Search

Four new dihydrostilbenes, malayheyneiins A–D (1–4) along with three known analogues, laevifolins A–B (5–6) and macarubiginosin C (7) were isolated from the leaves of Macaranga heynei. The structures of the compounds were elucidated using 1D and 2D NMR, UV, IR, MS as well as comparison with literature data. Compounds 2, 3 and 7 exhibited significant acetylcholinesterase inhibitory (AChEI) activity with IC50 of

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects.

Aromatic (ar)-turmerone is one of the aromatic constituents abundant in turmeric essential oil from Curcuma longa. Ar-turmerone exhibited anti-inflammatory properties. So far, antiplasmodial data for ar-turmerone is still not reported. The data showed the in vitro antiplasmodial effect of ar-turmerone against Plasmodium falciparum 3D7 (chloroquine-sensitive) via Plasmodium lactate dehydrogenase assay (pLDH) and cytotoxic effect against Vero mammalian kidney cells using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colourimetric assay. Selectivity indexes of ar-turmerone were calculated based on inhibition concentration at 50% of parasite growth (IC50) from MTT and pLDH assays and the effects of ar-turmerone were compared to the antimalarial reference drug chloroquine diphosphate. The inhibitory effect of ar-turmerone at the intraerythrocytic stages of plasmodial lifecycles was evaluated via a stage-dependant susceptibility test. The antiplasmodial and cytotoxic activities of ar-turmerone revealed IC50 values of 46.8 ± 2.4 μM and 820.4 ± 1.5 μM respectively. The selectivity index of ar-turmerone was 17.5. Ar-turmerone suppressed the ring-trophozoite transition stage of the intraerythrocytic life cycle of P. falciparum 3D7.

Adverse cardiac remodelling such as hypertrophy and fibrosis are strong determinants of heart failure and sudden death after myocardial infarction (MI). This study investigated the impact of S-allylcysteine therapy on adverse cardiac remodelling after MI in a preclinical rat model. Wistar rats (n = 6–8/group) were subjected to MI via isoprenaline overdose and were then administered with S-allylcysteine (50 or 100 mg/kg) orally for 7 days. Compared to the sham controls, untreated MI rats showed enhanced cardiac hypertrophy and fibrosis 7 days after MI, accompanied by a significant reduction in left ventricle glutathione and glutathione reductase activities with concomitant increase in protein oxidation. S-allylcysteine therapy however, significantly attenuated cardiac hypertrophy, fibrosis and oxidative stress after MI. S-allylcysteine therapy also prevented upregulation of angiotensin converting enzyme and angiotensin II type I receptor in these rat hearts. These findings altogether suggested that S-allylcysteine therapy reduced adverse cardiac remodelling after MI in rats.

Sialic acids are a group of nine-carbon α-keto acids. Sialic acid exists in more than 50 forms, with the natural types discovered as N-acetylneuraminic acid (Neu5Ac), deaminoneuraminic acid (2-keto-3-deoxy-nonulononic acid or Kdn), and N-glycolylneuraminic acid (Neu5Gc). Sialic acid level varies depending on the source, where edible bird's nest (EBN), predominantly Neu5Ac, is among the major sources of sialic acid. Due to its high nutritive value and complexity, sialic acid has been studied extensively through acid, aqueous, and enzymatic extraction. Although detection by chromatographic methods or mass spectrometry is common, the isolation and recovery work remained limited. Sialic acid is well-recognised for its bioactivities, including brain and cognition development, immune-enhancing, anti-hypertensive, anticancer, and skin whitening properties. Therefore, sialic acid can be used as a functional ingredient in the various industries. This paper reviews the current trend in the biochemistry, sources, extraction, and functions of sialic acids with special reference to EBN.

The bioactivity guided fractionation of Tetracera indica leaves crude ethanolic extract has afforded the isolation and characterization of six compounds including a new natural product viz., 5,7-dihydroxyflavone-O-8-sulphate (1) and five known flavonoids (2–6). The structures of the compounds were elucidated using 1D and 2D NMR and HRESIMS spectroscopic analyses. All the isolated compounds were evaluated for their in vitro inhibitory activity against alpha-glucosidase. Compound 1, 5 and 6 showed strong alpha-glucosidase inhibitory activity, 3 and 4 displayed weak activity while compound 2 was inactive. The interactions of the active compounds with alpha-glucosidase were further investigated using molecular docking to confirm their antidiabetic potential.

Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated sfrom the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 µg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 µg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (eNOS). ADMA is degraded by dimethylarginine dimethylaminohydrolase (DDAH). Elevated levels of ADMA lead to reduction in nitric oxide (NO) production, which is linked to endothelial dysfunction and atherosclerosis. Piper sarmentosum is an herb that has shown stimulation on endothelial NO production by increasing both expression and activity of eNOS. Thus, this study determined whether the positive effect of P. sarmentosum on NO production is related to its modulation on the DDAH–ADMA pathway in cultured human umbilical vein endothelial cells (HUVEC) exposed to tumor necrosis factor-α (TNF-α). HUVEC were divided into four groups: control, treatment with 250 µg/ml of aqueous extract of P. sarmentosum leaves (AEPS), treatment with 30 ng/ml of TNF-α, and concomitant treatment with AEPS and TNF-α for 24 h. After treatments, HUVEC were collected to measure DDAH1 messenger RNA (mRNA) expression using quantitative real-time polymerase chain reaction. DDAH1 protein level was measured using enzyme-linked immunosorbent assay (ELISA), and DDAH enzyme activity was measured using colorimetric assay. ADMA concentration was measured using ELISA, and NO level was measured using Griess assay. Compared to control, TNF-α-treated HUVEC showed reduction in DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05). Treatment with AEPS successfully increased DDAH1 mRNA expression (P < 0.05), DDAH1 protein level (P < 0.01), and DDAH activity (P < 0.05) in TNF-α-treated HUVEC. Treatment with TNF-α caused an increase in ADMA level (P < 0.01) and a decrease in endothelial NO production (P < 0.001). Whereas treatment with AEPS was able to reduce ADMA level (P < 0.01) and restore NO (P < 0.001) in TNF-α-treated HUVEC. The results suggested that AEPS promotes endothelial NO production by stimulating DDAH activity and thus reducing ADMA level in TNF-α-treated HUVEC.

Fucoidan is a sulfated polysaccharide that consists mainly of fucose and is found in brown seaweeds. In this study, fucoidan was extracted from Sargassum binderi (Fsar) from Malaysia and subsequently characterized in terms of composition, structure and toxicology. It was found that the molecular weight, polydispersity index, monosaccharide profile and degree of sulfation of Fsar differed from those of commercial food-grade fucoidan (Fysk). NMR analysis suggested that the main structure of Fsar was →3)fuc-2-OSO3 −(1→3)fuc-2-OSO3 −(1→. A cytotoxicity study employing up to 200 mg/mL Sargassum binderi extract showed that cell inhibition was less than 50% (IC50), while acute toxicity results classified S. binderi as category 5 (unclassified) according to the OECD Guideline 423, as no mortality was observed at the highest dosage (2,000 mg/kg). Both toxicity results showed that this material is safe to be consumed. The chemical characteristics and non-toxicity of Fsar demonstrate its potential in biological and food product applications.

Flavonoids have been reported to exert antihyperglycemic effects and have potential to enhance the current therapy options against type 2 diabetes mellitus. However, the structure activity relationships (SAR) studies of flavonoids against this disease have not been thoroughly comprehended. Hence, in the present study, 14 structurally related flavonoids viz. wogonin, techtochrysin, norwogonin, isoscutellarein, hypolaetin, kaempferol, quercetin, methyl ether of wogonin, acetate of wogonin, acetate of norwogonin, 8-hydroxy-7-methoxyflavone, chrysin, (+)-catechin and (-)-epicatechin were taken into account for in vitro antidiabetic evaluation. Cell viability of RIN-5F pancreatic cells and 3T3-L1 pre-adipocyte cells was initially tested, then an insulin secretion assay of RIN-5F as well as adipogenesis and glucose uptake measurements of adipocyte were investigated. Subsequently, protein expressions study through adipokines measurement (leptin, adiponectin, TNF-&alpha, RBP-4) via enzyme-linked immunosorbent assay (ELISA) kit, Western blotting analysis against GLUT4 and C/EBP-&alpha, as well as molecular docking against GLUT1 were analyzed. The results from cell culture antidiabetic assays (insulin secretion, adipogenesis, and glucose uptake), protein expressions and molecular docking pointed that the methoxy group at position C-8 is responsible for antidiabetic property of selected flavonoids via glucose uptake mechanism indicated by up regulation of GLUT4 and C/EBP-&alpha, expressions. The mechanism could be enhanced by the addition of an acetate group at C-5 and C-7 of the flavone skeleton.

A new tetramer oligostilbenoid possessing tetrahydrofuran ring, malaysianol C (1), was isolated from the acetone extract of the stem bark of Dryobalanops lanceolata, together with four known oligostilbenoids nepalensinol E (2), ϵ-viniferin (3), laevifonol (4), and ampelopsin F (5). The structures of isolated compounds were elucidated on the basis of spectral evidence. The antibacterial activity of the isolated compounds was evaluated using resazurin microtitre-plate assay, whereas the cytotoxic activity was tested using MTT assay. The plausible biogenetic routes of the isolated compounds are also discussed.

Aims: To screen fifty -six endophytic streptomyces isolates for anti -bacterial activity on two clinical strains of

T.decurrens is a species of brown algae (Phaeophyta) that has bioactivity potential. This study aims to determine the total phenolic, antioxidant activity, and toxicity effects of n-hexane, ethyl acetate, and methanol extract. The effect of toxicity was carried out using the Artemia salina L death test method. Meanwhile, the antioxidant test uses the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, and Folin Ciocalteu method is used for total phenolic content. The output of antioxidant activity of T. decurrens in ethyl acetate extract has an IC50 value of 180.54 g/mL. Similar results have been found in the effects of toxicity and total phenolic content, which showed that ethyl acetate extracts gave LC50 values of 25.41 μg/mL, and total values of phenolic content of 4.8091 mg EAG /g, respectively. This indicated that ethyl acetate extract from T. decurrens has the potential as anticancer.

A spore-forming streptomycete designated strain SUK12T was isolated from a Malaysian ethnomedicinal plant. Its taxonomic position, established using a polyphasic approach, indicates that it is a novel species of the genus Streptomyces . Morphological and chemical characteristics of the strain were consistent with those of members of the genus Streptomyces . Analysis of the almost complete 16S rRNA gene sequence placed strain SUK12T in the genus Streptomyces where it formed a distinct phyletic line with recognized species of this genus. The strain exhibited highest sequence similarity to Streptomyces corchorusii DSM 40340T (98.2 %) followed by Streptomyces chrestomyceticus NRRL B-3310T (98.1 %). The G+C content of the genomic DNA was 74 mol%. Chemotaxonomic data [MK-9(H8) as the major menaquinone; LL-diaminopimelic acid as a component of cell-wall peptidoglycan; C12 : 0, C14 : 0, C15 : 0 and C17 : 1 as the major fatty acids; phospholipid type II] supported the affiliation of strain SUK12T to the genus Streptomyces . The results of the phylogenetic analysis and phenotypic data derived from this and previous studies allowed the genotypic and phenotypic differentiation of strain SUK12T from the related species of the genus Streptomyces . The DNA–DNA relatedness value between strain SUK12T and S. corchorusii DSM 40340T is 18.85±4.55 %. Strain SUK12T produces phenazine-1-carboxylic acid, known as tubermycin B, an antibacterial agent. It is proposed, therefore, that strain SUK12T ( = DSM 42048T = NRRL B-24860T) be classified in the genus Streptomyces as the type strain of Streptomyces kebangsaanensis sp. nov.

Adipocytes are major tissues involved in glucose uptake second to skeletal muscle and act as the main adipocytokines mediator that regulates glucose uptake mechanism and cellular differentiation. The objective of this study were to examine the effect of the SDF7, which is a fraction consists of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8: 26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of insulin signalling and the adipocytokines expression on different cellular fractions of 3T3-F442a adipocytes.Morphology and lipid accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated with different concentrations of SDF7 and rosiglitazone were examined followed by the evaluation of glucose uptake activity expressions of insulin signalling downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four cellular fractions (plasma membrane, cytosol, high density microsome and low density microsome). Next, the expression level of adipocytokines (TNF-α, adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of 3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of adiponectin and PPAR-γ of 3T3-F442a adipocytes were induced and compared with basal concentration.It was found that SDF7 was able to induce adipocytes differentiation with great extends of morphological changes, lipid synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport on 3T3-F442a adipocytes are found to be dose independent, time-dependent and plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be able to suppress TNF-α and leptin expressions that were mediated by 3T3-F442a adipocytes, while stimulated adiponectin secretion on the cells. There was a significant expression (p0.01) of protein kinase C and small G protein TC10 on 3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7 was also found to be effective in stimulating adiponectin and PPAR-γ mRNA upregulation at 50 µg/ml.SDF7 exhibited good lipogenesis, adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a adipocytes.

A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum leaves led to the isolation and characterization of two new chromone alkaloid analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1 and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and 25.8% inhibition at 100 μg/ml, respectively.

Marine actinomycetes are now in demand as they are capable of producing unique and novel compounds with wide biological activities. Marine Streptomyces sp. UKMCC_PT15 previously isolated from seawater collected in Pulau Tinggi, Johor was used in this study. Molecular identification showed high similarity of Streptomyces sp. UKMCC_PT15 with Streptomyces fradiae and S. diastaticus subsp. ardesiacus based on partial sequence of 16S rRNA gene. Further characterisations of this bacterium include spore morphology using SEM, growth on various media, salt tolerance test and carbon utilisation profile. This bacterium had straight spore chain with smooth-surfaced spores and was able to tolerate up to 11% NaCl with capabilities of utilising >40 carbon sources. Undecylprodigiosin (C 25 H 35 N 3 O) was successfully purified through succession of column chromatography and finally using HPLC. Structure elucidation was confirmed through NMR spectroscopy, MS and comparison with established data. This compound demonstrated strong antibacterial activities against S. aureus , B. subtilis and C. albicans but weak antibacterial activities against E. coli, P. aeruginosa and Methicillin-resistant S. aureus (MRSA), Interestingly, undecylprodigiosin also demonstrated algicidal activity when tested against toxic dinoflagellates, A. minutum and P. bahamense, both of which are responsible for harmful algal blooms (HABs) . Undecylprodiogiosin with concentration of 10-100 μg/ml gave ~100% algicidal activity against both dinoflagellates. Further testing with undecylprodigiosin concentration < 10 µg/ml showed that undecylprodigision was capable of killing significantly high numbers of both dinoflagellates, giving a high algicidal activity. Findings from this study suggested the potential use of undecylprodigiosin as algicidal agent which could be used for the mitigation of HABs

Background/Objectives: Phyllanthus niruri, Orthosiphon stamineus and Labisia pumila are the three herbs listed in Malaysian National Key Economic Areas (NKEA). This study was conducted to determine the herbs extract yields and activities on antioxidant and cytotoxicity properties. Methods/Statistical Analysis: Cold maceration and soxhlet were the extraction methods employed and water, ethanol and 50% ethanol (v/v) were chosen as solvents. Findings: The results showed 50% ethanol (v/v) was the best solvent for all three herbs in terms of extraction yield. For cold maceration, the extract yields were 14.3%, 17.4% and 7.6% for P. niruri, O. stamineus and L. pumila, respectively. Whilst for soxhlet method, the same trend was observed where 50% ethanol (v/v) gave the highest extract yield of 21.2%, 14.3% and 6.8% for P. niruri, O. stamineus and L. pumila, respectively. Total phenolic content and antioxidant capacity were also highest using 50% ethanol and soxhlet method for all herbs. Application/Improvements: This shows that the food-grade solvents at a certain concentration are suitable for the best extraction of selected herbs.

Orthosiphon stamineus is one of the important herbal plants used in folk medicine to cure variety of diseases. Three compounds namely rosmarinic acid (RA), sinensetin (SEN) and eupatorin (EUP) were identified as the bioactive markers. However, a standardized extraction method for the preparation of O. stamineus extract enriched with the bioactive compounds was still undiscovered. Thus, this study aims to establish the optimal extraction method that can be used to prepare the enriched extract with anti-oxidant property. Maceration, reflux and Soxhlet were the extraction methods employed, with ethanol, 50% (v/v) aqueous ethanol and water were chosen as the solvents. Each extracts were evaluated for their biomarker contents (RA, SEN and EUP) and anti-oxidant capacity using thin layer chromatography (TLC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay respectively. Among the three extraction methods employed, the highest total extraction yield was obtained from reflux (72.73%) followed by Soxhlet (...

A study relating air quality with lichens was conducted at Universiti Kebangsaan Bangi campus. The aim is to determine the land of pollution in the area where the lichens are going. The site fulfils many characteristics for a good location such as the age of the campus which is more than 40 years, population density, buildings, traffic in the campus as well as at its periphery, hills surrounding the buildings, forest reserve, recreational gardens as well as daily activities in the campus. The palm trees in UKM comprise of 36 species, among them, Roystenia oleracea , R. regia, Veitchia merillii , Cocos nucifera , Bentinckia nicobarica , Archontophoenix alexandrae , Livistona rotundifolia, Areca catechu and Chrysalidocarpus lutescens which are good hosts to lichens. Twenty seven areas around the UKM campus were selected and they consist of 110 palm trees. The nitrogen content and pH values of each host at a height of 1 m and 2 m above the ground were collected. Each palm tree was selected according to the geographical position such as near to a road, hill, forest reserve, river, golf course and students’ residences. The locations were recorded using GPS and all data were entered in the GIS. The pH at the height of 1m of the pal host was 4.87±0.48, whilst the pH value at the height of 2 m was 4.88±0.46. The nitrogen content at the height of 1 m was 0.5940±0.4437% and for the height of 2 m was 0.6586±0.5698%. The lichens growing on the host are epiphytic lichens from the genus/species Arthonia, Caloplaca, Chrysothrix, Dirinaria, Hyperphyscia adglutinata, Laurera, Lecanographa, Lecanora, Parmotrema tinctorum, Parmotrema praesorediosum, Physcia, Pyxine cocoes, Rinodina, Trypethelium and Graphidaceae . Quadrant study at each host for epiphytic lichen gave values for air quality at the study site because each lichen will give a specific score according to its tolerance towards air pollution. The determination of air quality can be determined by the total lichen score in each quadrant. The results showed that the air quality can be categorized to 4 levels, that is, a score more than 10 is clean air, 0-10 is moderate, –10 to 0 is slightly polluted and less than -10 is highly polluted. The study showed that the location of the lichen at the palm host at UKM is consistent to the air quality. Overall, the Air Quality Score at UKM is 8.39±4.33 which is in the moderate category.

Andrographis paniculata Nees. (Acanthaceae) is an annual herbaceous plant widely cultivated in southern Asia, China, and Europe. It is used in the treatment of skin infections in India, China, and Malaysia by folk medicine practitioners.Antifungal activity of the whole plant extracts and isolation of active principles from A. paniculata were investigated.Dichloromethane (DCM) and methanol (MEOH) extracts of A. paniculata whole plant were screened for their antifungal potential using broth microdilution method in vitro against seven pathogenic fungal species responsible for skin infections. Active principles were detected through bioguided assays and isolated using chromatography techniques. Structures of compounds were elucidated through spectroscopy techniques and comparisons were made with previously reported data for similar compounds.DCM extract revealed lowest minimum inhibitory concentration (MIC) value (100 μg/mL) against Microsporum canis, Candida albicans, and Candida tropicalis, whereas MEOH extract revealed lowest MIC (150 µg/mL) against C. tropicalis and Aspergillus niger. DCM extract showed lowest minimum fungicidal concentration (MFC) value (250 µg/mL) against M. canis, C. albicans, C. tropicalis and A. niger, whereas MEOH extract showed lowest MFC (250 µg/mL) against Trichophyton mentagrophytes, Trichophyton rubrum, M. canis, C. albicans, C. tropicalis and A. niger. Bioassay guided isolation from DCM and MEOH extract afforded 3-O-β-d-glucosyl-14-deoxyandrographiside, 14-deoxyandrographolide, and 14-deoxy-11,12-didehydroandrographolide as antifungal compounds. The lowest MIC (50 µg/mL) and MFC (50 µg/mL) was exerted by 14-deoxyandrographolide on M. canis.This is first report on the isolation of antifungal substances through bioassay-guided assay from A. paniculata. Our finding justifies the use of A. paniculata in folk medicines for the treatment of fungal skin infections.

Six resveratrol dimers have been isolated from the stem bark of H. gregaria, ampelopsin A (1), balanocarpol (2), ε-viniferin (3), hopeafuran (4), heimiol A (5), and parviflorol (6). The structures of these compounds were determined based on spectroscopic evidence such as UV, IR, 1-D, 2-D NMR and comparison with the reported data. These compound inventions are strengthen conclusion that Hopea tends to produce resveratrol dimers. Biological activity of those compounds against murine leukemia P-388 cells showed that ε-viniferin (3) is the most active compound with IC50 value 5.1 ± 0.3 μg/mL. Keywords: H. gregaria, resveratrol dimers, murine leukemia P-388 cells

Fucoidan is a sulphated polysaccharide that consists mainly of fucose, normally found in brown seaweeds. In this study, fucoidan was extracted from Sargassum binderi (Fsar) from Malaysia and subsequently characterised. The chemical characteristics of Fsar were found to be different than those of commercial food grade fucoidan (Fysk) and those of previously studied fucoidans. NMR analysis proposed that the main structure of Fsar is →3)fuc-2-OSO3(-)(1→3)fuc(1→. The molecular weight (47.87kDa) and degree of sulphation (0.20) of Fsar were higher than those of Fysk, at 27.98kDa and 0.15, respectively. However, Fsar's polydispersity index (1.12) and fucose content (34.50%) were lower than those of Fysk, at 1.88 and 43.30%, respectively. Both Fsar and Fysk showed similar thermo-gravimetric properties with four mass losses, amorphous in nature and negative optical rotations. Results show that Fsar has fundamental characteristics of fucoidan with different structural conformation i.e. variation in glycosidic linkages and sulphate group orientation.

Phytochemical studies on the woods of Vatica pauciflora and Vatica lowii have been conducted. The woods of V. pauciflora were extracted with methanol by using Soxhlet apparatus while the woods of V. lowii were extracted with acetone at room temperature. The methanolic extract of V. pauciflora was semi-purified by using vacuum liquid chromatography (VLC) and further purified by high performance liquid chromatography (HPLC) to obtain a pure compound (1) . The same technique of semi-purification has been employed on V. lowii acetone extract which was further purified by radial chromatography to give a pure compound (2) . Based on the UV, IR, NMR and mass spectral data, the isolated compounds were characterized as (-)- cis -resveratrol-10- C -b-D-glucopyranoside and (-)-piceid respectively.

Streptomyces sp. has been known to produce antibiotics and other bioactive natural products. However, the production of these secondary metabolites depends on the culture conditions, where in most cases the secondary-metabolite genes are not expressed in fermentation culture. Recently, a novel fermentation method known as combined-culture has been introduced to unlock these “silent” genes, hence induces the production of cryptic metabolites. We report herein, our preliminary work on combined-culture using two soil-borne bacterial strains; Streptomyces and Tsukamurella. From the results, it is shown that the presence of Tsukamurella, a mycolic acid-containing bacterium induces the production of new metabolites in Streptomyces. Moreover, the production of compounds associated with Streptomyces was enhanced via combination-culture as compared to culture of Streptomyces strain alone. These findings may promote the feasibility of combined-culture in unlocking the “silent” genes of microorganisms which could lead to the discovery of novel metabolites.

Endophytic bacteria, such as Streptomyces, have the potential to act as a source for novel bioactive molecules with medicinal properties. The present study was aimed at assessing the antimalarial activity of crude extract isolated from various strains of actinobacteria living endophytically in some Malaysian medicinal plants. Using the four day suppression test method on male ICR strain mice, compounds produced from three strains of Streptomyces (SUK8, SUK10, and SUK27) were tested in vivo against Plasmodium berghei PZZ1/100 in an antimalarial screen using crude extracts at four different concentrations. One of these extracts, isolated from Streptomyces SUK10 obtained from the bark of Shorea ovalis tree, showed inhibition of the test organism and was further tested against P. berghei-infected mice for antimalarial activity at different concentrations. There was a positive relationship between the survival of the infected mouse group treated with 50 µg/kg body weight (bw) of ethyl acetate-SUK10 crude extract and the ability to inhibit the parasites growth. The parasite inhibition percentage for this group showed that 50% of the mice survived for more than 90 days after infection with the parasite. The nucleotide sequence and phylogenetic tree suggested that Streptomyces SUK10 may constitute a new species within the Streptomyces genus. As part of the drug discovery process, these promising finding may contribute to the medicinal and pharmaceutical field for malarial treatment.

Natural products play a crucial role in drug discovery. In the last decade, the advent of marine natural product research has produced a remarkable number of compounds, particularly those isolated from marine sponges, with a broad range of activities for the treatment of human and animal diseases. In this study, five known alkaloids namely aaptamine (1), 9-demethylaaptamine (2), 4- N-methylaaptamine (3), 9-methoxyaaptamine (4), 9-demethyloxyaaptamine (5), an uncommon amide in sponge, 4-hydroxybenzamide (6) and 3 β,5α-cholesterol (7) were isolated from the butanol extract of Aaptos aaptos (Schmidt, 1864) by bioactivity-guided isolation. Their structures were determined based on a detailed analysis of their 1D and 2D spectroscopic NMR and EIMS spectral data as well as comparison with literature data. Cytotoxic activity and anti-atherosclerotic property of the compounds were determined based on their ability to increase the transcriptional activity of SRB1 promoter and PPRE in human liver HepG2 cell line. The results showed that compounds 4 and 7 exhibited cytotoxic effects and compounds 1–4 and 7 increased the transcriptional activity of SRB1 promoter and PPRE. This suggests that compounds isolated from A. aaptos may have potential as anti-cancer agents and to reduce the progression of atherosclerosis. In addition, the compounds 1–4 displayed antibacterial activity against shrimp pathogenic bacteria, Vibrio harveyi and Vibrio sp. This suggests that the compounds have potential as vibriosis treatment.

Reactive species (RS) which are generated from the pollution, deep fried and spicy foods, leakage of electrons from mitochondrial electron transport chains etc. may result in an oxidative damage in the body. The oxidative damage may lead to various diseases such as Alzheimer, atherosclerosis and cancer. In order to prevent such diseases, antioxidants play important roles in reducing the powerful oxidizing agents. Vatica species that belongs to the family of Dipterocarpaceae has been widely known to contain abundant source of oligostilbenoids which demonstrated interesting result in biological activities such as anticancer and antioxidant. This may lead to a development of drugs as well as natural antioxidants. In this chapter, we are highlighting the oligostilbenoids isolated from Vatica species from various researcher as well as the biological activities.

Stilbenoids have been considered as an alternative phytotherapeutic treatment against methicillin-resistantStaphylococcus aureus(MRSA) infection. The combined effect ofε-viniferin and johorenol A with the standard antibiotics, vancomycin and linezolid, was assessed against MRSA ATCC 33591 and HUKM clinical isolate. The minimum inhibitory concentration (MIC) value of the individual tested compounds and the fractional inhibitory concentration index (FICI) value of the combined agents were, respectively, determined using microbroth dilution test and microdilution checkerboard (MDC) method. Only synergistic outcome from checkerboard test will be substantiated for its rate of bacterial killing using time-kill assay. The MIC value ofε-viniferin against ATCC 33591 and johorenol A against both strains was 0.05 mg/mL whereas HUKM strain was susceptible to 0.1 mg/mL ofε-viniferin. MDC study showed that only combination betweenε-viniferin and vancomycin was synergistic against ATCC 33591 (FICI 0.25) and HUKM (FICI 0.19). All the other combinations (ε-viniferin-linezolid, johorenol A-vancomycin, and johorenol A-linezolid) were either indifferent or additive against both strains. However, despite the FICI value showing synergistic effect forε-viniferin-vancomycin, TKA analysis displayed antagonistic interaction with bacteriostatic action against both strains. As conclusion,ε-viniferin can be considered as a bacteriostatic stilbenoid as it antagonized the bactericidal activity of vancomycin. These findings therefore disputed previous report thatε-viniferin acted in synergism with vancomycin but revealed that it targets similar site in close proximity to vancomycin’s action, possibly at the bacterial membrane protein. Hence, this combination has a huge potential to be further studied and developed as an alternative treatment in combating MRSA in future.

The lichen Usnea baileyi collected from different environments was characterised using Fourier transform infrared spectroscopy. This preliminary study was done to determine the effects of different environment populations on U. baileyi chemical composition. Results showed that the absorbance peaks of Golf Course 2 (GCU2) are more intense compared to Taman Awana (TA), Jalan Awana (JA) and Jalan Gohtong (JG). U. baileyi contains of dibenzofurans, depsides, depsidones, xanthones and terpenoids.

Tetracera scandens Linn. (Dilleniaceae), locally known as Mempelas Kasar, is traditionally used in folk remedies by various indigenous people in different countries including Malaysia for the treatment of rheumatism, inflammatory diseases, hepatitis, internal pains, urinary disorders, dysentery, sore throat, gout and diabetes infirmities; for lowering hypertension; and for child birth. In this study, phytochemical analysis of T. scandens leaf methanol (MeOH) extract was carried out for the first time and afforded three terpenoids (stigmasterol, betulinic acid and an isomeric mixture of sitosterol (∆5) glycoside and stigmasterol (∆5,22) glycoside) and six flavonoids (namely, kaempferol, quercetin, isoscutellarein, hypoletin, astragalin and kaempferol-3-O-(6″-O-p-trans-coumaroyl) glucoside, a rare compound which has been isolated for the first time from family Dilleniaceae). Structures of all compounds were elucidated through extensive UV–Vis, mass, IR and NMR spectral analysis. The occurrence of all these compounds is being reported for the first time from this plant. Due to the rare occurrence of hypoletin (3′,4′,5,7,8-pentahydroxyflavone) in plants, its in vitro antidiabetic effect was explored. Hence, the treatment of hypoletin in a dose-dependent manner was examined on the induction of lipid accumulation by using Oil Red O staining and glucose regulation in 3T3-L1 adipocytes in vitro with regard to its preventive role in the management of diabetes. After 8 days, morphological changes and high lipid accumulation activity were observed in cells treated with 10 μg/mL of hypoletin concentration (P < 0.01). In addition, the intracellular fat accumulation increased by up to 79.7 % relative to MDI-treated control cells at a dose of 10 μg/mL. Furthermore, insulin-induced 2-deoxy-d-[3H] glucose uptake was significantly increased (P < 0.001) in hypoletin-treated cells as compared to control (DMSO cells). Our results suggest that hypoletin could be useful for the management of type 2 diabetes due to its adipocyte stimulation and glucose uptake activity.

Two novel compounds, the lignan, (+)-2- (3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3,3,0]octane, and the coumarin, (+)-7-(3-methyl-4-carboxybutanoxy)umbelliferone methyl ester, have been isolated from the aerialparts of Melicope hayesii . The known compounds, eudesmin, kobusin, N - p -coumaroyltyramine, N -methyl-2-pyrrolidinone, umbelliferone and 7- (3-methylbut-2-enoxy)umbelliferone were alsoobtained. Their structures were determined by extensive NMR studies.

The title compound, 2C14H13NO4·3H2O, was isolated from the plant Acronychia pendunculata. The asymmetric unit consists of two quinoline mol­ecules and three water mol­ecules of crystallization. Intra- and inter­molecular hydrogen bonds are highly effective in forming infinite chains parallel to the b axis, thereby stabilizing the crystal structure.

Gracilaria species are red marine macroalgae that are found abundantly in Malaysia. Gracilaria changii from Morib, Selangor, G. manilaensis and Gracilaria sp. from Gelang Patah, Johor were used in this study. Five compounds were successfully isolated and identified as hexadecanoic acid (1), cholest-5-en-3-ol (2), 2-hydroxymyristic acid (3), cholesteryl myristate (4) and 1-(4'-methoxyphenyl)-3-(2”,4”,6”-trihydroxyphenyl)-3-hydroxypropanone (5) based on spectral data analysis (IR, UV, GC-MS,1H NMR,13C NMR, HMQC and HMBC). All compounds isolated were tested for cytotoxicity (MTT assay for HL-60 and MCF-7 cell lines), and antibacterial (disc diffusion method), antioxidant (DPPH free radical scavenging assay and xanthine oxidase inhibitory assay) and acetylcholinesterase inhibitory (AChE) activity (TLC bioautographic method). Compounds 1 and 3 exhibited strong cytotoxic activity against HL-60 and MCF-7 cell lines. Compound 5 showed high antioxidant activity in both the DPPH free radical scavenging and xanthine oxidase inhibition assays. Compound 1 showed positive activity for AChE inhibitory with a minimum inhibition dose of 0.625 μg sample. All compounds demonstrated antibacterial activity producing 8 to 14 mm inhibition zones. A positive control was applied to all bioassays and experiments were performed with three replicates. Results demonstrated that three edible red seaweeds are rich sources of bioactive compounds with potential application for pharmaceutical purposes.

The aim of this study is to determine the combined effects of stilbenoids from Shorea gibbosa and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). A total of nine pure compounds, five stilbenoid dimers ε-viniferin, ampelopsin A, balanocarpol, laevifonol and diptoindonesin G and four stilbenoid trimers a-viniferin, johorenol A, ampelopsin E and vaticanol G were evaluated for their antibacterial activities against ATCC 33591 and a HUKM clinical isolate. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for each active compound were determined using the serial microdilution and plate-streak techniques. The combined effect of stilbenoids with vancomycin against MRSA was evaluated using the checkerboard assay to determine their fractional inhibitory concentration (FIC) index values. The MIC value of a-viniferin on both MRSA strains was 100 μg/mL, whereas those of johorenol A on ATCC 33591 and HUKM strain were 100 μg/mL and 200 μg/mL, respectively. The MIC values of ampelopsin E and vaticanol G were higher than 400 μg/mL. Out of the five stilbenoid dimers, only ε-viniferin was capable of inhibiting the growth of both MRSA strains at MIC 400 μg/mL. The MBC value of ε-viniferin, a-viniferin and johorenol A showed bacteriostatic action against MRSA. The FIC index value of ε-viniferin and a-viniferin in combination with vancomycin showed an additive effect (0.5 < FIC ≤ 2.0) against both MRSA strains. Johorenol A-vancomycin combination was also additive against HUKM strain, but it showed synergistic interaction with vancomycin against ATCC 33591 (FIC < 0.5). Stilbenoid compounds from Shorea gibbosa have anti-MRSA activity and huge potential as an alternative phytotherapy in combating MRSA infections.

Myristica fragransHoutt is mostly cultivated for spices in Penang Island, Malaysia. The ethyl acetate and ethanol extracts of flesh, mace and seed ofMyristica fragranswas evaluated the bactericidal potential against three Gram-positive cariogenic bacteria (Streptococcus mutansATCC 25175,Streptococcus mitisATCC 6249, andStreptococcus salivariusATCC 13419) and three Gram-negative periodontopathic bacteria (Aggregatibacter actinomycetemcomitansATCC 29522,Porphyromonas gingivalisATCC 33277, andFusobacterium nucleatumATCC 25586). Antibacterial activities of the extracts was determined by twofold serial microdilution, with minimum inhibitory concentrations (MIC) ranging from 1.25 to 640 mg/mL and 0.075 to 40 mg/mL. The minimum bactericidal concentration (MBC) was obtained by subculturing method. Among all extracts tested, ethyl acetate extract of flesh has the highest significant inhibitory effects against Gram-positive and Gram-negative bacteria with mean MIC value ranging from 0.625 to1.25±0.00(SD) mg/mL;P=0.017) and highest bactericidal effects at mean MBC value ranging from 0.625 mg/mL to20±0.00(SD) mg/mL. While for seed and mace ofMyristica fragrans, their ethanol extracts exhibited good antibacterial activity against both groups of test pathogens compared to its ethyl acetate extracts. All of the extracts ofMyristica fragransdid not show any antibacterial activities againstFusobacterium nucleatumATCC 25586. Thus, our study showed the potential effect of ethyl acetate and ethanol extracts from flesh, seed and mace ofMyristica fragransto be new natural agent that can be incorporated in oral care products.

Papuabalanol A (Ib) shows moderate vasodilator effect on rat aorta while papuabalanol B (Ia) shows potent inhibition of mushroom tyrosinase and anti-melanogenesis in B16 mouse melanoma cells.

Two new dehydrohexahydroxydiphenoyl (DHHDP) esters of dihydrochalcone glycosides, papuabalanols A (1) and B (2) were isolated from the ethyl acetate extract of Balanophora papuana. Their structures were elucidated on the basis of spectroscopic data and chemical evidences. Papuabalanol A (1) showed moderate vasodilator effect on rat aorta and papuabalanol B (2) showed potent inhibition of mushroom tyrosinase and anti-melanogenesis in B16 mouse melanoma cells.

A new methylated flavonol, 5,7,2 ′,4 ′-tetrahydroxy-3-methoxyflavone (1), had been isolated from the methanol extract of the wood of Morus australis, along with nine known compounds, kuwanon C (2), morusin (3), morachalcone A (4), oxyresveratrol (5), 4 ′-(2-methyl-2-buten- 4-yl)oxyresveratrol (6), moracins M (7) and C (8), alboctalol (9), and macrourin B (10). The structures of these compounds were determined based on spectral evidence, including UV, IR, NMR, and mass spectra. Cytotoxic properties of compounds 1 →10 were evaluated against murine leukemia P-388 cells. The prenylated stilbene 6 and 2-arylbenzofuran 8, and morusin (3) were found to have strong cytotoxic effects with IC50 values of 6.9, 8.7, and 10.1 μM, respectively.

A new oligostilbenoid derivative, diptoindonesin F (1), along with five known oligostilbenoids, (-)-ampelopsin A (2), (-)-alpha-viniferin (3), ampelopsin E (4), (-)-vaticanol B (5), and (-)-hemsleyanol D (6), were isolated from the methanol extract of the tree bark of Shorea gibbosa. The structure of the new compound was determined based on the analysis of spectroscopic data, including UV, IR, NMR 1-D and 2-D, and mass spectra. Cytotoxic properties of the isolated oligostilbenoids were evaluated against murine leukemia P-388 cells with the result that compounds 2 and 4 showed the highest cytotoxicity.

A new resveratrol tetramer, named diptoindonesin E, was isolated from the acetone extract of the tree bark of Dipterocarpus hasseltii, together with five known resveratrol oligomers (−)-e-viniferin, laevifonol, (−)-α-viniferin, vaticanol B, (−)-hopeaphenol, and a coumarin, scopoletin. The structures of these compounds were determined from spectroscopic evidence. Cytotoxicity test of the isolated compounds showed that hopeaphenol strongly inhibited murine leukemia P-388 cells.

The title compound, C17H16O5, was isolated from the plant Lindera poliantha. The cyclo­pentenedione and phen­yl rings are connected by the central C3O fragment, which makes dihedral angles with these rings of 7.10 (6) and 16.24 (10)°, respectively.

Phytochemical studies on the woods and twigs of Vatica pauciflora (Dipterocarpaceae) have been conducted. The woods and twigs of V. pauciflora were extracted in methanol and ethanol respectively with Soxhlet apparatus. The crude methanol extracts from the woods were semi-purified by vacuum liquid chromatography to give 14 fractions (VMB01-VMB14). The VMB10 was further purified by radial chromatography to give pure dimmer stilbenoid. The same technique has been employed on the crude ethanol extracts from the twigs in which one pure fraction, VER612 was obtained. Based on the UV, IR, NMR and mass spectral data, the pure compounds were characterized as -viniferin and vaticanol G respectively. An oxidative damage test which was done on Chang liver cells has shown that -viniferin has a potential to be a chemopreventive agent to protect liver cells from oxidative damage.

Centre of Foundation Studies, MARA University of Technology, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; School of Chemical Sciences and Food Technology, Faculty of Sciences and Technology, National University of Malaysia, 43600 Bangi, Selangor, Malaysia; School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, National University of Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia; Faculty of Applied Science, MARA University of Technology, Pahang Campus, 26400 Bandar Tun Abdul Razak, Jengka, Pahang, Malaysia; E-mail: aisyahsalihah@yahoo.co.uk

Two new dihydroflavonol derivatives, macarecurvatins A and B, have been isolated from the leaves of Macaranga recurvata(Euphorbiaceaae), along with the known compounds diisoprenylaromadendrin, glyasperin A and broussoflavonol F. The structures of the new compounds were determined on the basis of spectroscopic evidence. Upon cytotoxic evaluation against P-388 cells, macarecurvatin B showed strong activity with an IC50 of 0.83 μM.