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Background: The genus Xylaria has been reported as a rich source of biologically active secondary metabolites. In the present study, an endophytic fungus Xylaria psidii has been isolated from the leaf sample of Aegle marmelos (L.) Corr., characterized on the basis of its morphological features and sequence data for the ITS region (KU291350) of the nuclear ribosomal DNA. Biological screening of ethyl acetate extract of Xylaria psidii displayed a potential therapeutic effect on pancreatic cancer cells.Hypothesis: This study was designed systematically to explore Xylaria psidii, an endophytic fungus for the identification of biologically active secondary metabolites against pancreatic cancer cells.Methods: While exploring the bioactive secondary metabolites, a sensitive and reliable LC-MS based dereplication approach was applied to identify four compounds A-D from fungal extract. Further bioactivity guided isolation of fungal extract yielded two major metabolites 1 and 2. The structures of 1 and 2 have been determined by detailed spectroscopic analysis including MS, NMR, IR and UV data and similarity with published data. Xylarione A (1) is new whereas (-) 5-methylmellein (2) is reported for the first time from X. psidii. Both the isolated compounds were screened for their effect on the viability and proliferation against a panel of cancer cell lines (MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2 and DU145) of different tissue origin.Results: Compounds 1 and 2 exhibited cytotoxicity against pancreatic cancer (MIA-Pa-Ca-2) cells with IC50 values of 16.0 and 19.0 µm, respectively. The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Cell death induced by 1 and 2 displayed features characteristic of apoptosis. Flow cytometry based analysis of 1 and 2 using Rhodamine-123 displayed substantial loss of mitochondrial membrane potential in a concentration dependent manner by both the compounds.Conclusion: Results conclude that the isolated compounds 1 and 2 are responsible for the activity shown by crude ethyl acetate extract and may act as potential leads for medicinal chemists for designing more potent analogs. [ABSTRACT FROM AUTHOR]

Clematis gouriana(Ranunculaceae), a perennial herb, is used by the local inhabitants of the western Himalayan region for its medicinal properties. Major bioconstituents ofC. gourianaleaves using different solvent extracts were obtained and analysed. The results revealed promising contents of phenolics (from 18.19 ± 0.10 to 22.17 ± 0.10 mg g− 1) as gallic acid and flavonoids (from 2.83 ± 0.01 to 6.52 ± 0.08 mg g− 1) as quercetin equivalent in different extracts. Aqueous acetone extract showed higher antioxidant activity with IC50value of 129.11 and 25.35 μg mL− 1against DPPH and ABTS free radicals, respectively. Antioxidant yield ranged from 16.87 ± 0.27 to 24.48 ± 0.13 mg g− 1of Trolox equivalent in different extracts as measured by the FRAP assay. Furthermore, ethylacetate extract exhibited strongin vitrocytotoxicity against Chinese hamster ovary and glioma cell lines. Proximate composition (proteins, fats, ash and minerals) ofC. gourianaleaves was also assessed. Results demonstrated the potential ofC. gourianabioconstituents as nutraceuticals. [ABSTRACT FROM PUBLISHER]

BACKGROUND Apple pomace is generated in huge quantities in juice-processing industries the world over and continuous efforts are being made for its inclusive utilization. In this study, apple seeds separated from industrial pomace were used for extraction of oil. The fatty acid composition, physicochemical and antioxidant as well as in vitro anticancer properties of extracted oil were studied to assess its suitability in food and therapeutic applications. RESULTS The fatty acid composition of seed oil revealed the dominance of oleic (46.50%) and linoleic acid (43.81%). It had high iodine (121.8 g I 100 g−1) and saponification value (184.91 mg KOH g−1 oil). The acid value, refractive index and relative density were 4.28 mg KOH g−1, 1.47 and 0.97 mg mL−1, respectively. The antioxidant potential ( IC50) of apple seed oil was 40.06 µg mL−1. Cytotoxicity of apple seed oil against CHOK1, SiHa and A549 cancer cell lines ranged between 0.5 ± 0.06% and 88.6 ± 0.3%. CONCLUSION The physicochemical properties of apple seed oil were comparable with edible food oil, indicating its better stability and broad application in the food and pharmaceutical industries. Apple seed oil could be a good source of natural antioxidants. Also, the in vitro cytotoxic activity against specific cell lines exhibited its potential as an anticancer agent. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Engineered nanoparticles (ENPs) are being increasingly produced as a result of the rapid development in nanotechnology. They are used to generate innovative and versatile goods in a wide range of industrial, medical and public sectors including healthcare, biomedicine, cosmetics, agriculture, transport, energy, materials, and information and communication technologies. Nanomaterials have very unique chemical and physical properties that do suggest potential health hazards, but a limited health and safety information exists for engineered nanomaterials. In vivo and in vitro experimental studies have shown that several types of ENPs (metallic nanoparticles, quantum dots, carbon nanotubes, Zinc oxide, Iron oxide) can have various types of biological effects, some detrimental on the various organs, both acutely and in the long term, resulting in cytotoxicity and/or genotoxicity. This review focus on the possible biological impact of engineered NPs, serving as a reminder that nanomaterials can become a double-edged sword if not handled properly and thus, the current efforts should include research to generate data for safety and nanotoxicological evaluation of potential or putative hazards to the human health in particular and the environment at large. [ABSTRACT FROM AUTHOR]

Abstract: Inula racemosa Hook.f. commonly known as Pushkarmula (Compositae) has been used as a traditional drug in India, China and Europe. In the present study, 95% ethanolic extract of roots and its fractions (n-hexane, chloroform, n-butanol and aqueous) were evaluated for in vitro cytotoxicity against cancer cell lines of colon, ovary, prostate, lung, CNS and leukemia. The n-hexane fraction containing alantolactone and isoalantolactone as its major constituents was further studied for its mode of action in HL-60 cells. The lowest IC50 value of n-hexane fraction was 10.25μg/ml for Colo-205, a colon cancer cell line whereas, 17.86μg/ml was the highest IC50 value observed against CNS cancer cell line SF-295. Further studies on HL-60 cells treated with n-hexane fraction at 10, 25 and 50μg/ml for 6h, revealed that it induces apoptosis through intrinsic as well as extrinsic pathways by generating reactive oxygen species (ROS) intermediates. Mitochondrial dysfunction prompted the release of cytochrome c, translocation of pro-apoptotic protein (Bax), activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP), which eventually leads to apoptosis. The results of present study strongly support further research and development of bioactive constituents from Inula racemosa as potential anticancer agent with possible therapeutic implication. [ABSTRACT FROM AUTHOR]

Abstract: Polyalthia longifolia is a lofty evergreen tree found in India and Sri Lanka. We are reporting first time the anticancer potential of P. longifolia leaves extract (A001) and its chloroform fraction (F002). Both inhibited cell proliferation of various human cancer cell lines in which colon cancer cells SW-620 showed maximum inhibition with IC50 value 6.1μg/ml. Furthermore, F002 induce apoptosis in human leukemia HL-60 cells as measured by several biological end points. F002 induce apoptotic bodies formation, DNA ladder, enhanced annexin-V-FITC binding of the cells, increased sub-G0 DNA fraction, loss of mitochondrial membrane potential (ΔΨ mt), release of cytochrome c, activation of caspase-9, caspase-3, and cleavage of poly ADP ribose polymerase (PARP) in HL-60 cells. All the above parameters revealed that F002-induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells. [Copyright &y& Elsevier]

Apple ( Malus domestica Borkh.) leaves are good source of polyphenols. Considering the increasing demand of such phytochemicals, particularly in healthcare sector, the objective of this study was to evaluate the bioactivity of apple leaves phenolics. Different solvent mediated extracts obtained from the apple leaves were assessed for presence of phenolic compounds. Among different extracts, the highest phenolic content of 30.38 ± 0.50 mg/g were recorded in 70% aqueous ethanol (ALE-7) with subsequent high antioxidant value (IC 50 49.16 μg/mL) by ABTS assay. RP-HPLC-DAD phenolic profiling of leaves extract, irrespective of solvent used for extraction, revealed presence of five major compounds with maximum yield of phloridzin (24.43 ± 0.05 mg/g), followed by quercitrin (2.06 ± 0.05 mg/g), quercetin-3- O -glucoside (1.55 ± 0.001 mg/g), epicatechin (0.37 ± 0.07 mg/g) and phloretin (0.15 ± 0.05 mg/g). ALE-7 extract was further fractionated with hexane (ALH) and ethyl acetate (ALEA), which were evaluated for their in vitro biological activities. ALEA extract exhibited higher nitric oxide (NO) scavenging activity (63.3%) at 200 μg/mL. This fraction also showed maximum lymphocyte proliferation (34%) at 25 μg/mL after 48 h. The antimicrobial testing of isolated fractions revealed that ALH fraction (MIC value ranging from 1.18–2.37 μg/mL) could be a good candidate, especially for controlling food borne pathogen. Furthermore, the in vitro cytotoxicity assessment of different apple leaves fractions was also performed against human cancer cell lines (KB, SiHa and A-549), but none of the fraction was found cytotoxic against selected cell line. In conclusion, the presence of biologically active phenolics in apple leaves makes it a feasible renewable bioresource for extraction of such phytochemicals for the development of nutraceuticals particularly against inflammation and microbial infections. [ABSTRACT FROM AUTHOR]

Docetaxel is one of the promising drugs and employed for the management of variety of cancers. However, challenges like poor-bioavailability, low tissue-permeability, compromised aqueous solubility and dose-dependent side-effects limit its clinical applications. Whereas, PLGA–based polymeric micelles possess the ability to enhance the tissue permeability of drugs and increase their biocompatibility. Henceforth, it was aimed to fabricate the dextran-PLGA-based polymeric-micelles loaded with docetaxel to explore the potential benefits in drug delivery. Dextran was chemically linked to PLGA and the linkage was confirmed by FT-IR, UV and NMR-spectroscopy. Critical-micelle-concentration of amphiphilic polymer was determined and drug was encapsulated by diffusion technique and erythrocyte compatibility. The system was evaluated for drug release profile and in vitro cytotoxicity studies. The pharmacokinetic profile was studied in rats. The micelles obtained were of 96.5 ± 2.5 nm and offered drug encapsulation of order of 54.85 ± 1.21%.The cytotoxicity of drug against MCF-7 and MDA-MB-231 cell lines was enhanced by approx. 100%. The pharmacokinetic profile was substantially modified and about 16-folds enhancement in bioavailability was observed vis-à-vis plain drug. The approach was not only able to control the drug release, but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of docetaxel and similar anticancer agents. [ABSTRACT FROM AUTHOR]

Abstract: A microwave assisted strategy for synthesis of series of 1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones has been developed and their biological evaluation as anticancer agents is described. The synthetic protocol involves simple procedure by oxidative coupling of 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide with different aldehydes in presence of K2S2O8 offering 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one compounds in excellent yields. The in vitro anticancer activity screening against human cancer cell lines HeLa, CAKI-I, PC-3, MiaPaca-2, A549 gave good results. The in detailed mechanistic correlation studies of compound 3m revealed that the compound shows anticancer activity through apoptosis mechanism and also inhibits mTOR with nonomolar potency. The design was based on docking with mTOR protein. The concentration dependent cell cycle analysis, western blotting experiment and nuclear cell morphology studies have been described. [Copyright &y& Elsevier]

Highlights: [•] Cryptosporiopsis sp. was isolated as an endophyte of Clidemia hirta. [•] Three molecules, two new and one known, were isolated from this fungus and their structures were elucidated by 2D NMR and mass spectrometry. [•] Compound 1 exhibited moderate cytotoxic activity in HL-60 cells (IC50 4μg/ml) whereas compounds 2 and 3 were moderately active against several bacterial pathogens. [Copyright &y& Elsevier]

Highlights: [•] Five of six fractions tested showed cytotoxicity effects on PC-3 and HL-60 cells with IC50 varied between 12 and 88μg/ml. [•] Ethyl acetate fraction of G. epunctata was the most active on HL-60 cells (IC50: 12μg/ml). [•] After 24h this fraction induced an increase of cells population in a sub-G1 phase in a dose-dependent. [•] EtOAc fraction induces apoptosis of HL-60 cells through G0/G1 phase arrest and loss of membrane mitochondrial potential. [ABSTRACT FROM AUTHOR]

Abstract: A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a–n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a–j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h–k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC50 values in the range of 0.08–0.70μM. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds. [Copyright &y& Elsevier]

• Identification and quantification of phenolics in industrial apple pomace extracts. • Cytotoxic effects of phenolic extracts against different human cancer cell lines. • Mechanism of apoptotic and necrotic cancer cell death. • Inhibition of nitric oxide production in murine macrophages. Apple processing industries around the globe generate huge quantity of pomace as waste material, whose sustainable and cost-effective utilization continually being attempted. In general, industrial apple pomace is a conglomeration of different varieties, however, rich in array of inherited nutritional and phytochemical constituents. In present study, aqueous-ethanol, -methanol and -acetone mediated extractions of phenolics from industrial apple pomace was performed. The obtained extracts from respective solvents were further partitioned with ethyl acetate. The phytochemical evaluation of ethyl acetate fractionated aqueous acetone fraction (APA1), aqueous ethanol fraction (APE1) and aqueous methanol fraction (APM1) by high pressure liquid chromatography and electrospray-ionization quadrupole time-of-flight tandem mass spectrometry showed the presence of phloridzin, phloretin, quercitrin and quercetin as major constituents. The cytotoxic effects of APA1, APM1, and APE1 fractions were evaluated against human cancer cell lines i.e. cervical squamous cell carcinoma (SiHa), oral carcinoma (KB) and colorectal adenocarcinoma (HT-29) cell lines. Significant differences were obtained for oral cancer cells in time and dose dependent manner. Cytotoxicity data validated by clonogenic cell survival assay showed significant inhibition of KB cancer cells by APA1 and APE1 after 24 and 36 h. Caspase 3/7 activity of fractions was also found to be increased in time dependent manner. Furthermore, the flow cytometer analysis revealed that KB cells follow apoptotic and necrotic mechanism for cell death after treatment with APA1 and APE1 fractions for 24 and 30 h. Results also showed significant nitric oxide inhibition in lipopolysaccharide– interferon gamma stimulated mice peritoneal macrophages at different concentrations. Present study established that industrial apple pomace indeed has substantial amount of bioactive phenolics that can be bioprocessed to develop variety of health supplements. [ABSTRACT FROM AUTHOR]