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Through the current comparative study, colloidal silver nanoparticles (AgNPs) were synthesized with various morphologies and sizes using Prunus domestica (P-dom) extract and sodium citrate as green and chemical reducing agents, respectively. AgNPs were synthesized employing different concentrations of the reducing agents in an aqueous solution at various pH values (3–10) and temperatures (25–85 °C). The UV–visible absorption spectrum indicated characteristic SPR peaks of AgNPs at 380–450 nm. Fourier transform infrared spectroscopy revealed aqueous-soluble polyols (such as glycosides, phenols, and flavanols) participation in Ag ions reduction to the corresponding AgNPs at various pH values. The crystallinity of AgNPs was detected by an X-ray diffractometer. Different morphologies (polygonal, oval, and spherical) of the AgNPs with varying pH values were confirmed conducting transmission electron microscopy (TEM). Average particle sizes of 16–50 nm were determined using scanning electron microscopy, TEM, and dynamic light scattering assessments for AgNPs synthesized at various reaction conditions. This study is a demonstration for a facile, cheap, and eco-friendly stimuli-sensitive preparation of the AgNPs.

Hypoxia-inducible factor-1 is a target for the management of cancer. Here, the anti-proliferation properties of corosolic acid (CA) against A549 human lung epithelial cancer cells in CoCl2-induced hypoxia is reported. CA was isolated from the roots of Salvia syriaca based on a bioassay-guided isolation platform and identified by 1D and 2D NMR experiments. Several cytotoxicies and genotoxicity analyses were performed using MTT, DAPI, cell cycle, DNA ladder, and annexin V/PI detection. Cobalt chloride (CoCl2) was used to stimulate hypoxia. The adaptation of A549 cells to a stimulated hypoxic condition in the presence of CA was evaluated. CA decreased the growth of A549 cells with an IC50 of 12 μg/mL at 48 h. Also, chromatin condensation and DNA fragmentation were detected as signs of apoptosis occurrence. CA induced ~85% apoptosis and even 1% necrosis. The expression of hypoxia-inducible factor-1 α (HIF-1α), HIF-1β and downstream genes was strongly suppressed in the presence of CA in CoCl2-stimulated hypoxia condition. Results indicated that CA has remarkable cytotoxicity against the cancerous cell in hypoxia condition and may be regarded for preparation of new formulations for possible uses as supplement and medicine in cancer therapy.

The adaptation of solid tumors to the low oxygen/nutrient environment is mediated by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, the HIF-1 and its subunits have been considered to be hopeful anti-cancer targets. Various natural compounds were reported to persuade cell cytotoxicity through targeting and downregulation of the HIF-1. The genus Salvia is a rich source of bioactive terpenoids which show promising anti-cancer activities. Here, the identification of natural anti-proliferative compound targeting the HIF-1α expression was reported. A bioassay-guided isolation was employed for the discovery of natural anti-proliferative compounds from Salvia extracts using MTT assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 2D NMR analysis. Results indicated that CDA has anti-proliferation activity (IC50 value of 35 μg/mL) which was confirmed by genotoxicity and apoptosis detection analyses. The quantitative qPCR analysis showed that the expression level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA compared to the untreated cells tolerated hypoxia. Findings exhibited that S. nemorosa and clerodermic acid have significant potential for reducing HIF-1α expression and could be considered for further studies for cancer therapy.

Objective This study aimed to evaluate the efficacy of Hop on early menopausal symptoms and hot flashes. Methods In this randomized controlled trial, 120 women were randomly allocated into two groups, receiving the Hop or placebo tablets for 12 weeks. Early menopausal symptoms were assessed using Greene scale and hot flashes were recorded in a diary before, and 4, 8 and 12 weeks after intervention. Results The mean Greene score was significantly lower in the Hop group than the placebo group at the end of weeks 4 (adjusted difference: -10.0, 95% confidence interval: -11.1–−8.9), 8 (−18.6, -20.1–−17.1) and 12 (−23.4, -25.1–−21.6). The number of hot flashes was significantly lower in the Hop group than the control group during the weeks 4 (−8.4, -9.8–−7.1), 8 (−17.1, -14.9–−19.3) and 12 (−23.8, -21.1–−26.4). Conclusions Hop effectively reduced the early menopausal symptoms. Clinical trial registration This study was approved (code 91209) by the Ethic Committee of Tabriz university of Medical Sciences and registered at the Iranian registry of clinical trials, with IRCT 2013010110324N7 on April 2013.

Introduction Ruscus species are important medicinal herbs because of their traditional uses. Steroidal saponins such as ruscogenin and neoruscogenin are considered to be some of their active ingredients. Methods In the present study, an HPLC-ESI-MS/MS analysis was used to determine steroidal saponins occurring in Ruscus hyrcanus roots. Cytotoxicity and antioxidant and antimicrobial properties of the herb were also investigated using MTT, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and inhibition zone and minimum inhibitory concentration (MIC) methods, respectively. Results LC-MS2 experiments showed the occurrence of seven spirostanol saponins and their derivatives in the roots; three of these were glycoside compounds and the others were aglycones, including ruscogenin and neoruscogenin. The saponin-rich extract showed 6–85% DPPH radical scavenging activity at the tested concentrations. Antiproliferative assays showed promising activity of the extract against MCF-7 and PC-3 cancer cell lines. Moreover, strong antimicrobial effects were observed against different gram-positive and gram-negative bacterial strains and fungal strains in growth inhibition and MIC assays. Conclusion The results of the present study suggest that LC-MS/MS is a suitable technique for the profiling of saponins in R. hyrcanus and that these saponins may have remarkable antioxidant and antimicrobial activities for designing novel applications.

Hypoxia Inducible Factor-1 plays a key transcriptional role in the adaptation of hypoxic solid tumors to low oxygen environment. Here, we aimed to investigate galbanic acid (GBA) inhibitory effects on HIF-1 activation during hypoxia and normoxia. MTT survival and Annexin V assays were used to evaluate GBA cytotoxicity and apoptosis in treated cells. Quantitative real time PCR and western blotting were used to estimate mRNA expression and translated protein, respectively. Results showed that GBA dose- and time-dependently decreased the in vitro growth of OVCAR-3 human epithelial carcinoma cells with an IC50 of approximately 37, 12.1 and 10μM GBA at 24, 48 and 72h, respectively. Following phosphatidylserine of outer leaflet of the plasma membrane revealed occurrence of early/late apoptosis in GBA treated cells. In addition, we found that GBA down-regulates HIF-1α and HIF-1β mRNA expression in both hypoxia and normoxia. To determine the mechanism of action, we showed that GBA did not inhibit Akt and EGFR mRNA expression, yet protein degradation investigation showed that GBA shortened the half-life of EGFR through decreasing its stability with a decrease of nearly 2 and 3h in A549 and OVCAR-3 cell lines, respectively. We also found that downstream genes contributed in glycolysis, including Eno 1 and GluT-1, are underexpressed in GBA treated cells in hypoxia. Conclusively, GBA may inhibit HIF-1 activation through down-regulation of its subunit expression in hypoxia, and increasing of EGFR degradation in normoxia.

Three new coumarins, 6-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-prenyletin, 3″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-oxypeucedanin hydrate and 2″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-oxypeucedanin hydrate, together with six known coumarins, 3″-O-[β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyl]-heraclenol, 3″-O-(β-d-glucopyranosyl)-heraclenol, tortuoside, 3″-O-(β-d-glucopyranosyl)-oxypeucedanin hydrate, heraclenol and oxypeucedanin hydrate, have been isolated from the roots of Prangos uloptera, and the structures of these coumarins were unequivocally determined by spectroscopic means, notably UV, HRESIMS, and 1D and 2D NMR spectroscopy.

The reversed-phase preparative HPLC analysis of the methanol (MeOH) extract of the seeds of Centaurea americana afforded a dibenzylbutyrolactone lignan, 3''-O-caffeoyl arctiin (named americanin), together with five known lignans, arctiin, arctigenin, matairesinol, matairesinoside and lappaol A, and two known phytoecdysteroids, 20-hydroxyecdysone and makisterone A. While the structures of the known compounds were determined by direct comparison of the spectral data with published data, the structure of americanin was elucidated by UV, MS and a combination of 1D and 2D NMR spectral analyses. The antioxidant properties and toxicity of the extracts and the isolated compounds were determined by the DPPH and the brine shrimp lethality assays, respectively.

A combination of vacuum liquid chromatography (VLC) and preparative thin layer chromatography (PTLC) of the dichloromethane extract of the aerial parts of the Iranian plant Pimpinella aurea afforded two phenylpropanoids, erythro-1'-(4-methoxyphenyl)-propan-1',2'-diol (1) and erythro-1'-[4-(sec-butyl)-phenyl]-propan-1',2'-diol (2), the latter being a natural product. The structures of these compounds were determined by spectroscopic means. The antioxidant properties of these compounds were assessed by the DPPH assay. The GC-MS analysis of the essential oils of P. aurea provided a chemical profile that was significantly different from the previously published reports.

The influence of glycyrrhizin extracted from Glycyrrhiza glabra var. glandulifera (licorice roots) on the percutaneous absorption of diclofenac sodium from sodium carboxymethylcellulose (NaCMC) gels or oil-in-water (o/w) emulsion was investigated. Skin permeation experiments were carried out using excised abdominal rat skin. The results showed that the efficiency of glycyrrhizin as an enhancer agent is greater in gel formulations than it is in the emulsions. The enhancer with the concentration of 0.1% w/w in gel increased diclofenac sodium flux value to tenfold compared with the control gel.

Extracts obtained from aerial parts of Stachys inflata have been used in Iranian folk medicine in infective, rheumatic and other inflammatory disorders. In the present study, the anti-inflammatory properties of total methanol extract isolated from aerial parts of Stachys inflata were investigated in two well-characterised inflammatory models in rats, carrageenan-induced paw oedema and formalin-induced paw licking. Intraperitoneal injection of the extract, 60 min before induction of inflammation, revealed a dose-related inhibition of carrageenan-induced rat paw oedema over the dose range 50-200 mg/kg. In the formalin test, the extract (50, 100 and 200 mg/kg) had no effect against the first phase (0-5 min) of the formalin-induced pain, but all three doses produced a significant blockade of the second phase (P < 0.001). Myeloperoxidase (MPO) activity was determined, and a histopathological study was carried out in paw tissue 4 h after induction of inflammation. The hydroalcoholic extract (200 mg/kg) substantially reduced MPO activity (P < 0.05), which was increased in the control group. Histological examination showed a marked reduction in tissue injury and inhibition in neutrophil infiltration in rats treated with the extract (200 mg/kg).