Tentative Pratique du Relation Quantitatives Structure-Activité/Propriété (QSAR/QSPR)

Différentes technique statistiques tel que la régression linéaire, non linéaire, ACP, PLS, et les réseaux de neurones artificiels (ANN) ont été utilisées pour mettre en place des modèles pour la prédiction des activités biologiques. Les descripteurs des modèles ont été sélectionnés dans un jeu étendu de plusieurs descripteurs (topologiques, géométriques et quantiques). La relation quantitative structure-activité/propriété (QSAR/QSPR) modélisation se rapporte à la construction de ces modèles prédictifs d'activités biologiques différentes, en fonction de l'information de structure moléculaire et d'une banque de composés. Cet avis vise à couvrir les concepts et techniques essentielles qui sont pertinents pour la réalisation d'études QSAR / QSPR grâce à l'utilisation d'exemples choisis dans nos travaux précédents

Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats

Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tailcuff method and endothelial function was assessed by carbachol (10-8 to 10-4M -induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-ω-nitroarginine (3 × 10-5M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10-5M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P< 0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10-5M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment

Circum-Mediterranean cultural heritage and medicial plant uses in traditional animal healthcare: a field survey in eight selected areas within the RUBIA project

During the years 2003¿2005, a comparative ethnobotanical field survey was conducted on remedies used in traditional animal healthcare in eight Mediterranean areas. The study sites were selected within the EU-funded RUBIA project, and were as follows: the upper Kelmend Province of Albania; the Capannori area in Eastern Tuscany and the Bagnocavallo area of Romagna, Italy; Cercle de Ouezanne, Morocco; Sierra de Aracena y Picos de Aroche Natural Park in the province of Huelva, Spain; the St. Catherine area of the Sinai Peninsula, Egypt; Eastern and Western Crete, Greece; the Paphos and Larnaca areas of Cyprus; and the Mitidja area of Algeria. One hundred and thirty-six veterinary preparations and 110 plant taxa were recorded in the survey, with Asteraceae and Lamiaceae being the most quoted botanical families. For certain plant species the survey uncovered veterinary phytotherapeutical indications that were very uncommon, and to our knowledge never recorded before. These include Anabasis articulata (Chenopodiaceae), Cardopatium corymbosum (Asteraceae), Lilium martagon (Liliaceae), Dorycnium rectum (Fabaceae), Oenanthe pimpinelloides (Apiaceae), Origanum floribundum (Lamiaceae), Tuberaria lignosa (Cistaceae), and Dittrichia graveolens (Asteraceae). These phytotherapeutical indications are briefly discussed in this report, taking into account modern phytopharmacology and phytochemistry. The percentage of overall botanical veterinary taxa recorded in all the study areas was extremely low (8%), however when all taxa belonging to the same botanical genus are considered, this portion increases to 17%. Nevertheless, very few plant uses were found to be part of a presumed "Mediterranean" cultural heritage in veterinary practices, which raises critical questions about the concept of Mediterraneanism in ethnobotany and suggests that further discussion is required. Nearly the half of the recorded veterinary plant uses for mammals uncovered in this survey have also been recorded in the same areas in human folk medicine, suggesting a strong link between human and veterinary medical practices, and perhaps also suggesting the adaptive origins of a few medical practices. Since most of the recorded data concern remedies for treating cattle, sheep, goats, and camels, it would be interesting to test a few of the recorded phytotherapeuticals in the future, to see if they are indeed able to improve animal healthcare in breeding environments, or to raise the quality of dairy and meat products in the absence of classical, industrial, veterinary pharmaceuticals

COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups

The inhibitory activity of aldose reductase of flavonoid compounds: Combining DFT and QSAR calculations

The DFT-B3LYP method, with the base set 6-31G (d), was used to calculate several quantum chemical descriptors of 44 substituted flavonoids. The best descriptors were selected to establish the quantitative structure activity relationship (QSAR) of the inhibitory activity against aldose reductase using principal components analysis (PCA), multiple regression analysis (MLR), nonlinear regression (RNLM) and an artificial neural network (ANN). We propose a quantitative model according to these analyses, and we interpreted the activity of the compounds based on the multivariate statistical analysis. This study shows that the MLR and MNLR predict activity, but compared to the results of the ANN model, we conclude that the predictions achieved by the latter are more effective and better than the other models. The results indicate that the ANN model is statistically significant and shows very good stability toward data variation for the validation method. The contribution of each descriptor to the structure–activity relationship was also evaluated

Predictive modelling of the LD50 activities of coumarin derivatives using neural statistical approaches: Electronic descriptor-based DFT

A study of structure–activity relationship (QSAR) was performed on a set of 30 coumarin-based molecules. This study was performed using multiple linear regressions (MLRs) and an artificial neural network (ANN). The predicted values of the antioxidant activities of coumarins were in good agreement with the experimental results. Several statistical criteria, such as the mean square error (MSE) and the correlation coefficient (R), were studied to evaluate the developed models. The best results were obtained with a network architecture [8-4-1] (R = 0.908, MSE = 0.032), activation functions (tansig–purelin) and the Levenberg–Marquardt learning algorithm. The model proposed in this study consists of large electronic descriptors that are used to describe these molecules. The results suggested that the proposed combination of calculated parameters may be useful for predicting the antioxidant activities of coumarin derivatives