Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by an Endophytic Fungus Isolated from Cinnamomum mollisimum

An endophytic fungus isolated from the plant Cinnamomum mollissimum was investigated for the bioactivity of its metabolites. The fungus, similar to a Phoma sp., was cultured in potato dextrose broth for two weeks, followed by extraction with ethyl acetate. The crude extract obtained was fractionated by high-performance liquid chromatography. Both crude extract and fractions were assayed for cytotoxicity against P388 murine leukemic cells and inhibition of bacterial and fungal pathogens. The bioactive extract fraction was purified further and characterized by nuclear magnetic resonance, mass spectral and X-ray crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was identified as the constituent of the bioactive fungal extract fraction. This compound inhibited the fungal pathogen Aspergillus niger (IC50 1.56 μg/mL) and was cytotoxic against murine leukemia cells (IC50 2.10 μg/mL). 5-Hydroxyramulosin was the major compound produced by the endophytic fungus. This research suggests that fungal endophytes are a good source of bioactive metabolites which have potential applications in medicine

A brief review of potential neuroprotective roles of the culinary herb Ocimum basilicum

Neurodegenerative diseases commonly affect elderly population and are characterised by progressive neuronal loss. Oxidative stress is highly associated with neurodegeneration. The targeted herbal plant in this review, Ocimum basilicum (O. basilicum), is typically used in Indochina and Italian cuisine. Pharmacological studies on O. basilicum have demonstrated potent antioxidant activities with some reports of neuroprotective actions. This brief review highlights the potential neuroprotective roles of O. basilicum by discussing previously documented antioxidative actions of the plant extract, essential oils and its phytochemical compounds on the nervous system based on in vitro and in vivo studies. Accumulating evidence on the neuroprotective action of O. basilicum points to a notion that neuroprotection is made possible by way of its antioxidant properties and largely due to the presence of polyphenol compounds such as rosmarinic acid which has been identified as the major constituent. Although the mechanisms of O. basilicum antioxidant action have been proposed, further studies are required for better understanding of its antioxidant action leading to neuroprotective roles. It is also possible that the antioxidant actions of O. basilicum are mediated through synergism of a mixture of various naturally-occurring bioactive compounds in the plant, as is with many other plant-based food supplements, to produce the putative effects instead of a single bioactive compound from the plant. Therefore, specific targeting of neuroprotection by means of antioxidant actions warrants further preclinical and clinical studies investigating the therapeutic potentials of O. basilicum particularly in view of the prevention of neurodegenerative processes

Isolation and characterization of cyclo-(tryptophanyl-prolyl) and chloramphenicol from Streptomyces sp. SUK 25 with antimethicillin-resistant Staphylococcus aureus activity

Background: Zingiber spectabile, commonly known as Beehive Ginger, is used as an ethnobotanical plant in many countries as an appetizer or to treat stomachache, toothache, muscle sprain, and as a cure for swelling, sores and cuts. This is the first report of isolation of Streptomyces strain from the root of this plant. Strain Universiti Kebangsaan 25 (SUK 25) has a very high activity to produce secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA), which is associated with high morbidity and mortality rates due to acquired multidrug resistance genes and causes medication failure in some clinical cases worldwide. Phylogenetic analysis based on the 16S ribosomal RNA gene sequence exhibited that the most closely related strain was Streptomyces omiyaensis NBRC 13449T (99.0% similarity). Aim: This study was conducted to carry out the extraction, identification, and biological evaluation of active metabolites isolated from SUK 25 against three MRSA strains, namely, MRSA ATCC 43300, MRSA ATCC 33591, and MRSA ATCC 49476. Materials and methods: The production of secondary metabolites by this strain was optimized through Thronton’s media. Isolation, purification, and identification of the bioactive compounds were carried out using reversed-phase high-performance liquid chromatography, high-resolution mass spectrometry, Fourier transform infrared, and one-dimensional and twodimensional nuclear magnetic resonance. Results: During screening procedure, SUK 25 exhibited good antimicrobial potential against several strains of MRSA. The best biological activity was shown from fraction number VII and its subfractions F2 and F3 with minimum inhibitory concentration values at 16 µg/mL and 8 µg/mL, respectively. These two subfractions were identified as diketopiperazine cyclo(tryptophanyl-prolyl) and chloramphenicol. Conclusion: On the basis of obtained results, SUK 25 isolated from Z. spectabile can be regarded as a new valuable source to produce secondary metabolites against bacteria, especially MRSA

Augmented cytotoxic, mutagenic and genotoxic response triggered by carvedilol and celecoxib combinations

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (

Neuroprotective effects of Ocimum basilicum extract against hydrogen peroxide-induced oxidative stress in SK-N-SH neuroblastoma cells

Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease are characterized by the progressive loss of neurons. One of the contributing factors for these diseases is oxidative stress, characterized by the imbalance of free radicals production and antioxidant defense mechanisms. In the present study, the neuroprotective effects of Ocimum basilicum var. thyrsiflora against hydrogen peroxide (H2O2)-induced oxidative stress in SK-N-SH neuroblastoma cells were evaluated. The exposure of SK-N-SH cells to 50 μM H2O2 for 24 h induced cytotoxicity and apoptosis as measured by cell viability and flow cytometry, respectively. Pretreatment with ethyl acetate (ObEA) fraction at 3.1-25 μg/mL showed the highest protection against H2O2-induced cell death compared to other fractions and crude extract by increasing cell viability and reducing apoptosis. The evaluation of antioxidant capacity via 1, 1-diphenyl-2-picrylahydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays showed ObEA possessed the highest antioxidative properties. The intracellular reactive oxygen species (ROS) production of H2O2 in untreated cells increased by 2.39-fold compared to the control and was significantly attenuated by the 2 h pre-treatment of O. basilicum (p<0.05). The reduction in intracellular superoxide dismutase (SOD) induced by H2O2 was also abrogated by the pretreatment of O. basilicum. These findings suggested that O. basilicum is potentially neuroprotective against oxidative damage in neuronal cells by scavenging free radicals, restoring SOD activities and eventually prevent cell death

Bioactive compounds fractionated from endophyte Streptomyces SUK 08 with promising ex-vivo antimalarial activity

Objective: To determine ex vivo antimalarial activity and cytotoxicity of endophytic Streptomyces SUK 08 as well as the main core structure fractionated from its crude extract. Methods: The activities of SUK 08 crude extract were evaluated by using the Plasmodium lactate dehydrogenase assay and synchronization test against rodent malaria parasite Plasmodium berghei, instead of human malarial parasite Plasmodium falciparum. The cytotoxicity of the crude extract was determined by MTT assay. The crude extract was analyzed by thin-layer chromatography and gas chromatography–mass spectrophotometry. Results: The ethyl acetate crude extract showed very promising antimalarial activity with IC50 of 1.25 mg/mL. The synchronization tests showed that ethyl acetate extraction could inhibit all stages of the Plasmodium life cycle, but it was most effective at the Plasmodium ring stage. On the basis of a MTT assay on Chang Liver cells, ethyl acetate and ethanol demonstrated IC50 values of >1.0 mg/mL. The IC50 of parasitemia at 5% and 30% for this extract was lower than chloroquine. Thin-layer chromatography, with 1: 9 ratio of ethyl acetate: hexane, was used to isolate several distinct compounds. Based on gas chromatography–mass spectrophotometry analysis, three core structures were identified as cyclohexane, butyl propyl ester, and 2,3-heptanedione. Structurally, these compounds were similar to currently available antimalarial drugs. Conclusions: The results suggest that compounds isolated from Streptomyces SUK 08 are viable antimalarial drug candidates that require further investigation

Isolation, purification, and characterization of five active diketopiperazine derivatives from endophytic streptomyces SUK 25 with antimicrobial and cytotoxic activities

In our search for new sources of bioactive secondary metabolites from Streptomyces sp., the ethyl acetate extracts from endophytic Streptomyces SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic Streptomyces SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as Enterococcus raffinosus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic Streptomyces SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as cyclo-(L-Val-L-Pro), cyclo-(L-Leu-L-Pro), cyclo-(L-Phe-L-Pro), cyclo-(L-Val-L-Phe), and N-(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and Enterococcus raffinosus, with low toxicity against human hepatoma HepaRG cells. Endophytic Streptomyces SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line

Anti-inflammatory and antioxidant activity of Syzygium polyanthum (Wight) walp

Syzygium polyanthum has been used as folk medicine to treat ailments related to oxidative stress and inflammation. In this study, the anti-inflammatory and antioxidant activity of stem bark and root bark of the plant were investigated. The experiments that have been carried out were estimation of total phenolic and total flavonoid in the methanol extracts and fractions of both parts, isolation and structure elucidation of chemical compounds, anti-inflammatory activity evaluation based on inhibition of prostaglandin E2 production in the LPS-induced human whole blood using radioimmunoassay technique as well as antioxidant activity based on assays by using free radical scavenging DPPH and FRAP. Results showed high amounts of phenolics and flavonoids in both parts of S. polyanthum. Seven compounds were succesfully isolated from the stem bark and identified as stigmasterol (1), 8-hydroxy-6-methoxy-3-pentylisocoumarin (2), 3,3’-di-O-methylellagic acid (3), methylgallate (4), asiatic acid (5), arjunolic acid (6), and daucosterol (7). The ethyl acetate fraction of the root bark showed potent inhibitory activity on the production of PGE2 (IC50 3.03 ± 0.83 μg/mL). The methanol extract of the stem bark displaying promising DPPH scavenging activity (SC50 = 2.82 ± 0.1 μg/mL) and FRAP activity (7.02 ± 0.1 μg/μg of equivalent trolox amount). Compounds 1, 5, 6 and 7 showed pronounced inhibitory activity on the PGE2 production with IC50 ranging from 0.052 to 1.25 μM. Meanwhile, compound 4 exhibited antioxidant activity toward DPPH (SC50 10.60 μM) and FRAP (20.5 ± 1.0 μg/μg). The study concluded that S. polyanthum as a potential source for therapeutic agents with anti-inflammatory and antioxidant activities

Inhibitory effects of phylligenin and quebrachitol isolated from Mitrephora vulpina on platelet activating factor receptor binding and platelet agregation.

Phylligenine, together with quebrachitol, stigmasterol and two aporphine alkaloids—oxoputerine and liriodenine—were isolated from the twigs of Mitrephora vulpina C.E.C. Fisch. They were evaluated for their ability to inhibit platelet activating factor (PAF) receptor binding to rabbit platelets using 3H-PAF as a ligand and their antiplatelet aggregation effect in human whole blood induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Of all the compounds tested, phylligenin and quebrachitol exhibited potent and concentration-dependent inhibitory effects on PAF receptor binding, with IC50 values of 13.1 and 42.2 µM, respectively. The IC50 value of phylligenin was comparable to that of cedrol (10.2 µM), a potent PAF antagonist. Phylligenin also showed strong dose-dependent inhibitory activity on platelet aggregation induced by AA and ADP

Bioassay-guided isolation of a potent platelet-activating factor antagonist alkenylresorcinol from Ardisia elliptica

In the course of our search for novel platelet-activating factor (PAF) antagonists from medicinal plants, the methanol extract of the leaves of Ardisia elliptica Thunb. was investigated for its inhibitory effects on PAF receptor binding to rabbit platelets using 3H-PAF as a ligand. The methanol extract showed inhibitory activity of 53.9% and its ethyl acetate, n-butanol, and methanol fractions exhibited 48.6%, 39.0%, and 22.0% inhibition, respectively. Bioassay-guided fractionation of the ethyl acetate fraction led to the isolation of a new alkenylresorcinol, 5-(Z-heptadec-4′-enyl)resorcinol, together with 5-pentadecylresorcinol. The alkenylresorcinol showed a strong inhibition with an IC50 value of 7.1 µM. The structures of the compounds were elucidated by spectroscopic techniques