Fractionation, identification of chemical constituents, and biological properties of cashew (Anacardium occidentale L.) leaf extracts.

The current study aimed to identify the chemical constituents and bioactivities of the crude ethanolic extract (CEE) and its fractions (ethyl acetate (EAF), hexane (HEF), and aqueous (AEF)) from leaves of cashew (Anacardium occidentale L.) grown in Vietnam. A total of 31 compounds which belong to alkanes, hydrocarbons, iodine, terpenoids, phenolics, and flavonoids were determined by a gas chromatography-mass spectrometry (GC-MS) analysis, with bis(2-ethylhexyl) phthalate being the most prevailing compound. The highest total phenolic and flavonoid contents were obtained in the EAF, followed by HEF, CEE, and AQF. All samples showed promising in vitro antibacterial activity, enzyme inhibition, and anticancer activity. Among the samples tested, the EAF exhibited the highest enzyme inhibition activity against α-amylase and α-glucosidase (IC50 values of 51.24 µg/mL and 99.29 µg/mL, respectively), cytotoxicity activity against HeLa cells (IC50 value of 79.49 µg/mL), and antibacterial activity against Bacillus subtilis and Escherichia coli with MIC values of 5 mg/mL and 2.5 mg/mL, respectively. These findings suggest that the leaves of A. occidentale cultivated in Vietnam are a promising source of bioactive components and that EAF is a promising bioactive material warranting further pharmaceutical investigation.

In Silico Approaches to Identify Polyphenol Compounds as α-Glucosidase and α-Amylase Inhibitors against Type-II Diabetes.

Type-II diabetes mellitus (T2DM) results from a combination of genetic and lifestyle factors, and the prevalence of T2DM is increasing worldwide. Clinically, both α-glucosidase and α-amylase enzymes inhibitors can suppress peaks of postprandial glucose with surplus adverse effects, leading to efforts devoted to urgently seeking new anti-diabetes drugs from natural sources for delayed starch digestion. This review attempts to explore 10 families e.g., Bignoniaceae, Ericaceae, Dryopteridaceae, Campanulaceae, Geraniaceae, Euphorbiaceae, Rubiaceae, Acanthaceae, Rutaceae, and Moraceae as medicinal plants, and folk and herb medicines for lowering blood glucose level, or alternative anti-diabetic natural products. Many natural products have been studied in silico, in vitro, and in vivo assays to restrain hyperglycemia. In addition, natural products, and particularly polyphenols, possess diverse structures for exploring them as inhibitors of α-glucosidase and α-amylase. Interestingly, an in silico discovery approach using natural compounds via virtual screening could directly target α-glucosidase and α-amylase enzymes through Monte Carto molecular modeling. Autodock, MOE-Dock, Biovia Discovery Studio, PyMOL, and Accelrys have been used to discover new candidates as inhibitors or activators. While docking score, binding energy (Kcal/mol), the number of hydrogen bonds, or interactions with critical amino acid residues have been taken into concerning the reliability of software for validation of enzymatic analysis, in vitro cell assay and in vivo animal tests are required to obtain leads, hits, and candidates in drug discovery and development.

Optimization of Ultrasound-Assisted Extraction of Flavonoids from Celastrus hindsii Leaves Using Response Surface Methodology and Evaluation of Their Antioxidant and Antitumor Activities.

Celastrus hindsii is a potential source of flavonoids with biological activities. This study aimed to develop an ultrasound-assisted technique for extracting flavonoids from leaves of C. hindsii. Response surface methodology was employed to optimize the extraction conditions for maximizing the total flavonoid content (TFC). A maximum TFC of 23.6 mg QE/g was obtained under the extraction conditions of ultrasonic power of 130 W, extraction temperature of 40°C, extraction time of 29 min, and ethanol concentration of 65%. The flavonoid-rich extracts were then studied for their antioxidant and anticancer activities. The results showed that the C. hindsii leaf extract exhibited potent radical scavenging activities against DPPH (IC50 of 164.85 µg/mL) and ABTS (IC50 of 89.05 µg/mL). The extract also significantly inhibited the growth of 3 cancer cell lines MCF7, A549, and HeLa with the IC50 values of 88.1 µg/mL, 120.4 µg/mL, and 118.4 µg/mL, respectively. Notably, the extract had no cytotoxicity effect on HK2 normal kidney cell line. This study suggests that flavonoid-rich extract is a promising antioxidant and anticancer agent and that ultrasound-assisted extraction is an efficient method for extracting flavonoids from C. hindsii leaves.

Effects of phytochemicals on cellular signaling: reviewing their recent usage approaches.

Most of the previous studies in last three decades report evidence of interactions between the different phytochemicals and the proteins involved in signal transduction pathways using in silico, in vitro, ex vivo, and in vivo analyses. However, extrapolation of these findings for clinical purposes has not been that fruitful. The efficacy of the phytochemicals in vivo studies is limited by parameters such as solubility, metabolic degradation, excretion, etc. Various approaches have now been devised to circumvent these limitations. Recently, chemical modification of the phytochemicals are demonstrated to reduce some of the limitations and improve their efficacy. Similar to traditional medicines several combinatorial phytochemical formulations have shown to be more efficient. Further, phytochemicals have been reported to be even more efficient in the form of nanoparticles. However, systematic evaluation of their efficacy, mode of action in pathway modulation, usage and associated challenges is required to be done. The present review begins with basic understanding of how signaling cascades regulate cellular response and the consequences of their dysregulation further summarizing the developments and problems associated with the dietary phytochemicals and also discuss recent approaches in strengthening these compounds in pharmacological applications. Only context relevant studies have been reviewed. Considering the limitations and scope of the article, authors do not claim inclusion of all the early and recent studies.

Effects of Sting Plant Extracts as Penetration Enhancers on Transdermal Delivery of Hypoglycemic Compounds.

Background and objectives: The percutaneous route is an interesting and inventive investigation field of drug delivery. However, it is challenging for drug molecules to pass through the skins surface, which is a characterized by its permeability barrier. The purpose of this study is to look at the effect of some penetration enhancers on in vivo permeation of insulin and insulin sensitizers (curcumin and rutin) through diabetes-induced mouse skin. Materials and Methods: Sting crude extracts of Dendrocnide meyeniana, Urtica thunbergiana Sieb. and Zucc, and Alocasia odora (Lodd.) Spach were used as the penetration enhancers. Mouse skin irritation was tested by smearing the enhancers for the measurements at different time points and the cell viability of the HaCaT human skin keratinocytes, which was determined by Trypan blue exclusion and MTT assays to evaluate human biosafety for these extracts after the mouse skin permeation experiments. Results: All enhancers induced a slight erythema without edema on the mouse skin that completely recovered after 6 h from the enhancer smears as compared with normal mouse skin. Furthermore, no damaged cells were found in the HaCaT keratinocytes under sting crude extract treatments. The blood sugar level in the diabetic mice treated with the insulin or insulin sensitizers, decreased significantly (p < 0.05) in the presence of enhancers. The area under the curve (AUC) values of transdermal drug delivery (TDD) ranged from 42,000 ± 5000 mg/dL x min without enhancers, to 30,000 ± 2000 mg/dL x min in the presence of enhancers. Conclusions: This study exhibited that natural plant extracts could be preferred over the chemically synthesized molecules and are safe and potent penetration enhancers for stimulating the transdermal absorption of drugs.

FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells.

Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation.

Preparation, Characterization and Antifungal Properties of Chitosan-Silver Nanoparticles Synergize Fungicide Against Pyricularia oryzae.

Rice (Oryza sativa L.) is one of the major staple food crops of nearly two-third of the world's population. However, rice blast caused by fungus Pyricularia oryzae is generally considered the most serious disease of cultivated rice worldwide due to its extensive distribution and destructiveness under favourable climatic conditions. In this report, the combination between chitosan (CS) and silver (Ag), Ag@CS, was introduced for antifungal activity against Pyricularia oryzae extracted from blast-infected leaves. In detail, Ag@CS nanoparticles (NPs) were first synthesized and further mixed with Trihexad 700 WP (Tri), Ag@CS-Tri, against the fungus by agar diffusion method. The prepared Ag@CS-Tri NPs were characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). In aqueous condition, Ag@CS-Tri NPs were successfully prepared and existed as spherical NPs with particle size of 17.26 ± 0.89 nm, which is an ideal size for their uptake into plant cells, indicating that the size of their parentally Ag@CS NPs is small enough to combine Tri, and their diameter is large enough to effectively penetrate the cellular membrane and kill fungi. More importantly, the antifungal property of Ag@CS-Tri NPs was significantly increased with inhibition zone around 25 nm compared with only around 12 nm of Ag@CS at the same concentration of Ag (2 ppm) and CS (4000 ppm). These results demonstrated that the synergistic effect of Tri and Ag@CS NPs can be a potential candidate with high antifungal activity for the use of antibiotics in agriculture.

Integrin αIIbß3-Dependent ERK Signaling Is Regulated by Src and Rho Kinases in Both Leu33 and Pro33 Polymorphic Isoforms.

Platelet integrin αIIbß3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbß3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings. We either treated the CHO cells with Mn2+ or allowed them to adhere to fibrinogen. Moreover, we studied which signaling cascades are involved in ERK2 activation. In contrast to immobilized fibrinogen, Mn2+ did not significantly increase ERK2 activation. However, Mn2+ had a synergistic effect on ERK2 phosphorylation when combined with immobilized fibrinogen. Pro33 cells adherent to fibrinogen exhibited a significantly greater ERK2 activity than Leu33 cells in the presence of Mn2+, which peaked after 10 min of adhesion. Our data showed that Src family and rho kinases play a crucial role in the integrin αIIbß3-dependent outside-in signaling to ERK2.