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Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

This study aimed to apply a quantitative microbial risk assessment (QMRA) model to estimate the annual risk probability of Salmonella infection associated with the consumption of crops, which were irrigated with raw wastewater abstracted by farmers without official permission. Data generated from the model were used to propose realistic standards for Salmonella in irrigation water needed for safe crop production. Results demonstrated the presence of total coliforms, fecal coliforms, fecal streptococci, and Salmonella in wastewater samples. Salmonella was recorded on lettuce and spinach in 3 different harvesting events, although it was not found in data obtained for parsley plant. The QMRA scenario included surface irrigation, consumption of raw crops, and 1-day withholding period before harvest. The annual risk probability of Salmonella infection for consumers exceeded the target tolerable risk (7.7 × 10 -4 ) for investigated crops. The Pearson's correlation coefficient between different annual risk probabilities showed significant correlation (p < 0.05). The levels of risk posed from spinach and lettuce were roughly similar, although they tended to be higher for lettuce. The optimum concentrations of Salmonella in irrigation water needed to satisfy the World Health Organization guidelines of disease burden (disability-adjusted life years 10 -6 ) per person per year ranged from 34 to 119 via multiple-tube fermentation technique/100 mL, for spinach and lettuce plants, respectively. The study concluded that unofficial reuse of wastewater in irrigation is a principle route for crop contamination. Water quality monitoring programs should be integrated with QMRA investigations for better estimation of risk level. The fit parameters used could be tailored to cover a wide array of local situations in different countries. Models applied for viruses, helminths, and bacteria other than Salmonella are encouraged in future studies. Integr Environ Assess Manag 2020;16:353-361. © 2019 SETAC., (© 2019 SETAC.)

Ethnopharmacological Relevance: various extracts of Moringa oleifera Lam. leaves, were reported to possess antiobesity effect in experimental animals models, yet its active doses and mechanism of action are still unclear., Materials and Methods: The metabolic profiling of 70% ethanol extract of M. oleifera (MO) leaves was performed using HPLC-MS/MS analysis. The antiobesity activity of MO was tested in high fat diet induced obesity in rats at 200 and 400 mg/kg body weight orally for 1 month. Total cholesterol (TC), high density lipoproteins (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGs), insulin resistance, insulin sensitivity, and adipose tissue index were monitored. In addition, fatty acid synthase (FAS) and HMG-CoA reductase mRNA from liver tissue, Peroxisome Proliferator-Activated Receptor alpha (PPARα) and Melanocortin-4 receptor (MC4R) RNA from adipose tissue were quantified using qRT-PCR. MO hard gelatin capsules (400 mg/capsule) were formulated and standardized using HPLC-RP analysis and tested on fifteen female participants, aged 45-55 with a BMI of 29-34 kg/m 2 ., Results: Thirteen metabolites were tentatively identified using HPLC-MS/MS analysis including flavonols, flavones and a phenolic acid. MO 400 showed a prominent effect on reducing the rats' final weights, % weight increase and adiposity index (P < 0.05). Glucose, insulin and HOMA-IR were significantly reduced and R-QUICKI was significantly increased by MO 400 (P < 0.001). Mean tissue level of leptin and vaspin were significantly reduced, adiponectin, omentin and GLUT-4 expression were increased significantly by MO 400 (P < 0.01). MO 400 significantly suppressed FAS and HMG-CoA reductase and increased mRNA expression of MC4R and PPAR-α (P < 0.01). Eight weeks administration of MO hard gelatin capsules to obese patients showed significant reduction of the average BMI, TC and LDL compared to the baseline values (p < 0.05)., Conclusion: Our results presented a scientific evidence for the traditional use of M. oleifera leaves as antiobesity herbal medicine., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ficus deltoidea var. deltoidea Jack (FD) is a well-known plant used in Malay folklore medicine to lower blood glucose in diabetic patients. For further research of the antihyperglycemic mechanisms, the protein tyrosine phosphatase 1B (PTP1B)-inhibitory effect of FD was analysed both in vitro and in vivo. To optimise a method for FD extraction, water, 50, 70, 80, 90 and 95 % ethanol extracts were prepared and determined for their total phenolic and triterpene contents, and PTP1B-inhibition capacity. Among the tested extracts, 70 % ethanol FD extract showed a significant PTP1B inhibition (92·0 % inhibition at 200 µg/ml) and high phenolic and triterpene contents. A bioassay-guided fractionation of the 70 % ethanol extract led to the isolation of a new triterpene (3β,11β-dihydroxyolean-12-en-23-oic acid; F3) along with six known compounds. In vivo , 4 weeks' administration of 70 % ethanol FD extract (125, 250 and 500 mg/kg/d) to streptozotocin-nicotinamide-induced type 2 diabetic rats reversed the abnormal changes of blood glucose, insulin, total Hb, GLUT2, lipid profile, and oxidative stress in liver and pancreas. Moreover, FD reduced the mRNA expression of the key gluconeogenic enzymes (phosphoenolpyruvate carboxykinase and glucose 6-phosphatase) and restored insulin receptor and GLUT2 encoding gene ( Slc2a2 ) expression. In addition, FD significantly down-regulated the hepatic PTP1B gene expression. These results revealed that FD could potentially improve insulin sensitivity, suppress hepatic glucose output and enhance glucose uptake in type 2 diabetes mellitus through down-regulation of PTP1B. Together, our findings give scientific evidence for the traditional use of FD as an antidiabetic agent., (© The Author(s) 2020.)

Plant-derived natural products have long been considered a valuable source of lead compounds for drug development. Natural extracts are usually composed of hundreds to thousands of metabolites, whereby the bioactivity of natural extracts can be represented by synergism between several metabolites. However, isolating every single compound from a natural extract is not always possible due to the complex chemistry and presence of most secondary metabolites at very low levels. Metabolomics has emerged in recent years as an indispensable tool for the analysis of thousands of metabolites from crude natural extracts, leading to a paradigm shift in natural products drug research. Analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are used to comprehensively annotate the constituents of plant natural products for screening, drug discovery as well as for quality control purposes such as those required for phytomedicine. In this review, the current advancements in plant sample preparation, sample measurements, and data analysis are presented alongside a few case studies of the successful applications of these processes in plant natural product drug discovery., Competing Interests: The authors declare no conflict of interest.

Phyllanthus niruri L. is a widespread tropical plant which is used in Ayurvedic system for liver and kidney ailments. The present study aims at specifying the most active hepatoprotective extract of P. niruri and applying a bio-guided protocol to identify the active compounds responsible for this effect. P. niruri aerial parts were extracted separately with water, 50%, 70% and 80% ethanol. The cytoprotective activity of the extracts was evaluated against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cells. Bioassay-guided fractionation of the aqueous extract (AE) was accomplished for the isolation of the active compounds. Antioxidant activity was assessed using DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and ferric reducing antioxidant power (FRAP). The in vivo hepatoprotective activity of AE was evaluated in CCl4-induced hepatotoxicity in rats at different doses after determination of its LD50. Pretreatment of clone-9 and Hepg2 with different concentrations of AE (1, 0.1, 0.01 mg/ml) had significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) against CCl4 injures, and restored the activity of the natural antioxidants; glutathione (GSH) and superoxide dismutase (SOD) towards normalization. Fractionation of AE gave four fractions (I-IV). Fractions I, II, and IV showed a significant in vitro hepatoprotective activity. Purification of I, II and IV yielded seven compounds; corilagin C1, isocorilagin C2, brevifolin C3, quercetin C4, kaempferol rhamnoside C5, gallic acid C6, and brevifolin carboxylic acid C7. Compounds C1, C2, C5, and C7 showed the highest (p< 0.001) hepatoprotective potency, while C3, C4, and C6 exhibited a moderate (p< 0.001) activity. The AE exhibited strong antioxidant DPPH (IC50 11.6 ± 2 μg/ml) and FRAP (79.352 ± 2.88 mM Ferrous equivalents) activity. In vivo administration of AE in rats (25, 50, 100 and 200 mg/kg) caused normalization of AST, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total cholesterol (TC), triglycyrides (TG), total bilirubin (TB), glucose, total proteins (TP), urea and creatinine levels which were elevated by CCl4. AE also decreased TNF-α, NF-KB, IL-6, IL-8, IL10 and COX-2 expression, and significantly antagonizes the effect of CCl4 on the antioxidant enzymes SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GSP). The histopathological study also supported the hepatoprotective effect of AE. P. niruri isolates exhibited a potent hepatoprotective activity against CCl4-induced hepatotoxicity in clone-9 and Hepg2 cell lines through reduction of lipid peroxidation and maintaining glutathione in its reduced form. This is attributable to their phenolic nature and hence antioxidative potential., Competing Interests: Natural Wellness Biotech organization provided support in the form of research materials. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Chemical structures derived from marine foods are highly diverse and pharmacologically promising. In particular, chitooligosaccharides (COS) present a safe pharmacokinetic profile and a great source of new bioactive polymers. This review describes the antioxidant, anti-inflammatory, and antidiabetic properties of COS from recent publications. Thus, COS constitute an effective agent against oxidative stress, cellular damage, and inflammatory pathogenesis. The mechanisms of action and targeted therapeutic pathways of COS are summarized and discussed. COS may act as antioxidants via their radical scavenging activity and by decreasing oxidative stress markers. The mechanism of COS antidiabetic effect is characterized by an acceleration of pancreatic islets proliferation, an increase in insulin secretion and sensitivity, a reduction of postprandial glucose, and an improvement of glucose uptake. COS upregulate the GLUT2 and inhibit digestive enzyme and glucose transporters. Furthermore, they resulted in reduction of gluconeogenesis and promotion of glucose conversion. On the other hand, the COS decrease inflammatory mediators, suppress the activation of NF- κ B, increase the phosphorylation of kinase, and stimulate the proliferation of lymphocytes. Overall, this review brings evidence from experimental data about protective effect of COS., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Ilias Marmouzi et al.)

Dioscorea species, known as "Yams," belong to family Dioscoreaceae . This genus consists of more than 600 species distributed from Africa, Asia, the Caribbean's South America, and the South Pacific islands. Their organoleptic properties make them the most widely used carbohydrate food and dietary supplements. The underground and/or aerial tubers represent valuable sources of proteins, fats, and vitamins for millions of people in West Africa. This review gives a shot of secondary metabolites of Dioscorea plants, including steroids, clerodane diterpenes, quinones, cyanidins, phenolics, diarylheptanoids, and nitrogen-containing compounds. This review collected the evidence on biological properties of description Dioscorea , including in-vitro and in-vivo studies. Dioscorea species contain promising bioactive molecules i.e. diosgenin that support their different biological properties, including antioxidant, hypoglycaemic, hypolipidemic, anti- antimicrobial, inflammatory, antiproliferative, androgenic, estrogenic, and contraceptive drugs. Indeed, besides its nutrient values, Dioscorea is a potential source of bioactive substances of interest in the prevention/treatment of several diseases, and thus represents a great challenge in developing countries. However, ethnomedicinal potential should be validated and further researches on pharmacological properties and phytochemical composition should be carried out. Particularly, doing some studies to convert the preclinical results to clinical efficacy should be guaranteed. Dioscorea, Food plant, Traditional use, Phytochemistry, Pharmacological activities.

Symphytum species belongs to the Boraginaceae family and have been used for centuries for bone breakages, sprains and rheumatism, liver problems, gastritis, ulcers, skin problems, joint pain and contusions, wounds, gout, hematomas and thrombophlebitis. Considering the innumerable potentialities of the Symphytum species and their widespread use in the world, it is extremely important to provide data compiling the available literature to identify the areas of intense research and the main gaps in order to design future studies. The present review aims at summarizing the main data on the therapeutic indications of the Symphytum species based on the current evidence, also emphasizing data on both the efficacy and adverse effects. The present review was carried out by consulting PubMed (Medline), Web of Science, Embase, Scopus, Cochrane Database, Science Direct and Google Scholar (as a search engine) databases to retrieve the most updated articles on this topic. All articles were carefully analyzed by the authors to assess their strengths and weaknesses, and to select the most useful ones for the purpose of review, prioritizing articles published from 1956 to 2018. The pharmacological effects of the Symphytum species are attributed to several chemical compounds, among them allantoin, phenolic compounds, glycopeptides, polysaccharides and some toxic pyrrolizidine alkaloids. Not less important to highlight are the risks associated with its use. In fact, there is increasing consumption of over-the-counter drugs, which when associated with conventional drugs can cause serious and even fatal adverse events. Although clinical trials sustain the folk topical application of Symphytum species in musculoskeletal and blunt injuries, with minor adverse effects, its antimicrobial potency was still poorly investigated. Further studies are needed to assess the antimicrobial spectrum of Symphytum species and to characterize the active molecules both in vitro and in vivo ., Competing Interests: The authors declare no conflict of interest.

Ethnopharmacological Relevance: Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus are the most famous varieties of netted muskmelon or cantaloupe in Egypt. Cantaloupe has a great reputation as an anti-inflammatory drug for hot inflammation of liver, cough, eczema, and kidney disorders such as ulcers in the urinary tract, and our objective was to confirm this use scientifically., Materials and Methods: Inflammation was induced in adult male Sprague Dawley rats by subcutaneous injection of 0.05 ml of carrageenan (1% solution in saline) into the plantar surface of the right hind paw 30 min after oral pretreatment of the rats with 95% ethanolic extracts of Cucumis melo var. cantalupensis peels (CCP) and pulps (CCU) and Cucumis melo var. reticulatus peels (CRP) and pulps (CRU) at doses of 25 and 50 mg/kg. Indomethacin (10 mg/kg) was used as a standard drug. The effect of the tested samples was measured on the oedema volume, as well as PGE-2, TNF-α, IL-6 and IL-1β levels. Metabolic profiling of the extracts was performed using UPLC-MS/MS analysis., Results: Pretreatment of rats with the ethanol extract of the pulps and peels of the two varieties at doses of 25 and 50 mg/kg significantly inhibited the carrageenan-induced increase in the oedema volume of the rat paws after 3 h, except for the low dose of the French cantaloupe pulp. CRP at 50 mg/kg caused the most significant reductions in both TNF-α (P < 0.05) and IL-1β (P < 0.001) levels, while CCP caused the most significant reductions in PGE-2 and IL-6 (P < 0.05) levels. Increases in PGE-2, TNF-α, IL-6 and IL-1β levels were also significantly prevented by indomethacin (10 mg/kg). UPLC-MS/MS facilitated the identification of 44 phenolic compounds, including phenolic acids and flavonoids., Conclusion: This is the first report of the chemical and biological study of the peels of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus., (Copyright © 2019. Published by Elsevier B.V.)

Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power for men. Metabolic profiling of the aqueous extract of E. longifolia (AEEL) using UPLC-MS/MS in both positive and negative modes allowed the identification of seventeen metabolites. The identified compounds were classified into four groups: quassinoids, alkaloids, triterpenes, and biphenylneolignans. AEEL is considered safe with oral LD 50 cut-off >5000 mg/kg. Oral administration of 50, 100, 200, 400, or 800 mg/kg of AEEL for 10 consecutive days to Sprague-Dawley male rats caused significant reductions in mounting, intromission, and ejaculation latencies and increased penile erection index. AEEL increased total body weight and relative weights of seminal vesicles and prostate. Total and free serum testosterone and brain cortical and hippocampal dopamine content was significantly elevated in treated groups with no significant effects on serotonin or noradrenaline content.

Background. Eurycoma longifolia Jack (Fam.: Simaroubaceae), known as Tongkat Ali (TA), has been known as a symbol of virility and sexual power. The aim of the study was to screen E. longifolia aqueous extract (AE) and isolates for ROCK-II inhibition. Results. The AE (1-10 μ g/ml) showed a significant inhibition for ROCK-II activity (62.8-81%) at P < 0.001 with an IC 50 (651.1 ± 32.9 ng/ml) compared to Y-27632 ([(+)-( R )- trans -4-(1-aminoethyl)- N -(4-pyridyl)cyclohexanecarboxamide dihydrochloride]) (68.15-89.9 %) at same concentrations with an IC 50 (192 ± 8.37 ng/ml). Chromatographic purification of the aqueous extract (AE) allowed the isolation of eight compounds; stigmasterol T1 , trans- coniferyl aldehyde T2, scopoletin T3 , eurycomalactone T4 , 6 α - hydroxyeurycomalactone T5 , eurycomanone T6 , eurycomanol T7 , and eurycomanol-2- O - β -D-glucopyranoside T8 . This is the first report for the isolation of T1 and T3 from E. longifolia and for the isolation of T2 from genus Eurycoma . The isolates (at 10 μ g/ml) exhibited maximum inhibition % of ROCK-II 82.1 ± 0.63 (T2), 78.3 ± 0.38 (T6), 77.1 ± 0.11 (T3), 76.2 ± 3.53 (T4), 74.5 ± 1.27 (T5), 74.1 ± 2.97 (T7), 71.4 ± 2.54 (T8), and 60.3 ± 0.14 (T1), where the newly isolated compound trans- coniferyl aldehyde T2 showed the highest inhibitory activity among the tested isolated compounds and even higher than the total extract AE. The standard Y-27632 (10 μ g/ml) showed 89.9 ± 0.42 % inhibition for ROCK-II activity when compared to control at P < 0.0001. Conclusion. The traditional use of E. longifolia as aphrodisiac and for male sexual disorders might be in part due to the ROCK-II inhibitory potential.

Hepatocellular carcinoma (HCC) is progressively increasing tumor with lack of accurate prognosis and inadequate systemic treatment approaches. Solanum sp. (such as Solanum melongena) is a folk herb which is reported to possess anticancer properties. In a continuity for our interest in pursuing the anticancer activity of compounds isolated from the fruit peels of Solanum melongena, the HPLC profiling and ESI-MS assessment for the methanolic extract evidenced the presence of bioactive glycoalkaloids (solasonine, solasodine and solamargine). These glycoalkaloids were isolated, purified and proved to possess in vitro cytotoxicity against human liver cancer cell lines (Huh7 and HepG2). Herein, we investigated the potential mechanism of action of these compounds using DNA content flow-cytometry and apoptosis/necrosis differential anaylsis using annexin-V/FITC staining. Solasonine, solasodine and solamargine inducd significant antiproliferative effect against liver cancer cells (Huh7 and HepG2) which was attributed to cell cycle arrest at S-phase. Solamargine, solasodine and solasonine induced significant apoptosis in Huh7 cells. Only solamargine-induced cell cycle arrest, was reflected as apoptotic cell killing effect against HepG2 cells. In conclusion, glycoalkaloids derived from Solanum melongena and particularly, solamargine are promising antiproliferative agents with potential anticancer effects.

Diabetes mellitus (DM) is a chronic metabolic disease with high morbimortality rates. DM has two types: type 1, which is often associated with a total destruction of pancreatic beta cells, and non-insulin-dependent or type 2 diabetes mellitus (T2DM), more closely associated with obesity and old age. The main causes of T2DM are insulin resistance and/or inadequate insulin secretion. Protein-tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling pathways and plays an important role in T2DM, as its overexpression may induce insulin resistance. Thus, since PTP1B may be a therapeutic target for both T2DM and obesity, the search for novel and promising natural inhibitors has gained much attention. Hence, several marine organisms, including macro and microalgae, sponges, marine invertebrates, sea urchins, seaweeds, soft corals, lichens, and sea grasses, have been recently evaluated as potential drug sources. This review provides an overview of the role of PTP1B in T2DM insulin signaling and treatment, and highlights the recent findings of several compounds and extracts derived from marine organisms and their relevance as upcoming PTP1B inhibitors. In this systematic literature review, more than 60 marine-derived metabolites exhibiting PTP1B inhibitory activity are listed. Their chemical classes, structural features, relative PTP1B inhibitory potency (assessed by IC 50 values), and structure⁻activity relationships (SARs) that could be drawn from the available data are discussed. The upcoming challenge in the field of marine research-metabolomics-is also addressed.

Athyrium plants consist of more than 230 species that are largely distributed in the Sino-Himalayan region and the Western Pacific islands. Athyrium species are being used in traditional medicine worldwide to treat various ailments such as cough, rheumatic pain, scorpion stings, sores, burns and scalds, intestinal fever, pain, specifically breast pain during child birth, to increase milk flow, as an antiparasitic, anthelmintic, and carminative. A deep look in the literature has revealed that Athyrium species have been poorly investigated for their food preservative applications and in vivo and in vitro biological and phytochemical studies. However, some Athyrium species have demonstrated antimicrobial, anti-inflammatory, antioxidant, antiproliferative and anti-HIV potential. Athyrium multidentatum (Doll.) Ching is the most investigated species and the biological activities of their extracts, such as they antioxidant properties, seem to be related to the sulfate contents of their polysaccharides. This review provides an update on the ethnopharmacology, phytochemistry and biological properties of Athyrium plants that might be useful for further research. Of course, well-designed clinical trials will be required for some species to be used as therapy.

One-pot synthesis of a new magnetic disinfectant was achieved through the polymerization of thiourea and formaldehyde in the presence of magnetite nanoparticles (MTUF). The obtained magnetic chelating resin was loaded with Ag(I) ions. This material was tested as a disinfectant for water pathogenic microorganism's deactivation. The toxicity of MTUF before and after Ag(I) loading was estimated. The antimicrobial activity tests of MTUF-Ag were carried out against Escherichia coli, Salmonella Typhimurium, and Pseudomonas aeruginosa as examples of Gram-negative bacteria; Listeria monocytogenes, Staphylococcus aureus, Enterococcus faecalis, and Bacillus subtilis as examples of Gram-positive bacteria; and Candida albicans as representative for fungi. The results showed that the minimum inhibitory dosage (MID) of MTF-Ag against Escherichia coli, Salmonella Typhimurium, Listeria monocytogenes, Staphylococcus aureus, and mixed culture were 1.5, 2.0, 1.0, 1.5, and 1.5 mg/mL, respectively, after 40 min of contact time. While C. albicans was more resistant to the magnetic disinfectant, only three log reductions were done at 2.5 mg/mL. The studied MTUF-Ag was successfully tested for water and wastewater pathogenic microorganism's deactivation. It can be concluded that MTUF-Ag could be a good candidate for water disinfection.

Few studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells' (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo , hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-β1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (α-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro , GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC 50 = 45 and 19 μg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo , GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-β1 level, α-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction.

Ethnopharmacological Relevance: Ginger (Zingiber officinale Roscoe) is a well known anti-inflammatory drug in the Egyptian, Indian and Chinese folk medicines, yet its mechanism of action is unclear., Aim of the Study: To explore its mechanism of action and to correlate it to its biophytochemicals., Materials and Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated using protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated using carrageenan-induced rat paw edema in rats at doses 25, 50, 100 and 200mg/kg b.wt., Results: All the tested extracts showed significant (p< 0.1) in vitro anti-inflammatory activities. The strongest anti-lipoxygenase activity was observed for AE that was more significant than that of diclofenac (58% and 52%, respectively) at the same concentration (125μg/ml). Purification of AE led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G1, G2 and G8 exhibited potent activity in all the studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw edema in a dose-dependent manner. AE (at 200mg/kg) showed significant reduction in production of PGE2, TNF-α, IL-6, monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES), myeloperoxidase (MPO) activity by 60%, 57%, 60%, 41%, 32% and 67%, respectively. AE at 100 and 200mg/kg was equipotent to indomethacin in reduction of NO x level and in increasing the total antioxidant capacity (TAC). Histopathological examination revealed very few inflammatory cells infiltration and edema after administration of AE (200mg/kg) prior to carrageenan., Conclusions: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. This was evidenced by the dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenishment the total antioxidant capacity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The objective of our study is to highlight the therapeutic effect and mechanism of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich fraction exerts its anticancer activity on a human breast cancer cell line (T47D) and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH's of six flaxseed cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed the most significant cytotoxic activity against ER-receptor positive breast cell lines MCF7 and T47D with IC 50 13.8 and 15.8 µg/ml, respectively. Moreover, PFH-G9 reduced the expression of the metastasis marker, 1-α, metalloproteinases and vascular endothelial growth factor (VEGF), one of the most potent stimulators of angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO) or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites carcinoma (EAC) resulted in reducing the tumor volume, the expression of estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced expression of caspase-3.

Schistosomiasis is the most noteworthy parasitic disease after malaria. Furthermore, the significant activity of the genus Solanum against Schistosoma worms and its intermediate host snails reinforced the study of Solanum seaforthianum Andr. (SS) and Solanum macrocarpon L. (SM) for their molluscicidal and schistosomicidal potentiality. In this study, different extracts, fractions and isolated compounds of both Solanum species are evaluated for the molluscicidal and schistosomicidal potentialities. The niclosamide was used as positive molluscicide control against Biomphalaria alexandrina snails. Different extracts, fractions, or isolated compounds were used at a concentration of 100 μg/ml and dead snails were counted in each case. On the other hand, washed and sterilized Schistosoma mansoni adult worms were used in three replicates, and three worm pairs were placed in each well with 2 ml test solution of 100 μg/ml concentration. Positive (praziquantel [PZQ] 0.2 ug/ml) and negative controls were concurrently used and examined daily for 3 days for viability. The mortality rate was calculated and then both LC 50 and LC 90 were determined in triplicates. Highest potency was indicated to total glycoalkaloid (TGA) fraction of SM followed by TGA of SS. On the other hand, TGA fractions of both species showed higher potency than other extracts and isolated compounds. Meanwhile, solasodine-free aglycone showed declined activity compared to its glycosides. Promising molluscicidal and schistosomicidal activities were displayed which are attributed to the glycoalkaloid content. Therefore, this study can efficiently contribute toward validation of the traditional use of SS and SM in schistosomiasis control., Summary: The current study evaluated the molluscicidal and schistosomicidal activities of different extracts and fractions of two Solanum species. The glycoalkaloids content depicted a promising activity against both the snails and the adult worms. Abbreviations Used: PZQ; Praziquantel, SM; Solanum macrocarpon , SS; Solanum seaforthianum , TGA; total glycoalkaloid., Competing Interests: There are no conflicts of interest.

We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC 50 of 68 ± 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G 2 /M regulators cyclin B 1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead.

Context: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are traditionally known for the treatment of hyperglycaemia. Several in vitro and in vivo studies proposed some mechanisms of action. However, clinical trials in human beings were never reported to date., Objectives: To investigate the antidiabetic efficacy of the 70% ethanol extract of the pericarps of B. aegyptiaca (BE) within a nutritional intervention in elderly people., Materials and Methods: Ultra-performance electrospray ionization-mass spectroscopy (UPLC-ESI-MS/MS) analysis was used for metabolic profiling of BE which was incorporated in hard gelatine capsules (400 mg/day) and tested on 30 type 2 diabetes (T2D) Egyptian patients for 8 weeks. According to sex, age and body mass index participants were divided into two equivalent groups, placebo and treatment., Results: Thirteen compounds were identified in BE using UPLC-ESI-MS/MS analysis among which five steroidal saponins, seven phenolic compounds and a sterol glucoside. At the end of the 8-week treatment, the treated group showed 26.88% decrease in 2 h postprandial plasma glucose relative to 2.6% increase in the placebo group, while fasting plasma glucose was reduced to 10.3%. Treatment with BE capsules for 8 weeks produced significant reduction in the plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol by 9.0, 12.76 and 21.35%, respectively, with 29.8% increase in the high-density lipoprotein cholesterol. Plasma alanine transaminase and aspartate transaminase were reduced by 42.6 and 43.3%, respectively., Discussion and Conclusion: Administration of the BE capsules to T2D resulted in significant improvements in the glycaemic markers and the lipid profile, without adverse effects or hypoglycaemia.

Context: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear., Objectives: Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds., Materials and Methods: A bio-guided protocol based on the evaluation of α-glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks., Results: Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-β-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3β,16β,20(R)-trio1-3-O-β-d-glucopyranoside; a furostanol saponin, (3) 26-(O-β-d-glucopyranosyl)-22-O-methylfurost-5-ene-3β,26-diol-3-O-β-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC 50  = 3.12 ± 0.17 and 1.04 ± 0.02 μg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively., Discussion and Conclusions: We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications.

Two wild-type (WT) Aspergillus strains, A. flavus HAk1 and A. oryzae HAk2, were selected for kojic acid (KA) biosynthesis. Malt extract sucrose culture medium (MES) was the best culture medium for maximum production of KA. The maximum production of KA has been estimated at pH 4 after 7 days of incubation at 30 °C. Overproduction of KA was attained by mutagenesis of both A. flavus HAk1 and A. oryzae HAk2 through their exposer to different doses of gamma irradiation. The mutant strains (MT) A. flavus HAk1-M2 and A. oryzae HAk2-M26 were the most stable mutants for maximum production of KA through four generations. Yield of KA by A. oryzae HAk2-M26 and A. flavus HAk1-M2 has been 2.03-fold and 1.9-fold, respectively, higher than their wild-type strains. All WT and MT strains were used for KA production from different agricultural raw materials. Apple peel was the best waste for KA production by WT strains of A. flavus and A. oryzae, while orange peel and rice stalk are best material for KA production by MT strains, A. flavus HAk1-M2 and A. oryzae HAk2-M26, respectively. All experimental strains have the ability to produce considerable amounts of KA from sugarcane molasse (SCM) and sugar-beet molasse (SBM). SBM was better than SCM for KA production by all strains. The antioxidant activity of biosynthesizing KA was strongly affected with production conditions, where the highest antioxidant activity of all strains was recorded at the optimum environmental and nutritional conditions for KA production.

Investigation of the ethanol extract of the corms of Liatris spicata (L.) willd led to the isolation of two sterols: stigmasterol and its 3-O-glucoside, a triterpene: obtusifoliyl acetate, two benzofurans: euparin and 6-hydroxy-3-methoxytremetone, three phenolic acids: protocatechuic, vanillic and ferulic acid and a sesquiterpene lactone igalan. The structures of the isolated compounds were established on the basis of physicochemical properties and spectral analysis (IR, EI/MS, 1 H NMR and 13 C NMR). The ethanol extract and its isolated compounds evidenced cytotoxic activities against human liver cancer cell line (HepG2), where igalan showed the highest potency (3.83 ± 0.043) μg/mL, its effect was comparable to that of the standard drug doxorubicin® (3.73 ± 0.036) μg/mL.

Objective: To investigate the antifibrotic role of rosmarinic acid (RA), a natural polyphenolic compound, on HSCs activation/proliferation and apoptosis in vitro and in vivo., Methods: The impact of RA on stellate cell line (HSC-T6) proliferation, activation and apoptosis was assessed along with its safety on primary hepatocytes. In vivo, rats were divided into: (i) normal; (ii) thioacetamide (TAA)-intoxicated rats for 12 weeks; (iii) TAA + silymarin or (iv) TAA + RA. At the end of experiment, liver functions, oxidative stress, inflammatory and profibrogenic markers, tissue inhibitor metalloproteinases type-1 (TIMP-1) and hydroxyproline (HP) levels were evaluated. Additionally, liver histopathology and immunohistochemical examinations of alpha-smooth muscle actin (α-SMA), caspase-3 and proliferation cellular nuclear antigen (PCNA) were determined., Results: RA exhibited anti-proliferative effects on cultured HSCs in a time and concentration dependent manner showing an IC 50 of 276 μg/mL and 171 μg/mL for 24 h and 48 h, respectively, with morphological reversion of activated stellate cell morphology to quiescent form. It significantly improved ALT, AST, oxidative stress markers and reduced TIMP-1, HP levels, inflammatory markers and fibrosis score (S1 vs S4). Furthermore, reduction in α-SMA plus elevation in caspase-3 expressions of HSCs in vitro and in vivo associated with an inhibition in proliferation of damaged hepatocytes were recorded., Conclusions: RA impeded the progression of liver fibrosis through inhibition of HSCs activation/proliferation and induction of apoptosis with preservation of hepatic architecture., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

The bioactive petroleum ether fraction of Verbesina encelioides, previously studied by the authors, was chosen for the isolation of antiprotozoal metabolites. Pseudotaraxasterol-3β-acetate (1), benzyl 2,6-dimethoxy benzoate (2), 16β-hydroxy-pseudotaraxasterol-3β-palmitate (3) and pseudotaraxasterol (4), in addition to β-sitosterol glucoside (5) and β-sitosterol galactoside (6) were isolated and identified based on one-dimensional and two-dimensional spectral analysis. This is the first report describing (3) and (6) in genus Verbesina. The isolated compounds were tested in vitro against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Cytotoxicity was evaluated on MRC-5 cells. Compound 1 showed moderate to weak activity against L. infantum T. brucei and P. falciparum and was inactive against T. cruzi. Compound 3 showed moderate activity against L. infantum, compound 4 revealed weak activity against T. cruzi, while 5 and 6 were inactive against all tested protozoa. All compounds were non-cytotoxic. The isolated constituents showed less antiprotozoal activity than the crude fraction.

Flaxseed ( Linum usitatissimum L.) is a multipurpose crop with health promoting potential. This study was undertaken to investigate the fatty acid profile and yield of fixed oil of six Egyptian flaxseed cultivars. The selected cultivars with the highest content of polyunsaturated fatty acids (PUFAs) (G9 and G10) were assessed for their antidepressant-like effect in rat model of postpartum depression (PPD) induced by hormone-simulated pregnancy followed by hormone withdrawal and compared to fluoxetine. As compared to control group, administration of G9 and G10 (270 mg/kg/day, p.o) for two weeks during the postpartum period can alleviate anxiety and depressive-like behaviors and biochemical changes in PPD-induced rats. This was confirmed by evaluation of anxiety-like behaviors (elevated plus maze, open field test, and forced swim test tests), in addition to biochemical analysis (brain monoamine oxidase-A, corticosterone level, proinflammatory cytokines, and hippocampal redox state). In conclusion, flaxseed oil of Egyptian cultivars G9 and G10 exhibited significant antidepressant-like effect in rat model of PPD without affecting locomotor activity. At the treatment doses, the antidepressant-like activity of Giza 9 oil is comparable to fluoxetine.

Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities., Objectives: To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyanin-rich extract of H. sabdariffa calyces (HSARE)., Materials and Methods: The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks) by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLC-qTOF-PDA-MS)., Results: The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAA-intoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma (INF-γ), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3 positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively., Discussion and Conclusion: HSARE revealed pronounced antioxidant and anti-inflammatory potential where SOD and INF-γ were significantly improved. HSARE possesses the added value of being more water-soluble and of natural origin with fewer side effects expected compared to silymarin.

As a part of ongoing investigation of Acokanthera oppositifolia (Lam.) Codd., four compounds were isolated from its seeds, a new compound; lup-20(29)-en-3β-O-(3'-β-hydroxy) palmitate (1), three known compounds; a triterpene; lupeol (2), a cardiac glycoside; acovenoside A (3) and a sterol; β-sitosterol (4). Their structures were investigated using 1D & 2D- 1 H and 13 CNMR spectroscopy. Antimicrobial potential of the compounds was evaluated against 10 microorganisms responsible for endocarditis. The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. The new compound (1) evidenced significant antibacterial activity especially aganist Pseudomonas aeruginosa with (MIC 7.81 μg/ml). Lupeol (2) exhibited remarkable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, Aspergillus fumigates and Candida albicans (MIC 3.9, 0.24 and 3.9 μg/ml, respectively). On the other hand, acovenoside A (3) inhibited the growth of Escherichia coli (MIC 0.98 μg/ml). We herein present the potential of A. oppositifolia as a cardioprotective agent against the microorganisms responsible for endocarditis.

Context: Solidago virgaurea L. (Asteraceae) is traditionally used as an anti-inflammatory for the treatment of various symptoms including cystitis. However, little is known concerning the constituents responsible for this activity and the mechanism of their action., Objective: To assess the anti-inflammatory activity of the phenolic-rich fraction of S. virgaurea aerial parts in rats, isolate and assess the activity of the major compounds present., Materials and Methods: An HPLC method was developed for the analysis of the phenolic-rich fraction (EtFr). The in vivo anti-inflammatory activity of the EtFr and four isolated compounds (at 25 and 50 mg/kg) were assessed in adult male rats using the carrageenan-induced rat paw oedema model. The levels of the pro-inflammatory cytokines (TNF-α and IL-1β) were measured using ELISA., Results: 3,5-O-Dicaffeoylquinic acid (1), 3,4-O-dicaffeoylquinic acid (2), 3,4,5-O-tricaffeoylquinic acid (3) and 4,5-O-dicaffeoylquinic acid (4) were isolated from EtFr. Compound 3 (50 mg/kg) showed a highly significant activity in inhibiting the oedema volume after 3 h (88% of the activity of indomethacin at 10 mg/kg). The EtFr and the isolated compounds largely inhibited the excessive production of the inflammatory mediators TNF-α and IL-1β., Discussion and Conclusion: This is the first report of 3,4,5-tri-O-caffeoylquinic acid (3) in Solidago species. The tricaffeoylquinic acid (3) showed a significantly higher activity than the other three dicaffeoylquinic acids (1, 2, 4) and indomethacin in reduction of TNF-α and IL-1β concentrations (8.44 ± 0.62 and 5.83 ± 0.57 pg/mL compared to 12.60 ± 1.30 and 52.91 ± 5.20 pg/mL induced by indomethacin, respectively).

Ocimum is a genus of considerable importance in traditional medicine worldwide. The goal of this study was to examine the anti-acetylcholinesterase activity of Ocimum essential oils and to correlate the activity with their chemical profiles using a metabolome based GC-MS approach coupled to chemometrics. Further, molecular docking was adopted to rationalize the activity of some essential oil isolates. Essential oil prepared from the four species O. basilicum, O. africanum, O. americanum, and O. minimum exhibited significant anti-acetylcholinesterase activity with (IC50 0.22, 0.175, 0.57 and 0.152 mg/mL, respectively) comparable to that of physostigmine (IC50 0.27 mg/mL). The phenylpropanoids (i.e. estragole) constituted the most dominant chemical group in O. basilicum (sweet basil) and O. minimum, whereas camphor (a ketone) was the most abundant in O. africanum and O. americanum. Supervised and unsupervised multivariate data analyses clearly separated O. africanum and O. americanum from other accessions, with estragole, camphor and, to less extent, β-linalool contributing to species segregation. Estragole was found the most active AchE inhibitor (IC50 0.337 µM) followed by cineole (IC50 2.27 µM), camphor (IC50 21.43 µM) and eugenol (IC50 40.32 µM). Molecular docking revealed that these compounds bind to key amino acids in the catalytic domain of AchE, similar to standard drugs.

The genus Aloe comprises over 400 species of flowering succulent plants. Aloe leaves are used in the treatment of asthma, gastrointestinal ulcers, cardiovascular disease, tumors, burns, and diabetes. They are rich in anthraquinones, such as aloin, aloe-emodin, chrysophanol, aloinoside A, and aloinoside B. The various species of Aloe show chemical and morphological similarity and diversity, which depend on the genotype and environmental conditions. In a continuity to our interest in the genus Aloe , this study targets the authentication of eight different Aloe species, Aloe vera (A 1 ) , Aloe arborescens (A 2 ) , Aloe eru (A 3 ) , Aloe grandidentata (A 4 ) , Aloe perfoliata (A 5 ), Aloe brevifolia (A 6 ) , Aloe saponaria (A 7 ), and Aloe ferox (A 8 ), grown in Egypt by using the technique of random amplified polymorphic DNA. Twelve decamer primers were screened in amplification with genomic DNA extracted from all species, of which five primers yielded species-specific reproducible bands. Out of 156 loci detected, the polymorphic, monomorphic, and unique loci were 107, 26, and 23, respectively. Based on a dendrogram and similarity matrix, the eight Aloe species were differentiated from each other and showed more divergence. Aloe species prevailed similarity coefficients of 54-70 % by which they could be classified into three major groups. Thus, this technique may contribute to the identification of these Aloe species that have great morphological similarity in the Egyptian local markets., (Georg Thieme Verlag KG Stuttgart · New York.)

The current study aimed to investigate the protective effect of the cardenolide glycoside acovenoside A (AcoA) against doxorubicin-induced cardiotoxicity in mice. AcoA was isolated from the pericarps of Acokanthera oppositifolia to chemical homogeneity and characterized by means of one- and two-dimensional nuclear magnetic resonance spectroscopy. AcoA exhibited relatively low toxicity in mice (LD50 = 223.3 mg/kg bw). Repeated administration of doxorubicin induced cardiotoxicity manifested by reduced activity of myocardial membrane-bound ion pumps and elevated serum biomarkers of myocardial dysfunction, oxidative stress, and inflammation. Pretreatment of doxorubicin-exposed mice with AcoA (11.16 or 22.33 mg/kg bw, i.p.) for 2 weeks after 2 weeks of combined administration of AcoA and doxorubicin protected the animals dose dependently against doxorubicin-induced cardiotoxicity as indicated by normalization of the levels of different myocardial markers of oxidative stress (malondialdehyde, nitric oxide, total antioxidant capacity, and cardiac glutathione), serum myocardial diagnostic marker enzymes (serum cardiac troponin T, creatine kinase isoenzyme MB, aspartate aminotransferase, and lactate dehydrogenase), and inflammatory markers (c-reactive protein, tumor necrosis factor-α, and interleukin-6), as well as myocardial Na(+)/K(+)-ATPase activity. These effects were attributed to the negative impact of AcoA on transcription factors nuclear factor κB and interferon regulatory factor 3/7. Thus acovenoside A might act as a cardioprotective agent to prevent doxorubicin-induced cardiotoxicity., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Phytochemical investigation of the flowering aerial parts of Asteriscus maritimus (L.) Less (Asteraceae) led to the isolation of a new compound: patuletin 7-O-β-D-[(2″'S) 6″(3″'-hydroxy-2″'-methyl-propanoyl)] glucopyranoside, together with five known metabolites; β-sitosterol 2, chlorogenic acid 3, P-hydroxy -methylbenzoate 4, luteolin 5 and protocatechuic acid 6. The structures of the isolated compounds were determined by comprehensive analyses of its 1D and 2D NMR, HRMS and compared with previously known analogues. The ethanolic extract of the flowering aerial parts of A. maritimus was found to be safe (LD50 = 4.6 mg/kg) and possess significant antioxidant and anti-inflammatory activities and this was in accordance with its high phenolic content (107.36 ± 0.051 mg GAE/g extract).

The anti-wrinkle activity of defatted rosemary extract (DER) was assessed, and its effect was optimized by encapsulation in transferosomes (TFs). DER was standardized to a rosmarinic acid content of 4.58 ± 0.023 mg% using reversed-phase high performance liquid chromatography (Rp-HPLC), and its components were identified by HPLC-diode array detection-tandem mass spectrometry. In vitro free radical scavenging assays showed DER had high free radical scavenging activity against 2,2-diphenyl-2-picryl hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and superoxide radicals. DER also inhibited bleaching of β-carotene with high Fe(III) and Fe(II) chelating ability. In vivo anti-wrinkle activities of topically applied DER (20, 50, and 100 mg) and a TF formulation (TF4, 20 mg of DER) were evaluated in UVB-irradiated mice using a wrinkle scoring method, metalloproteinase (MMP) expression, and histopathology. Among the nanovesicles, TF4 was the most deformable, and had an acceptable size and encapsulation efficiency and enhanced permeation of DER through rat skin compared with unencapsulated DER. DER (50 and 100 mg) and TF4 significantly inhibited MMP-2 and MMP-9 expression and improved wrinkle scores. DER and TF4 moderately decreased epidermal thickness without pigmentation. DER is a potent natural antioxidant for combating skin aging. Moreover, encapsulation of DER in TFs will enhance its skin permeation and anti-wrinkle activity.

Ocimum (sweet basil) is a plant of considerable commercial importance in traditional medicine worldwide as well as for the flavor and food industry. The goal of this study was to examine Ocimum extracts anti-acetylcholinesterase activity and to correlate the activity with their secondary metabolites profiles via a metabolome based ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) approach coupled to chemometrics. The metabolomic differences in phenolics from leaves derived from 4 Ocimum species: Ocimum basilicum, Ocimum africanum, Ocimum americanum and Ocimum minimum were assessed. Under optimized conditions, 81 metabolites were identified including 21 hydroxy cinnamic acids, 4 benzoic acid conjugates, 14C/O flavonoid conjugates, 2 alcohols, 5 acyl sugars, 4 triterpenes and 12 fatty acids. Several salviolanic acid derivatives including salviolanic acid A, B, C & I found in Salvia, were found in Ocimum herein for the first time. Unsupervised principal component analysis (PCA) and supervised orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were further used for comparing and classification of samples. A clear separation among the four investigated Ocimum species was revealed, with O. africanum samples found most enriched in hydroxy cinnamates conjugates (HC) and flavonoids. To the best of our knowledge, this is the first report for compositional differences among Ocimum leaves via a metabolomic approach revealing that among examined species O. africanum leaves present a better source of Ocimum bioactive metabolites. The anticholinesrase activity of examined species was further assessed with a potent IC50 values for O. americanum, O. africanum, O. basilicum ranging from 2.5 to 6.6mg/ml, whereas O. minimum was least active with IC50 of 31.4mg/ml. Furthermore, major HC i.e., caftaric, chlorogenic and rosmarinic acids identified in extracts via UPLC-MS analysis exhibited IC50 values of 24, 0.5 and 7.9mg/ml respectively, suggesting that HCs are likely to mediate for the anticholinesterase effect in Ocimum extracts., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Context: Despite the traditional use of Bergia ammannioides Henye ex Roth. (Elatinaceae) for the treatment of wounds in India, there is a scarcity of scientific data supporting this use., Objective: The objective of this study is to assess wound-healing potentiality of the plant, to study pharmacological activities that may contribute in eliminating wound complications, and to investigate the biologically active fractions., Material and Methods: The ethanolic extract (EtOH) of the aerial parts was fractionated to obtain n-hexane (HxFr), chloroform (ClFr), ethyl acetate (EtFr), and n-butanol (BuOH) fractions. EtOH and its fractions were formulated in strength of 5 and 10% w/w ointment and tested for wound-healing activity using the excision model. The topical anti-inflammatory, in vitro antioxidant, and antibacterial activities were evaluated. HxFr and EtFr were chemically investigated to isolate their constituents., Results: Application of EtOH, HxFr, and EtFr (10% w/w ointments) leads to 71.77, 85.62, and 81.29% healing of the wounds with an increase in the collagen content. HxFr had the strongest anti-inflammatory (64.5% potency relative to Voltaren®) and antibacterial activity (MIC = 104 μg/ml against Staphylococcus aureus), while EtFr showed the strongest antioxidant activity against DPPH, ABTS(•+), and super oxide radical with an IC50 value of 10.25 ± 0.01, 66.09 ± 0.76, and 167.33 ± 0.91 µg/ml, respectively. β-Sitosterol, lupeol, cyclolaudenol, and cycloartenol were isolated from HxFr. Quercetin, ellagic acid, kaempferol-3-O-α-l-rhamnoside, and quercetin-3-O-α-l-rhamnoside were isolated from EtFr., Discussion and Conclusion: Our study presents scientific evidence for the efficacy of B. ammannioides in enhancing wound healing, and the first isolation of cyclolaudenol and cycloartenol from Bergia.

Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens., Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood., Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section., Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.

The present study attempts to explore the phytochemical constituents of different extracts from Cynara cornigera and Cichorium endivia plant materials. The two species studied are native in Egypt. Five different solvents, viz., aqueous, methylene chloride, petroleum ether, ethyl acetate, and n-butanol were used. Phytochemical analysis revealed the presence of phenols, flavonoids, sterols (stigmasterol and beta-sitosterol), terpenes (α-amyrin, ursolic and oleanolic acid), and hydrocarbons (n-alkane), the latter found in low amount. The ethyl acetate and water extracts of C. cornigera root showed lower mass fractions of phenolic compounds ranged from 20 to 81 g/100 g, and higher amounts in ethyl acetate extract of the inflorescences and butanol extract of the root where values ranged from 195 to 399 g/100 g. The β-sitosterol and stigmasterol were present in all plant extracts. Oleanolic and ursolic acids were detected in roots, leaves and inflorescences of C. cornigera and in C. endivia shoot. The ethyl acetate extracts from C. cornigera leaf and inflorescence attained higher chemical diversity than the other extracts. Alternatively, sterols and triterpenes were the major constituents. The high chemical diversity of active constituents justifies the future potential use of the two species at commercial level.

α-Glucosidase inhibitors (AGIs) represent a class of oral antidiabetic drugs that delay the absorption of ingested carbohydrates, reducing the postprandial glucose and insulin peaks to reach normoglycaemia. In this study, a bioassay-guided fractionation of the ethanolic extract of the aerial parts of Achillea fragrantissima (Forssk.) Sch. Bip. growing in Egypt led to the isolation of a new potent AGI; acacetin-6-C-(6″-acetyl-β-D-glucopyranoside)-8-C-α-L-arabinopyranoside (5) alongside with four known compounds: chondrillasterol (1), quercetin-3,6,7-trimethyl ether (chrysosplenol-D) (2), isovitexin-4'-methyl ether (3) and isovitexin (4). The structure of the new compound (5) was elucidated on the basis of its spectral data, including HR-FAB-MS, UV, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC. The new compound (5) exhibited the most significant α-glucosidase inhibitory activity (IC₅₀ 1.5 ± 0.09 μg/mL). Under the assay conditions, all the tested compounds were more potent than the positive control acarbose (IC50 224 ± 2.31 μg/mL).

Pd(MME)Cl2 complex (MME = methionine methyl ester) was synthesised and characterized by physicochemical measurements. The reaction of [Pd(MME)(H2O)2](2+) with amino acids, peptides, or dicarboxylic acids was investigated at 25°C and 0.1 M ionic strength. Amino acids and dicarboxylic acids form 1 : 1 complexes. Peptides form both 1 : 1 complexes and the corresponding deprotonated amide species. The stability of the complexes formed was determined and the binding centres of the ligands were assigned. Effect of solvent on the stability constant of Pd(MME)-CBDCA complex, taken as a representative example, shows that the complex is more favoured in a medium of low dielectric constant. The concentration distribution diagrams of the complexes were evaluated.

Applying a bioactivity-guided isolation strategy for the ethanolic extract of crown gall tumours induced on an Eucalyptus tereticornis tree, two new compounds in addition to a known one were isolated. The new compounds were identified as an amino acid derivative named 1-ethyl-6-(1'-methyl-1'-phenylethyl) piperidin-2-one (1) and a lanostane tetracyclic triterpene named 3beta-hydroxy-24-methyllanosta-8,17(20),24(28)-trien-22-oic acid (2), together with stigmasterol-3-O-glucoside (3). The three compounds exhibited significant cytotoxic activity against two human cell lines, breast (MCF7) and colon (HCT116), with IC50 values of 1.01, 1.54, and 2.15 microg/ml, respectively, against MCF7 and 3.49, 3.83, and 3.39 microg/ ml, respectively, against HCT116. Furthermore, in rats elevated levels of blood cholesterol, triglycerides, and low-density lipoprotein (LDLc) were significantly reduced, while the level of high-density lipoprotein (HDLc) was significantly increased by administration of the ethanolic extract as well as of 3. These results support a correlation between the reduction of blood cholesterol levels and improvement of colorectal cancer.

The sulforhodamine B (SRB) assay was used to assess the cytotoxicity of the aqueous (AqEx) and ethanolic (AlEx) extracts, respectively, of the aerial parts of Cleome droserifolia (Forssk.) Del. against two human cancer cell lines, breast (MCF7) and colon (HCT116) adenocarcinoma. AqEx exhibited higher cytotoxic activity, thus its four subfractions, namely n-hexane (HxFr), chloroform (ClFr), ethyl acetate (EtFr), and n-butanol (BuFr) fractions, were also tested. Purification of the more active ClFr and EtFr yielded nine compounds. Six terpenoids, guai-7(11),8-diene (C1), 1-hydroxy-guai-3,10(14)-diene (C2), 18-hydroxydollabela-8(17)-ene (C3), (24E)-stigmasta-5,8-dien-3beta-ol (C4), teucladiol [1alpha,5beta-guai-10(14)-ene-4beta,6beta-diol] (C5), and buchariol (4,10-epoxy-6a-hydroxyguaiane) (C6), were isolated from ClFr and three flavonol glycosides, isorhamnetin-3-O-beta-D-glucoside (F1), quercetin-3'-methoxy-3-O-(4"-acetylrhamnoside)-7-O-alpha-rhamnoside (F2), and kaempferol-4'-methoxy-3,7-O-dirhamnoside (F3), were isolated from EtFr. Compounds C3 and F2 are new in nature. The isolated compounds were identified using various spectroscopic methods (UV, IR, 1H NMR, 13C NMR, HMQC, HMBC, and COSY). Compounds C1, C3, F2, and F3 showed significant cytotoxic activities against the two tested cell lines comparable to those of the anticancer drug doxorubicin. The new compound C3 was the most active as it had the lowest IC50 values, (1.9 +/- 0.08) and (1.6 +/- 0.09) microg/ml corresponding to 6.5 and 5.4 microM, against MCF7 and HCT116 cells, respectively.

An investigation of the aqueous ethanolic extract (AE) of the aerial parts of Torilis radiata Moench yielded two triterpenes (lupeol acetate (1) and α-amyrin (2)), a sterol (spinasterol (3)) from its n-hexane fraction (HF), a flavone (acacetin (4)), a coumarin (scopoletin (5)), a phenolic acid (ferulic acid (6)) from the chloroform fraction (CF) and a flavone glycoside (luteolin-7-O-glucoside (7)) from the n-butanol fraction (BF). The hepatoprotection of the AE and its fractions was assessed in terms of the reduction in histological damage, accompanied by restoration of the liver enzymes (alanine amino transferase (ALT), aspartate amino transferase (AST), lactate dehydrogenase (LDH)), a reduction in the inflammatory markers (tumour necrosis-α (TNF-α), nitric oxide (NO), N-acetyl-β-D-glucosaminidase (NAG) and myloperoxidase (MPO) in serum) and restoration of the oxidant balance by decreasing the serum and hepatic malondialdehyde (MDA) levels, along with increasing the activity of hepatic catalase (CAT), glutathione peroxidase (GSHPx) and the non-enzymatic antioxidant glutathione (GSH).

A chemical study of the red type of the seeds of Eragrostis tef (Zucc.) Trotter (Poaceae) led to the isolation of seven compounds from its ethanol extract, namely β-sitosterol (1), β-amyrin-3-O-(2'-acetyl(glucoside (2), β-sitosterol-3-O-β-D-glucoside (3), naringenin (4), naringenin-4'-methoxy-7-O-α-L-rhamnoside (5), eriodictyol-3',7-dimethoxy-4'-O-β-D-glucoside (6) and isorhamnetin-3-O-rhamnoglucoside (7), which are reported for the first time in the genus Eragrostis. This is the first report for the isolation of compounds (2) and (6) in nature. The isolated compounds were identified using different spectroscopic methods (EIMS, UV, ¹H NMR, ¹³C NMR, HMQC and HMBC). A proximate analysis revealed the high nutritive value of the seeds: carbohydrates (57.27%), protein (20.9%), essential amino acids (8.15%) with major leucine and lysine (1.71 and 1.35%, respectively), vitamin B₁ (1.56 mg/100 g) and potassium and calcium (32.4 and 9.63%, respectively). The seeds yielded 22% w/w of fixed oil rich in unsaturated fatty acids (72.46%), among which oleic acid, was predominant (32.41%), followed by linolenic acid (23.83%). The ethanolic extract and fixed oil of the seeds exhibited anti-hyperlipedaemic and anti-hyperglycaemic activities. Oral administration of the fixed oil for 10 days resulted in a rise in serum calcium levels in rats.

The antidiabetic activities of the aqueous (AqEx) and ethanolic (AlEx) extracts of Cleome droserifolia (Forssk.) Del., were tested in cultured C2C12 skeletal muscle cells and 3T3-L1 adipocytes. An 18-h treatment with the AqEx increased basal glucose uptake by 33% [insulin equivalent (IE)=1.3±0.04] in muscle cells comparable to a 25.5% increase caused by 100 nM insulin (IE=1±0.03). Fractionation of the tested AqEx yielded hexane (HxFr), chloroform (ClFr) and ethyl acetate (EtFr) fractions which exerted 38, 52 and 35% increase in the glucose uptake corresponding to an IE of 1.5±0.06, 2.0±0.04 and 1.4±0.04, respectively. Only the ClFr and EtFr accelerated the triglyceride accumulation [rosiglitazone equivalent (RE) was 0.9±0.13 and 0.63±0.12, respectively] in pre-adipocytes undergoing differentiation comparably with 10 μM rosiglitazone. Six terpenoids (C1-C6) and three flavonol glycosides (F1-F3) were isolated from the active ClFr and EtFr, respectively, and identified. C5, C2 and C4 had an IE of 0.86±0.05, 1.01±0.04 and 0.9±0.08, while F1, F2 and F3 gave an IE of 1.3±0.05, 2.3±0.05 and 2.0±0.04, respectively. We could conclude that the reported antihyperglycemic activity of Cleome droserifolia is attributed to significant insulin-like effects in peripheral tissues, and that compounds F2 and F3, being highly active, could be used as bioactive markers to standardize the C. droserifolia herbal extract., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

A bioactivity-guided fractionation of the ethyl acetate fraction of the flowers of Onopordum alexandrinum L. (Asteraceae) yielded a new flavonoidal glycoside designated as acacetin-7-O-galacturonide (9), alongside with nine known flavonoids; 6-methoxy-apigenin (hispidulin) (1), acacetin (2), apigenin (3), luteolin (4), kaempferol (5), eriodictyol (6), apigenin-7-O-glucoside (7), luteolin-7-O-glucoside (8), and kaempferol-3-O-rutinoside (10). The compounds were assayed for their hepatoprotective activity against CCl4-induced hepatic cell damage in rats and free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 4, 6, 9, and 10 have not been previously reported from flowers of O. alexandrinum L., and this is the first report of acacetin-7-O-galacturonide (9) in nature which has also shown significant hepatoprotective and free radical scavenging effects. The isolated compounds were identified using different spectroscopic methods (UV, 1H NMR, 13C NMR, HMQC, HMBC, and COSY).

Different extracts of Nigella sativa L. seed waste; aqueous (AE) 200 mg/kg, ethanol 70% (EE) 250 mg/kg and hexane (HE) 10 mg/kg, were evaluated for their hepatoprotective activities. They were administered orally, once daily, for 5 consecutive days. On day 5, liver injury was induced in animals by a single i.p. injection of carbon tetrachloride (10 mg/kg b. w. of 0.25% (v/v). Hepatoxicity produced, was evaluated by both biochemical and histopathological investigations. The aqueous extract attenuated the CCl(4) -induced liver damage likely due to the decrease of proinflammatory cytokines and T-cell proliferation. This was noticed by a significant decrease in both serum and tissue cytokines; tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) and interlukin-beta (IL-1β), in the markers of liver functions; bilirubin and glutamic pyruvic transaminase (GPT) and in the oxidative stress markers; malondialdehyde (MDA) and glutathione content (GSH). Fractionation of this extract was performed and its component, protein, saponin, and polyphenol fractions were evaluated by appropriate analytical procedures. The crude protein of the seed waste reached 36.85% while protein fingerprint showed four bands ranging from 91.97 KD and 29.00 KD. The saponin content was evaluated through the determination of the haemolytic index and reached 15.56 mg/g dry powder. Finally, Folin Ciocalteu method was used for the determination of the total polyphenols. The same biochemical and histopathological studies were again performed on the different fractions of the aqueous extract; protein fraction (PF) 10 mg/kg, saponin fraction (SF) 5 mg/kg and polyphenol fraction (FF) 10 mg/kg. The biochemical changes were improved only by the protein fraction (PF) of the seed waste of Nigella sativa. This was manifested by a significant reduction in both serum and tissue cytokines in the liver markers and in the oxidative stress markers. Moreover, liver histopathology showed that (PF) reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis and fibrous connective tissue proliferation induced by CCl(4) in mice. From this study, it is concluded that the protein fraction of the aqueous extract of Nigella sativa seed waste exhibited a promising hepatoprotective effect in the management of different liver disorders., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Moringa peregrina is a wild plant that grown in the eastern desert mountains in Egypt. Although, this plant is native to Egypt, no details studies were traced on its chemical composition and biological activity., Materials and Methods: The different fractions of the ethanolic extract of the dried aerial parts of the plants were subjected to fractionation and purification on various silica and sephadex columns for the isolation of the major compounds which were tested for there anticancer activity. The aqueous and ethanolic extract as well as its different fractions were tested for antihyperglycemic effect on Streptozitocin-induced diabetes in rats., Results: Investigation of the different fractions of the ethanolic extract of the aerial parts of M. peregrina yielded lupeol acetate (1), β-amyrin (2), α-amyrin (3), β-sitosterol (4), β-sitosterol-3-O-glucoside (5), apigenin (6), rhamnetin (7), neochlorogenic acid (10), rhamnetin-3-O-rutinoside (12), and 6-methoxy-acacetin-8-C-β-glucoside (13) which were isolated for the first time from the plant. Compound (13) was isolated for the first time from genus Moringa. In addition, quercetin (8), chryseriol-7-O-rhamnoside (9) and quercetin-3-O-rutinoside (11) were also isolated. Identification has been established by spectral data (UV, MS, IR, 1H, 1H -1H COSY, and 13C-NMR). The major isolated compounds were found to have valuable cytotoxic activities against breast (MCF 7) and colon (HCT 116) cancer cell lines and their activities were comparable to the reference drug doxorubicin. On the other hand, the aqueous and ethanolic extracts as well as the n-hexane fraction were found to have potent antihyperglycemic effect on Streptozitocin-induced diabetes in rats., Conclusion: The Egyptian plant M. peregrina is rich in biologically active ingredients which showed potent cytotoxic activity and also its ethanolic extraxt exert a significant antihyperglycemic effect.