How does water stress affect the bioaccumulation of galanthamine and lycorine, growth performance, phenolic content and defense enzyme activities in summer snowflake (Leucojum aestivum L.)?

Leucojum aestivum L. is an Amaryllidaceae bulbous plant with two alkaloids that have remarkable medicinal potential: galanthamine and lycorine. Although the presence of galanthamine in L. aestivum has commercial value for the pharmaceutical industry and the effect of water stress (WS) applications on secondary metabolite enhancement is well established in a variety of plants, no studies have been carried out to reveal the effectiveness of WS on this beneficial medicinal plant. Objective of the study was to investigate the effects of eight different WS treatments [Control, waterlogging (WL) condition, and drought stress conditions (water deficiency generated by water deficit irrigation-WDI 25%, 50%, and 75%- and polyethylene glycol-PEG 6000 15%, 30%, and 45%-)] on growth parameters, alkaloid levels (galanthamine and lycorine), non-enzymatic antioxidant activities (total phenol-flavonoid content and free radical scavenging activity), and enzymatic antioxidant activities [superoxide dismutase (SOD) and catalase (CAT)] of L. aestivum in a pot experiment. Based on the findings, maximum increases in growth parameters were obtained with PEG-induced WS treatments. Moderate water deficiency (50% WDI) produced the highest levels of galanthamine and lycorine, total phenol-flavonoid content, and antioxidant capacity, along with moderately elevated CAT activity in the bulbs. All WS treatments resulted in increased CAT activity in the bulbs. It was observed that bulbs had higher SOD and CAT activities under WL conditions had lower fresh weights and were close to control in terms of alkaloid levels, total phenol-flavonoid content, and free radical scavenging activity. When all of the outcomes were taken into account, it can be concluded that moderate water-deficit stress (50% WDI) was regarded as the most effective treatment for increasing the pharmaceutical value of L. aestivum.

Evaluation of the Phenolic Content and the Nutraceutical Potential of Ancestor and Cultivated Artichokes.

Wild cardoon (Cynara cardunculus var. sylvestris) is the ancestor of many cultivated forms, including globe artichoke (C. cardunculus var. scolymus). Four organs (receptacles, bracts, leaves and stems) of wild and cultivated artichokes (organic and conventional) were assessed considering their individual phenolic constituents (HPLC-DAD), total phenol-flavonoid content, and pharmaceutical potentials (antibacterial and antioxidant). All three sources of artichokes had the highest concentration of 1,3-dicaffeoylquinic acid (cynarin) in their receptacles and cultivated artichoke receptacles had more cynarin than wild one. On the other hand, receptacles of wild cardoon had the highest 1,5-dicaffeoylquinic acid and caffeic acid than the cultivated ones. Generally, receptacles, stems and leaves of wild cardoon were superior to both cultivated artichokes on antioxidant potential, and total phenol-flavonoid content. The rise in total phenolic content can be attributed to an increase in antioxidant capacity in all artichoke organs. Only the leaves of all different artichokes showed antibacterial activity against Gram-positive bacteria. The investigated wild cardoon was believed to be a true ancestor since a comparison of wild and cultivated varieties revealed similar trends in terms of phenolic profile and biological properties. The nutraceutical industry can profit from this invasive wild cardoon due to their strong antioxidant potential and phenolic content.

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial.

Immature dendritic cells (IDc), 'dexosomes', are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/106 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMaskTM membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between -15 to -20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the "BioNanoMaterial" after DOX loading via ultrasonication technique.

Synthesis, molecular docking studies, and biological evaluation of novel alkyl bis(4-amino-5-cyanopyrimidine) derivatives.

A series of bis(4-amino-5-cyano-pyrimidines) was synthesized and evaluated as dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To further explore the multifunctional properties of the new derivatives, their antioxidant and antibacterial activities were also tested. The results showed that most of these compounds could effectively inhibit AChE and BChE. Particularly, compound 7c exhibited the best AChE inhibitory activity (IC50 = 5.72 ± 1.53 µM), whereas compound 7h was identified as the most potent BChE inhibitor (IC50 = 12.19 ± 0.57 µM). Molecular modeling study revealed that compounds 7c, 7f, and 7b showed a higher inhibitory activity than that of galantamine against both AChE and BChE. Anticholinesterase activity of compounds 7h, 7b, and 7c was significant in vitro and in silico for both enzymes, since these compounds have hydrophobic rings (Br-phenyl, dimethyl, and methoxyphenyl), which bind very well in both sites. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activities. Indeed, in the superoxide-dimethyl sulfoxide alkaline assay, compound 7j showed very high inhibition (IC50 = 0.37 ± 0.28 µM). Also, compound 7l exhibited strong and good antibacterial activity against Staphylococcus epidermidis and Staphylococcus aureus, respectively. Taking into account the results of biological evaluation, further modifications will be designed to increase potency on different targets. In this study, the obtained results can be a new starting point for further development of multifunctional agents for the treatment of Alzheimer's disease.

Chitosan/poly(ethylene glycol)/hyaluronic acid biocompatible patches obtained by electrospraying.

Electrospray is a promising technique to scale-up production of microparticles and nanoparticles. In this study, electrospraying was used in order to produce candidate biopatches (CPH) by using chitosan, poly(ethylene glycol) (PEG) and hyaluronic acid (HA). Four different ratios of polymer blend compositions (CPH1, CPH2, CPH3 and CPH4) were tested by dissolving in 2% acetic acid solution (Ac.A.). The HA amount in each blend was kept the same to designate the optimum surface with different chitosan/PEG ratios for electrospray process. Fourier-transform infrared (FTIR) microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies showed that obtained patches had highly adhesive surfaces with the aid of heterogeneously distributed micro- and nano-particles. Additionally, video images of FTIR microscopy and AFM images proved that all surfaces have similar heterogeneity except CPH2. The most homogenous surface was obtained by CPH3. Patches were directly subjected to antibacterial tests against ten different types of gram positive and gram negative bacteria using disc diffusion assay (Kirby-Bauer method). Extraordinarily there was no antibacterial property of patches coated with microparticles. Finally, biocompatibility studies were performed by using mouse fibroblast L929 cell lines (ATTC number CCL-1) to test cell adhesion and proliferation properties of the patches. Results of 72 h viability tests proved the electrospray of ternary blends had displayed good biocompatibility; in particular, CPH3 had the highest cell viability.

Does stinging nettle (Urtica dioica) have an effect on bone formation in the expanded inter-premaxillary suture?

OBJECTIVE: To determine whether systemically given stinging nettle (SN) has an effect on bone formation in response to expansion of the rat inter-premaxillary suture. MATERIALS AND METHODS: A total of 28 male Wistar albino rats were randomly divided into 4 equal groups: control (C), only expansion (OE), SN extract given only during the expansion and retention periods (SN group; a total of 17days), and SN extract given during the nursery phase before expansion (a period of 40days) and during the expansion and retention periods (N+SN group; a total of 57days). After the 5-day expansion period was completed, the rats in the OE, SN, and N+SN groups underwent 12days of mechanical retention, after which they were sacrificed, and their premaxilla were dissected and fixed. A histologic evaluation was done to determine the number of osteoblasts, osteoclasts, and capillaries, as well as the number and intensity of inflammatory cells and new bone formation. RESULTS: Statistically significant differences were found between the groups in all histologic parameters except the ratio of intensities of inflammatory cells. New bone formation and the number of capillaries were significantly higher in the SN groups than in the other groups. The statistical analysis also showed that the numbers of osteoblasts, osteoclasts, and capillaries were highest in the N+SN group. CONCLUSION: Systemic administration of SN may be effective in accelerating new bone formation and reducing inflammation in the maxillary expansion procedure. It may also be beneficial in preventing relapse after the expansion procedure.