Optimization of ultrasound-aided extraction of bioactive ingredients from Vitis vinifera seeds using RSM and ANFIS modeling with machine learning algorithm.

Plant materials are a rich source of polyphenolic compounds with interesting health-beneficial effects. The present study aimed to determine the optimized condition for maximum extraction of polyphenols from grape seeds through RSM (response surface methodology), ANFIS (adaptive neuro-fuzzy inference system), and machine learning (ML) algorithm models. Effect of five independent variables and their ranges, particle size (X1: 0.5-1 mm), methanol concentration (X2: 60-70% in distilled water), ultrasound exposure time (X3: 18-28 min), temperature (X4: 35-45 °C), and ultrasound intensity (X5: 65-75 W cm-2) at five levels (- 2, - 1, 0, + 1, and + 2) concerning dependent variables, total phenolic content (y1; TPC), total flavonoid content (y2; TFC), 2, 2-diphenyl-1-picrylhydrazyl free radicals scavenging (y3; %DPPH*sc), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radicals scavenging (y4; %ABTS*sc) and Ferric ion reducing antioxidant potential (y5; FRAP) were selected. The optimized condition was observed at X1 = 0.155 mm, X2 = 65% methanol in water, X3 = 23 min ultrasound exposure time, X4 = 40 °C, and X5 = 70 W cm-2 ultrasound intensity. Under this situation, the optimal yields of TPC, TFC, and antioxidant scavenging potential were achieved to be 670.32 mg GAE/g, 451.45 mg RE/g, 81.23% DPPH*sc, 77.39% ABTS*sc and 71.55 µg mol (Fe(II))/g FRAP. This optimal condition yielded equal experimental and expected values. A well-fitted quadratic model was recommended. Furthermore, the validated extraction parameters were optimized and compared using the ANFIS and random forest regressor-ML algorithm. Gas chromatography-mass spectroscopy (GC-MS) and liquid chromatography-mass spectroscopy (LC-MS) analyses were performed to find the existence of the bioactive compounds in the optimized extract.

Mimosa pudica Linn. extract improves aphrodisiac performance in diabetes-induced male Wister rats.

Male sexual dysfunction is considered one of the major consequences of diabetes mellitus. The medicinal plant, Mimosa pudica Linn. is believed to have numerous therapeutic effects, including anti-diabetic, anti-obesity, aphrodisiac, and a sexual behaviour-enhancing properties. In the present study, the significant effect of ethanolic extract of M. pudica L. to scavenge excessive free radicals and alleviate the deleterious effects of alloxan-induced diabetes on the male sexual system of rats was demonstrated. The rats treated with the M. pudica L. extract recovered their body weight, the weight of their reproductive organs, the characteristics of the sperm and the histocellular arrangement of the testes. In addition, significant levels of hormones (testosterone, follicle-stimulating hormone and luteinising hormone) increased in both serum and testicular homogenates of male diabetic rats treated with M. pudica L. extract. Further, antioxidant enzymes, SOD, CAT, GSH, and GPx levels are increased, and oxidative stress markers MDA and ROS are reduced in both serum and testicular homogenates of M. pudica L. extract treated male rats. Furthermore, an in silico molecular docking study was performed to predict high potential compounds of M. pudica L. extract against the PDE5 receptor. Two bioactive compounds, namely 3-Dibenzofuranamine (-11.1 kcal × mol-1), Stigmasta-7,16-dien-3-ol (-10.4 kcal × mol-1) showed the highest binding affinities with PDE5 enzyme, much higher than the reference drug sildenafil (-9.9 kcal × mol-1). According to these findings, bioactive compounds rich in ethanolic extract of M. pudica L. have significant aphrodisiac performance in diabetic rats.Communicated by Ramaswamy H. Sarma.

An In Silico Molecular Modelling-Based Prediction of Potential Keap1 Inhibitors from Hemidesmus indicus (L.) R.Br. against Oxidative-Stress-Induced Diseases.

The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch-Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 µg × mL-1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 µg × mol (Fe (II)) g-1 ferric ion reducing power. The three top-scored hits, namely Hemidescine (-11.30 Kcal × mol-1), Beta-Amyrin (-10.00 Kcal × mol-1), and Quercetin (-9.80 Kcal × mol-1), were selected based on their binding affinities. MD simulation studies showed that all the protein-ligand complexes (Keap1-HEM, Keap1-BET, and Keap1-QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018-Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications.

Cytotoxic Potential of Bioactive Compounds from Aspergillus flavus, an Endophytic Fungus Isolated from Cynodon dactylon, against Breast Cancer: Experimental and Computational Approach.

Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 µg/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3α, 5 α-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.