Endoplasmic reticulum stress is a cellular phenomenon that has been associated with metabolic disorders, contributing to the development of obesity, fatty liver disease, and dyslipidemias. Under metabolic overload conditions, in cells with a high protein-secretory activity, such as hepatocytes and Langerhans β cells, the unfolded protein response (UPR) is critical in to maintain protein homeostasis (proteostasis). UPR integrated by a tripartite signaling system, through activating transcription factor 6, protein kinase R-like endoplasmic reticulum kinase (PERK), and inositol-requiring enzyme 1, regulates gene transcription and translation to resolve stress and conserve proteostasis. In the current study, we demonstrated in hepatocytes under metabolic overload by saturated palmitic and stearic fatty acids, through activation of PERK signaling and CCAAT-enhancer-binding protein homologous protein (CHOP) transcription factor, an association with the expression of cyclooxygenase 2. More important, isolated exosomes from supernatants of macrophages exposed to lipopolysaccharides can also induce a metainflammation phenomenon, and when treated on hepatocytes, induced a rearrangement in cholesterol metabolism through sterol regulatory element-binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), apolipoprotein A-I, and ABCA1. Moreover, we demonstrate the cellular effect of terpene-derived molecules, such as cryptotanshinone, isolated of plant Salvia brandegeei, regulating metainflammatory conditions through PERK pathway in both hepatocytes and β cells.Our data suggest the presence of a modulatory mechanism on specific protein translation process. This effect could be mediated by eukaryotic initiation factor-4A, evaluating salubrinal as a control molecule. Likewise, the protective mechanisms of unsaturated fatty acids, such as oleic and palmitoleic acid were confirmed. Therefore, modulation of metainflammation suggests a new target through PERK signaling in cells with a high secretory activity, and possibly the regulation of cholesterol in hepatocytes is promoted via exosomes.

In the current study, chemical composition of cultivated Salvia canariensis L was determined. In this work, carnosol was the main product isolated, and the concentration of rosmanol is also significant. We prepared more lipophilic derivatives from carnosol, and both isolated and semisynthetic abietane diterpenes were evaluated in vitro as inhibitors of squalene synthase isolated from rat liver.Among the compounds tested, carnosol was the most potent inhibitor with an IC 50 value of 17.6 μM. These results highlight the great potential of this species for the commercial production of extracts of interest for their possible uses as ingredients in nutritional supplements for the treatment of hyperlipidemia. 2 1. EXPERIMENTAL General experimental proceduresThe NMR spectra were recorded on BrukerAvance 300 MHz and Bruker Avance 400 MHz spectrometers in CDCl 3, unless otherwise noted. Chemical shifts are given in ppm with TMS as the internal standard. IR spectra were obtained on a Bruker IFS 28/55 (FTIR) spectrometer and UV spectra on a JASCO V-560. Low resolution mass spectra were run on a VG Micromass ZAB-2F and high-resolution mass spectra on a VG Micromass ZAB-2F at 70 eV. Merck silica gel 60 Å 0.063-0.200 mm (70-230 mesh) was used for column chromatography. Analytical thin-layer chromatography (TLC) and preparative TLC were carried out on precoated Schleicher and Schüll plates.

No abstract

The evaluation of the antioxidant capacity of grape cultivars Cabernet sauvignon is important because it varies according to the production area. In this work, it was evaluated the content of phenolic compounds and the total antioxidant capacity (CAT) of grape skins and grape seed Cabernet sauvignon (Vitis vinifera L.) in three vineyards located in the Valley of Guadalupe, B.C, México. The content of total phenols was determined by the Folin-Ciocalteau method and the CAT of grape skin and seed extracts by the stabilization methods of the (ABTS•+) and DPPH• radicals. The CAT in the seed extracts was increased (P < 0.05) in the following order: vineyard 2 < vineyard 1 < vineyard 3. The highest contents of gallic acid, resveratrol and rutin were found in the extracts that presented the highest CAT, which corresponded to the cultivars of vineyard 3. The same happened in extract of skins, having vineyard 3 the contents of CAT (ABTS•+) higher. The total phenolic seed compound was presented in vineyard 2 with 1,545, followed by vineyard 1 with 1,523, vineyard 3 with 1,146 expressed as g GAE.100 g of sample. In skin, the behavior was as follows; vineyard 3 <vineyard 2 <vineyard 1. 1,062, 1,086, 1,115 expressed as g GAE.100 g sample respectively.Keywords: antioxidant, phenolics, ABTS, gallic acid.

The antioxidant, antimicrobial, antiproliferative, and enzyme inhibitory properties of five extracts from aerial parts of Salvia pachyphylla Epling ex Munz were examined to assess the prospective of this plant as a source of natural products with therapeutic potential. These properties were analyzed by performing a set of standard assays. The extract obtained with dichloromethane showed the most variety of components, as they yielded promising results in all completed assays. Furthermore, the extract obtained with ethyl acetate exhibited the greatest antioxidant activity, as well as the best xanthine oxidase inhibitory activity. Remarkably, both extracts obtained with n-hexane or dichloromethane revealed significant antimicrobial activity against the Gram-positive bacteria; additionally, they showed greater antiproliferative activity against three representative cell lines of the most common types of cancers in women worldwide, and against a cell line that exemplifies cancers that typically develop drug resistance. Despite that, other extracts were less active, such as the methanolic or aqueous; their results are promising for the isolation and identification of novel bioactive molecules.