Optimization of Extraction Process for Antidiabetic and Antioxidant Activities of Kursi Wufarikun Ziyabit Using Response Surface Methodology and Quantitative Analysis of Main Components

By using extraction yield, total polyphenolic content, antidiabetic activities (PTP-1B and α-glycosidase), and antioxidant activity (ABTS and DPPH) as indicated markers, the extraction conditions of the prescription Kursi Wufarikun Ziyabit (KWZ) were optimized by response surface methodology (RSM). Independent variables were ethanol concentration, extraction temperature, solid-to-solvent ratio, and extraction time. The result of RSM analysis showed that the four variables investigated have a significant effect (p<0.05) for Y1, Y2, Y3, Y4, and Y5 with R2 value of 0.9120, 0.9793, 0.9076, 0.9125, and 0.9709, respectively. Optimal conditions for the highest extraction yield of 39.28%, PTP-1B inhibition rate of 86.21%, α-glycosidase enzymes inhibition rate of 96.56%, and ABTS inhibition rate of 77.38% were derived at ethanol concentration 50.11%, extraction temperature 72.06°C, solid-to-solvent ratio 1 : 22.73 g/mL, and extraction time 2.93 h. On the basis of total polyphenol content of 48.44% in this optimal condition, the quantitative analysis of effective part of KWZ was characterized via UPLC method, 12 main components were identified by standard compounds, and all of them have shown good regression within the test ranges and the total content of them was 11.18%

Discovery of Novel DPP-IV Inhibitors as Potential Candidates for the Treatment of Type 2 Diabetes Mellitus Predicted by 3D QSAR Pharmacophore Models, Molecular Docking and De Novo Evolution

Dipeptidyl peptidase-IV (DPP-IV) rapidly breaks down the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Thus, the use of DPP-IV inhibitors to retard the degradation of endogenous GLP-1 is a possible mode of therapy correcting the defect in incretin-related physiology. The aim of this study is to find a new small molecule and explore the inhibition activity to the DPP-IV enzyme using a computer aided simulation. In this study, the predicted compounds were suggested as potent anti-diabetic candidates. Chosen structures were applied following computational strategies: The generation of the three-dimensional quantitative structure-activity relationship (3D QSAR) pharmacophore models, virtual screening, molecular docking, and de novo Evolution. The method also validated by performing re-docking and cross-docking studies of seven protein systems for which crystal structures were available for all bound ligands. The molecular docking experiments of predicted compounds within the binding pocket of DPP-IV were conducted. By using 25 training set inhibitors, ten pharmacophore models were generated, among which hypo1 was the best pharmacophore model with the best predictive power on account of the highest cost difference (352.03), the lowest root mean squared deviation (RMSD) (2.234), and the best correlation coefficient (0.925). Hypo1 pharmacophore model was used for virtual screening. A total of 161 compounds including 120 from the databases, 25 from the training set, 16 from the test set were selected for molecular docking. Analyzing the amino acid residues of the ligand-receptor interaction, it can be concluded that Arg125, Glu205, Glu206, Tyr547, Tyr662, and Tyr666 are the main amino acid residues. The last step in this study was de novo Evolution that generated 11 novel compounds. The derivative dpp4_45_Evo_1 by all scores CDOCKER_ENERGY (CDOCKER, -41.79), LigScore1 (LScore1, 5.86), LigScore2 (LScore2, 7.07), PLP1 (-112.01), PLP2 (-105.77), PMF (-162.5)&mdash;have exceeded the control compound. Thus the most active compound among 11 derivative compounds is dpp4_45_Evo_1. Additionally, for derivatives dpp4_42_Evo_1, dpp4_43_Evo2, dpp4_46_Evo_4, and dpp4_47_Evo_2, significant upward shifts were recorded. The consensus score for the derivatives of dpp4_45_Evo_1 from 1 to 6, dpp4_43_Evo2 from 4 to 6, dpp4_46_Evo_4 from 1 to 6, and dpp4_47_Evo_2 from 0 to 6 were increased. Generally, predicted candidates can act as potent occurring DPP-IV inhibitors given their ability to bind directly to the active sites of DPP-IV. Our result described that the 6 re-docked and 27 cross-docked protein-ligand complexes showed RMSD values of less than 2 &Aring;. Further investigation will result in the development of novel and potential antidiabetic drugs

Development of HPLC Protocol and Simultaneous Quantification of Four Free Flavonoids from Dracocephalum heterophyllum Benth.

Quantification of the four flavonoids, namely, luteolin, kaempferol, diosmetin, and chrysosplenetin, has been performed for the first time in 80% ethanolic extract of Dracocephalum heterophyllum B. through HPLC coupled to UV detector after optimization of extracting solvent and chromatographic conditions. Total flavonoids quantified were 0.324 mg/mL of the extract. HPLC analysis delivered contents of the luteolin, kaempferol, diosmetin, and chrysosplenetin as 0.08%, 0.14%, 0.28%, and 0.79% of the dried extract, respectively. LOD (%) values calculated were 0.04, 0.03, 0.03, and 0.08 and LOQ (%) values were 0.08, 0.12, 0.11, and 0.28 for luteolin, kaempferol, diosmetin, and chrysosplenetin, respectively. The recovery percentages for these flavonoids were within the acceptable range of 95% to 105%. Standard deviation and %RSD were calculated for each target analytes individually in extract for determining the reproducibility and accuracy of the method. In no case the %RSD was higher than 1 taking retention time as a factor while in the case of area under the curve maximum %RSD was noted in the case of diosmetin as 2.85. From our literature review regarding the plant species under study, it appears that these flavonoids have not been quantified before and are reported for the first time in this paper

Development of HPLC Protocol and Simultaneous Quantification of Four Free Flavonoids from Dracocephalum heterophyllum Benth.

Quantification of the four flavonoids, namely, luteolin, kaempferol, diosmetin, and chrysosplenetin, has been performed for the first time in 80% ethanolic extract of Dracocephalum heterophyllum B. through HPLC coupled to UV detector after optimization of extracting solvent and chromatographic conditions. Total flavonoids quantified were 0.324 mg/mL of the extract. HPLC analysis delivered contents of the luteolin, kaempferol, diosmetin, and chrysosplenetin as 0.08%, 0.14%, 0.28%, and 0.79% of the dried extract, respectively. LOD (%) values calculated were 0.04, 0.03, 0.03, and 0.08 and LOQ (%) values were 0.08, 0.12, 0.11, and 0.28 for luteolin, kaempferol, diosmetin, and chrysosplenetin, respectively. The recovery percentages for these flavonoids were within the acceptable range of 95% to 105%. Standard deviation and %RSD were calculated for each target analytes individually in extract for determining the reproducibility and accuracy of the method. In no case the %RSD was higher than 1 taking retention time as a factor while in the case of area under the curve maximum %RSD was noted in the case of diosmetin as 2.85. From our literature review regarding the plant species under study, it appears that these flavonoids have not been quantified before and are reported for the first time in this paper

A New Non-Enzymatic Amperometric Sensor Based on Nickel Decorated ZIF-8 Derived Carbon Nanoframe for the Glucose Determination in Blood Samples

The present study demonstrated a highly sensitive non-enzymatic glucose biosensor in real blood samples based on simple evaluated nickel deposited on N-doped porous carbon modified glassy carbon electrode (Ni/NPC/GCE) by applying electrochemical deposition method. The prepared material initially were characterized by cyclic voltammetry, the morphology structure of the as-prepared samples was observed by SEM, and composition, crystals structure of Ni/NPC were identified by SEM mapping and EDS tests. The Ni/NPC/GCE compared with NPC/GCE and NiNPs/GCE performed the best electrocatalytic behavior towards oxidation of glucose in 0.1 M KOH medium. By applied potential of +0.6 V Ni/NPC/GCE showed very high sensitivity of 3753.78 mu AmM(-1)cm(-2) in linear range of 1-7940 mu M with the correlation coefficient of R-2=0.995. The linear ranges get views above the concentration up to 7940 mu M with the detection limit of 0.3 mu M (S/N= 3). Amperometric time responses of prepared electrode towards different glucose concentrations are 0.8-1.3s. Finally, several positive characteristics such as very high sensitivity, weak working potential, nice anti-interference properties, long stability, good selectivity, and comparison with some other non-enzymatic sensors Ni/NPC/GCE executed high sensitivity, low detection limit and wide linear range to glucose sensing, thus the selected electrode is supplying for future glucose level determination design

Phytochemical Profiling and Evaluation of Pharmacological Activities of Hypericum scabrum L.

Phytochemical investigations of ethyl acetate-soluble part of the aerial part of Hypericum scabrum L. delivered eight pure phenolic compounds 1–8. The pure compounds were identified through physico-chemical, NMR (1D, 2D) and mass spectrometric studies as: 3-8′′-bisapigenin (1), quercetin (2), quercetin-3-O-α-l-arabinofuranoside (3), quercetin-3-O-α-l-rhamnoside (4), quercetin-3-O-β-d-glucopyranoside (5), quercetin-3-O-β-d-galactopyranoside (6), (−)-epicatechin (7), (+)-catechin (8). Total polyphenolic compounds and total flavonoids contents were determined in the extract as 0.107 mg∙mg−1 and 0.023 mg∙mg−1 of the dried extract, respectively. Antioxidant activity using DPPH free radical scavenging assay delivered very strong activity for compounds 2 and 5, 6 and crude extract 10. Protein tyrosine phosphatase 1B (PTP-1B) inhibition experiment of isolated compounds and crude extracts resulted in significant inhibition activity for samples 2, 7a, 8a, 11 and 12 with IC50 values ranging from 1.57 to 2.91 µM. Antimicrobial activity of the pure compounds and extracts produced average results against Staphylococcus aureus, Escherichia coli and Candida albicans strains. From our literature survey, it appears that all pure compounds except 2 were isolated and reported for the first time in H. scabrum

Assessment of Artemisinin Contents in Selected <i>Artemisia</i> Species from Tajikistan (Central Asia)

Background: Central Asia is the center of origin and diversification of the Artemisia genus. The genus Artemisia is known to possess a rich phytochemical diversity. Artemisinin is the shining example of a phytochemical isolated from Artemisia annua, which is widely used in the treatment of malaria. There is great interest in the discovery of alternative sources of artemisinin in other Artemisia species. Methods: The hexane extracts of Artemisia plants were prepared with ultrasound-assisted extraction procedures. Silica gel was used as an adsorbent for the purification of Artemisia annua extract. High-performance liquid chromatography with ultraviolet detection was performed for the quantification of underivatized artemisinin from hexane extracts of plants. Results: Artemisinin was found in seven Artemisia species collected from Tajikistan. Content of artemisinin ranged between 0.07% and 0.45% based on dry mass of Artemisia species samples. Conclusions: The artemisinin contents were observed in seven Artemisia species. A. vachanica was found to be a novel plant source of artemisinin. Purification of A. annua hexane extract using silica gel as adsorbent resulted in enrichment of artemisinin