Identification of the effective α-amylase inhibitors from Dalbergia odorifera: Virtual screening, spectroscopy, molecular docking, and molecular dynamic simulation.

Inhibiting the activity of α-amylase has been considered as one efficient way to prevent and treat type 2 diabetes recently. Dalbergia odorifera, a kind of Leguminosae plant, has a positive therapeutic effect on type 2 diabetes, possibly contributing by some constituents that can inhibit the activity of α-amylase. In this study, we found that eriodictyol was one potential constituent through virtual screening. The interaction mode between eriodictyol and α-amylase was elucidated by molecular docking, multi-spectroscopic analysis, and molecular dynamic simulation. The results revealed that eriodictyol quenched the intrinsic fluorescence of α-amylase, and the quenching mode was static quenching. Eriodictyol could spontaneously interact with α-amylase, mostly stabilized and influenced by the hydrophobic interaction, while the binding sites (n) was 1.13 ± 0.07 and binding constant (Kb) was (1.43 ± 0.14) × 105 at 310 K, respectively. In addition, FT-IR and CD had been applied to identify that eriodictyol can trigger the conformational change of α-amylase. Taken together, the results provided some experimental data for developing new α-amylase inhibitors from Dalbergia odorifera, which may further prevent and treat diabetes and diabetes complications.

Inhibitory mechanism of sinensetin on α-glucosidase and non-enzymatic glycation: Insights from spectroscopy and molecular docking analyses.

Inhibition of α-glucosidase and non-enzymatic glycation is regarded as an effective method to prevent and treat type 2 diabetes and its complications. In this study, the inhibition of sinensetin on α-glucosidase and non-enzymatic glycation was studied with multi-spectroscopic techniques and molecular docking analysis. The results of fluorescence spectroscopy analysis indicated that sinensetin quenched the endogenous fluorescence of α-glucosidase in static manner. The binding of sinensetin with α-glucosidase was a spontaneous process primarily driven by hydrophobic interaction. At 298 K, the binding constant was (5.70 ± 0.12) × 104 L·mol-1 and the binding site number was 1. The conformation of α-glucosidase was altered by sinensetin, which was revealed by circular dichroism (CD), FTIR spectra, synchronous fluorescence and three-dimensional (3D) fluorescence spectroscopy methods. Molecular docking analysis demonstrated that sinensetin interacted with the amino acid residues of α-glucosidase, which might prevent the entrance of substrate, leading to the decrease of catalytic efficiency of α-glucosidase. Furthermore, glycation assays showed that sinensetin stabilized the structure of bovine serum albumins (BSA), interacted with BSA, strongly inhibited the formation of dityrosine, N'-formylkynurenine and advanced glycation end products (AGEs). This study provided useful information concerning sinensetin preventing and treating type 2 diabetes and its related complications.

Spectroscopy and molecular docking analysis reveal structural specificity of flavonoids in the inhibition of α-glucosidase activity.

The inhibition of α-glucosidase activity is a prospective approach to prevent postprandial hyperglycemia. As two flavonoids extracted from citrus fruits, eriocitrin and eriodictyol have similar structures and show multiple pharmacological activities. In order to investigate the effects of flavonoids structure on enzyme inhibition, spectroscopy and molecular docking analysis were used. Saccharomyces cerevisiae α-glucosidase (GH13) was used for studying the inhibitory mechanism by multi-spectroscopic analysis. Results indicated that they could quench the intrinsic fluorescence of α-glucosidase, the binding constants at 298 K were (7.02 ± 0.22) × 104 and (4.57 ± 0.16) × 104 L mol-1, respectively. The interaction between them with α-glucosidase were mainly driven by hydrophobic interaction, they induced conformational changes of α-glucosidase. The human α-glucosidase (C-terminal maltase-glucoamylase, GH31) was used in the molecular docking analysis to determine the interaction of eriocitrin and eriodictyol with the α-glucosidase. The results revealed that they could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The inhibitory effect of eriocitrin was stronger than that of eriodictyol, which might be due to the position and amount of hydroxyl groups. This work confirmed two novel α-glucosidase inhibitors and provided the structure-function relationship of flavonoids in inhibition of α-glucosidase activity.

Antitumor activity of alantolactone in lung cancer cell lines NCI-H1299 and Anip973.

Alantolactone is a sesquiterpene lactone extracted from Inula helenium L. plants possessing many biological activities, including anti-inflammatory, antiproliferation, and antimicrobial. The inhibitory effects and the underlying mechanisms of alantolactone on lung cancer cells NCI-H1299 and Anip973 were investigated in this study. The results showed that alantolactone could decrease cell viability and induce cell apoptosis of NCI-H1299 and Anip973. After the cells were treated with alantolactone, the expression of Bcl-2 decreased, while the expression of Bax increased, the expression of MMP-9, MMP-7, and MMP-2 gradually decreased after alantolactone treatment. Furthermore, results showed that alantolactone could activate p38 MAPK pathway and suppress NF-κB pathway, which are involving in lung cancer development. These results indicated that alantolactone was a potential agent for lung cancer treatment. PRACTICAL APPLICATIONS: Lung cancer is one of the most common contributors of cancer death in the world. Chemoprevention and chemotherapy with natural substances are prospective methods for lung cancer treatment. In recent years, the anti-cancer activity of various sesquiterpene lactones has attracted a great deal of interest. Alantolactone is the major active sesquiterpene lactones isolated from Inula helenium L, which is used as a medicine in ancient Romans due to wide range of pharmacological activities. The results obtained from this study revealed the inhibitory effects of alantolactone on lung cancer cells and might provide some experimental basis for prevention and treatment of lung cancer with alantolactone.

Nobiletin inhibits breast cancer via p38 mitogen-activated protein kinase, nuclear transcription factor-κB, and nuclear factor erythroid 2-related factor 2 pathways in MCF-7 cells.

INTRODUCTION: Breast cancer is one of the most commonly diagnosed cancers in women, with a high mortality rate. OBJECTIVE: In the present study, we evaluated the anticancer effect of nobiletin, a flavone glycoside, on the breast cancer cell line MCF-7. RESULT: Cell viability and proliferation decreased and cell morphology changed from diamond to round after being treated with nobiletin. Nobiletin induced apoptosis of breast cancer MCF-7 cells via regulating the protein expression of Bax, Bcl-2, cleaved caspase-3, and p53. The expression of Bcl-2 decreased, while the expression of Bax and p53 increased in MCF-7 cells treated with nobiletin. Meanwhile, nobiletin inhibited cell migration by downregulating the protein expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Moreover, phosphorylation of p38 was increased, and the translocation of p65 and nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus was decreased, which suggested that the anticancer effects of nobiletin might at least partially rely on mediating the p38 mitogen-activated protein kinase, nuclear transcription factor-κB, and Nrf2 pathways in MCF-7 breast cancer cells. CONCLUSION AND RECOMMENDATION: Our data showed that nobiletin was a potential antitumor drug, and it provided some experimental basis for the clinical application of tumor therapy.

Spectroscopic and molecular modeling studies on the interactions of fluoranthene with bovine hemoglobin.

This study aims to investigate the interaction between fluoranthene (FLA) and Bovine hemoglobin (BHb) by ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopy and molecular docking method. The results showed that the fluorescence intensity of BHb was declined with the increase of FLA concentration. The binding procedure was spontaneous mainly driven by hydrophobic force. The number of binding sites were 0.709 (298 K), and 1.41 (310 K). The binding constants were equal to 4.68 × 103 mol·L-1 at 298 K and 6.17 × 105 mol·L-1 at 310 K. The binding distance between FLA and the tryptophan residue of BHb was 4.50 nm. The results of UV-vis spectra, synchronous fluorescence and CD spectra revealed that FLA could change the conformation of BHb, which might affect the physiological functions of hemoglobin. Moreover, molecular modeling results showed that the fluorescence experimental results were in agreement with the results obtained by molecular docking.