Wilawan Mahabusarakam

Rhodomyrtone: A new candidate as natural antibacterial drug from Rhodomyrtus tomentosa

Rhodomyrtone [6,8-dihydroxy-2,2,4,4-tetramethyl-7-(3-methyl-1-oxobutyl)-9-(2-methylpropyl)-4,9-dihydro-1H-xanthene-1,3(2H)-di-one] from Rhodomyrtus tomentosa (Aiton) Hassk. displayed significant antibacterial activities against gram-positive bacteria including Bacillus cereus, Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Streptococcus gordonii, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus salivarius. Especially noteworthy was the activity against MRSA with a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) ranging from 0.39 to 0.78 microg/ml. As shown for S. pyogenes, no surviving cells were detected within 5 and 6h after treatment with the compound at 8MBC and 4MBC concentrations, respectively. Rhodomyrtone displays no bacteriolytic activity, as determined by measurement of the optical density at 620 nm. A rhodomyrtone killing test with S. mutans using phase contrast microscopy showed that this compound caused a few morphological changes as the treated cells were slightly changed in color and bigger than the control when they were killed. Taken together, the results support the view that rhodomyrtone has a strong bactericidal activity on gram-positive bacteria, including major pathogens.

Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin

Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.

Effects of compounds from Garcinia mangostana on inflammatory mediators in RAW264.7 macrophage cells

ETHNOPHARMACOLOGICAL RELEVANCE The fruit hull of Garcinia mangostana Linn. has been used in Thai traditional medicine for treatment of abscess and skin infection. AIM OF THE STUDY The mangosteen fruit hull and its compounds were carried out to investigate for anti-inflammatory activity. MATERIAL AND METHODS The extract of Garcinia mangostana together with alpha- and gamma-mangostins were tested for anti-inflammatory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-4 (IL-4) releases as well as their mechanisms in transcriptional levels using RAW264.7 macrophage cells. RESULTS Mangosteen extract possessed potent NO inhibitory effect with an IC50 value of 1.0 microg/ml. The isolated compounds from the extract including alpha-mangostin and gamma-mangostin, possessed marked inhibitory effect against NO release with IC50 values of 3.1 and 6.0 microM, respectively. The extract exhibited potent inhibitory effect on PGE2 release (IC50=6.0 microg/ml), whereas those of alpha- and gamma-mangostins were 13.9 and 13.5 microM, respectively. However, mangostins possessed only moderate effects towards TNF-alpha and IL-4 releases with IC50 values ranging from 31.8 to 64.8 microM. Both extract and alpha-mangostin suppressed transcription of gene encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in dose-dependent manners, whereas gamma-mangostin had only an inhibitory effect on transcription of iNOS. CONCLUSION The present study may support the Thai traditional use of Garcinia mangostana fruit hull for treatment of inflammatory-related diseases through the inhibition of NO and PGE2 releases, but moderate effect through TNF-alpha and IL-4.

Tomentosones A and B, Hexacyclic Phloroglucinol Derivatives from the Thai Shrub Rhodomyrtus tomentosa

Two phloroglucinols named tomentosones A and B (1 and 2) that each possess a novel hexacyclic ring system were isolated from the CH(2)Cl(2) extract of Rhodomyrtus tomentosa leaves. Their structures were elucidated from analyses of 2D NMR spectroscopic data. Tomentosone A inhibited the growth of chloroquine-resistant and -sensitive strains of the malaria parasite Plasmodium falciparum, with IC(50) values of 1.49 μM and 1.0 μM, respectively, while tomentosone B was significantly less active.

Assessment of Antistaphylococcal Activity of Partially Purified Fractions and Pure Compounds from Eleutherine americana

Ready-to-eat foods were investigated for contamination with methicillin-resistant Staphylococcus aureus (MRSA), and the partially purified fractions from the bulb of Eleutherine americana were evaluated for their anti-MRSA activity. Partially purified fractions Ea6.3 and Ea9 demonstrated good antibacterial activity with a MIC of 125 to 500 microg/ml and MBC of 250 to > or =1000 microg/ml against all the food isolates. Fraction Ea6.3 produced a MIC and MBC of 250 and 500 microg/ml, respectively, whereas fraction Ea9 yielded MIC and MBC of 125 and > or =1000 microg/ml, respectively, against the enterotoxin-producing reference strains. Growth curves in the presence of fraction Ea6.3 at 4 x MIC resulted in total elimination of all the test strains between 20 and 24 h, while fraction Ea9 reduced bacterial population by at least 6 log relative to the control. The partially purified fractions were further purified to obtain pure compounds identified as eleutherol, eleutherin, isoeleutherin, hongconin, two anthraquinones, and elecanacin. The antibacterial activities of these compounds were also investigated; they produced MICs ranging from 31.25 to > or =1000 microg/ml. This study suggests that E. americana crude extract or its partially purified fractions have potentials for application as natural food preservatives.

Alkaloid and coumarins from the green fruits of Aegle marmelos

Five (1-5) and 15 known compounds were isolated from the acetone extract of the green fruits of Aegle marmelos. The structure of compounds 1-5, marmesiline (1), 6-(4-acetoxy-3-methyl-2-butenyl)-7-hydroxycoumarin (2), 6-(2-hydroxy-3-hydroxymethyl-3-butenyl)-7-hydroxycoumarin (3), marmelonine (4) and 8-hydroxysmyrindiol (5), were determined on the basis of spectroscopic analyses. Antifungal and antibacterial activities of selected compounds were also evaluated.

A triterpenoid saponin from Maesa ramentacea

The structure of a piscicidal triterpenoid saponin (saponin A) isolated from the leaves of Maesa ramentacea has been shown to be 3-O-[[(alpha-rhamnopyranosyl (1-->2)-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl (1-->3)]-[beta-D-glucopyranosyl(1-->2)]-beta-D-glucuronopyranosyl] barringtogenol C21, 22-O-diangeloate. Extensive use was made of homo- and heteronuclear 2D NMR techniques.

Inhibitory Effect of Eleutherine americana Merr. Extract on Staphylococcus aureus Isolated from Food

About 106 samples of ready-to-eat foods were purchased over a period of 3 mo out of which 76 (71.69%) were contaminated with Staphylococcus aureus. S. aureus isolated from the food samples were characterized phenotypically using traditional biochemical methods. Ninety-four percent of the isolates were mannitol fermenters, 86% positive for coagulase test, while 80% produced lipase enzyme. Antibiotic susceptibility test revealed that 21% and 63% of the food isolates were resistant to oxacillin and penicillin, respectively. The antibacterial activity of the bulb of Eleutherine americana used in Thai cuisine was investigated by agar disc diffusion using 2.5 mg of the crude extract and produced inhibition zone between 14.5 and 15.7 mm, while the minimum inhibitory concentration (MIC) value ranged from 0.06 to 1.00 mg/mL on both food isolates and reference strains. Growth curve in the presence of the crude ethanol extract at 4 MIC showed bacteriostatic effect by 5 log reduction relative to the control. Partially purified fractions tentatively identified by column chromatography were suspected to be responsible for the antibacterial property. This study suggests that E. americana bulb has potential for application as a natural preservative in foods.

A new flavellagic acid derivative and phloroglucinol from Rhodomyrtus tomentosa

A new flavellagic acid derivative, 3,3′,4,4′-tetra-O-methylflavellagic acid and six known compounds were isolated from the stems of Rhodomyrtus tomentosa while a new phloroglucinol, named rhodomyrtosone I, and six known compounds were isolated from the fruit. Their structures were elucidated by spectroscopic analyses as well as by comparisons with related compounds.

Morelloflavone blocks injury-induced neointimal formation by inhibiting vascular smooth muscle cell migration

BACKGROUND In-stent restenosis, or renarrowing within a coronary stent, is the most ominous complication of percutaneous coronary intervention, caused by vascular smooth muscle cell (VSMC) migration into and proliferation in the intima. Although drug-eluting stents reduce restenosis, they delay the tissue healing of the injured arteries. No promising alternative anti-restenosis treatments are currently on the horizon. METHODS In endothelium-denudated mouse carotid arteries, oral morelloflavone-an active ingredient of the Thai medicinal plant Garcinia dulcis-significantly decreased the degree of neointimal hyperplasia, without affecting neointimal cell cycle progression or apoptosis as evaluated by Ki-67 and TUNEL staining, respectively. At the cellular level, morelloflavone robustly inhibited VSMC migration as shown by both scratch wound and invasion assays. In addition, morelloflavone prevented VSMCs from forming lamellipodia, a VSMC migration apparatus. Mechanistically, the inhibition by morelloflavone of VSMC migration was through its negative regulatory effects on several migration-related kinases, including FAK, Src, ERK, and RhoA. Consistently with the animal data, morelloflavone did not affect VSMC cell cycle progression or induce apoptosis. RESULTS These data suggest that morelloflavone blocks injury-induced neointimal hyperplasia via the inhibition of VSMC migration, without inducing apoptosis or cell cycle arrest. GENERAL SIGNIFICANCE We propose morelloflavone to be a viable oral agent for the prevention of restenosis, without compromising effects on the integrity and healing of the injured arteries.