Cannonagger5627

Lithraea caustica (Molina) Hook. and Arn. (Anacardiaceae), common name Litre, is an evergreen endemic plant used in the Mapuche Chilean folk medicine. The stem juice of L. caustica mixed with Rubus ulmifolius (blackberry) is used to treat cough and the infusion of leaves is used in baths to treat joint inflammations. In this study, the activities of 3-n-alk(en)yl-catechols, obtained from the dichloromethane extract of the epicuticular compounds of fresh leaves (DCME), stem bark petroleum ether extract (PEE), fractions of phenols and phenol-acid compounds obtained from the methanolic extract (methanolic extract) of defatted leaves and aqueous infusion (AE) from fresh leaves, were evaluated as in vitro inhibitors of soybean 15-lipoxygenase (15-sLOX) and human 5-lipoxygenase (5-hLOX), one of the inflammation pathways. The 3-n-alk(en)yl-catechols were characterized by gas chromatography-mass spectrometry and 1D and 2D nuclear magnetic resonance analysis as mixtures of 3-[(10E)-pentadec-10'-en-1-yl]-catechol, 3-[(t 15-sLOX and the AE, showed a good inhibition against 5-hLOX. These results would be in agreement with the use of L. caustica, as an anti-inflammatory in Mapuche ethnomedicine.Background Macrophages can selectively recognize and eliminate senescent cells, but this function is impaired with age, resulting in excessive accumulation of senescent cells in the skin, which ultimately causes skin aging. Therefore, enhancing the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts from aging skin may be an effective skin rejuvenation strategy. Methods In this study, a macrophage and senescent skin cell co-culture model was established whereby THP-1-derived macrophages and tert-butyl hydroxide-induced senescent skin cells (HaCaT and HFF-1) were grown in the same culture. Senescent skin cells were detected by the SPiDER-βgal assay, and the expression of secretory phenotype factors related to senescence was assayed by qPCR. The effect of carnosine on the number of SA-β-gal positive skin cells in the macrophage-senescent skin cell co-culture was evaluated and compared with that in the senescent skin cell monoculture. Results Carnosine promoted macrophage-mediated elimination of senescent skin cells in the co-culture. Through the AKT2 signaling pathway, carnosine upregulated the expression of CD36 and receptors for advanced glycation end products and elevated the phagocytic capacity of the macrophages, thereby promoting the ability of the macrophages to eliminate the senescent skin cells. Conclusions Carnosine could boost the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts in the macrophage-senescent skin cell co-culture by activating the AKT2 signaling pathway, suggesting the possibility of using carnosine as an agent to reverse skin aging.Idiopathic pulmonary fibrosis is a chronic, progressive, and lethal lung disease of unknown etiology. Antifibrotic drugs, including pirfenidone, are currently used for the treatment of the disease. The oral administration of pirfenidone is an effective therapy, as demonstrated by several clinical trials, although it causes severe adverse events in some patients. MEK phosphorylation We hypothesized that low-dose intrapulmonary delivery of pirfenidone is effective in human transforming growth factorβ1-driven pulmonary fibrosis. To demonstrate our hypothesis, we compared the therapeutic efficacy of varying doses of pirfenidone administered by oral and intranasal routes in a human transforming growth factor-β1 transgenic mouse with established pulmonary fibrosis. We found similar amelioration of lung cell infiltration, inflammatory and fibrotic cytokines, lung fibrosis score, and hydroxyproline content in mice with human transforming growth factor-β1-mediated pulmonary fibrosis treated with low-dose intranasal pirfenidone and high-dose oral pirfenidone. This study showed that pirfenidone is a potent inhibitor of human transforming growth factor-β1-driven lung fibrosis and that intrapulmonary delivery of low-dose pirfenidone produces therapeutic responses equivalent to high-dose of oral pirfenidone.Hydroxychloroquine has gained much attention as one of the candidate drugs that can be repurposed as a prophylactic agent against SARS-CoV-2, the agent responsible for the COVID-19 pandemic. Due to high transmissibility and presence of asymptomatic carriers and presymptomatic transmission, there is need for a chemoprophylactic agent to protect the high-risk population. In this review, we dissect the currently available evidence on hydroxychloroquine prophylaxis from a clinical and pharmacological point of view. In vitro studies on Vero cells show that hydroxychloroquine effectively inhibits SARS-CoV-2 by affecting viral entry and viral transport via endolysosomes. However, this efficacy has failed to replicate in in vivo animal models as well as in most clinical observational studies and clinical trials assessing pre-exposure prophylaxis and postexposure prophylaxis in healthcare workers. An analysis of the pharmacology of HCQ in COVID-19 reveals certain possible reasons for this failure-a pharmacokinetic failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells. Currently, many clinical trials on HCQ prophylaxis in HCW are ongoing; these factors should be taken into account. Using higher doses of HCQ for prophylaxis is likely to be associated with increased safety concerns; thus, it may be worthwhile to focus on other possible interventions.Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity.