New ent-Kaurane and cleistanthane diterpenoids with potential cytotoxicity from Phyllanthus acidus (L.) Skeels.

Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC50 values ranging from 1.96 to 29.15 µM. They also showed moderate anti-inflammatory activities (IC50 = 6.30-12.05 µM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC50 = 2.00 µM) and MCF-7 (IC50 = 3.55 µM) cells, and anti-inflammatory activity (IC50 = 6.47 µM).

Construction of sulfur-containing compounds with anti-cancer stem cell activity using thioacrolein derived from garlic based on nature-inspired scaffolds.

Sulfur-containing compounds, such as cyclic compounds with a vinyl sulfane structure, exhibit a wide range of biological activities including anticancer activity. Therefore, the development of efficient strategies to synthesize such compounds is a remarkable achievement. We have developed a unique approach for the rapid and modular preparation of nature-inspired cyclic and acyclic sulfur-containing compounds using thioacrolein, a naturally occurring chemically unstable intermediate. We constructed thiopyranone derivatives through the regioselective sequential double Diels-Alder reaction of thioacrolein produced by allicin, a major component in garlic, and two molecules of silyl enol ether as the diene partner. The cytotoxicity toward cancer stem cells of the thiopyranones was equal to or higher than that of (Z)-ajoene (positive control) derived from garlic, and the thiopyranones had higher chemical stability than (Z)-ajoene.

Novel Phenolic Compounds as Potential Dual EGFR and COX-2 Inhibitors: Design, Semisynthesis, in vitro Biological Evaluation and in silico Insights.

INTRODUCTION: Epidermal growth factor receptor (EGFR) inhibition is an imperative therapeutic approach targeting various types of cancer including colorectal, lung, breast, and pancreatic cancer types. Moreover, cyclooxygenase-2 (COX-2) is frequently overexpressed in different types of cancers and has a role in the promotion of malignancy, apoptosis inhibition, and metastasis of tumor cells. Combination therapy has been emerged to improve the therapeutic benefit against cancer and curb intrinsic and acquired resistance. METHODS: Three semi-synthetic series of compounds (C1-4, P1-4, and G1-4) were prepared and evaluated biologically as potential dual epidermal growth factor receptor (EGFR) and COX-2 inhibitors. The main phenolic constituents of Amaranthus spinosus L. (p-coumaric, caffeic and gallic) acids have been isolated and subsequently subjected to diazo coupling with various amines to get novel three chemical scaffolds with potential anticancer activities. RESULTS: Compounds C4 and G4 showed superior inhibitory activity against EGFR (IC50: 0.9 and 0.5 µM, respectively) and displayed good COX-2 inhibition (IC50: 4.35 and 2.47 µM, respectively). Moreover, the final compounds were further evaluated for their cytotoxic activity against human colon cancer (HT-29), pancreatic cancer (PaCa-2), human malignant melanoma (A375), lung cancer (H-460), and pancreatic ductal cancer (Panc-1) cell lines. Interestingly, compounds C4 and G4 exhibited the highest cytotoxic activity with average IC50 values of 1.5 µM and 2.8 µM against H-460 and Panc-1, respectively. The virtual docking study was conducted to gain proper understandings of the plausible-binding modes of target compounds within EGFR and COX-2 binding sites. DISCUSSION: The NMR of prepared compounds showed characteristic peaks that confirmed the structure of the target compounds. The synthesized benzoxazolyl scaffold containing compounds showed inhibitory activities for both COXs and EGFR which are consistent with the virtual docking study.

Chemical and Green ZnO nanoparticles ameliorated adverse effects of cisplatin on histological structure, antioxidant defense system and neurotrophins expression in rat hippocampus.

Cisplatin (CP) is a chemotherapy agent used in the treatment of cancer, but it has various side effects, in particular, neurotoxicity. Zinc oxide nanoparticles (ZnO NPs) are a potent antioxidant. However, there is limited knowledge about the protective effects of ZnO NPs against CP-induced hippocampal toxicity. The present study aimed to explore the potential protective effects of ZnO NPs against CP-induced oxidative stress, loss of neurotrophins support, and tissue damage in the hippocampus of the rats. Eighty adult male Wistar rats were dividing into ten groups including: control (Con), sham, ZnO Bulk (ZnB), chemical ZnO NPs (ChZnO NPs), Green ZnO NPs (GrZnO NPs), CP, CP + ZnB, CP + ChZnO NPs, CP + GrZnO NPs and CP + AE. CP was administrated (5 mg/kg/weekly) for four weeks, and animals were treated simultaneously with different forms of ZnO (5 mg/kg/day). At the end of the experiment, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), changes of reduced glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio, histological changes, expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) genes were assessed in the hippocampus. The results revealed that a decrease in BDNF and NGF mRNA expression, GSH concentration and GSH/GSSG ratio, increasing of GSSG and MDA levels, and neuronal loss in the CP-treated rats were reversed following the administration of different forms of ZnO, especially Gr ZnO NPs and ch ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT). The results showed that in most of the evaluated factors, Gr ZnO NPs showed a greater protective effect than other forms of ZnO. The results suggest that ZnO NPs, in particular Green ZnO NPs (GrZnO NPs) had more potential protective effects against CP-induced oxidative stress, inadequate support neurotrophin and tissue damage in rat hippocampus.

Review on Green Synthesis of Silver Nanoparticles through Plants.

Nature has the potential to reduce metal salts to their relative nanoparticles. Traditionally, physical and chemical methods were used for the synthesis of nanoparticles but due to the use of toxic chemicals, non-ecofriendly methods and other harmful effects, green chemistry approaches are now employed for synthesizing nanoparticles which are basically the most cost effective, ecofriendly and non-hazardous methods. In this review, we aimed to evaluate and study the details of various mechanisms used for green synthesis of silver nanoparticles from plants, their size, shape and potential applications. A total of 150 articles comprising both research and review articles from 2009 to 2019 were selected and studied in detail to get in-depth knowledge about the synthesis of silver nanoparticles specifically through green chemistry approaches. Silver ions and their salts are well known for their antimicrobial properties and have been used in various medical and non-medical applications since the emergence of human civilization. Miscellaneous attempts have been made to synthesize nanoparticles using plants and such nanoparticles are more efficient and beneficial in terms of their antibacterial, antifungal, antioxidant, anti-biofilm and cytotoxic activities than nanoparticles synthesized through physical and chemical processes. Silver nanoparticles have been studied as an important research area due to their specific and tunable properties and their application in the field of biomedicine such as tissue and tumor imaging and drug delivery. These nanoparticles can be further investigated to find out their antimicrobial potential in cell lines and animal models.

Anti-Cancer and Anti-Bacterial Effects of Terfezia boudieri-Derived Silver Nanoparticles.

BACKGROUND: The use of nanoparticles has markedly increased in biomedical sciences. The silver nanoparticles (AgNPs) have been investigated for their applicability to deliver chemotherapeutic/antibacterial agents to treat cancer or infections disease. However, the existing chemical and physical methods of synthesizing AgNPs are considered inefficient, expensive and toxic. METHODS: Natural products have emerged as viable candidates for nanoparticle production, including the use of Terfezia boudieri (T. boudieri), a member of the edible truffle family. Accordingly, our goal was to synthesize AgNPs using an aqueous extract of T. boudieri (green synthesized AgNPs). Since certain infectious agents are linked to cancer, we investigated their potential as anti-cancer and antibacterial agents. RESULTS: The synthesis of AgNPs was confirmed by the presence of an absorption peak at 450nm by spectroscopy. The physico-chemical properties of green synthesized AgNPs were analyzed by UV-Vis, FT-IR, XRD, SEM, and TEM. In addition, their potential to inhibit cancer cell (proliferation and the growth of infectious bacteria were investigated. CONCLUSION: The size of nanoparticles ranged between 20-30nm. They exerted significant cytotoxicity and bactericidal effects in a concentration and time-dependent manner compared to T. boudieri extract alone. Interestingly, the synthesis of smaller AgNPs was correlated with longer synthesis time and enhanced cytotoxic and bactericidal properties.

Photo-irradiation coupled biosynthesis of magnesium oxide nanoparticles for antibacterial application.

In recent times, magnesium oxide (MgO) nanoparticles are proven to be an excellent antibacterial agent which inhibits the growth of bacteria by generating reactive oxygen species (ROS). Release of ROS by nanoparticles will damage the cell membrane of bacteria and leads to the leakage of bacterial internal components and cell death. However, chemically synthesized MgO nanoparticles may possess toxic functional groups which may inhibit healthy human cells along with bacterial cells. Thus, the aim of the present study is to synthesize MgO nanoparticles using leaf extracts of Amaranthus tricolor and photo-irradiation of visible light as a catalyst, without addition of any chemicals. Optimization was performed using Box-Behnken design (BBD) to obtain the optimum condition required to synthesize smallest nanoparticles. The parameters such as time of reaction, the concentration of precursor, and light intensity have been identified to affect the size of biosynthesized nanoparticles and was optimized. The experiment performed with optimized conditions such as 0.001 M concentration of magnesium acetate as precursor, 5 cm distance of light (intensity), and 15 min of reaction time (light exposure) has led to the formation of 74.6 nm sized MgO nanoparticles. The antibacterial activities of MgO nanoparticles formed via photo-irradiation and conventional biosynthesis approach were investigated and compared. The lethal dosage of E. coli for photo-irradiated and conventional biosynthesis MgO nanoparticles was 0.6 ml and 0.4 ml, respectively. Likewise, the lethal dosage of S. aureus for both biosynthesis approaches was found to be 0.4 ml. The results revealed that the antibacterial activity of MgO nanoparticles from both biosynthesis approaches was similar. Thus, photo-irradiated MgO nanoparticles were beneficial over heat-mediated conventional method due to the reduced synthesis duration.

Green Synthesis of Gold and Silver Nanoparticles Using Leaf Extract of Clerodendrum inerme; Characterization, Antimicrobial, and Antioxidant Activities.

Due to their versatile applications, gold (Au) and silver (Ag) nanoparticles (NPs) have been synthesized by many approaches, including green processes using plant extracts for reducing metal ions. In this work, we propose to use plant extract with active biomedical components for NPs synthesis, aiming to obtain NPs inheriting the biomedical functions of the plants. By using leaves extract of Clerodendrum inerme (C. inerme) as both a reducing agent and a capping agent, we have synthesized gold (CI-Au) and silver (CI-Ag) NPs covered with biomedically active functional groups from C. inerme. The synthesized NPs were evaluated for different biological activities such as antibacterial and antimycotic against different pathogenic microbes (B. subtilis, S. aureus, Klebsiella, and E. coli) and (A. niger, T. harzianum, and A. flavus), respectively, using agar well diffusion assays. The antimicrobial propensity of NPs further assessed by reactive oxygen species (ROS) glutathione (GSH) and FTIR analysis. Biofilm inhibition activity was also carried out using colorimetric assays. The antioxidant and cytotoxic potential of CI-Au and CI-Ag NPs was determined using DPPH free radical scavenging and MTT assay, respectively. The CI-Au and CI-Ag NPs were demonstrated to have much better antioxidant in terms of %DPPH scavenging (75.85% ± 0.67% and 78.87% ± 0.19%), respectively. They exhibited excellent antibacterial, antimycotic, biofilm inhibition and cytotoxic performance against pathogenic microbes and MCF-7 cells compared to commercial Au and Ag NPs functionalized with dodecanethiol and PVP, respectively. The biocompatibility test further corroborated that CI-Ag and CI-Au NPs are more biocompatible at the concentration level of 1-50 µM. Hence, this work opens a new environmentally-friendly path for synthesizing nanomaterials inherited with enhanced and/or additional biomedical functionalities inherited from their herbal sources.

Quantification of One Prenylated Flavanone from Eysenhardtia platycarpa and Four Derivatives in Ex Vivo Human Skin Permeation Samples Applying a Validated HPLC Method.

Prenylated flavanones are polyphenols that have diverse biological properties. The present paper focuses on a HPLC method validation for the quantification of prenylated flavanones (2S)-5,7-dihydroxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1Benzopyran-4-one 1 and derivatives (2S)-5,7-bis(acetyloxy)-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one A; (2S)-5-hydroxy-7-methoxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one B; (8S)-5-hydroxy-2,2-dimethyl-8-phenyl-3,4,7,8-tetrahydro-2H,6H-Benzo[1,2-b:5,4-b']dipyran-6-one C; and (8S)-5-hydroxy-2,2-dimethyl-8-phenyl-7,8-dihydro-2H,6H-Benzo[1,2-b:5,4-b']dipyran-6-one D applied in biopharmaceutic studies. The linear relationships are proven with significant correlation coefficients (R2 ˃ 0.999) in the range of 1.56 to 200 µg/mL with low limits of detection and quantification, on average of 0.4 µg/mL and 1.2 µg/mL, respectively. The validation method used in this work is highly accurate and precise, with values lower than 15%. The relative standard deviation values of repeatability of the instrumental system are demonstrated with less than 0.6% for all studied flavanones. Therefore, the applicability method of the quantification of the prenylated flavanones was established using the permeation of human skin in the Franz cell system. During the method previously described, there was no interference observed from human skin components in ex vivo permeation studies.

Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells.

Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC50 value of 2.83 µM and 1.98 µM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death.

Efficiency of the Green Synthesized Nanoparticles as New Tools in Cancer Therapy: Insights on Plant-Based Bioengineered Nanoparticles, Biophysical Properties, and Anticancer Roles.

The aim of this work is to review the current knowledge on the efficiency of plant-based synthesized nanoparticles in medical field, particularly in the prevention, diagnosis, and therapy of cancer. For this, we examine the advantages of nanotechnological tools. Besides, a particular attention was given to understand the mechanism by which plant-based bioengineered nanoparticles can interact with components of cancerous cells. Green biosynthesized nanoparticles seem to be novel tool for prognostic biomarkers for cancer diagnosis and drug delivery in tumor cells. They can act either by leading to the damage of tumor cells, or by the protection of healthy cells, via mechanisms involving the specific properties of nanoparticles themselves and the antioxidative and antitumor properties found in plants. However, special attention should be given to the choice of plant species, extracts, and the toxic dose of some phytocompounds during the biosynthesis process. An increase in metal or trace element release from metal and metal oxide biosynthesized nanoparticles can lead to greater oxidative stress, which is associated with higher risk of cancer. Hence, plant-based nanosystems should be more developed to increase their specific targeting of the cancerous cells, in order to preserve the healthy ones.

Resveratrol: a review of plant sources, synthesis, stability, modification and food application.

Resveratrol, a stilbene molecule belonging to the polyphenol family, is usually extracted from a great many natural plants. The technologies of preparation and extraction methods are developing rapidly. As resveratrol has many beneficial properties, it has been widely utilized in food and medicine industry. In terms of its structure, it is susceptible to degradation and can undergo chemical changes during food processing. Different studies have therefore given more attention to various aspects of resveratrol, including anti-aging, anti-oxidant, and anti-cancer activity. This review classifies the study of resveratrol, considers plant sources, synthesis, stability, common reactions, and food applications, and provides references to boost its food and medical utilization. © 2019 Society of Chemical Industry.

Isolation, synthesis, and biological activities of a bibenzyl from Empetrum nigrum var. japonicum.

4-(2-Hydroxyphenethyl)-2,6-dimethoxyphenol, a bibenzyl, was isolated from the leaves of Empetrum nigrum var. japonicum, collected from Mount Tateyama. Japanese rock ptarmigans frequently eat the leaves and fruits of this plant. The structure of the bibenzyl was confirmed by NMR spectroscopic analysis and fully characterized. A synthesis of this compound was accomplished by coupling 2-hydroxyphenylacetic acid with syringaldehyde, decarboxylation of the resultant isoaurones, and hydrogenation of the double bond in the corresponding stilbene. This compound displayed cytotoxic activity against human cancer cells (HCT116 and Hela cells) and leukemia cells (HL-60 cells). The present study suggests that this plant serves as a source of biologically active natural products. Also, our findings provide information on the secondary metabolites in the diet of Japanese rock ptarmigans.

Enriched zinc oxide nanoparticles by Nasturtium officinale leaf extract: Joint ultrasound-microwave-facilitated synthesis, characterization, and implementation for diabetes control and bacterial inhibition.

The leaf extract of a medicinally important plant, watercress (Nasturtium officinale), was obtained through an ultrasound-facilitated method and utilized for the preparation of ZnO nanoparticles via a joint ultrasound-microwave assisted procedure. The characteristics of the extract enriched nanoparticles (Ext/ZnO) were determined by SEM, TEM, XRD, EDX, BET, FTIR, TGA, and UV-Vis DRS analyses and compared to that of ZnO prepared in the absence of the extract (ZnO). The presence of carbon and carbonaceous bonds, changes in the morphology, size, band gap energy, and weight-decay percentage were a number of differences between ZnO and Ext/ZnO that confirmed the link of extract over nanoparticles. Ext/ZnO, watercress leaf extract, ZnO, and insulin therapies were administrated to treat alloxan-diabetic Wister rats and their healing effectiveness results were compared to one another. The serum levels of the main diabetic indices such as insulin, fasting blood glucose, and lipid profile (total triglyceride, total cholesterol, and high-density lipoprotein cholesterol) were estimated for healthy, diabetic, and the rats rehabilitated with the studied therapeutic agents. The watercress extract-enriched ZnO nanoparticles offered the best performance and suppressed the diabetic status of rats. Moreover, both ZnO samples satisfactory inhibited the activities of Staphylococcus aureus and Escherichia coli bacteria. Based on the results, the application of Nasturtium officinale leaf extract can strongly empower ZnO nanoparticles towards superior antidiabetic and enhanced antibacterial activities.

Discovery, synthesis and antibacterial evaluation of phenolic compounds from Cylicodiscus gabunensis.

BACKGROUND: Cylicodiscus gabunensis Harms (Family Leguminosae) (CG) is an African medicinal plant used as a treatment of various ailments including malaria, liver diseases, and gastrointestinal disturbances. Its extracts showed potent in vitro antibacterial activity. However, the antibacterial components are unknown. METHODS: In this study, the stem bark of the CG plant was extracted and its antibacterial property against a panel of Gram-negative and Gram-positive bacterial strains assessed using the disk diffusion assay method. Bioassay-guided fractionation of the bioactive extracts was employed to identify bioactive constituents using both gas and liquid chromatography mass spectrometry. Chemical synthesis was used to make the analogues of gallic acid. Microplate dilution assays and scanning electron microscopy (SEM) were used to evaluate the antibacterial properties and mechanism of action of the active fractions and pure compounds. RESULTS: The most bioactive sub-fractions derived from CG comprised of ethyl gallate, gallic acid and polyphenols. Five alkyl/alkenyl gallates were synthesized. A preliminary structure-activity relationship of gallic acid derivatives was obtained using the synthetic analogues and a series of commercially available phenolic compounds. Increasing the length of alkyl chains generally increases the potency of the alkyl gallates. Introducing a double bond with restricted conformations of the C-5 side chain has little effect on the antibacterial property. SEM analysis of the effect of alkyl gallates on Staphylococcus aureus indicates that they appear to interrupt S. aureus bacterial cell wall integrity. CONCLUSIONS: The results of this research rationalise the ethnobotanical use of C. gabunensis and suggest that gallate derivatives may serve as promising antibacterial agents for the treatment of infectious diseases.

Green synthesis and biological activities of silver nanoparticles prepared by Carpesium cernuum extract.

The extract of Carpesium cernuum whole plant was successfully used as a green factory for the synthesis of silver nanoparticles in a one-step, one-pot process. The extract efficiently reduced silver ions to spherical silver nanoparticles. The size was measured as 13.0 ± 0.2 nm from high resolution transmission electron microscopic images. The reaction yield was determined to be 99.6% using inductively coupled plasma optical emission spectroscopy. The silver nanoparticles were highly stable for 28 days at ambient temperature without forming agglomeration or aggregation of nanoparticles. Dose-dependent antioxidant activity of the silver nanoparticles was observed in terms of the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl radicals. The silver nanoparticles also exerted cytotoxicity on Mus musculus skin melanoma cells (B16F10) and human lung cancer cells (A549) in a dose-dependent manner. Specifically, the cytotoxicity of the silver nanoparticles on A549 cells was closely associated with apoptotic cell death. Cellular uptake of the silver was evaluated via inductively coupled plasma mass spectrometry, and a higher percentage of silver was taken up by A549 cells (22.6%) than by B16F10 cells (17.3%). This result indicated that higher cellular uptake of silver nanoparticles resulted in higher cytotoxicity on A549 cells. Therefore, plant extracts are capable of being valuable natural sources for the green synthesis of silver nanoparticles that exhibit potent biological activities for pharmaceutical and biomedical applications in future nanomedicine.

Eco-friendly synthesis, characterization, in vitro and in vivo anti-inflammatory activity of silver nanoparticle-mediated Selaginella myosurus aqueous extract.

INTRODUCTION: There is emerging interest in medicinal plants in the biomedical field, due to their multitude of chemicals which show anti-inflammatory, antimicrobial, antiviral, or antitumoral potential. Research on medicinal plants has shown that nanotechnology could offer new solutions in the quality control, delivery aspects, or in sustaining herbal biological activities. This work reports on the preparation and characterization of silver nanoparticle-mediated Selaginella myosurus plant extract. METHODS: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, energy dispersive X-ray spectroscopy, high-resolution scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction have been used to characterize the prepared silver nanoparticles. The synthetic stability was studied by varying concentrations and pH of reactants. Egg albumin denaturation and carrageenan-induced rat paw edema model were used to ascertain the anti-inflammation. RESULTS: Ultraviolet-visible spectroscopy gave plasmon resonance ranging between 420 and 480 nm while Fourier transform infrared spectroscopy proved nano interface functionalized with organics. The powder X-ray diffraction pattern is in agreement with silver and silver chloride nanoparticles of crystallite size 33.7 nm and 44.2 nm for silver and silver chloride, respectively. Energy dispersive X-ray spectroscopy enables elemental characterization of the particles consisting of silver and silver chloride among main elements. Spherical silver grain of 58.81 nm average size has been depicted with high-resolution scanning electron microscopy and high-resolution transmission electron microscopy. Inhibitions of 99% and 60% were obtained in vitro and in vivo, respectively. CONCLUSION: The albumin denaturation and carrageenan-induced rat hind paw edema model to assess the anti-inflammatory potential of generated nanoparticles suggests that the silver nanoparticles may act as reducing/inhibiting agents on the release of acute inflammatory mediators. Hence, this work clearly demonstrated that silver nanoparticles mediated-Selaginella myosurus could be considered as a potential source for anti-inflammatory drugs.

Natural and synthetic avenanthramides activate caspases 2, 8, 3 and downregulate hTERT, MDR1 and COX-2 genes in CaCo-2 and Hep3B cancer cells.

Avenanthramides (AVNs) are natural polyphenols obtained from oat sprouts and can also be chemically synthetized. The aim of the present study was to assess the anticancer, anti-inflammatory and antioxidant effects of individual synthetized AVNs (s-2c, s-2p, s-2f) and a natural AVN mixture (n-MIX) on CaCo-2 and Hep3B cancer cells. In CaCo-2, the AVN s-2c was found to be the most cytotoxic followed by the n-MIX. In Hep3B cells, a marked cytotoxic effect was found but no significant difference was observed between the synthesized AVNs and the n-MIX. In both CaCo-2 and Hep3B cells, natural and synthetic AVNs activated caspases 8 and 3, and the n-MIX and the AVN s-2c were also able to activate caspase 2. Both synthetic and natural AVNs downregulated pro-survival genes hTERT, COX-2 and MDR1, inhibited the activity of pro-inflammatory COX-2 enzyme and reduced prostaglandin E2 levels, showing the potent chemopreventive effects of these oat-derived phytochemicals. Synthetic AVN s-2c was found to have the highest chemical antioxidant capacity, as indicated by ORAC, DPPH and ABTS values, whereas all AVNs and n-MIX were shown to have similar intracellular antioxidant activity, evaluated by means of the DCFH-DA assay. As AVNs have high bioavailability in humans, results of this study suggest that oat-based foods, fortified with AVNs, could be an alternative to produce functional foods with anticancer, anti-inflammatory and antioxidant effects for health benefits.

Biogenic synthesis of copper oxide nanoparticles using olea europaea leaf extract and evaluation of their toxicity activities: An in vivo and in vitro study.

Copper oxide nanoparticles (CUNPs) were synthesized using Olea europaea leaf extract as reducing and protecting agent. The formation of nanoparticles was observed through a color change from yellowish to brownish black. The CUNPs were confirmed with UV-Vis spectrophotometer, which revealed a peak absorbance at 289 nm. The synthesized CUNPs were characterized by XRD, FTIR, SEM, and TEM. The XRD pattern revealed that CUNPs were crystalline in nature with a diameter around 20 nm. FTIR spectral analysis showed that CUNPs were capped with plant constituents. From SEM and TEM analyses, the CUNPs were generally found to be spherical in shape, and the size range was 20-50 nm. Free radical scavenging potential of CUNPs against DPPH was confirmed by its stable antioxidant effects. In addition, the toxicity of CUNPs in mice was also assessed by body weight and weights of liver, kidneys, spleen, and thymus. The immune response in mice was signaled through an obvious change in spleen and thymus index, with a decrease of ADA enzyme activity in serum, spleen, and thymus after CUNPs treatment. The CUNPs were found to exert cell growth arrest against AMJ-13 and SKOV-3 cancer cells in a dose-dependent manner and induce cell death by apoptosis. Less significant cytotoxic effect was observed in normal dermal fibroblast cells. These findings suggest that CUNPs may have the potential to be anticancer agents. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:218-230, 2018.

Synthesis, characterization and inhibitory effects of crocetin derivative compounds in cancer and inflammation.

Crocetin is a natural product possessing extraordinary therapeutic effects for various diseases. However, its extremely low solubility limits its application greatly. Conjugation of organic compounds containing heteroatoms such as N to poor soluble molecules can help the synthesized derivative to form stable hydrogen bonds by lowering the salvation energy, which will improve the solubility of the synthesized compounds. Herein, crocetin was modified by conjugating with piperidyl, diethylin and benzylamine to improve their solubility and bioactivities. In the present study, the conjugation of crocetin with piperidyl, diethylin and benzylamine and their influence on the solubility and the pharmacological effects of crocetin were investigated. With the described strategy, crocetin derivatives were synthesized and their structures were elucidated by 1H NMR, 13C NMR and UPLC-MS spectroscopic analysis. The solubility of crocetin and its derivatives were identified. Upon that, the pharmacological effects of the crocetin derivatives on the tumor and inflammation treatment were investigated. It was shown that, in contrast to crocetin, of which, the solubility and pharmacological effects were low and limited, the synthesized compounds have significantly higher solubility and possess broad spectrum of anticancer effects in multiple tumor cell lines, including B16F10, MCF-7, A549 and SKOV3, as well as enhanced anti-inflammation efficacy in macrophage (RAW264.7) without causing cells damage. Conjugation of piperidyl, diethylin and benzylamine with the crocetin was demonstrated to be a highly efficient strategy to improve the solubility of crocetin. The synthesized crocetin derivatives were shown the promising therapeutics for the tumor and inflammation treatment with high safety.