Low concentrations of Ambrosia maritima L. phenolic extract protect endothelial cells from oxidative cell death induced by H2O2 and sera from Crohn's disease patients.

ETHNOPHARMACOLOGICAL RELEVANCE: A rising resort to herbal therapies in Crohn's disease (CD) alternative treatments has been recently observed due to their remarkable natural efficiency. In this context, the weed plant Ambrosia maritima L., traditionally known as Hachich el Aouinet in Algeria and as Damsissa in Egypt and Sudan, is widely used in North African folk medicine to treat infections, inflammatory diseases, gastrointestinal and urinary tract disturbances, rheumatic pain, respiratory problems, diabetes, hypertension and cancer. AIM OF THE STUDY: To assess an Ambrosia maritima L. phenolic extract for its phenolic profile composition, its potential antioxidant activity in vitro, and its cytoprotective effect on cultured primary human endothelial cells (ECs) stressed with H2O2 and sera from CD patients. MATERIALS AND METHODS: Phenolic compound extraction was performed with a low-temperature method. Extract chemical profile was attained by HPLC-DAD/ESI-MS. The extract in vitro antioxidant activity was assessed using several methods including cupric ion reducing power, DPPH radical scavenging assay, O-Phenanthroline free radical reducing activity, ABTS cation radical decolourisation assay, Galvinoxyl free radicals scavenging assay. Intracellular reactive oxygen species levels were evaluated in human endothelial cells by H2DCFDA, while cell viability was assessed by MTT. RESULTS: The phenolic compounds extraction showed a yield of 17.66% with three di-caffeoylquinic acid isomers detected for the first time in Ambrosia maritima L. Using different analytical methods, a significant in vitro antioxidant activity was reported for the Ambrosia maritima L. extract, with an IC50 value of 14.33 ± 3.86 µg/mL for the Galvinoxyl antioxidant activity method. Challenged with ECs the Ambrosia maritima L. extract showed a biphasic dose-dependent effect on H2O2-treated cells, cytoprotective and antioxidant at low doses, and cytotoxic and prooxidant at high doses, respectively. Viability and ROS levels data also demonstrated a prooxidant and cytotoxic effect of CD sera on cultured ECs. Interestingly, 10 µg/mL of Ambrosia maritima L. extract was able to counteract both CD sera-induced oxidative stress and ECs death. CONCLUSION: Our data indicated Ambrosia maritima L. as a source of bioactive phenolics potentially employable as a natural alternative for CD treatment.

Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and in vitro Approaches.

Acetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure-based virtual screening (SBVS) using the Institut Curie-CNRS chemical library (ICCL), which contained at the screening date 14307 compounds. The strategy undertaken in this work consisted of the use of several docking programs in SBVS calculations followed by the application of a consensus method (vSDC) and a scrupulous visual analysis. It allowed us to obtain a high degree of success, with a yield of almost 86 %, since 12 hits were identified among only 14 molecules tested in vitro. Still more remarkably, 6 of these hits were more active than galantamine, the reference inhibitor. These hits were predicted to have good ADMET properties. The two most promising compounds can serve as leads for AD treatment.