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Objective: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats., Methods: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded., Key Findings: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo., Conclusion: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 μg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli . Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC 50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P . roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation.

Urease plays a significant role in the pathogenesis of urolithiasis pyelonephritis, urinary catheter encrustation, hepatic coma, hepatic encephalopathy, and peptic acid duodenal ulcers. Salvinia molesta was explored to identify new bioactive compounds with particular emphasis on urease inhibitors. The aqueous methanol extract was fractionated using solvents of increasing polarity. A series of column chromatography and later HPLC were performed on butanol extract. The structures of the resulting pure compounds were resolved using NMR (1D and 2D), infrared, and mass spectroscopy. The novel isolate was evaluated for antioxidant activity (using DPPH, superoxide anion radical scavenging, oxidative burst, and Fe +2 chelation assays), anti-glycation behavior, anticancer activity, carbonic anhydrase inhibition, phosphodiesterase inhibition, and urease inhibition. One new glucopyranose derivative 6'-O-(3,4-dihydroxybenzoyl)-4'-O-(4-hydroxybenzoyl)-α/β-D-glucopyranoside (1) and four known glycosides were identified. Glycoside 1 demonstrated promising antioxidant potential with IC 50 values of 48.2 ± 0.3, 60.3 ± 0.6, and 42.1 ± 1.8 μM against DPPH, superoxide radical, and oxidative burst, respectively. Its IC 50 in the Jack bean urease inhibition assay was 99.1 ± 0.8 μM. The mechanism-based kinetic studies presented that compound 1 is a mixed-type inhibitor of urease with a K i value of 91.8 ± 0.1 μM. Finally, molecular dynamic simulations exploring the binding mode of compound 1 with urease provided quantitative agreement between estimated binding free energies and the experimental results. The studies corroborate the use of compound 1 as a lead for QSAR studies as an antioxidant and urease inhibitor. Moreover, it needs to be further evaluated through the animal model, that is, in vivo or tissue culture-based ex-vivo studies, to establish their therapeutic potential against oxidative stress phosphodiesterase-II and urease-induced pathologies., (© 2021 Wiley Periodicals LLC.)

Chromatographic purification of the alcoholic extract from the aerial parts of the Saudi plant Nuxia oppositifolia (Hochst.), Benth., resulted in five isolated phenolic compounds. Two flavones, hispidulin ( 1 ) and jaceosidin ( 2 ), and the phenylethanoid glycosides, verbascoside ( 3 ), isoverbascoside ( 4 ), and conandroside ( 5 ), were identified and their chemical structures were determined by spectroscopic analyses. The insecticidal activity of compounds 1 and 2, in addition to 11 compounds isolated in a previous research ( 6 - 16 ), was evaluated against the Yellow Fever mosquito, Aedes aegypti . Four compounds displayed adulticidal activity with LD 50 values of 2-2.3 μg/mosquito. Free radical scavenging properties of the plant extracts and compounds ( 1 - 5 ) were evaluated by measuring the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate radical cation (ABTS •+ ) scavenging activity. All compounds exhibited notable activity, compared with the positive control, l-Ascorbic acid. This study suggests that N. oppositifolia could be a promising source of secondary metabolites, some with lethal adulticidal effect against Ae. aegypti .

Breynia retusa (Dennst.) Alston (also known as Cup Saucer plant) is a food plant with wide applications in traditional medicine, particularly in Ayurveda. Extracts obtained with four solvents (dichloromethane, methanol, ethyl acetate and water), from three plant parts, (fruit, leaf and bark) were obtained. Extracts were tested for total phenolic, flavonoid content and antioxidant activities using a battery of assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum) and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase and α-glucosidase as target enzymes. Results showed that the methanolic bark extract exhibited significant radical scavenging activity (DPPH: 202.09 ± 0.15; ABTS: 490.12 ± 0.18 mg Trolox equivalent (TE)/g), reducing potential (FRAP: 325.86 ± 4.36: CUPRAC: 661.82 ± 0.40 mg TE/g) and possessed the highest TAC (3.33 ± 0.13 mmol TE/g). The methanolic extracts were subjected to LC-DAD-MS n and NMR analysis. A two-column LC method was developed to separate constituents, allowing to identify and quantify forty-four and fifteen constituents in bark and fruits, respectively. Main compound in bark was epicatechin-3- O -sulphate and isolation of compound was performed to confirm its identity. Bark extract contained catechins, procyanidins, gallic acid derivatives and the sulfur containing spiroketal named breynins. Aerial parts mostly contained flavonoid glycosides. Considering the bioassays, the methanolic bark extract resulted a potent tyrosinase (152.79 ± 0.27 mg kojic acid equivalent/g), α-amylase (0.99 ± 0.01 mmol acarbose equivalent ACAE/g) and α-glucosidase (2.16 ± 0.01 mmol ACAE/g) inhibitor. In conclusion, methanol is able to extract the efficiently the phytoconstituents of B. retusa and the bark is the most valuable source of compounds.

Stratiotes aloides L. is common water plant in central Poland. Due to its expansive character, S. aloides L. can strongly affect the functioning of aquatic ecosystems. S. aloides L. was an important famine plant in central Poland. This plant was commonly collected and cooked until the turn of the 20th century. It has also been used to heal wounds, especially when these are made by an iron implement. The objective of the present work was to study the phenolic profile in the leaves and roots of S. aloides as well as their antioxidant potential and ability to inhibit lipoxygenase (LOX) in the light of their potential bioaccessibility. The dominant compound in its leaves was luteolin-7-O-hexoside-glucuronide (5.84 mg/g DW), whereas the dominant root component was chrysoeriol-7-O-hexoside-glucuronide (0.83 mg/g DW). Infusions from leaves, roots, and their 1:1 ( v / v ) mixture contained potentially bioaccessible antiradical compounds. S. aloides is a good source of water-extractable reductive compounds. Especially valuable are the leaves of this plant. The roots of S. aloides contained very active hydrophilic compounds able to chelate metal ions. However, their potential bioaccessibility was relatively low. The hydrophilic compounds from the leaves were the most effective XO inhibitors (EC 50 = 9.91 mg DW/mL). The water-extractable compounds derived from the leaves and roots acted as uncompetitive LOX inhibitors.

Hair loss is becoming increasingly prevalent as dietary and living habits change. The search for natural products to limit hair loss has led to tapping into traditional cosmetic knowledge. We studied three plants of the Polynesian cosmetopoeia, Bidens pilosa , Calophyllum inophyllum and Fagraea berteroana , to determine their ability to promote hair growth. Their chemical content was characterized by liquid chromatography coupled to mass spectrometry (LC-MS). Their proliferative activity on dermal papilla cells (DPCs) was assessed via MTT assay and molecular targets were evaluated by RT-qPCR analysis of seven factors involved in the modulation of the hair cycle, CCND1 , LEF1 , DKK1 , WNT5A PPARD , TGFΒ1 , PPARD and RSPO2 . Our results show that our extracts significantly increased proliferation of dermal papilla cells. Furthermore, LC-MS/MS analysis revealed a diversity of molecules, flavonoids, iridoids and organic acids, some known for hair-inducing properties. Finally, specific extracts and fractions of all three plants either upregulated CCND1 , LEF1 and PPARD involved in stimulating hair follicle proliferation and/or lowered the gene expression levels of hair growth inhibiting factors, DKK1 and TGFB1 . Our findings suggest that extracts from B. pilosa, C. inophyllum and F. berteroana are interesting candidates to stimulate hair growth.

Glioblastoma (GBM) is the most malignant central nervous system tumor, with poor prognosis. Temozolomide (TMZ) has been used as a first-line drug for the treatment of GBM for over a decade, but its treatment benefits are limited by acquired resistance. Polysaccharides from Cibotium barometz (CBPs) are polysaccharides purified from the root of Cibotium barometz (L.) J. Sm., possessing sensitizing activity. The purpose of this study was to investigate the anti-cancer effect of CBP from different processing methods on U87 cells using a 1 H NMR-based metabolic approach, complemented with qRT-PCR and flow cytometry, to identify potential markers and discover the targets to explore the underlying mechanism. Cibotium barometz is usually processed under sand heating in clinical applications. Polysaccharides from both the processed (PCBP) and raw (RCBP) C. barometz were prepared, and the effect on enhancing the sensitivity to TMZ was investigated in vitro. CBP can significantly increase the toxicity of TMZ to the U87 cell line, promote apoptosis, enhance cell cycle changes, and arrest cells in S phase, and RCBP demonstrated better activity. Multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), were used to identify metabolic biomarkers, and 12 metabolites in the cell extract samples were clearly identified as altered after RCBP exposure. NMR-based cell metabolomics provided a holistic method for the identification of CBP's apoptosis-enhancing mechanisms and the exploration of its potential applications in preclinical and clinical studies., Competing Interests: Declaration of competing Interest These authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Foodborne pathogens are a real public health concern in an escalating antimicrobial resistance scenario. Natural products represent a promising source of bioactive molecules, and essential oils have attracted much attention due to their myriad of biological properties, including antibacterial activities. In this context, essential oils obtained from the leaves of Chromolaena squalida , Campomanesia sessiliflora, Myrsine guianensis, Matayba guianensis, Siparuna guianensis, Ocotea minarum and Endlicheria paniculata -species from the Cerrado biome of Midwest Brazil-were extracted and evaluated for their antibacterial activity against a panel of four standard and three clinical multidrug-resistant bacterial strains. All tested oils showed moderate to good activity against at least four bacterial strains, including Salmonella Typhi and oxacillin-resistant Staphylococcus. The essential oils from C. squalida , C. sessiliflora , My. guianensis and Ma. guianensis showed strong inhibition of clinical Staphylococcus strains, which cause bovine mastitis and are related to milk-borne diseases. Their chemical profiles were investigated by gas chromatography coupled to mass spectrometry (GC/MS), which revealed a predominance of mono- and sesquiterpene hydrocarbons, some of which with well-known antimicrobial properties. The essential oil from Cerrado plants proved active against resistant Gram-positive and Gram-negative bacteria, revealing their potentialities for the development of new alternative agents to prevent the spreading of resistant bacterial contamination.

The paper presents experimental results concerning the ultrasonically-assisted extraction of bioactive compounds from Erodium glaucophyllum roots. A comparison with conventional methodology is presented, and thereby the phytochemical composition and the antioxidant and anti-inflammatory activities of extracts are evaluated. The phenolic profile of Erodium extracts was analyzed by TOF-LC-MS-MS. The identification of phenolic compounds revealed that the major component was (+)-gallocatechin in the aqueous extracts obtained for the different extraction methodologies. The highest quantity of phenolic compounds and antioxidant capacity was found in the hydroethanolic extract obtained by conventional extraction (29.22-25.50 mg GAE/g DM; 21.174 mM Trolox equivalent). The highest content of carotenoids, varying from 0.035 to 0.114 mg/g dry matter, was reached by ultrasonic-assisted extraction. Furthermore, Erodium extracts showed a potent inhibition of the inflammatory reaction by means of the inhibition of tumor necrosis factor-alpha (TNF-α). The extracts obtained when ultrasound extraction was combined with ethanol:water (50:50, v/v) presented the greatest inhibition (92%).

Thirty-three compounds ( 1 - 33 ) were isolated from the rhizomes of Osmunda japonica . Their structures were elucidated on the basis of spectral analysis and identified as ent -kaurene terpenoids (1-3), anthraquinones (4-8), flavonoids (9-12), steroids (13-15), and other compounds ( 16 - 33 ). Compound 1 - 14 , 19 - 27 were isolated from the genus osmunda for the first time. Compound 28-29 were isolated from the plant for the first time. Cytotoxicities of all compounds against Hela, HepG2 and A549 cell lines were measured by MTT assay, and their antioxidant activities were determined by DPPH and ABTS radical scavenging assays. Compound 2 exhibited potent cytotoxicity against Hela, HepG2 cell lines with IC 50 values of 9.31 and 9.66 μM, respectively. Compound 9 showed good antioxidant activity. The Trolox-equivalent antioxidant capacity (TEAC) value was 0.95 mM in ABTS assay, and the IC 50 value was 18.63 μM in DPPH assay.

Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant ( p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly ( p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1 H -[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly ( p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.

Nuxia oppositifolia is traditionally used in diabetes treatment in many Arabian countries; however, scientific evidence is lacking. Hence, the present study explored the antidiabetic and antioxidant activities of the plant extracts and their purified compounds. The methanolic crude extract of N. oppositifolia was partitioned using a two-solvent system. The n -hexane fraction was purified by silica gel column chromatography to yield several compounds including katononic acid and 3-oxolupenal. Antidiabetic activities were assessed by α-amylase and α-glucosidase enzyme inhibition. Antioxidant capacities were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging assays. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (3-oxolupenal and katononic acid) was followed by fluorescence quenching and molecular docking studies. 3-oxolupenal and katononic acid showed IC 50 values of 46.2 μg/mL (101.6 µM) and 52.4 μg/mL (119.3 µM), respectively against the amylase inhibition. 3-oxolupenal (62.3 µg/mL or 141.9 μM) exhibited more potent inhibition against α-glucosidases compared to katononic acid (88.6 µg/mL or 194.8 μM). In terms of antioxidant activity, the relatively polar crude extract and n -butanol fraction showed the greatest DPPH and ABTS scavenging activity. However, the antioxidant activities of the purified compounds were in the low to moderate range. Molecular docking studies confirmed that 3-oxolupenal and katononic acid interacted strongly with the active site residues of both α-amylase and α-glucosidase. Fluorescence quenching results also suggest that 3-oxolupenal and katononic acid have a good affinity towards both α-amylase and α-glucosidase enzymes. This study provides preliminary data for the plant's use in the treatment of type 2 diabetes mellitus.

Conifers have evolved complex oleoresin terpene defenses against herbivores and pathogens. In co-evolved bark beetles, conifer terpenes also serve chemo-ecological functions as pheromone precursors, chemical barcodes for host identification, or nutrients for insect-associated microbiomes. We highlight the genomic, molecular and biochemical underpinnings of the large chemical space of conifer oleoresin terpenes and volatiles. Conifer terpenes are predominantly the products of the conifer terpene synthase (TPS) gene family. Terpene diversity is increased by cytochromes P450 of the CYP720B class. Many conifer TPS are multiproduct enzymes. Multisubstrate CYP720B enzymes catalyse multistep oxidations. We summarise known terpenoid gene functions in various different conifer species with reference to the annotated terpenoid gene space in a spruce genome. Overall, biosynthesis of terpene diversity in conifers is achieved through a system of biochemical radiation and metabolic grids. Expression of TPS and CYP720B genes can be specific to individual cell types of constitutive or traumatic resin duct systems. Induced terpenoid transcriptomes in resin duct cells lead to dynamic changes of terpene composition and quantity to fend off herbivores and pathogens. While terpenoid defenses have contributed much to the evolutionary success of conifers, under new conditions of climate change, these defences may become inconsequential against range-expanding forest pests., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Background: Rapid emergence of multidrug resistant (MDR) organisms in hospital and community settings often result into treatment failure, thus leading the clinicians with fewer treatment options. Cyathea gigantea, an ethnomedicinally important fern used in cuts and wound infections. So, if this medicinal plant is used in treating the MDR infections then it might bring certain relief in future treatment options., Methods: Antibacterial activity of C. gigantea against MDR bacteria was assed using well diffusion and broth microdilution methods to determine the diameters of growth inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Synergistic activity was also determined with the conventional antibiotics by disc diffusion method followed by FIC index of each of the tested antibiotic was calculated. The active extract was then subjected to fractionation by column chromatography and antibacterial activity was done with each of the collected fractions., Results: Crude extract of C. gigantea was found to be active against all the tested organisms. The MIC was 200 μg/ml against Gram-positive i.e., Staphylococcus aureus ATCC 25923 and 400 μg/ml against Gram-negative i.e., Escherichia coli ATCC 25922 and Pseudomonas aeruginosa PAO1, while the MBC was 400 μg/ml in case of Gram-positive and 800 μg/ml for Gram-negative. The synergistic activity revealed that the plant extract increased the antibacterial property of the studied antibiotics and the FIC index showed that significant synergistic activity was shown by ciprofloxacin followed by tetracycline, ampicillin and oxacillin. Antibacterial activity with the fractionated extract showed that the FR II, FR III and FR IV were active against both Gram-positive and Gram-negative bacteria, whereas FR I, FR V and FR VI did not show antibacterial property against any of the tested bacteria., Conclusions: Extracts of C. gigantea was found active against both selected Gram-positive and Gram-negative organisms and thus offers the scientific basis for the traditional use of the fern. The present study also provides the basis for future study to validate the possible use against multidrug resistant organisms.

In the current study, the green synthesis of zinc oxide nanoparticles (ZnONPs) using the leaf extract of Cyanometra ramiflora and zinc acetate precursor is presented. The phyto-components of the extract aided the reduction and the formation of nanoparticles. The purified ZnONPs were characterized by UV-Vis spectroscopy, SEM, EDS, XRD, BET, and FTIR techniques. A sharp absorption maximum at 360 nm in the UV-Vis data affirmed the formation of ZnONPs. SEM image revealed the nanoflower morphology and EDS showed strong signals for zinc and oxygen elements. XRD spectrum confirmed the hexagonal wurtzite crystalline structure of size 13.33 nm. A significant large surface area of 16.27 m 2 /g with mesopores, was affirmed using BET analysis. FTIR substantiated the existence of the characteristic zinc and oxygen bonding vibrations at 557 cm -1 , 511 cm -1 and 433 cm -1 . The photocatalytic activity of the ZnONPs was examined using the pollutant dye, Rhodamine B. A remarkable degradation efficiency of 98% within 200 min was achieved under sunlight irradiation and a degradation constant of 0.017 min -1 was obtained. Therefore, ZnONPs synthesized using a cheap and abundant source - the leaf extract of C.ramiflora possibly will play a promising part in the degradation of toxic dyes present in the wastewater., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bone metabolism is a homeostatic process, imbalance in which leads to the onset of diseases such as osteoporosis and osteopenia. Although several drugs are currently available to treat such conditions, they are associated with severe side effects and do not enhance bone formation. Thus, identifying alternative treatment strategies that focus on enhancing bone formation is essential. Herein, we explored the osteogenic potential of Turpinia formosana Nakai using human osteoblast (HOb) cells. The plant extract was subjected to various chromatographic techniques to obtain six compounds, including one new compound: 3,3'-di- O -methylellagic acid-4- O -α-l-arabinofuranoside ( 1 ). Compounds 3,3'-di- O -methylellagic acid-4- O -α-l-arabinofuranoside ( 1 ), gentisic acid 5- O - β -d-(6'- O -galloyl) glucopyranoside ( 2 ), strictinin ( 3 ), and (-)-epicatechin-3- O - β -d-allopyranoside ( 6 ) displayed no significant cytotoxicity toward HOb cells, and thus their effects on various osteogenic markers were analyzed. Results showed that 1 - 3 and 6 significantly increased alkaline phosphatase (ALP) activity up to 120.0, 121.3, 116.4, and 125.1%, respectively. Furthermore, 1 , 2 , and 6 also markedly enhanced the mineralization process with respective values of up to 136.4, 118.9, and 134.6%. In addition, the new compound, 1 , significantly increased expression levels of estrogen receptor-α (133.4%) and osteogenesis-related genes of Runt-related transcription factor 2 (Runx2), osteopontin (OPN), bone morphogenetic protein (BMP)-2, bone sialoprotein (BSP), type I collagen (Col-1), and brain-derived neurotropic factor (BDNF) by at least 1.5-fold. Our results demonstrated that compounds isolated from T. formosana possess robust osteogenic potential, with the new compound, 1, also exhibiting the potential to enhance the bone formation process. We suggest that T. formosana and its isolated active compounds deserve further evaluation for development as anti-osteoporotic agents.

New therapeutic approaches are necessary to control strongyloidiasis due to the side effects of, and resistance to, currently available drugs thiabendazole, albendazole, and ivermectin. This study examined the anthelmintic properties of extracts and isolated compounds from Siparuna guianensis against Strongyloides venezuelensis eggs and larvae, using the egg hatching test (EHT) and larval motility test (LMT). Albendazole (0.025 mg/ml) and ivermectin (0.316 mg/ml) were used as the positive controls for the EHT and LMT assays, respectively. Strongyloides venezuelensis eggs or larvae (±50 specimens) were treated with ethanol extract (0.05-1.0 mg/ml), ethyl acetate and aqueous fractions (0.05-0.8 mg/ml), essential oil (0.2-1.0 mg/ml) and α-bisabolol (0.2-1.0 mg/ml) from S. guianensis, and analysed by optical microscopy after 48 h (EHT), or after 24, 48 and 72 h (LMT). All the tested compounds exhibited ovicidal activity equivalent to the positive control and changed the morphology of the eggs. The S. guianensis ethanol extract and aqueous fraction were as effective as the positive control. Phytochemical analysis of the ethanol extract and fractions revealed the presence of phenolic compounds, tannins and flavonoids. Therefore, S. guianensis is effective against S. venezuelensis eggs and larvae in vitro, and can be considered as a potential alternative treatment for strongyloidiasis.

p-coumaric acid and fucose-rich polysaccharide have been studied for many bio-functions in skin including cutaneous protection from oxidative damage and antiageing, respectively, as well as wound healing. The physiological activities of various bird's nest fern extracts (BNFE), containing considerable fucose-rich mucilage and p-coumaric acid, on fibroblast and human skin were first investigated. BNFE with higher polysaccharide content generally contributed to a better moisture holding capability. Furthermore, BNFE showed pronouncedly enhancing effect on collagen production and growth of fibroblast (NIH-3T3), clinical trial results revealed that the emulsions with 1% BNFE showed good moisturising effect and improved the elasticity of human skins effectively. The potential of BNFE for cosmetics and medical applications such as natural moisturiser, antiageing and wound repairing was possibly related to the fucose-rich mucilage and various phenolic compounds including p-coumaric acid in BNFE.

Due to the emergence of virulent and antibiotic-resistant microbes, natural antimicrobials from herbal origins have been given more attention as an alternative therapy. This study provides an in vitro research framework to investigate the antibacterial activities of 5 herbal (marjoram, garlic, onion, cinnamon and black seed) oil extracts against 16 multidrug-resistant (MDR) and virulent P. multocida serogroup A isolates recovered from dead and clinically diseased rabbits. Pathogenicity of the screened isolates was further proven experimentally and was verified by PCR analyses of 5 randomly selected virulence genes encoding attachment and colonization proteins (ptfA, pfhA, and omp87), sialidases (nanB) and dermonecrotoxin (toxA). A total of 12 P. multocida isolates were highly pathogenic with the possession of all examined virulence genes, while the other 4 isolates were of lower pathogenicity with expression of the target genes except toxA. In vitro anti-P. multocida activities of the 5 extracts and their synergism rates with 4 antibiotic drugs revealed that marjoram and cinnamon extracts had the highest antibacterial activities and the highest synergism rates against the screened isolates. Pasteurella multocida virulence gene expression profiles were assessed via real-time quantitative reverse transcription PCR (qRT-PCR) in response to marjoram extract. The quantitative analyses showed less than five-fold reduction in the targeted virulence genes expression in presence of marjoram extract compared with the control. The findings from this study document a novel molecular inhibitory activity of marjoram against P. multocida multiple virulence genes and provide a proof of concept for its implementation as an alternative candidate for the treatment of pasteurellosis in farm animals in future., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Araucaria angustifolia extract (AAE) is a polyphenol-rich extract that has gained interest as a natural anticancer agent. Recent work suggests that AAE induces oxidative damage and apoptosis through its action on decreasing complex I activity of the mitochondrial Electron Transport Chain (ETC)., Aims and Methods: In the present study, we aimed to further examine the specific targets by which AAE exerts proapoptotic effects in HEp-2 cancer cells. Specifically, the effect of AAE on the: 1) levels of pyruvate dehydrogenase was assessed by ELISA assay; 2) levels of mitochondrial ETC complexes, focusing on complex I at the gene transcript and protein level relevant to ROS generation was evaluated by multiplex ELISA followed by qRT-PCR and immunoblotting; 3) mitochondrial network distribution analysis was assessed by MitoTracker Red CMXRos; and 4) chemical variations on DNA was evaluated by dot-blotting in HEp-2 cells., Results: Results demonstrated that AAE increased protein levels of PDH, switching energy metabolism to oxidative metabolism. Protein expression levels of complex I and III were found decreased in AAE-treated HEp-2 cells. Analyzing the subunits of complex I, changes in protein and gene transcript levels of NDUFS7 and NDUFV2 were found. Mitochondria staining after AAE incubation revealed changes in the mitochondrial network distribution. AAE was able to induce DNA hypomethylation and decreased DNA (cytosine-5)-methyltransferase 1 activity., Conclusion: Our data demonstrate for the first time that AAE alters expression of NDUFS7 and NDUFV2 mitochondrial subunits and induce epigenetic changes in HEp-2 cancer cells leading to a possible suppression of oncogenes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Toxoplasmosis is a worldwide parasitic disease responsible for serious health problems to human. The currently available drugs used for toxoplasmosis treatment showed a limited efficacy and cause serious host toxicity. The in vitro screening for toxoplasmicidal activity of Araucaria heterophylla resin (AHR) extract and its major component 13-epi-cupressic acid (CUP) showed that both AHR (EC 50  = 3.90) and CUP (EC 50  = 3.69) have high toxoplasmicidal activity in comparison with standard cotrimoxazole (EC 50  = 4.28). The antiprotozoal effects of AHR and CUP were investigated against acute and chronic toxoplasmosis using mice models. Two groups of Swiss albino mice were infected by RH Toxoplasma strain intraperitoneally and by Me49 strain orally. Both groups were treated with AHR and CUP in different doses. Their effects were evaluated by survival rate, peritoneal, spleen and liver parasite burdens, brain cyst burden, NO serum level and histopathological lesions. The ultrastructural changes of tachyzoites of acutely infected mice were studied using scanning electron microscopy (SEM). There is an evidence of toxoplasmicidal activity of AHR and CUP in acute and chronic experimental toxoplasmosis. In the acute model, mice treated with AHR and CUP showed prolonged survival rates, a significant decrease in the parasite density in peritoneal lavage and pathological insult in both liver and spleen compared with that of untreated ones. SEM results denote evident morphological alterations of treated tachyzoites. In chronic experimental toxoplasmosis, AHR and CUP treated groups could significantly reduce brain cyst burden by 96.05% and 98.02% respectively. This study indicates that AHR and CUP showed potent toxoplasmicidal activities experimentally and could be used as a potential natural nontoxic agent for treatment of toxoplasmosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Plant exine capsules are natural microscale capsules that are highly physically robust and chemically resilient. They are extracted from pollen grains and plant spores, and can be used as renewable and safe microcapsules for encapsulation applications. Herein, we report the successful evacuation of natural sunflower pollen grains (SPGs) and Lycopodiastrum casuarinoides spore exine capsules (SECs) and investigated the effects of different loading methods on the encapsulation and release of nobiletin, a model hydrophobic nutraceutical. The compositional and morphological characterizations of SPGs and SECs obtained by the developed extraction protocol confirmed that the inside contents had been removed and hollow pollen cavities were obtained successfully. In addition, coumarin-6, a hydrophobic fluorescent probe, was encapsulated into SPGs and SECs, which proved the possibility of using them to encapsulate hydrophobic nutraceuticals. Furthermore, controlled release in simulated digestive fluids (SDF) was achieved by coating calcium alginate onto the outside of the SPGs and SECs. Looking forward, this may provide an effective and potential delivery model to protect loads from degradation in the stomach and achieve pH-responsive delivery of hydrophobic nutraceuticals after oral administration.

Food by-products containing bioactive substances have attracted attention due to the possibility of adding values to residues of the food industry. In this work, the extraction of phenolic compounds from pinhão seed coats (Araucaria angustifolia (Bertol.) Kuntze) using a central composite rotatable design was applied to obtain prediction models for the extract volume yield, total phenolic content, total phenolic acids and total flavonoids. Principal component analysis and hierarchical cluster analysis were implemented showing an evident poor effect of the temperature on phenolic compounds extraction, which is in accordance with the prediction model obtained by the experimental design for total phenolic acids. Volume yield presented a high positive correlation with extraction temperature, followed by solvent composition. Scanning electron microscopy showed that higher temperatures and lower ethanol percentages resulted in highly defibrillated pinhão coats that retained more extract after the extraction process, leading to lower volume yield percentages., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ultra-high performance liquid chromatography (UHPLC) coupled with diode array detection (DAD) was applied to improve separation and detection of mono- and bis-glucosyl esters of crocetin (crocins), the main red-colored constituents of saffron ( Crocus sativus L.), and other polar components. Response surface methodology (RSM) was used to optimise the chromatographic resolution on the Kinetex C18 (Phenomenex) column taking into account of the combined effect of the column temperature, the eluent flow rate and the slope of a linear eluent concentration gradient. A three-level full-factorial design of experiments was adopted to identify suitable combinations of the above factors. The influence of the separation conditions on the resolutions of 22 adjacent peaks was simultaneously modelled by a multi-layer artificial neural network (ANN) in which a bit string representation was used to identify the target analytes. The chromatogram collected under the optimal separation conditions revealed a higher number of crocetin esters than those already characterised by means of mass-spectrometry data and usually detected by HPLC. Ultra-high performance liquid chromatography analyses carried out on the novel Luna Omega Polar C18 (Phenomenex) column confirmed the large number of crocetin derivatives. Further work is in progress to acquire mass-spectrometry data and to clarify the chemical structure to the newly found saffron components.

Puerarin is an isoflavonoid extracted from Pueraria lobata roots, and displays a broad range of pharmacological activities, including antidiabetic activity. However, information about the pharmacokinetics of puerarin in diabetics is scarce. This study was conducted to investigate the difference in pharmacokinetic effects of puerarin in normal rats and rats with diabetes mellitus (DM), and the mechanism involved. DM was induced by a combined high-fat diet (HFD) and streptozotocin (STZ) injection. Plasma concentrations of puerarin in DM, HFD, and control rats were determined after intravenous (20 mg/kg) and oral administration (500 mg/kg) of puerarin, and pharmacokinetic parameters were estimated. The messenger RNA (mRNA) and protein expression levels of Ugt1a1 and Ugt1a7 in rat livers and intestines were measured using qRT-PCR and western blot, respectively. The area under the concentration⁻time curve and the clearance of puerarin in the DM rats statistically differed from those in the control rats ( p <0.05) with both administration routes. The hepatic and intestinal gene and protein expressions of Ugt1a1 and Ugt1a7 were significantly increased in the DM rats ( p <0.05). Therefore, the metabolic changes in diabetes could alter the pharmacokinetics of puerarin. This change could be caused by upregulated uridine diphosphate (UDP)-glucuronosyltransferase activity, which may enhance puerarin clearance, and alter its therapeutic effects.

Pseudomonas aeruginosa is an opportunistic pathogen implicated in nosocomial infections for which no vaccines have been approved. Larrea divaricata Cav. (Jarilla) is a widely spread plant in America and it is used in folk medicine to treat several pathologies. It has also been shown that antibodies elicited against Jarilla proteins of crude extract (JPCE) cross-react with proteins from gram-negative bacteria. In this study we aim to assess the contribution of anti-JPCE antibodies in the opsonophagocytosis of P. aeruginosa by murine macrophages. Levels of reactivity of anti-JPCE IgG and IgA antibodies against cell and membrane proteins suggest that these proteins induce a response that could favor opsonic bacterial recognition, which is important for the elimination of bacteria on mucous membranes, useful in the early stages of infection. Opsonophagocytosis assays also show that these antibodies could favor bacteria intake. These results together with previous observations that indicate that anti-JPCE antibodies are able to neutralize P. aeruginosa enzymes point L. divaricata proteins as candidates for vaccine development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study describes the first antibiofilm and antibacterial screening for plants from Caatinga against Ralstonia solanacearum, a causal agent of bacterial wilt that presents serious difficulties in control. There were prepared 22 aqueous extracts of plants collected in the Vale do Catimbau-PE, Brazil. The potential antibacterial activity was evaluated by absorbance in OD 600 and the antibiofilm activity through the crystal violet method, both of them performed in microplate against isolates of R. solanacearum biofilm formers. The results of the screening showed that Jacaranda rugosa presented antimicrobial activity higher than 90%, while Harpochilus neesianus and Myroxylon peruiferum presented antibiofilm activity higher than 50% for all tested isolates. However, Croton heliotropiifolius showed both the activities, being thus very promising for application in the control of this phytopathogen. The search for viable alternatives to the development of new bioactive compounds safe for the environment, humans, and animals from an adverse and scarce environment such as the Caatinga and encouraged us to find plants that produce effective metabolites against phytopathogenic microorganisms. This in vitro screening is important to guide the development of new products in addition to guide research studies of bioactive compounds.

In recent years, considerable attention has been given to plant colorants for use in dyeing applications because of their newly discovered properties such as insect repellency, deodorizing, antioxidant, sun protection, and antibacterial activity. In view of their better biocompatibility, biodegradability, less-toxicity, natural colorants are gaining worldwide interest for producing elegant hues and highly functional value-added textiles. In the present work, we investigated the coloring and functional finishing of wool with Tectona grandis L. leaves extract with the emphasis on effect of metallic salt mordants on colorimetric potential, fastness, radical scavenging potential, and antibacterial activity in an attempt to develop bioactive fibres for use in health care applications. The pretreatment of wool with ferrous sulfate, potassium aluminium sulfate and stannous chloride provided a significant enhancement in CIELa*b* parameters and fastness properties. Antioxidant tests showed that the control dyed wool had excellent radical scavenging activity than mordanted samples. In addition, metal mordants particularly ferrous sulfate enhanced the durability of antibacterial efficacy to several laundering cycles. It can be concluded that the extract of Tectona grandis may be developed as multifunctional finishing agent to impart simultaneous color, antioxidant and antibacterial properties to wool based fabrics., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Herb-drug interaction (HDI) limits clinical application of herbs and drugs, and inhibition of herbs towards uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) has gained attention as one of the important reasons to cause HDIs. Sauchinone, an active lignan isolated from aerial parts of Saururus chinensis (Saururacease), possesses anti-oxidant, anti-inflammatory, and anti-viral activities. In pharmacokinetics of sauchinone, sauchinone is highly distributed to the liver, forming extensive metabolites of sauchinone via UGTs in the liver. Thus, we investigated whether sauchinone inhibited UGTs to explore potential of sauchinone-drug interactions. In human liver microsomes (HLMs), sauchinone inhibited activities of UGT1A1, 1A3, 1A6, and 2B7 with IC 50 values of 8.83, 43.9, 0.758, and 0.279 μM, respectively. Sauchinone also noncompetitively inhibited UGT1A6 and 2B7 with K i values of 1.08 and 0.524 μM, respectively. In in vivo interaction study using mice, sauchinone inhibited UGT2B7-mediated zidovudine metabolism, resulting in increased systemic exposure of zidovudine when sauchinone and zidovudine were co-administered together. Our results indicated that there is potential HDI between sauchinone and drugs undergoing UGT2B7-mediated metabolism, possibly contributing to the safe use of sauchinone and drug combinations., Competing Interests: The authors declare no conflicts of interest.

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones-3-hydroxy-1,2,6,7,8-pentamethoxy xanthone ( A ) and 6- O -β-d-glucopyranosyl-1,7-dimethoxy xanthone ( C )-together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity. Furthemore, 14 xanthones as XO inhibitors were selected to develop three-dimensional quantitative structure-activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The CoMFA model predicted a q² value of 0.613 and an r² value of 0.997. The best CoMSIA model predicted a q² value of 0.608 and an r² value of 0.997 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active XO inhibitors., Competing Interests: The authors declare no conflict of interest.

Green synthesis of gold (CB-AuNps) and silver (CB-AgNps) nanoparticles using Cibotium barometz root extract was highlighted. CB-AuNps were synthesized almost instantly and CB-AgNps were formed after 25 min in a heated aqueous extract. The formation of CB-AuNps and CB-AgNps was detected at 548 and 412 nm; they were spherical with crystallite sizes of 6 nm and 23 nm, respectively. CB-AgNps were further investigated for their antimicrobial activity against Escherichia, Staphylococcus aureus, Salmonella enterica, and Pseudomonas aeruginosa. Furthermore, scavenging activity against 1,1-diphenyl-2-picrylhydrzyl (DPPH) free radicals was demonstrated. Lastly, the cytotoxic properties of CB-AuNps and CB-AgNps were explored in murine macrophages (RAW264.7) cells and MCF-7 breast cancer cells. This study demonstrated the prospective biomedical applications of CB-AuNps and CB-AgNps as antioxidant, antimicrobial agents, and drug-delivery agents.

Our previous study reported that the fruit of Gordonia axillaris , an edible wild fruit, possessed strong antioxidant activity. In this study, a microwave-assisted extraction (MAE) method was established to extract antioxidants from the fruit of Gordonia axillaris . The influence of five parameters, including ethanol concentration, solvent/material ratio, extraction time, extraction temperature and microwave power, was investigated by single-factor experiments. Three factors, namely ethanol concentration, solvent/material ratio, extraction time, were found to exert a major influence on extraction efficacy, and were further studied by response surface methodology to investigate their interactions. Ethanol concentration of 36.89%, solvent/material ratio of 29.56 mL/g, extraction time of 71.04 min, temperature of 40 &#176;C, and microwave power of 400 W were found to be the optimal condition. The TEAC value was 198.16 &#177; 5.47 µmol Trolox/g DW under the optimal conditions, which was in conformity to the predicted value (200.28 µmol Trolox/g DW). In addition, the MAE method was compared with two conventional methods (Soxhlet extraction and maceration extraction). Results showed that the antioxidant capacity of the extract obtained by MAE method was stronger than that obtained by maceration (168.67 &#177; 3.88 µmol Trolox/g DW) or Soxhlet extraction (114.09 &#177; 2.01 µmol Trolox/g DW). Finally, several phenolic compounds in the extract were identified and quantified by UPLC-MS/MS, which were rutin, gallic acid, protocatechuic acid, epicatechin, epicatechin gallate, 2-hydrocinnamic acid, p -coumaric acid, quercetin, chlorogenic acid and ferulic acid., Competing Interests: The authors declare no conflict of interest.

This work reports the phytochemical analysis of the ethanolic extract obtained from the leaves of Agathis robusta (C. Moore ex F. Muell.) F.M. Bailey. The methodology utilised during this study comprised classical chromatographic and spectroscopic techniques. Six compounds were identified: agathisflavone (1), 7″-O-methyl-agathisflavone (2), cupressuflavone (3), rutin (4), shikimic acid (5) and (2S)-1,2-Di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-β-d-galactopyranosyl glycerol (6). These belong to four major classes of natural compounds: bi-flavonoids (1-3); diglycosidic flavonoids (4); cycloexen-carboxylic acids (5); glycerol-glycolipids (6). To the best of our knowledge, compounds (3-6) were identified for the first time in this study as constituents of A. robusta. Anyway, the majority of these compounds has chemotaxonomic relevance and is mostly in accordance with the current botanical classification of this species. Moreover, they also present several pharmacological properties among which, the antibacterial, anti-inflammatory and protective ones are the most important and may explain why this species is used in the ethno-medicinal field.

Ionic liquids (ILs) based ultrasonic-assisted extract has been applied for the extraction of essential oil from Persicaria minor leaves. The effects of temperature, sonication time, and particle size of the plant material on the yield of essential oil were investigated. Among the different ILs employed, 1-ethyl-3-methylimidazolium acetate was the most effective, providing a 9.55% yield of the essential oil under optimum conditions (70 ℃, 25 min, IL:hexane ratio of 7:10 (v/v), particle size 60-80 mesh). The performance of 1-ethyl-3-methylimidazolium acetate in the extraction was attributed to its low viscosity and ability to disintegrate the structural matrix of the plant material. The ability of 1-ethyl-3-methylimidazolium acetate was also confirmed using the conductor like-screening model for realistic solvents. This research proves that ILs can be used to extract essential oils from lignocellulosic biomass.

The association of herbal products with standard antimicrobial drugs has recently gained more attention as a hope to overcome infectious diseases caused by multidrug-resistant microorganisms. Here, we investigated for the first time the antimicrobial (antifungal and antibacterial) activity of ethanolic and aqueous extracts of R. echinus against multiresistant strains of bacteria (E. coli, P. aeruginosa and S. aureus) and fungi (C. albicans, C. krusei and C. tropicalis), as well as potential to enhance the activity of antibiotics drugs. In addition, both extract were chemically characterized and their toxicity was assessed in Artemia salina. Our results demonstrate that aqueous extract of R. echinus caused a significant increase in the activity of antibiotics gentamicin and imipenem, while the ethanolic extract strongly enhanced the antibiotic activity of gentamicin, amikacin, imipenem and ciprofloxacin against P. aeruginosa. However, neither the ethanolic nor the aqueous extracts significantly affect the antibiotic activity of the drugs when tested against S. aureus. Phytochemical analysis of the extracts indicated ellagic acid, caffeic acid and chlorogenic acid as the major components which can be at least in part responsible for the enhanced activity of antibiotics. None of the extracts showed toxicity in A. salina even at the highest concentration tested (1000 μg/mL). All together, our results suggest that the leaf extract of R. echinus can be an effective source of modulating agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The present study was focused on the preparation of gold, silver, and gold-silver-alloy nanoparticles using Rhodomyrtus tomentosa acetone extract (RAE). The synthesized nanoparticles showed the surface plasmon resonance absorption peak corresponding to gold and silver nanoparticle. However, Au-Ag-Alloy nanoparticles showed the single peak between the peaks of AuNPs and AgNPs. TEM observation ascertained the shape and size of nanoparticles. FTIR results indicated the involvement of RAE for the synthesis and capping of nanoparticles. Study on antibacterial activity demonstrated the enhanced activity of RAE capped on silver and Au-Ag-Alloy nanoparticles against Escherichia coli., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study was carried out with the objective to investigate the antibacterial activity of Hertia cheirifolia L. extracts against Gram-positive and Gram-negative strains including Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Bacillus licheniformis, Esherichia coli (ATCC 8739), Pseudomonas aeruginosa (ATCC 9027), Salmonella enterica (CIP 8039) and Salmonella typhimirium. The results of this antibacterial screening showed that the ethyl acetate (EtOAc) extracts had the best activity against the tested microorganisms. A bioassay-oriented fractionation approach for the more active extract (roots ethyl acetate extract) led to the obtaining five sub-fractions. Furthermore, these sub-fractions were also tested for antimicrobial activity and the best results were obtained for the roots EtOAc sub-fraction (C) with MICs values between 0.039 and 0.156 mg/mL. Reversed-phase high performance liquid chromatography (RP-HPLC) analysis indicated that the major phenolic components of active (EtOAc) extracts and sub-fraction (C) are fisetin hydrate (82.06%), trans cinnamic acid (63.66%), gallic acid (38.97%) and myricetin (20.92%). These results may help to improve these natural antibacterial substances that could serve as selective agents for bacterial diseases., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose metabolism. Here, we demonstrated that shizukaol F, a natural compound isolated from Chloranthus japonicus, can activate AMPK and modulate glucose metabolism both in vitro and in vivo. Shizukaol F increased glucose uptake in differentiated C2C12 myotubes by stimulating glucose transporter-4 (GLUT-4) membraned translocation. Treatment of primary mouse hepatocytes with shizukaol F decreased the expression of phosphoenolpyruvate carboxykinase 2 (PEPCK), glucose-6-phosphatase (G6Pase) and suppressed hepatic gluconeogenesis. Meanwhile, a single oral dose of shizukaol F reduced gluconeogenesis in C57BL/6 J mice. Further studies indicated that shizukaol F modulates glucose metabolism mainly by AMPKa phosphorylation activity. In addition, we also found that shizukaol F depolarizes the mitochondrial membrane and inhibits respiratory complex I, which may result in AMPK activation. Our results highlight the potential value of shizukaol F as a possible treatment of metabolic syndrome.

Stems are the important residues of Trapa quadrispinosa Roxb., which are abundant in phenolic compounds. Ultrasonic-assisted enzymatic extraction (UAEE) is confirmed as a novel extraction technology with main advantages of enhancing extraction yield and physiological activities of the extracts from various plants. In this study, UAEE was applied to obtain the highest yield of phenolic content, strongest antioxidant, and antitumor activities and to optimize the extraction conditions using response surface methodology (RSM). The extracts from the stems of T. quadrispinosa were characterized by determination of their antioxidant activities through 2,2-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazxyl (DPPH) radical scavenging, total antioxidant capacity (TAC), ferric reducing antioxidant capacity (FRAC) methods and of their antitumor activity by MTT method. The selected key independent variables were cellulase concentration ( X ₁: 1.5%-2.5%), extraction time ( X ₂: 20-30 min) and extraction temperature ( X ₃: 40-60 °C). The optimal extraction conditions for total phenolic content (TPC) value of the extracts were determined as 1.74% cellulase concentration, 25.5 min ultrasonic extraction time and 49.0 °C ultrasonic temperature. Under these conditions, the highest TPC value of 53.6 ± 2.2 mg Gallic acid equivalent (GAE)/g dry weight (DW) was obtained, which agreed well with the predicted value (52.596 mg GAE/g·DW. Furthermore, the extracts obtained from UAEE presented highest antioxidant activities through ABTS, DPPH, TAC and FRAC methods were of 1.54 ± 0.09 mmol Trolox equivalent (TE)/g·DW; 1.45 ± 0.07 mmol·TE/g·DW; 45.2 ± 2.2 mg·GAE/g·DW; 50.4 ± 2.6 μmol FeSO₄ equivalent/g·DW and lowest IC 50 values of 160.4 ± 11.6 μg/mL, 126.1 ± 10.8 μg/mL, and 178.3 ± 13.1 μg/mL against Hela, HepG-2 and U251 tumor cells, respectively. The results indicated that the UAEE was an efficient alternative to improve extraction yield and enhance the antioxidant and antitumor activities of the extracts. The phenolic extracts from the stems of T. quadrispinosa had significant antioxidant and antitumor activities, which could be used as a source of potential antioxidant and antitumor agents.

Oxidative stress is a crucial factor in diabetes, where the abnormal metabolic ambience leads to hyperglycemia resulting in the onset of several vascular complications. Under homeostasis, innate antioxidants efficiently inhibit the oxidative stress, thereby restrain further progression of diabetes. In the present study, a potential antioxidant marker was identified from hepatic tissue of diabetic Wistar rats after oral administration of biogenic gold nanoparticles (GNPs). Diabetic animals treated with GNPs showed increase in insulin level and subsequently reduced the concentration of blood glucose level to normal. Further, GNPs favoured to retain the hepatic enzymatic markers, serum lipid levels and followed by renal biochemical profile in the rats. In addition, GNPs treated rats displayed an elevated level of lipid peroxidation, superoxide dismutase, glutathione peroxidase, and catalase enzymatic activity. Consequently, GNPs treated rats showed diminished level of histological injury in the hepatic, renal, and pancreatic tissues. Taken together, these results suggested that among the several antioxidant enzymes, catalase elucidated the highest area under curve (AUC) with 0.80 accomplished by receiver operating characteristic (ROC) curve. Collectively, our findings enlighten that GNPs treated rat able to alleviate the hyperglycemic condition due to the enzymatic activity of catalase., (Copyright © 2017 Elsevier B.V. All rights reserved.)

High-speed countercurrent chromatography combined with preparative high-performance liquid chromatography was successfully used to separate seven phenolic compounds from Stenoloma chusanum Ching. A biphasic solvent system composed of hexane/ethyl acetate/methanol/water (1:2:1:2, v/v) was used for the first step high-speed countercurrent chromatography separation in elution-extrusion mode. A mobile phase composed of acetonitrile (18%) and pure water (82%) was used for further preparative high-performance liquid chromatography purification. In total, the combined separation yielded seven compounds, including 3,4-dihydroxy benzoic acid, 3,4-dihydroxy benzaldehyde, esculetin, caffeic acid, syringic acid, luteolin, and apigenin, at a purity of over 90%. Esculetin was separated from Stenoloma chusanum Ching for the first time. The results suggest that the proposed combination method is a useful strategy for separating compounds from complex samples., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pierisketolide A (1) and pierisketones B and C (2 and 3), three diterpenes with an unusual A-homo-B-nor-ent-kaurane carbon skeleton, were isolated from the roots of Pieris formosa. Their structures were characterized by a series of spectroscopic methods, X-ray diffraction, and electronic circular dichroism (ECD). Pierisketolide A (1) exhibited an analgesic effect with a 45% writhe inhibition rate at a dose of 10.0 mg/kg. The plausible biosynthetic pathways of 1-3 are proposed.

Stauntonia hexaphylla (Thunb.) Decne. (Lardizabalaceae) leaves (SHL) have been used traditionally as analgesics, sedatives, diuretics, and so on, in China. To date, no data have been reported on the inhibitory effect of SHL and its constituents on rat lens aldose reductase (RLAR) and advanced glycation end products (AGEs). Therefore, the inhibitory effect of compounds isolated from SHL extract on RLAR and AGEs was investigated to evaluate potential treatments of diabetic complications. The ethyl acetate (EtOAC) fraction of SHL extract showed strong inhibitory activity on RLAR and AGEs; therefore, EtOAc fraction (3.0 g) was subjected to Sephadex LH-20 column chromatography, for further fractionation, with 100% MeOH solvent system to investigate its effect on RLAR and AGEs. Phytochemical investigation of SHL led to the isolation of seven compounds. Among the isolated compounds, chlorogenic acid, calceolarioside B, luteolin-3'- O - β -D-glucopyranoside, quercetin-3- O - β -D-glucopyranoside, and luteolin-7- O - β -D-glucopyranoside exhibited significant inhibitory activity against RLAR with IC 50 in the range of 7.34-23.99  μ M. In addition, 3-(3,4-dihydroxyphenyl) propionic acid, neochlorogenic acid, and luteolin-3'- O - β -D-glucopyranoside exhibited the most potent inhibitory activity against formation of AGEs, with an IC 50 value of 115.07-184.06  μ M, compared to the positive control aminoguanidine (820.44  μ M). Based on these findings, SHL dietary supplements could be considered for the prevention and/or treatment of diabetes complication., Competing Interests: The authors have declared that there is no conflict of interests.

The leaves of Cyclosorus extensa are used in the preparation of rice beer in Assam, India. The optimal conditions of time and temperature of fermentation for extraction of bioactive compounds from the dried leaves were obtained using response surface methodology. The central composite rotatable design was used and 13 experimental runs based on two-factor-five-level design were generated and performed for each of the solvents. The independent variables were extraction time (12 and 48 h) and temperature (25 and 55°C). The responses studied were total polyphenol content, radical scavenging activity, antibacterial activity, and antifungal activity. The analysis of variance of the test data was performed and the sequential sum of squares, F-value, R 2 , and adjusted R 2 were deduced. The predicted models for all the response variables were adequately fitted to the observed experimental data (p ≤ 0.001). The maximum extraction of bioactive compounds under the optimum conditions of extraction temperature and time for hexane, ethyl acetate, methanol, and distilled water were found to be 25°C for 29.43 h, 28.28°C for 41.27 h, 43.95°C for 29.61 h, and 55.00°C for 48.00 h, respectively. It was also observed that the solubility of the polyphenols was higher in methanol, followed by ethyl acetate, and the highest antibacterial activity against Escherichia coli was shown by the ethyl acetate extracts.

Phytochemicals present in vegetables, fruits, and herbs are believed to reduce the risk of several major diseases including cardiovascular or neurodegenerative disorders. The roots of the fern Helminthostachys zeylanica (L.) Hook. (Ophioglossaceae) have been used for centuries in the treatment of inflammation and as a folk medicine in several countries. The plant has been shown to possess an array of medicinal properties, including antioxidants and anti-inflammatory activities. Moreover, a rising level of matrix metalloproteinase-9 (MMP-9) has been found in blood fluid of these patients suffering from brain inflammatory diseases, which may be considered an inflammatory biomarker in several inflammatory diseases including the central nervous system (CNS) inflammation. Previously, we have demonstrated the signaling mechanisms of bradykinin (BK)-induced MMP-9 expression in brain astrocytes. Herein, we evaluate the effects of H. zeylanica extracts on BK-induced MMP-9 expression in brain astrocytes and its influencing mechanism. The results showed that H. zeylanica extracts, including E0, E1, and E2 significantly reduce MMP-9 induced by BK in brain astrocytes (RBA-1 cells). These H. zeylanica extracts can inhibit BK-stimulated phosphorylation of c-Src, Pyk2, and PKC(α/δ). Moreover, BK-stimulated NADPH oxidase (Nox)-derived reactive oxygen species (ROS) generation has also been attenuated by pretreatment with these extracts, suggesting that the H. zeylanica extracts have an antioxidative activity. We further demonstrated that the H. zeylanica extracts blocked activation of MAPKs (e.g., ERK1/2 and p38 MAPK) by BK. These data indicated that the H. zeylanica extracts may be has anti-inflammatory activity by reducing BK-induced ROS-dependent MMP-9 expression via these related pathways in brain astrocytes.

Background: Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae., Methods: Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting., Result: Active fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 μg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA., Conclusion: Our findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.

Objective: Toona sinensis leaf extract (TSL) has been shown to have anti-tumor effects on cancer cell lines. This study aimed to investigate the chemopreventive potential and the underlying mechanism of TSL during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis., Methods: One hundred hamsters were divided into control (n=30), carcinogenic (n=20), preventive (n=42), and therapeutic (n=8) groups. The animals in carcinogenic and preventive groups were administered reverse osmosis water (carcinogenic group) or TSL (1g/kg bw) (preventive group) by gavage daily for 4 weeks, and their bilateral pouches were painted with a 0.5% DMBA solution for 4, 9, and 12 weeks. The animals in the therapeutic group were treated with DMBA for 12 weeks prior to TSL administration for 4 weeks. Expression levels of survivin, X chromosome-linked inhibitor of apoptosis (XIAP), proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins were analyzed by immunohistochemistry. Apoptotic activity was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, cytochrome C, and poly (ADP-ribose) polymerase (PARP)., Results: In the preventive group, the results showed significant decreases not only in the incidences of squamous cell carcinoma (SCC) (50%) and epithelial dysplasia (62.5%) but also in the tumor number, tumor volume, tumor burden, and the severity of dysplastic lesions. The down-regulation of survivin, XIAP, PCNA, iNOS, and COX-2 proteins and the increased apoptotic activity indicated anti-proliferative and apoptosis-inducing abilities of TSL on DMBA-induced HBP carcinogenesis., Conclusions: The results suggested that TSL might be a promising candidate for the prevention of oral cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Torilis japonica extract (TJE) has been reported to possess diverse medicinal properties including anti‑inflammatory and antibacterial activities. However, the precise mechanism of its anticancer effect is not understood. Thus, we evaluated the apoptotic effects of TJE and examined its underlying molecular mechanisms in HCT116 colorectal cancer cells. Our results show that TJE induces apoptosis through the generation of intracellular reactive oxygen species (ROS), and that it regulates the mitochondrial outer membrane potential via the AMPK/p38 MAPK signaling pathway. Importantly, ~50% of cancer cells have p53 mutations. Thus, the ability to induce apoptosis in a p53-independent manner would be of great value in cancer treatment. Our results show that not only does TJE regulate the AMPK/p38 signaling pathway, but it induces apoptosis in cells in which p53 has been knocked down using siRNA. Moreover, as in in vitro studies, TJE induced apoptosis and regulated apoptosis related-proteins in an HCT 116 xenograft model. Taken together, our results demonstrate that TJE, a natural compound that may provide a substitute for chemotherapeutic drugs, has potential as an anticancer agent.

Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.