastrointestinal tract remain unclear. The present study was designed to determine the effects of five TiO2 particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Twenty-four-hour exposure to anatase (primary particle size: 50 and 100 nm) and rutile (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner in THP-1 macrophages, but in not Caco-2 cells. However, 72-h exposure of Caco-2 cells to anatase (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner. The highest dose (50 µg/mL) of anatase (100 nm), rutile (50 nm), and P25 TiO2 particles also reduced cellular viability in Caco-2 cells. The production of reactive oxygen species tended to increase in both types of cells, irrespective of the type of TiO2 particle. Exposure of THP-1 macrophages to 50 µg/mL of anatase (50 nm) TiO2 particles increased interleukin (IL)-1ß expression level, and exposure of Caco-2 cells to 50 µg/mL of anatase (50 nm) TiO2 particles also increased IL-8 expression. The results indicated that anatase TiO2 nanoparticles induced inflammatory responses compared with other TiO2 particles. Further studies are required to determine the in vivo relevance of these findings to avoid the hazards of ingested particles.