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Various Vinca species have been traditionally used for their antihypertensive, sedative, and hemostatic properties, as well as for treating diabetes. In this study, some flavonoids, phenolic acids and iridoids were isolated from an endemic Vinca species, Vinca soneri for the first time. α-Glucosidase inhibitory effects of the isolates were tested and kaempferol-3-O-α-rhamnopyranosyl (1→6) β-galactopyranoside (1) was found to be the most active one with an IC 50 value of 285.73 ±7.35 μM. Enzyme kinetic assay revealed that it inhibited α-glucosidase in competitive manner. Molecular geometry of 1 was predicted and Frontier molecular orbital analysis was performed using Density Functional Theory (DFT) calculations. Molecular docking and MM-GBSA calculations predicted good fit for 1 in the enzyme active site and key interactions with the catalytic residues. As a result, current study identifies 1 as a promising competitive α-glucosidase inhibitor to be developed as a potential antidiabetic drug candidate., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The infusions prepared from some Quercus L. species are used in folk medicine for medicinal purposes and consumed as tea. Quercus pontica K. Koch was selected in this study, for which no phytochemical isolation studies have been performed so far. Quercetin 3- O - β-D-glucopyranoside, kaempferol 3- O -(6""- O -galloyl)-β-D-glucopyranoside, kaempferol 3- O -β-D-glucopyranoside, kaempferol 3- O -(6"'-coumaroyl-β-D-glucopyranoside, phlorizin, rosmarinic acid, and catechin were isolated from the titled plant for the first time. Some polyphenolic compounds have been shown to inhibit histone deacetylase (HDAC) enzymes. However, there is no study on the any activities of Quercus species in the literature. In this study, we demonstrated that the extract has in vitro pan-HDAC inhibition activity. Through a virtual screening study, the compounds were found to inhibit HDAC7 more strongly than the other HDAC isoforms; therefore, the HDAC7 inhibition activities were studied in vitro . Kaempferol 3- O-β -D-glucopyranoside and kaempferol 3- O -(6'"-coumaroyl- β -D-glucopyranoside) showed the best anti-HDAC7 activity with 37% and 41% inhibition at 500 μM.

Flavonoids are widely distributed in plants and constitute the most common polyphenolic phytoconstituents in the human diet. In this study, the in vitro inhibitory activity of 44 different flavonoids ( 1-44 ) against mushroom tyrosinase was studied, and an in silico study and type of inhibition for the most active compounds were evaluated too. Tyrosinase inhibitors block melanogenesis and take part in melanin production or distribution leading to pigmentation diseases. The in vitro study showed that quercetin was a competitive inhibitor (IC 50 =44.38 ± 0.13 µM) and achieved higher antityrosinase activity than the control inhibitor kojic acid. The in silico results highlight the importance of the flavonoid core with a hydroxyl at C7 as a strong contributor of interference with tyrosinase activity. According to the developed statistical model, the activity of molecules depends on hydroxylation at C3 and methylation at C8, C7, and C3 in the benzo- γ -pyrane ring of the flavonoids.

Polydatin or piceid, is the 3-O-glucoside of resveratrol and is found abundantly in grapes, peanuts, wine, beer, and cacao products. Although anticancer activity of polydatin was reported before, and potential antiproliferative mechanisms of polydatin have been proposed, its direct effects on DNA and inhibitory potential against topoisomerase enzymes have remained unknown. In this study we aimed to reveal the link between polydatin's effects on DNA and DNA-topoisomerases and its antiproliferative promise. For this purpose, we evaluated the effects of polydatin on DNA and DNA topoisomerase using in vitro and in silico techniques. Polydatin was found to protect DNA against Fenton reaction-induced damage while not showing any hydrolytic nuclease effect. Further, polydatin inhibited topoisomerase II but not topoisomerase I. According to molecular docking studies, polydatin preferably showed minor groove binding to DNA where the stilbene moiety was important for binding to the DNA-topoisomerase II complex. As a result, topoisomerase II inhibition might be another anticancer mechanism of polydatin., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

The immune system is one of the main defence mechanisms of the human body. Inadequacy of this system or immunodeficiency results in increased risk of infections and tumours, whereas over-activation of the immune system causes allergic or autoimmune disorders. A well-balanced immune system is important for protection and for alleviation of these diseases. There is a growing interest to maintain a well-balanced immune system, especially after the Covid-19 pandemic. Many biological extracts, as well as natural products, have become popular due to their wide array of immunomodulatory effects and influence on the immune system. Triterpenes, one of the secondary metabolite groups of medicinal plants, exhibit immunomodulatory properties by various mechanisms. Different triterpenes, including components of commonly consumed plants, can promote some protection and alleviation of disease symptoms linked with immune responses and thus enhance overall well-being. This review aims to highlight the efficacy of triterpenes in light of the available literature evidence regarding the immunomodulatory properties of triterpenes. We have reviewed widely investigated immunomodulatory triterpenes; oleanolic acid, glycyrrhizin, glycyrrhetinic acid, pristimerin, ursolic acid, boswellic acid, celastrol, lupeol, betulin, betulinic acid, ganoderic acid, cucumarioside, and astragalosides which have important immunoregulatory properties. In spite of many preclinical and clinical trials were conducted on triterpenes related to their immunoregulatory actions, current studies have several limitations. Therefore, especially more clinical studies with optimal design is essential., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

In this study, we tested tyrosinase and α-glucosidase effects of different extracts of Ziziphus jujuba fruits. The n -BuOH subextract inhibited both tyrosinase and α-glucosidase (IC 50  = 18.82 ± 1.13 and 25.03 ± 0.77 µg/mL, respectively) better than the positive controls kojic acid and acarbose (IC 50  = 58.26 ± 0.25 and 46.10 ± 2.3 µg/mL, respectively). Thus, the n -BuOH extract was selected for further phytochemical studies. Indole-3-lactic acid methylester, catechin, magnoflorine, kaempferol 3- O -α-rhamnopyranosyl-(1 → 6)-β-galactopyranoside, quercetin 3- O -α-rhamnopyranosyl-(1 → 6)-β-galactopyranoside, and procyanidin B4 were isolated from the extract. We tested α-glucosidase and tyrosinase inhibitory effects, as well as DNA nuclease effects of the isolated compounds. Procyanidin B4 exhibited the best activity against both tyrosinase and α-glucosidase (IC 50  = 60.25 ± 0.88 and 170.18 ± 5.60 µg/mL, respectively). The isolates did not show any nuclease effect at increasing concentrations. Molecular docking studies provided insights into inhibition mechanisms of the isolates against tyrosinase and α-glucosidase at the molecular level., Supplementary Information: The online version contains supplementary material available at 10.1007/s00217-021-03946-0., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Chrysosplenetin is a methoxyflavone with reported anti-cancer effect. We tested its cytotoxic effect on the MCF-7 breast cancer cell line, and determined its effect on DNA intercalation and on the activity of topoisomerases I and II. The compound inhibited proliferation MCF-7 with an IC 50 value of 0.29 μM. Chrysosplenetin did not initiate plasmid DNA cleavage but, in a concentration-dependent manner, protected plasmid DNA against damage induced by Fenton reagents. Furthermore, it possessed dual Topoisomerase I and II inhibitory properties. Especially, it inhibited topoisomerase II by 83-96% between the range 12.5-100 μM. In the light of these experimental findings, molecular docking studies were performed to understand binding mode, interactions and affinity of chrysosplenetin with DNA, and with topoisomerases I and II. These studies showed that of 4-chromone core and the hydroxyl and methoxy groups important for both intercalation with DNA and topoisomerase I and II inhibition., Competing Interests: Declaration of competing interest The authors have declared that these are no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Tyrosinase is a multifunctional copper-containing oxidase enzyme that catalyses the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture., Objective: To develop an analytical method that allows identification of drug-like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition., Method: Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations., Results: All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with the half maximal inhibitory concentration (IC 50 ) values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were non-competitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B-ring of these flavones faced the catalytic site in the enzyme., Conclusions: The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design., (© 2020 John Wiley & Sons, Ltd.)

In the present study, we aimed to identify the tyrosinase enzyme inhibitory potential of Vinca major L. extract and its secondary metabolites. The extract possessed remarkable tyrosinase enzyme inhibitory effect with IC 50 value of 20.39 ± 0.44 µg/mL compared to the positive control, kojic acid (IC 50 8.56 ± 0.17 µg/mL). Compounds 1 and 5 were the most potent isolates with IC 50 values of 32.41 ± 0.99 and 31.34 ± 0.75 µM, they were more potent than kojic acid (IC 50 : 60.25 ± 0.54 µM). Compound 2 also exhibited remarkable tyrosinase inhibition with an IC 50 value of 64.51 ± 1.29 µM. An enzyme kinetics analysis revealed that 1 was a mixed-type, 2 and 5 were noncompetitive inhibitors. Using molecular docking, we predicted binding affinity and interactions of the compounds, which were in good alignment with a pharmacophore hypothesis generated out of a number of known tyrosinase inhibitors. The modelling studies underlined crucial interactions with the copper ions and residues around them such as Asn260, His263, and Met280., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bark of Quercus coccifera is widely used in folk medicine. We tested tyrosinase and α-glucosidase inhibitory effects of Q. coccifera bark extract and isolated compounds from it. The extract inhibited tyrosinase with an IC 50 value of 75.13 ± 0.44 µg/mL. Among the isolated compounds, polydatin (6) showed potent tyrosinase inhibition compared to the positive control, kojic acid, with an IC 50 value of 4.05 ± 0.30 µg/mL. The Q. coccifera extract also inhibited α-glucosidase significantly with an IC 50 value of 3.26 ± 0.08 µg/mL. (-)-8-Chlorocatechin (5) was the most potent isolate, also more potent than the positive control, acarbose, with an IC 50 value of 43.60 ± 0.67 µg/mL. According to the kinetic analysis, 6 was a noncompetitive and 5 was a competitive inhibitor of tyrosinase, and 5 was a noncompetitive α-glucosidase inhibitor. In the light of these findings, we performed in silico molecular docking studies for 5 and 6 with QM/MM optimizations to predict their tyrosinase inhibition mechanisms at molecular level and search for correlations with the in vitro results. We found that the ionized form of 5 (5i) showed higher affinity and more stable binding to tyrosinase catalytic site than its neutral form, while 6 bound to the predicted allosteric sites of the enzyme better than the catalytic site., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Some Geranium species have been used to treat diabetes. To evaluate the scientific basis of this ethnopharmacological use, we aimed to isolate potent α-glucosidase inhibitory metabolites of Geranium asphodeloides Burm. through in vitro bioactivity-guided fractionation. All the tested extracts showed high α-glucosidase inhibitory effect compared to acarbose. Among the tested extracts, the ethyl acetate subextract showed the highest activity with an IC 50 value of 0.85 ± 0.01 µM. A hydrolysable tannin, 1,2,4-tri-O-galloyl-β-d-glucopyranose (1), and five flavonoid glycosides, kaempferol-3-O-α-rhamnopyranoside (2), kaempferol-3-O-α-arabinofuranoside (3), quercetin-3-O-β-glucopyranoside (4), quercetin-3-O-α-rhamnopyranoside (5), and quercetin-3-O-α-rhamnofuranoside (6), were isolated from the ethyl acetate subextract. Their structures were identified by 1D- and 2D-NMR experiments. 1 exhibited the highest α-glucosidase inhibitory effect, approximately 61 times more potent than positive control, acarbose, with an IC 50 value of 0.95 ± 0.07 µM. Also, 2 was more potent than acarbose. An enzyme kinetics analysis revealed that compounds 2, 3 and 4 were competitive, whereas 1 and 6 uncompetitive inhibitors. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolated compounds in the light of the enzyme kinetic studies using various binding sites of the enzyme model., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Flavonoids are main polyphenolic groups widely distributed to fruits, vegetables and beverages we consumed daily. They exhibit many biological effects. We tested tyrosinase inhibitor potential of structurally related (1-9) flavonoids and found that all the tested materials possessed tyrosinase inhibitory effect compared to the positive control, kojic acid. 2 exhibited the strongest tyrosinase inhibitory effect with an IC 50 value of 40.94 ± 0.78 µM in a competitive manner. According to kinetic analysis 1, 4 and 7 were found to be competitive inhibitors, 3, 5, and 6 noncompetitive inhibitors of tyrosinase. According to the docking studies, A and C ring of the flavonoid structure, hydroxyl substituent at the 7th position, and hydroxyl substituents at para or para and meta position of ring B play key role for competitive inhibition of the enzyme., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neolignans are a large group of polyphenols found in plants and exhibit a wide range of bioactivities including cytotoxicity, apoptosis inducer, antimalarial and antifungal effects, acetylcholinesterase, tyrosinase, and α-glucosidase inhibition. In this study we tested acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tyrosinase, and α-glucosidase inhibitory effects of a rare neolignan, (-)-4-O-methyldehydrodiconiferyl alcohol 9'-O-β-glucopyranoside (1) in search for its new pharmaceutical effects. This compound exhibited good tyrosinase inhibition with an IC 50 value of 44.62 ± 3.99 μg/mL. Enzyme kinetics and molecular modelling studies were performed to provide insights into its tyrosinase inhibition mechanism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Beside other pharmaceutical benefits, flavonoids are known for their potent α-glucosidase inhibition. In the present study, we investigated α-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3″-O-galloyl)-β-galactopyranoside (8) and quercetin 3-O-(6″-O-galloyl)-β-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC 50 values of 0.97 ± 0.02 and 1.35 ± 0.06 µM, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the α-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the present study we aimed to identify the α-glucosidase enzyme inhibitory potential of Potentilla inclinata Vill. MeOH and n-BuOH extracts which possessed remarkable α-glucosidase enzyme inhibitory effects with IC 50 values of 1.06±0.02 and 0.93±0.01μg/ml respectively, compared to that of acarbose (IC 50 31.92±0.17). Thus, BuOH extract was chosen for further phytochemical investigations. A phenolic acid, six flavonol glycosides, and two hydrolysable tannins were isolated from the most active n-BuOH extract of the title plant. Structures of the isolated compounds were elucidated by 1D- and 2D-NMR experiments. All the compounds exhibited remarkable α-glucosidase inhibitory activity compared to the positive control, acarbose. Rutin (2) showed the highest activity with an IC 50 value of 26.31±0.02μg/ml. An enzyme kinetics analysis revealed that compounds 5 and 7 were competitive, 4 and 6 noncompetitive, and 3 was uncompetitive inhibitors of α-glucosidase enzyme. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolates considering their inhibition type using various binding sites of the enzyme model we previously reported., (Copyright © 2017 Elsevier B.V. All rights reserved.)

α-Glucosidase enzyme inhibitors are clinically used for the treatment of Type 2 diabetes mellitus. We tested α-glucosidase inhibitory effects of Potentilla astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts, prunetin 5-O-β-glucopyranoside (3) and genistein 5-O-β-glucopyranoside (4), and their aglycon forms (5 and 6). All the tested materials possessed remarkable α-glucosidase inhibitor activity compared to the positive control, acarbose. Genistein (6) showed the highest activity with an IC 50 value of 1.47 (±0.11) μg/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5 was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling techniques we tried to provide insight into molecular mechanisms of their activity and how allosteric binding of 6 affected binding interactions between the agonist (maltose) and the enzyme., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Context: Bellis perennis L. (Asteraceae) (common daisy) is a herbaceous perennial plant known as a traditional wound herb; it has been used for the treatment of bruises, broken bones, and wounds. Bellis perennis has also been used in the treatment of headache, common cold, stomachache, eye diseases, eczema, skin boils, gastritis, diarrhea, bleeding, rheumatism, inflammation, and infections of the upper respiratory tract in traditional medicine., Objective: Antitumor activities of different fractions of B. perennis flowers at different concentrations were evaluated and through bioassay-guided fractionation and isolation procedures a saponin derivative (1) was isolated from the active fraction obtained from the n-butanol extract of flowers of the title plant by column chromatography., Materials and Methods: Antitumor activities of different fractions of B. perennis flowers at different concentrations were evaluated using Potato Disc Tumor Induction Bioassay. Structure elucidation of 1 was accomplished by spectroscopic methods [1D- and 2D-NMR, and LC-ESI(APCI)-TOF-MS(MSn)]., Results: The present study showed the antitumor activity of fractions obtained from B. perennis flowers for the first time. The most active fraction showed 99% tumor inhibition at 3000 mg/L. An oleanane-type saponin was isolated through bioassay-guided studies., Discussion and Conclusion: Through antitumoral bioassay-guided fractionation and isolation procedures, 1 was isolated from the active fraction of B. perennis. The detailed NMR data of compound 1 is given for the first time.