Design and synthesis of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs as bacterial peptide deformylase inhibitors

Herein, we report the synthesis and screening of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs 11(a–j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC₅₀ value = 139.28 μm ), 11g (IC₅₀ value = 136.18 μm ), and 11h (IC₅₀ value = 131.65 μm ) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36–167.26 μg/mL), 11g (MIC range = 93.75–145.67 μg/mL), and 11h (MIC range = 63.61–126.63 μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00–250.00 μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a–j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.     

Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells

Primary cells are ideal for in vitro toxicity studies since they closely resemble tissue environment. Here, we report a detailed study on the in vitro interactions of 7-20 nm spherical silver nanoparticles (SNP) with primary fibroblasts and primary liver cells isolated from Swiss albino mice. The intended use of silver nanoparticles is in the form of a topical antimicrobial gel formulation for the treatment of burns and wounds.Upon exposure to SNP for 24 h, morphology of primary fibroblasts and primary liver cells remained unaltered up to 25 μg/mL and 100 μg/mL SNP, respectively, although with minor decrease in confluence. IC₅₀ values for primary fibroblasts and primary liver cells as revealed by XTT assay were 61 μg/mL and 449 μg/mL, respectively. Ultra-thin sections of primary cells exposed to 1/2 IC₅₀ SNP for 24 h, visualized under Transmission electron microscope showed the presence of dark, electron dense, spherical aggregates inside the mitochondria, and cytoplasm, probably representing the intracellular SNP. When the cells were challenged with ∼ 1/2 IC₅₀ concentration of SNP (i.e. 30 μg/mL and 225 μg/mL for primary fibroblasts and primary liver cells, respectively), enhancement of GSH (∼ 1.2 fold) and depletion of lipid peroxidation (∼ 1.4 fold) were seen in primary fibroblasts which probably protect the cells from functional damage. In case of primary liver cells; increased levels of SOD (∼ 1.4 fold) and GSH (∼ 1.1 fold) as compared to unexposed cells were observed. Caspase-3 activity assay indicated that the SNP concentrations required for the onset of apoptosis were found to be much lower (3.12 μg/mL in primary fibroblasts, 12.5 μg/mL in primary liver cells) than the necrotic concentration (100 μg/mL in primary fibroblasts, 500 μg/mL in primary liver cells). These observations were confirmed by CLSM studies by exposure of cells to 1/2 IC₅₀ SNP (resulting in apoptosis) and 2× IC₅₀) cells (resulting in necrosis).These results clearly suggest that although silver nanoparticles seem to enter the eukaryotic cells, cellular antioxidant mechanisms protect the cells from possible oxidative damage. This property, in conjunction with the finding that primary cells possess much higher SNP tolerance than the concentration in the gel (∼ 20 μg/g), indicates preliminary safety of the formulation and warrants further study for possible human application.     

Valorisation of Salicornia ramosissima biowaste by a green approach – An optimizing study using response surface methodology

The purpose of this study was to optimize the extraction of antioxidants from Salicornia ramosissima by-product through Response Surface Methodology (RSM). The impacts of time (10–60 min) and temperature (40–80 °C) in total phenolic content (TPC) and antioxidant/antiradical activity were assessed. The optimal extract was attained at the binomial 80 °C/10 min and characterized regarding phenolic composition, pigments quantification, radicals quenching capacity, anti-acetylcholinesterase (AChE) activity, and cell viability effects. The optimal extract was characterized by low carotenoids content (8.15 μg/g on dry weight (dw)) and high amounts of hydroxycinnamic acid derivatives (23.12 mg/g dw). A remarkable scavenging efficiency was observed, particularly for HOCl (IC₅₀ = 27.61 μg/mL) and ONOO^? (IC₅₀ = 47.32 μg/mL). No adverse effects were detected on HaCaT and HFF-1 viability up to 1000 μg/mL. Additionally, the neuroprotective properties of the optimal extract were demonstrated by AChE inhibition (32.34% at 1000 μg/mL). This study encourages the sustainable recovery of antioxidants from the undervalued biowaste of S. ramosissima as a new raw material for different industries.     

Potential antioxidant,anticholinergic, antidiabetic and antiglaucoma activities and molecular docking of spiraeoside as a secondary metabolite of onion (Allium cepa)

Onion contains many dietary and bioactive components including phenolics and flavonoids. Spiraeoside (quercetin-4-O-β-D-glucoside) is one of the most putative flavonoids in onion. Several antioxidant techniques were used in this investigation to assess the antioxidant capabilities of spiraeoside, including 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·) scavenging, N,N-dimethyl-p-phenylenediamine radical (DMPD^•+) scavenging, 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS^•+) scavenging activities, cupric ions (Cu²⁺) reducing and potassium ferric cyanide reduction abilities. In contrast, the water-soluble α-tocopherol analogue trolox and the conventional antioxidants butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), and α-tocopherol were utilized as the standards for evaluation. Spiraeoside scavenged the DPPH radicals an IC₅₀ of 28.51 μg/mL (r²: 0.9705) meanwhile BHA, BHT, trolox, and α-tocopherol displayed IC₅₀ of 10.10 μg/mL (r²: 0.9015), 25.95 μg/mL (r²: 0.9221), 7.059 μg/mL (r²: 0.9614) and 11.31 μg/mL (r²: 0.9642), accordingly. The results exhibited that spiraeoside had effects similar to BHT, but less potent than α-tocopherol, trolox and BHA. Also, inhibitory effects of spiraeoside were evaluated toward some metabolic enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase II (CA II) and α-glycosidase, which are related to a number of illnesses, such as Alzheimer’s disease (AD), diabetes mellitus and glaucoma disorder. Spiraeoside exhibited IC₅₀ values of 4.44 nM (r²: 0.9610), 7.88 nM (r²: 0.9784), 19.42 nM (r²: 0.9673) and 29.17 mM (r²: 0.9209), respectively against these enzymes. Enzyme inhibition abilities were compared to clinical used inhibitors including acetazolamide (for CA II), tacrine (for AChE and BChE) and acarbose (for α-glycosidase). Spiraeoside demonstrated effective antioxidant, anticholinergic, antidiabetic and antiglaucoma activities. With these properties, it has shown that Spiraeoside has the potential to be a medicine for some metabolic diseases.     

Antimalarial and free radical scavenging activities of rhizomes of Polygonatum verticillatum supported by isolated metabolites

Antimalarial activity of the crude extract of Polygonatum verticillatum rhizomes and its sequentially partitioned fractions were investigated against Plasmodium falciparum. The crude extract possessed notable activity (IC₅₀: 21.67?μg/mL) that enhanced reasonably upon fractionation. The antiparasitic potency of the n-hexane fraction was maximum (IC₅₀: 2.33?μg/mL) followed by chloroform (IC₅₀: 4.62?μg/mL). However, the remaining fractions showed insignificant activity in the assay. The extracts of the plant showed marked scavenging activity on stable free radical, DDPH. The most potent antioxidant was the chloroform fraction (IC₅₀: 90?μg/mL) followed by ethyl acetate (IC₅₀: 93?μg/mL) and n-butanol (IC₅₀: 95?μg/mL) fractions. In the brine shrimps lethality test, the extracts were found nontoxic with the exception of ethyl acetate fraction (LD₅₀: 492.846?μg/mL). The bioactivity-guided isolation resulted into 5-hydroxymethyl-2-furaldehyde (HMF) and diosgenin which strongly supports the present experimental findings.     

Chemistry and functional properties in prevention of neurodegenerative disorders of five Cistus species essential oils

The chemical composition of Cistus creticus, Cistus salvifolius, Cistus libanotis, Cistus monspeliensis and Cistus villosus essential oils has been examined by GC and GC–MS analysis. Height-nine constituents were identified in C. salvifolius oil, sixty in C. creticus, fifty-six in C. libanotis, fifty-four in C. villosus, forty-five in C. monspeliensis. Although the five species belong to the same genus, the composition showed interesting differences. Essential oils were screened also for their potential antioxidant effects (by DPPH, ABTS, FRAP and β-carotene bleaching test) and their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, useful for prevention and treatment of Alzheimer’s disease. C. monspeliensis exhibited the most promising activity in β-carotene bleaching test (IC₅₀ of 54.7 μg/mL). In FRAP test C. libanotis showed a value of 19.2 μM Fe(II)/g. C. salvifolius showed the highest activity against AChE (IC₅₀ of 58.1 μg/mL) while C. libanotis, C. creticus, C. salvifolius demonstrated a good inhibitory activity against BChE with IC₅₀ values of 23.7, 29.1 and 34.2 μg/mL, respectively. Overall our results could promote the use of the essential oil of different Cistus species as food additives and for formulation of herbal infusion or nutraceutical products.     

Genotoxicity and antileishmanial activity evaluation of Physalis angulata concentrated ethanolic extract

Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA)ResultsEEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000 μg/plate and did not induce mutagenic effects after two oral administrations with a 24 h interval at a dose level of 2000 mg/kg. EEPA presented antileishmanial activity and presented an IC₅₀ value of 5.35 ± 2.50 μg/mL and 4.50 ± 1.17 μg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC₅₀ of 6.14 ± 0.59 μg/mL. Importantly, the IC₅₀ against L. amazonensis intracellular amastigotes was 1.23 ± 0.11 μg/mL.ConclusionEEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites.     

Essential oil composition and antioxidant activities of Curcuma aromatica Salisb.

The chemical composition of the hydro-distilled essential oil from leaves of Curcuma aromatica Salisb. was analysed by GC–MS. Twenty-three compounds representing 94.29% of the total oil were identified. The antioxidant activities of the oil and various extracts of C. aromatica were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical-scavenging assays. The oil and methanol extract showed potent DPPH radical-scavenging activities (IC₅₀ = 14.45 and 16.58 μg/ml, respectively), which were higher than butylated hydroxyanisole (IC₅₀ = 18.27 μg/ml). The extracts also exhibited remarkable superoxide radical-scavenging activities (IC₅₀ = 22.6–45.27 μg/ml) and the activity in the methanol extract was superior to all other extracts (IC₅₀ = 22.6 μg/ml). Furthermore, the amount of total phenolic compounds was determined and its content in ethyl acetate extract was the highest as compared to other extracts. The results indicate that the oil and extracts of C. aromatica could serve as an important bio-resource of antioxidants for using in the food industries.     

Analysis of Peganum harmala,Melia azedarach and Morus alba extracts against six lethal human cancer cells and oxidative stress along with chemical characterization through advance Fourier Transform and Nuclear Magnetic Resonance spectroscopic methods towards green chemotherapeutic agents

Traditional medicines implicate consumption of plant crude extracts, which may consist of extensive phytochemical diversity. Overall, the most biologically active extract of Peganum harmala (seeds) exhibited significant cytotoxic activity on Artemia salina with LC₅₀ value of 61.547 µg/mL, while P. harmala (roots) [LC₅₀ = 124.229 µg/mL] and M. azedarach (fruits) [LC₅₀ = 147.813 µg/mL] showed moderate cytotoxic potential. P. harmala (seeds) extract also showed the maximum antitumor potential with 52.278 µg/mL LC₅₀. Branches of P. harmala and Morus alba were not active in both bioassays. These outcomes were further reinforced by the levels of phenolics and flavonoids checked against gallic acid and quercetin equivalents, respectively, by standard curves. Current study aims to isolate, structurally characterize and analyze the bioactive compound from plant extracts by using chromatographic and spectrophotometric techniques. Bioactivity guided isolation of extracts led to the isolation of PH-HM-16 from ethyl acetate fraction P. harmala seeds. Chemical structure of PH-HM-16 was elucidated by ESI-MS, ¹H NMR, ¹³C NMR, HSQC and IR spectrum. The results demonstrated significant positive anticancer activities against six human cancer cell lines assessed through MTT cancer cell growth inhibition assay. PH-HM-16 was most effective against prostate cancer cell lines [IC₅₀ = 17.63 µg/mL] followed by breast cancer cell line MCF7 [IC₅₀ value of 41.81 µg/mL]. IC₅₀ value of PH-HM-16 against human myeloid leukemia cell line HL-60 and human colorectal tumor cells HCT-116 was observed as 68.77 µg/mL and 71.54 µg/mL respectively. The IC 50 value of PH-HM-16 compound was not significant against human gastric cancer SGC-7901 (111.89 µg/mL) and human lung adenocarcinoma epithelial cell line A549 (176.04 µg/mL). Isolated bioactive metabolite PH-HM-16 possesses significant antitumor potential so this could be the first step to develop an effective anticancer agent. Hence, this compound represents a promising potential to be chemically standardized or developed into pharmaceuticals for the chemoprevention and/or the treatment of certain types of cancer, especially as adjuvant phytotherapeutics in conventional chemotherapy.     

In‐vitro antileishmanial potential of peptide drug hirudin

Hirudin is clinically an important drug used for the treatment of cardiac diseases, but has never been elucidated for antileishmanial potential. This study was designed to determine the therapeutic utility of hirudin against leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were screened computationally against leishmanolysin (GP63), out of which hirudin exhibited higher binding affinity with GP63 and good expected IC₅₀ values. Experimentally, hirudin showed most promising activity against promastigote and axenic amastigote forms of leishmanial parasites with IC₅₀ values of 0.60 ± 0.36 μg/mL and 0.43 ± 0.23 μg/mL, respectively, in a dose‐ and time‐dependent assay. The cytotoxicity assay revealed no adverse effects on human macrophages with LD₅₀ value of 860.11 ± 53.44 μg/mL. Hirudin caused leishmanial cell death mainly by apoptosis and membrane permeability. In spite of the basic knowledge obtained, hirudin mechanism is considerably less prone to the induction of resistance than classical drugs. Collectively, this study fosters further studies for the hirudin as new antileishmania lead with a new mode of action.     

Synthesis,Biological Evaluation,and Computer‐Aided Drug Designing of New Derivatives of Hyperactive Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitors

The synthesis and biological evaluation of a novel series of compounds based on suberoylanilide hydroxamic acid (SAHA) had been designed as potential histone deacetylase inhibitors (HDACis). Molecular docking studies indicated that our derivatives had better fitting in the binding sites of HDAC8 than SAHA. Compounds 1–5 were synthesized through the synthetic routes. In biological test, compounds also showed good inhibitory activity in HDAC enzyme assay and more potent growth inhibition in human glioma cell lines (MGR2, U251, and U373). A representative compound, N3F, exhibited better inhibitory effect (HDAC, IC₅₀ = 0.1187 μm ; U251, IC₅₀ = 0.8949 μm ) and lower toxicity for human normal cells (LO2, IC₅₀ = 172.5 μm and MRC5, IC₅₀ = 213.6 μm ) compared with SAHA (HDAC, IC₅₀ = 0.8717 μm ; U251, IC₅₀ = 8.938 μm ; LO2, IC₅₀ = 86.52 μm and MRC5, IC₅₀ = 81.02 μm ). In addition, N3F obviously increased Beclin‐1 and Caspase‐3 and 9 as well as inhibited Bcl‐2 in U251 cells. All of our results indicated that these SAHA cap derivatives could serve as potential lead compounds for further optimization. In addition, N3F and N2E both displayed promising profile as antitumor candidates for the treatment of human glioma.     

Cassia grandis Lf nanodispersion is a hypoglycemic product with a potent α-glucosidase and pancreatic lipase inhibitor effect

Purpose

This study aimed to evaluate the hypoglycemic effect, antioxidant, α-glucosidase and lipase inhibitory activity, and the cytotoxicity of the Cassia grandis nanodispersion (CgND).

Metronidazole containing pyrazole derivatives potently inhibit tyrosyl‐tRNA synthetase: design,synthesis, and biological evaluation

As an important enzyme in bacterial protein biosynthesis, tyrosyl‐tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole‐based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity, especially against Gram‐negative organisms. Of the compounds obtained, 4f is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525 (MIC = 0.98 μg/mL) and exhibited TryRS inhibitory activity (IC₅₀ = 0.92 μm ). Docking simulation was performed to further understand its potency. Membrane‐mediated apoptosis in P. aeruginosa was verified by flow cytometry.     

Antibacterial and antiparasitic effects of Bothrops marajoensis venom and its fractions: Phospholipase A2 and l-amino acid oxidase

Some proteins present in snake venom possess enzymatic activities, such as phospholipase A₂ and l-amino acid oxidase. In this study, we verify the action of the Bothrops marajoensis venom (BmarTV), PLA₂ (BmarPLA₂) and LAAO (BmarLAAO) on strains of bacteria, yeast, and Leishmania sp. The BmarTV was isolated by Protein Pack 5PW, and several fractions were obtained. Reverse phase HPLC showed that BmarPLA₂ was isolated from the venom, and N-terminal amino acid sequencing of sPLA₂ showed high amino acid identity with other lysine K49 sPLA₂s isolated from Bothrops snakes. The BmarLAAO was purified to high molecular homogeneity and its N-terminal amino acid sequence demonstrated a high degree of amino acid conservation with others LAAOs. BmarLAAO was able to inhibit the growth of P. aeruginosa, C. albicans and S. aureus in a dose-dependent manner. The inhibitory effect was more significant on S. aureus, with a MIC = 50 μg/mL and MLC = 200 μg/mL. However, the BmarTV and BmarPLA₂ did not demonstrate inhibitory capacity. BmarLAAO was able to inhibit the growth of promastigote forms of L. chagasi and L. amazonensis, with an IC₅₀ = 2.55 μg/mL and 2.86 μg/mL for L. amazonensis and L. chagasi, respectively. BmarTV also provided significant inhibition of parasitic growth, with an IC₅₀ of 86.56 μg/mL for L. amazonensis and 79.02 μg/mL for L. chagasi. BmarPLA₂ did not promote any inhibition of the growth of these parasites. The BmarLAAO and BmarTV presented low toxicity at the concentrations studied. In conclusion, whole venom as well as the l-amino acid oxidase from Bothrops marajoensis was able to inhibit the growth of several microorganisms, including S. aureus, Candida albicans, Pseudomonas aeruginosa, and Leishmania sp.     

Free radical scavenging activity and chemical constituents of Urvillea ulmaceae

The methanol extract of Urvillea ulmaceae Kunth (Sapindaceae) aerial parts and the hexane, ethyl acetate, and hydromethanol fractions were evaluated for their free radical scavenging activity with the DPPH assay. Among all the tested fractions, the ethyl acetate fraction was the most active, exhibiting an IC₅₀ of 16.33?μg/mL, comparable to that of the commercial antioxidant BHT. Fractionation of the ethyl acetate fraction through chromatographic methods afforded trans-N-methyl-5-hydroxypipecolic acid, epicatechin, and proanthocyanidin A2 as the main constituents. Epicatechin and proanthocyanidin A2 showed potent DPPH radical scavenging activity, with IC₅₀ values of 18.34 and 11.45?μg/mL, respectively. A new compound, trans-N-methyl-5-hydroxypipecolic acid, did not show any antioxidant effect (IC₅₀?>?500?μg/mL).     

Leishmanicidal and cytotoxic activities of Nigella sativa and its active principle,thymoquinone

Abstract

Context: Leishmaniasis is a complex disease with a broad spectrum of clinical presentations.

Objective: We evaluated the anti-leishmanial effects of Nigella sativa L. (Ranunculaceae) against Leishmania tropica and Leishmania infantum with an in vitro model.

Materials and methods: Antileishmanial effects of essential oil and methanolic extract of N. sativa (0–200?µg/mL) and thymoquinone (0–25?µg/mL) on promastigotes of both species and their cytotoxicity activities against murine macrophages were evaluated using the MTT assay at 24, 48, and 72?h. Moreover, their leishmanicidal effects against amastigotes were investigated in a macrophage model, for 48 and 72?h.

Results: The findings showed that essential oil (L. tropica IC₅₀ 9.3?μg/mL and L. infantum IC₅₀ 11.7?μg/mL) and methanolic extract (L. tropica IC₅₀ 14.8?μg/mL and L. infantum IC₅₀ 15.7?μg/mL) of N. sativa, particularly thymoquinone (L. tropica IC₅₀ 1.16?μg/mL and L. infantum IC₅₀ 1.47?μg/mL), had potent antileishmanial activity on promastigotes of both species after 72?h. In addition, essential oil (L. tropica IC₅₀ 21.4?μg/mL and L. infantum IC₅₀ 26.3?μg/mL), methanolic extract (L. tropica IC₅₀ 30.8?μg/mL and L. infantum IC₅₀ 34.6?μg/mL), and thymoquinone (L. tropica IC₅₀ 2.1?μg/mL and L. infantum IC₅₀ 2.6?μg/mL) mediated a significant decrease in the growth rate of amastigote forms of both species. Thymoquinone (CC₅₀ 38.8?μg/mL) exhibited higher cytotoxic effects against murine macrophages than the other extracts.

Conclusion: N. sativa, especially its active principle, thymoquinone, showed a potent leishmanicidal activity against L. tropica and L.infantum with an in vitro model.     

Structure–activity relationship studies of benzyl‐, phenethyl‐, and pyridyl‐substituted tetrahydroacridin‐9‐amines as multitargeting agents to treat Alzheimer's disease

A library of substituted tetrahydroacridin‐9‐amine derivatives were designed, synthesized, and evaluated as dual cholinesterase and amyloid aggregation inhibitors. Compound 8e (N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was identified as a potent inhibitor of butyrylcholinesterase (BuChE IC₅₀ = 20 nm ; AChE IC₅₀ = 2.2 μm ) and was able to inhibit amyloid aggregation (40% inhibition at 25 μm ). Compounds 9e (6‐chloro‐N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC₅₀ = 0.8 μm ; BuChE IC₅₀ = 1.4 μm ; Aβ‐aggregation inhibition = 75.7% inhibition at 25 μm ) and 11b (6‐chloro‐N‐(3,4‐dimethoxyphenethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC₅₀ = 0.6 μm ; BuChE IC₅₀ = 1.9 μm ; Aβ‐aggregation inhibition = 85.9% inhibition at 25 μm ) were identified as the best compounds with dual cholinesterase and amyloid aggregation inhibition. The picolylamine‐substituted compound 12c (6‐chloro‐N‐(pyridin‐2‐ylmethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was the most potent AChE inhibitor (IC₅₀ = 90 nm ). These investigations demonstrate the utility of 3,4‐dimethoxyphenyl substituent as a novel pharmacophore possessing dual cholinesterase inhibition and anti‐Aβ‐aggregation properties that can be used in the design and development of small molecules with multitargeting ability to treat Alzheimer's disease.     

Scavenging capacity of strawberry tree (Arbutus unedo L.) leaves on free radicals

Despite strawberry tree (Arbutus unedo L.) leaves had a long use in traditional medicine due to its antiseptic, diuretic, astringent and depurative properties, the potential of their antioxidant activity are still lacking. Our study goals to assess the antioxidant and free radical scavenging potential of water, ethanol, methanol and diethyl ether extracts of A. unedo leaves. Total phenols content was achieved spectrophotometrically using Folin–Ciocalteau reagent with gallic acid as standard. Antioxidant activity was evaluated using three different methods: reducing power of iron (III)/ferricyanide complex assay, scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and scavenging effect on superoxide radicals by using the PMS–NADH–nitroblue tetrazolium system. Ethanol extracts of A. unedo leaves were the highest in reducing power (IC₅₀ 232.7 μg/mL) and DPPH scavenging effect (IC₅₀ 63.2 μg/mL) followed by water extracts (with IC₅₀ of 287.7 and 73.7 μg/mL, respectively); whereas diethyl ether extracts were the lowest. In the scavenging on superoxide radical assay, methanol extracts obtained the best results (IC₅₀ 6.9 μg/mL). For all the methods tested the antioxidant activity was concentration dependent. In accordance with antioxidant activity, highest total phenols content were found in ethanol, followed by water, methanol and diethyl ether extract. The results indicated that A. unedo leaves are a potential source of natural antioxidants.     

Anticancer,antioxidant and antibiotic activities of mushroom Ramaria flava

Ramaria flava is a species of edible mushroom with some bioactivity. The anticancer, antioxidant and antibiotic activities and chemical composition of R. flava ethanol extract (EE) were evaluated. The present study exhibited that the EE displayed the strongest inhibitory activity against tumor cell MDA-MB-231 with an IC₅₀ value of 66.54 μg/mL in three tested tumor cell lines, and the inhibition percent was 71.66% at the concentration of 200 μg/mL (MTT assay). The total phenolic compounds varied among four fractions of the EE from 6.66 to 61.01 mg gallic acid equivalent (GAE) per g dry weight. Water fraction exhibited high DPPH and OH radical-scavenging activities with low IC₅₀ values of 5.86 and 18.08 μg/mL, respectively. Meanwhile, three phenolic compounds from water fraction were also identified by HPLC. The antibiotic activities of the EE were evaluated against three microorganisms and three fungi strains by means of the agar well diffusion method and the poisoned medium technique, respectively. The EE also showed moderate antibiotic activities. These results suggest that R. flava could hold a good potential source for human health.     

Antiviral activity of Rheum palmatum methanol extract and chrysophanol against Japanese encephalitis virus

Rheum palmatum, Chinese traditional herb, exhibits a great variety of anti-cancer and anti-viruses properties. This study rates antiviral activity of R. palmatum extracts and its components against Japanese encephalitis virus (JEV) in vitro. Methanol extract of R. palmatum contained higher levels of aloe emodin, chrysophanol, rhein, emodin and physcion than water extract. Methanol extract (IC₅₀ = 15.04 μg/ml) exhibited more potent inhibitory effects on JEV plaque reduction than water extract (IC₅₀ = 51.41 μg/ml). Meanwhile, IC₅₀ values determined by plaque reduction assay were 15.82 μg/ml for chrysophanol and 17.39 μg/ml for aloe-emodin, respectively. Virucidal activity of agents correlated with anti-JEV activity, while virucidal IC₅₀ values were 7.58 μg/ml for methanol extract, 17.36 μg/ml for water extract, 0.75 μg/ml for chrysophanol and 0.46 μg/ml for aloe-emodin, respectively. In addition, 10 μg/ml of extract, chrysophanol or aloe emodin caused 90 % inhibition of JEV yields in cells and significantly activated gamma activated sequence-driven promoters. Hence, methanol extract of R. palmatum and chrysophanol with high therapeutic index might be useful for development of antiviral agents against JEV.