Juriyati Jalil

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.

Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines.

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.

Inhibitory effect of compounds from Goniothalamus tapis Miq. and Goniothalamus uvaroides King on platelet-activating factor receptor binding.

Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl‐lactones, (−)‐cryptomeridiol, liriodenine, 3‐methyl‐1H‐benz[f]indole‐4,9‐dione, (−)‐stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet‐activating factor (PAF) receptor binding on rabbit platelets using 3H‐PAF as a ligand. Among the compounds tested, (−)‐cryptomeridiol, (+)‐goniothalamin and (+)‐isoaltholactone exhibited a significant and concentration‐dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)50 values of 17.5, 19.7 and 46.5 µm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors. Copyright

Inhibitory Effects of Phylligenin and Quebrachitol Isolated from Mitrephora vulpina on Platelet Activating Factor Receptor Binding and Platelet Aggregation

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.

Inhibitory effects of acetylmelodorinol, chrysin and polycarpol from mitrella kentii on prostaglandin E2 and thromboxane B2 production and platelet activating factor receptor binding

Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using 3H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE2 production (IC50 value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB2 production with IC50 values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC50 values of 24.3 and 24.5 µM, respectively.

Antiplatelet Aggregation and Platelet Activating Factor (PAF) Receptor Antagonistic Activities of the Essential Oils of Five Goniothalamus Species

Nine essential oils, hydrodistilled from different parts of five Goniothalamus species (G. velutinus Airy-Shaw, G. woodii Merr., G. clemensii Ban, G. tapis Miq. and G. tapisoides Mat Salleh) were evaluated for their ability to inhibit platelet aggregation in human whole blood using an electrical impedance method and their inhibitory effects on platelet activating factor (PAF) receptor binding with rabbit platelets using 3H-PAF as a ligand. The chemical composition of the oils was analyzed by gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS). The bark oil of G. velutinus was the most effective sample as it inhibited both arachidonic acid (AA) and ADP-induced platelet aggregation with IC50 values of 93.6 and 87.7 µg/mL, respectively. Among the studied oils, the bark oils of G. clemensii, G. woodii, G. velutinus and the root oil of G. tapis showed significant inhibitory effects on PAF receptor binding, with IC50 values ranging from 3.5 to 10.5 µg/mL. The strong PAF antagonistic activity of the active oils is related to their high contents of sesquiterpenes and sesquiterpenoids, and the individual components in the oils could possibly produce a synergistic effect in the overall antiplatelet activity of the oils.

Platelet-activating factor (PAF) receptor binding activity of the roots of Enicosanthellum pulchrum

Context: Enicosanthellum pulchrum (King) Heusden (Annonaceae) is a coniferous tree that is confined to mountain forests. The chemical constituents of this species have been studied previously; however, its biological activity has never been investigated before and is reported here for the first time. Objective: The extracts, fractions and compounds from the roots of E. pulchrum were investigated for their inhibitory effects on platelet-activating factor (PAF) receptor binding to rabbit platelets using 3H-PAF as a ligand. Materials and methods: The PAF receptor binding inhibitory effect using rabbit platelets was determined in vitro by measuring the difference between total amount of bound 3H-PAF in the presence and the absence of excess unlabelled PAF. The compounds were isolated by bioassay-guided fractionation and their structures were elucidated by spectroscopic techniques. Results and discussion: Among the extracts tested, the ethyl acetate extract was the most active with 85.6% inhibition, while hexane and methanol extracts showed 40.2 and 42.5% inhibition, respectively. Fractionation of the ethyl acetate extract using vacuum liquid chromatography (VLC) yielded six fractions AEA(I-–VI). Chromatography fraction AEA(VI) yielded a new compound, 1-(2′,3′,4′-trimethoxyphenyl)hexan-1-ol, while fraction AEA(III) afforded three compounds, namely liriodenine, cleistopholine and dehydroanonaine. 1-(2′,3′,4′-Trimethoxyphenyl)hexan-1-ol, cleistopholine and dehydroanonaine showed relatively strong inhibition with IC50 values of 26.6, 50.2 and 45.4 µM, respectively. Conclusion: The results suggest that these compounds could be responsible for the PAF antagonistic activity of the ethyl acetate extract of this plant.

Protective effects of Labisia pumila var. alata on biochemical and histopathological alterations of cardiac muscle cells in isoproterenol-induced myocardial infarction rats

The study was designed to evaluate the cardioprotective effects of the standardized aqueous and 80% ethanol extracts of Labisia pumila var. alata (LPva) in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. The extracts were administered to Wistar rats orally for 28 days with three doses (100, 200 and 400 mg/kg of body weight) prior to ISO (85 mg/kg)-induced MI in two doses on day 29 and 30. The sera and hearts were collected for biochemical and histopathological analysis after the rats were sacrificed 48 h after the first induction. The main components of the extracts, gallic acid, alkylresorcinols and flavonoids were identified and quantitatively analyzed in the extracts by using a validated reversed phase HPLC method. The extracts showed significant protective effects as pretreated rats showed a significant dose-dependent decrease (p < 0.05) in cardiac enzyme activities, i.e., cardiac troponin I (cTnI), creatine kinase MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT) and aspartate transaminase (AST), when compared with ISO-control rats. There were significant rises (p < 0.05) in the activity of oxidase enzymes, i.e., glutathione peroxide (GPx), catalase (CAT) and superoxide dismutase (SOD) of the pretreated rats, when compared with ISO-control group. Histopathological examination showed an improvement in membrane cell integrity in pre-treated rats compared to untreated rats. The major components of LPva extracts can be used as their biomarkers and contributed to the cardioprotective effects against ISO-induced MI rats.

Antiplatelet aggregation activity of compounds isolated from Guttiferae species in human whole blood.

Twenty compounds isolated from Calophyllum inophyllum L., C. inophylloides King, Garcinia opaca King, G. bancana Miq., and G. parvifolia Miq. (Guttiferae) were evaluated for their ability to inhibit platelet aggregation in human whole blood induced by arachidonic acid (AA), collagen, and adenosine diphosphate (ADP). The compounds inhibited platelet aggregation in a dose-dependent manner. Among the compounds tested, 2-(3-methylbut-2-enyl)-1,3,5-trihydroxyxanthone and 2-(3-methylbut-2-enyl)-1,3,5,6- tetrahydroxyxanthone showed strong inhibitory activity on platelet aggregation induced by AA with IC50 values of 115.9 and 113.0 μM, respectively. Rubraxanthone showed inhibitory activity against aggregation caused by the three inducers, and was the most effective antiplatelet compound against collagen-induced platelet aggregation with an IC50 value of 47.0 μM. Macluraxanthone, GB-1a, pyranoamentoflavone, and a neoflavonoid showed selective inhibitory activity on platelet aggregation induced by 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.