New Phenylpropanoids and Disulphides Dimers from Ferula Kuhistanica.

Five undescribed compounds, including three phenylpropanoid derivatives, 4'-methoxycinnamyl isobutyrate (1), 4'-methoxycinnamyl-2"-methyl butyrate (2) and (2Z)-3',4'-dimethoxycinnamyl isovalerate (3) and two disulphides dimers, kuhistanicasulphide A (7) and kuhistanicasulphide B (8) together with five known ones, including three phenylpropanoids (4-6) and two disulphides (9-10), were isolated from the roots of Ferula kuhistanica Korovin. Their structures were elucidated on the basis of spectroscopic analysis, including IR, UV, HRESIMS, NMR and quantum 13C NMR DP4+ probability. Anti-inflammatory and cytotoxic (Hela, A549 and HT-29 cell lines) activities of the obtained compounds was tested, which compounds 4 and 5 demonstrated good anti-inflammatory with IC50 values of 25.41±2.30 µM and 31.70±3.82 µM, respectively.

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)-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 Å. Further investigation will result in the development of novel and potential antidiabetic drugs.

Total polyphenolic compounds, total flavonoids, GC-MS analysis of volatile constituents, evaluation of antioxidant and antimicrobial activities of Prunus dulcis nuts.

Prunus dulcis has been known as a source of nutrients in many traditional foods and as a source of important biologically active compounds in traditional medicines. The present study describes the determination of total polyphenolic compounds, total flavonoids and GC-MS analysis of hexane and chloroform fractions of 70% ethanol extract of whole almond shelled seed. Antioxidant and antimicrobial activities of various extracts of the nuts were evaluated. Folin-Ciocalteau procedure resulted in total polyphenolic compounds as 0.008 mg (gallic acid equivalents)/mg of the dried extract and amount of total flavonoids contents yielded were 0.001 mg (quercetin equivalents)/mg of the nuts dried extracts. GC-MS analysis of the hexane and chloroform fractions yielded a number of volatile constituents, resulting in highest amounts of 6-Octadecenoic acid and 1,1,3,3-Tetramethyl cyclopentane as 37.52% and 24.54% in hexane and chloroform fractions respectively. Antioxidant activity using the DPPH radical scavenging assay resulted in very low activity in all the extracts. Only n-butanol extract showed mild activity against the gram negative E. coli with inhibition zone diameter 8 mm while rest of samples did not show any activity against any microbial strains under study.

Evaluation of the Antidiabetic Activity and Chemical Composition of Geranium collinum Root Extracts-Computational and Experimental Investigations.

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum. The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC50 values of 0.10 µg/mL and 0.09 µg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum, led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra-O-methylellagic acid (1), 3,3'-di-O-methylellagic acid (2), quercetin (3), caffeic acid (4), (+)-catechin (5), (-)-epicatechin (6), (-)-epigallocatechin (7), gallic acid (8), ß-sitosterol-3-O-ß-d-glucopyranoside (9), and corilagin (10). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC50 values below 0.9 µg/mL, more effective than the positive control (1.46 µg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and ß-sitosterol-3-O-ß-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum.

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-ß-d-glucopyranoside (5), quercetin-3-O-ß-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.

Unveiling the anti-vitiligo, anti-inflammatory, and antitumor activities of sesquiterpene coumarins isolated from Ferula kuhistanica.

Six undescribed bicyclic sesquiterpene coumarins, kuhistanin A, ferukrin isovalerate, 9'ß,12'α - ferukrin isovalerate, (17'E)- 9'α, 12'ß - isomarcandin, (17'Z)- 9'α, 12'ß - isomarcandin and (17'E) - isomarcandin, together with nine known ones were isolated from the roots of Ferula kuhistanica Korovin. The structures of them were elucidated using NMR and HRESIMS data analysis. The relative configurations of the isolates were confirmed by NOE correlations and NMR calculation. The absolute configurations of them were confirmed by X-ray diffraction analysis and ECD calculation. Anti-vitiligo, anti-inflammatory and cytotoxicity of the isolates were tested. Acetyl feselol, feselol, ferusingensine I and farnesiferol A significantly increased the melanin content at the concentration of 10 µM. (17'E) - 9'α, 12'ß - isomarcandin exhibited strong cytotoxicity against HT-29 cell line with IC50 values of 8.94 ± 0.47 µM, and (17'E) - isomarcandin demonstrated strong cytotoxicity against Hela, A549 and HT-29 cell lines with IC50 values of 5.29 ± 0.25, 4.01 ± 0.20, and 4.16 ± 0.21 µM, respectively. This study concluded that, isolated compounds from F. kuhistanica demonstrated strong bioactivity towards anti-vitiligo and cytotoxicity and active compounds are suggested as anti-vitiligo and cytotoxicity agent for future drug development.

New coumarin from the roots of Prangos pabularia growing wild in Tajikistan.

Dichloromethane and butanol extracts of the roots of Prangos pabularia were analyzed to determine chemical constituents and biological activity. The new coumarin 1, yuganin B ((5-(((2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-2-((2-oxo-2H-chromen-7-yl)oxy)tetrahydro-2H-pyran-3-yl)oxy)-3,4-dihydroxytetrahydrofuran-3-yl)methyl 4-hydroxy-3-methoxybenzoate) along with three phenolic and twenty-four known coumarins were isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by UV, HR-ESIMS, and 1 D and 2 D NMR spectroscopy. In addition, the anti-melanogenic effect of several of the isolated individual compounds and their inhibitory effect on B16 cells were evaluated. Isolating and testing compounds may proof to be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

New Triterpenoids from the Fruiting Bodies of Laetiporus sulphureus and Their Anti-Inflammatory Activity.

Laetiporus sulphureus is a popular medicinal mushroom with diverse pharmacological activities in many Asian countries. Four new triterpenoids, named sulphurenoids A-D (1-4), along with 12 known analogues, were isolated from the fruits of L. sulphureus. Nuclear magnetic resonance, infrared spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques were used for the investigation of the chemical structure of isolated compounds. In addition, the anti-inflammatory activity of three new compounds (2-4) was tested for NO production in lipopolysaccharide-induced RAW 264.7 cells. The IC50 values of isolated triterpenoids ranged from 14.3 to 42.3 µM, which were more effective than the positive control (IC50 for minocycline was 73.0 µM). The experimentally obtained anti-inflammatory activity data of L. sulphureus are in agreement with its traditional use.

Chemical components of Hyssopus cuspidatus Boriss.: isolation and identification, characterization by HPLC-DAD-ESI-HRMS/MS, antioxidant activity and antimicrobial activity.

Eighteen compounds were isolated from the ethyl acetate fraction of the aerial part of Hyssopus cuspidatus. Their structures were established by analysis of mass and NMR data, as well as comparison with previous published data in the literatures. Among them, ten compounds were found from the Hyssopus genus for the first time, and one compound was isolated from H. cuspidatus for the first time. HPLC-DAD-ESI-HRMS/MS investigations was applied to further obtain the phenolic profiling of the ethyl acetate fraction, and nine derivatives of caffeic acid and ferulic or isoferulic acid were identified. Antioxidant activity against DPPH free radical and antibacterial activity against Candida albicans, Escherichia coli and Staphylococcus aureus were evaluated. The ethyl acetate fraction exhibited weak antioxidant activity and moderate antibacterial activity. The isolated compounds showed weak to potent antioxidant and antibacterial activity. To the best of our knowledge, this is the first report on the antioxidant and antibacterial activity of H. cuspidatus.

The chemical components of Coreopsis tinctoria Nutt. and their antioxidant, antidiabetic and antibacterial activities.

Seventeen compounds were isolated from the capitula of Coreopsis tinctoria Nutt. with various column chromatographic methods and semi-preparative HPLC. Their structures were identified by the spectroscopic data and comparison with literatures as 2'-hydroxy-4,4'-dimethoxy-chalcone; (1), isoliquiritigenin (2), eriodictyol (3), naringenin (4), maritimetin (5), butin (6), taxifolin (7), luteolin (8), 7,3',4'-trihydroxyflavone (9), 8,3',4'-trihydroxyflavone-7-O-ß-d-glucoside (10), quercetin (11), quercetagitin-7-O-ß-d-glucoside (12), quercetin-7-O-ß-d-glucoside (13), 3,4-dihydroxybenzoic acid (14), caffeic acid (15), coreoside B (16), and myo-inositol (17). Compounds 1, 4, 9, 10 and 17 were isolated from C. tinctoria Nutt. for the first time. Compounds 7 and 12 possessed the highest antioxidant activity (IC50 = 64.37 and 32.86 µg/ml, respectively) among the tested compounds (IC50 value of positive control was 5.34 µg/ml). Compound 7 exhibited potent PTP1B enzymatic inhibition with an IC50 value of 7.73 µg/ml (IC50 value of positive control is 1.46 µg/ml). Furthermore, compound 5 showed strong antibacterial activity against the Gram-positive bacterium, S. aureus.

Chemical and Pharmacological Evaluation of Hulls of Prunus dulcis Nuts.

Researchers have shown that the almond hulls, normally wasted after utilization of nuts, contain a number of biologically active compounds based on which the present study has been carried out. Focus is placed on the mass spectrometric determination of the analytes along with the estimation of total polyphenolic and total flavonoid contents in the 70% ethanol extract. After partitioning the 70% ethanol extract in hexane, chloroform, ethyl acetate, n-butanol, and water, all the extracts were evaluated for their antioxidant, antidiabetic, and antimicrobial activities. The results delivered total polyphenolic compounds as gallic acid equivalents (1% w/w) of the dried extract and total flavonoid contents as quercetin equivalents (0.2% w/w) of the dried extract. Mass spectrometric analysis resulted in the identification of 15 compounds containing various derivatives of (epi)catechin, chlorogenic acid, kaempferol, isorhamnetin and their glycosides, ursolic acid, amygdalactone, and benzoic acid derivatives. Antioxidant activity experiments showed that highest activity was found in n-butanol extract among the studied samples with IC50 value as 76.04 µg/ml, while hexane and chloroform extracts were active against the PTP1B enzyme with IC50 values 9.66 µg/ml and 37.95 µg/ml, respectively. Hexane and chloroform fractions were active against Staphylococcus aureus with the zone of inhibition diameter 9 mm and 12 mm, respectively.

Chemical components of Hyssopus seravshanicus: antioxidant activity, activations of melanogenesis and tyrosinase, and quantitative determination by UPLC-DAD.

Hyssopus seravshanicus (Dubj.) Pazij has been used as traditional herb and food due to its wide biological properties. Seventeen known compounds were isolated from the ethyl acetate fraction. Their structures were identified by spectroscopic data and comparison with published data. Among them, 14 ones were identified from H. seravshanicus for the first time. DPPH and ABTS radical scavenging activities for crude ethanol extract (CEE), ethyl acetate fraction (EAF), butanol fraction (BF) and compounds 1, 3, 8, 10, 11 and 13 were performed. CEE, compounds 1, 3, 11 and 13 exhibited potent antioxidant activities. Compound 1 was found to increase the melanin content and tyrosinase activity of B16 melanoma cells. Moreover, the quantitative estimation of compound 1 in the ethyl acetate fraction was carried out by UPLC-DAD and the method was validated. This is the first report on the isolation and bioactivity research on the non-valotile components of H. seravshanicus.

Assessment of Artemisinin Contents in Selected Artemisia 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.

Brassinosteroid analogues from the fruiting bodies of Laetiporus sulphureus and their anti-inflammatory activity.

Three new brassinosteroid analogues, named sulphurenolide A, sulphurenolide B and sulphurenolide C, were isolated from the methanolic extract of fruiting bodies of Laetiporus sulphureus. Their structures were established on the basis of extensive spectroscopic analysis (1D, 2D NMR, and HRESIMS) and ECD calculation. Sulphurenolides A and B are a pair of C-20 epimer, and sulphurenolide B represents the first naturally occurring 20R-brassinosteroid. Moreover, sulphurenolides A-C are firstly reported 5-hydroxylation and homo-6-oxa derivatives of brassinosteroids from natural sources. Anti-inflammatory assay revealed that sulphurenolides B and C exhibited significant inhibitory effects on NO production in lipopolysaccharide-induced RAW264.7 cells, and sulphurenolide C showed stronger inhibition than that of positive control, minocycline.

New coumarin from the roots of Prangos pabularia.

The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3-methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O-ß-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-ß-D-glucopyranoside (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7), heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose (11), have been isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by spectroscopic means, especially, UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic effect of yuganin A and its inhibitory effect on B16 cells were evaluated. Yuganin A may be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

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%.

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.