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Individual Eucalyptus trees in south-eastern Australia vary considerably in susceptibility to herbivores. On the one hand, studies with insect herbivores have suggested that variation in the concentrations of foliar monoterpenes is related to variation in susceptibility. On the other, studies with marsupial folivores have suggested that variation in the concentrations of sideroxylonals (a group of formylated phloroglucinol compounds) is responsible for variation in susceptibility. We examined relative importance of sideroxylonals and 1,8-cineole (a dominant monoterpene) in host tree selection by Christmas beetles (Anoplognathus species: Coleoptera: Scarabaeidae) by using no-choice experiments, choice/no-choice experiments, and manipulative experiments in which concentrations of sideroxylonals or 1,8-cineole were altered. We used two species of host Eucalyptus, one species of non-host Eucalyptus, and three species of non-host non-Eucalyptus trees. Leaf consumption by Christmas beetles was negatively correlated with the concentrations of sideroxylonals and 1,8-cineole. Artificial increases in the concentration of sideroxylonals or 1,8-cineole reduced leaf consumption by Christmas beetles. An artificial reduction in foliar monoterpenes had no effect on leaf consumption by the beetles when leaves contained high or very low concentrations of sideroxylonals. However, when the concentration of sideroxylonals was moderate, a reduction in the foliar monoterpenes increased leaf consumption by the beetles. Therefore, monoterpenes such as 1,8-cineole may be used as a negative cue by Christmas beetles. The pattern of food consumption on non-host Eucalyptus species and non-host non-Eucalyptus species suggest that both positive and negative cues may be used by Christmas beetles to select host trees.

Counter-current chromatography (CCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L. The petroleum ether extract was separated by the solvent system of n-heptane-methanol-acetonitrile (1.5:0.5:0.5, v/v) and n-heptane-methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane-ethyl acetate-methanol-water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol-ethyl acetate-water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC-MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, ¹HNMR and ¹³CNMR., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Statistical experimental design was used to optimize the concentration of trace elements for production of antifungal compound, 2,4-diacetylphloroglucinol (DAPG), from fluorescent pseudomonad R62 in shake-flask cultivation. The selection of the trace metal ions, influencing DAPG production, was done using Plackett-Burman design (PBD). Only Zn(2+), Mn(2+) and MoO(4)(2-) were the most significant components (p<0.05). A quadratic model was used to fit the response. Application of response surface methodology (RSM) revealed that the optimum values of the salts of the trace elements Zn(2+) (ZnSO(4)·7H(2)O), Mn(2+) (MnCl(2)·4H(2)O), and MoO(4)(2-) (Na(2)MoO(4)·2H(2)O) were 83, 42 and 135μM, respectively, to achieve 125 mg/L of DAPG, which was nearly 13-fold more compared to its production in basal synthetic medium in shake flask. The studies in 14L bioreactor resulted in 135 mg/L of DAPG at the end of 36 h of cultivation. The culture broth containing 125 mg/L of DAPG was found to be sufficient for keeping the bio-inoculant viable in non-sterile talcum powder-based formulations (which contained 25μg DAPG/g carrier) when stored at 28°C for 6 months. The structure of the purified DAPG was confirmed using (1)H NMR and mass spectrometry., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Context:  This study describes the antispasmodic, bronchodilator, and cardiovascular-modulatory activities of Hypericum perforatum Linn. (Hypericaceae) fractions and constituents., Aim of Study:  Pharmacological investigation of H. perforatum fractions and active principles., Materials and Methods:  H. perforatum extract fractions [petroleum spirit (HpPet), chloroform (HpCHCl(3)), ethyl acetate (HpEtAc), and aqueous (HpAq)] and its compounds (hyperforin, hypericin, and hyperoside) were studied in various isolated tissue preparations., Results:  In rabbit jejunum, HpCHCl(3), HpEtAc and HpAq, like papaverine, inhibited both spontaneous and K(+) (80 mM)-induced contractions at similar concentrations, whereas HpPet was relatively potent against K(+), as verapamil. All fractions caused rightward of Ca(2+) concentration-response curves (CRCs), similar to verapamil. HpCHCl(3), HpEtAc, and HpAq shifted isoprenaline-inhibitory CRCs to left, like papaverine, while HpPet was devoid of any such effect, as verapamil. In guinea-pig trachea, HpCHCl(3), HpEtAc, and HpAq equipotently relaxed carbachol and K(+)-induced contractions and shifted the isoprenaline-curves to the left, whereas HpPet was more effective against K(+), without potentiating isoprenaline effect. When tested in rabbit aorta, all fractions exhibited vasoconstrictor and vasodilator effects, except HpEtAc, which did not produce vasoconstriction. In guinea-pig atria HpCHCl(3), HpEtAc, and HpAq initially caused cardiac stimulation, followed by inhibition, similar to papaverine, whereas HpPet, like verapamil, caused only cardiac suppression. Hyperforin, hypericin, and hyperoside showed a similar pattern of spasmolytic effect to verapamil., Discussion and Conclusion:  Thus, all tested fractions of H. perforatum exhibit a combination of Ca(2+) antagonist and phosphodiesterase-inhibition, except petroleum spirit which was devoid of later mechanism. The compounds tested showed only Ca(2+) channel blocking effect.

Two new norlignans, hyperiones A (1) and B (2), three new acylphloroglucinols, aspidinol C (3) and hyperaspidinols A (5) and B (6), the known compound aspidinol D (4), and the symmetrical dimeric xanthone hyperidixanthone (7) were isolated from Hypericum chinense. Their structures were established by spectroscopic analysis. In an antibacterial assay using a panel of multidrug-resistant (MDR) strains, compounds 3 and 4 exhibited promising activity against the NorA efflux protein overexpressing MDR Staphylococcus aureus strain SA-1199B with a minimum inhibitory concentration (MIC) of 2 μg/mL (8.4 μM) and 4 μg/mL (16.8 μM), respectively. The positive control antibiotic norfloxacin showed activity at MIC 32 μg/mL (100 μM).

Seven new prenylated acylphloroglucinols, yungensins A-G, were isolated from the diethyl ether extract of the scaly rhizomes and roots of an Argentine collection of the fern Elaphoglossum yungense. All the compounds contained a geranyl group attached to the filicinic acid-type residue. The diethyl ether extract and yungensins A-F displayed antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa with MICs ranging from 10 to 200 μg/mL. All tested acylphloroglucinols, except for yungensin D, caused bacteriolysis of S. aureus at MBC or higher doses (50-200 μg/mL). At 10 μg/mL, the ether extract as well as yungensins A, B, and D-F altered the biofilm production in both microoganisms.

Loxophlebal A, a new antibacterial formylated phloroglucinol was isolated from the mother liquor obtained after separation of sideroxylonals from the chloroform-methanol extract of leaves of Eucalyptus loxophleba ssp lissophloia. The structure of loxophlebal A was determined to be 3-desformyl sideroxylonal A by spectroscopic methods including 1D- and 2D-NMR. The stereochemistry of loxophlebal A was determined by chemical correlation with sideroxylonal A. This article also reports an efficient, simple and economic method for large scale isolation of sideroxylonals in a purity of >90% from the leaves of Eucalyptus loxophleba ssp lissophloia., (Copyright © 2010 Elsevier B.V. All rights reserved.)

With bioassay-guided fractionation, five new polyprenylated benzoylphloroglucinol derivatives, garcimultiflorone D (1), 18-hydroxygarcimultiflorone D (2), garcimultiflorone E (3), garcimultiflorone F (4), and isogarcimultiflorone F (5), and five known compounds, guttiferone E (6), guttiferone F (7), aristophenone A (8), isoxanthochymol (9), and morelloflavone (10), were isolated from the acetone extract of the twigs of Garcinia multiflora. The compounds were evaluated for their apoptotic effects against HeLa-C3 cells, which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. Compounds 1 and 3-9 activate caspase-3 in HeLa-C3 cells within 72 h after treatment at a concentration of 100 microM or lower. In particular, compounds 6, 8, and 9 showed strong apoptosis-inducing effects at a concentration of 25 microM.

Ten phenolic compounds (1-10) were isolated from a methanol extract of Lawsonia inermis leaves including two new ones, lawsoniasides A (1) and B (2). Their structures were elucidated by spectroscopic methods (NMR and FTICRMS) in combination with acid hydrolysis and GC analyses. Compounds 4 and 5 showed a significant inhibition on receptor activator for nuclear factor-kappaB ligand-induced osteoclast formation in murine bone-marrow macrophages., (2010. Published by Elsevier Ltd.)

Four new prenylated acylphloroglucinols, petiolins J-M (1-4), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum, and the structures were elucidated by spectroscopic data and a single-crystal X-ray diffraction analysis. Petiolin J (1) exhibited antimicrobial activity., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Upon activation, microglia, the immunocompetent cells in the brain, get highly phagocytic and release pro-inflammatory mediators like nitric oxide (NO). Excessive NO production is pivotal in neurodegenerative disorders, and there is evidence that abnormalities in NO production and inflammatory responses may at least support a range of neuropsychiatric disorders, including depression. Although extracts of St. John's wort (Hypericum perforatum L.) have been used for centuries in traditional medicine, notably for the treatment of depression, there is still considerable lack in scientific knowledge about the impact on microglia. We used N11 and BV2 mouse microglia, as well as RAW 264.7 macrophages to investigate the effects of St. John's wort extract and constituents thereof on NO production Moreover, flow cytometry and fluorescence microscopy were employed to analyze the influence on phagocytosis, transcription factor activation states, and cell motility. We found that extracts of St. John's wort efficiently suppress lipopolysaccharide-induced NO release and identified hyperforin as the responsible compound, being effective at concentrations between 0.25 and 0.75 microM. The reduced NO production was mediated by diminished inducible nitric oxide synthase expression on the mRNA and protein level. In addition, at similar concentrations, hyperforin reduced zymosan phygocytosis to 20-40% and putatively acted by downregulating the CD206 macrophage mannose receptor and modulation of cell motility. We found that the observed effects correlate with a suppression of the activated state of Nf-kappaB and phospho-CREB, while c-JUN, STAT1, and HIF-1alpha activity and cyclooxygenase-2 expression remained unaffected by hyperforin. These results reveal that hyperforin influences pro-inflammatory and immunological responses of microglia that are involved in the progression of neuropathologic disorders.

Five new prenylated phloroglucinols were isolated from the diethyl ether extracts of the ferns Elaphoglossum gayanum and E. piloselloides. Their structures were established by analysis of their spectroscopic data (1D and 2D NMR, HRMS, and IR) and chemical derivatization. The two major compounds exhibited moderate molluscicidal activity against the snail Biomphalaria peregrina, a vector of the tropical disease schistosomiasis, with LD(50) 7.2 microg/mL (14.4 microM) and 11.7 microg/mL (22.2 microM).

Three new phloroglucinols, named lysidicins F-H (1-3), were isolated from the roots of Lysidice rhodostegia. These compounds have a unprecedented benzyl benzo[b]furo[3,2-d]furan skeleton, and lysidicin F (1) is the first example of natural product with trans-fused furan rings. Their structures were established on the basis of extensive spectroscopic analysis, and the absolute configurations of them were determined by computational methods. A possible biosynthetic pathway for 1-3 was also postulated.

An unusual polyprenylated acylphloroglucinol derivative unsubstituted at C-2 and C-6, garcicowin A (1), together with three other new (garcicowins B-D, 2-4) and nine known analogues, was isolated and characterized from the twigs of Garcinia cowa. The structures of 1-4 were elucidated by interpretation of their spectroscopic data. The compounds isolated were evaluated for their cytotoxicity against two cancer cell lines (HT-29 and HCT116) and against normal colon cells (CCD-18Co), and the results demonstrated their selective toxicity toward the cancer cells.

Five new phloroglucinol glycosides, eucalmainosides A-E (1-5), were isolated from the fresh fruits of Eucalyptus maideni, along with 15 flavonoids (6-20), seven (+)-oleuropeic acid derivatives (15, 16, and 22-26), three hydrolyzable tannins (32-34), and six simple phenolic compounds (21, 27-31). Their structures were determined on the basis of spectroscopic analyses, including HSQC, HMBC, and acidic hydrolysis. The in vitro anti-herpes simplex virus 1 (HSV-1) assay indicated that the flavonols, myricetin (6) and quercetin (7), and the ellagitannin isocoriariin F (33) showed weak anti-HSV-1 activity with TIC values of 0.31, 0.33, and 0.12 mM, respectively.

Two new C(30)-epimeric polycyclic polyprenylated acylphloroglucinols (PPAPs), named uralodins B and C (1 and 2, resp.), were isolated from the aerial parts of Hypericum henryi subsp. uraloides together with two new chromone glucosides, urachromones A and B (3 and 4, resp.), as well as 16 known compounds. Their structures were established by extensive NMR techniques and MS analysis. The epimers 1 and 2 always behaved like a single compound when examined by TLC, and were separated by HPLC. Their configuration was distinguished by comparative analysis of the NMR data with known analogues together with the ROESY experiment. All the isolated PPAPs were evaluated for their cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines. Compound 1 showed modest cytotoxic activities against SGC7901 and HL-60 cell lines, and 2 showed modest cytotoxic activities against HepG2, SGC7901, HL-60, and K562 cell lines.

The rhizomes of Dryopteris species have popularly been used as vermifuge in flatworm infections. The aim of this work was to evaluate the in vitro schistosomicidal activity of some phloroglucinol compounds, obtained from the rhizomes of Dryopteris species, against Schistosoma mansoni adult worms. All worm pairs were dead after 24 h of incubation with aspidin 25 to 100 microM (1), flavaspidic acid 50 and 100 microM (2), methylene-bis-aspidinol 100 microM (3), and desaspidin 25 to 100 microM (4). Worms incubated with 1 (25 to 100 microM) and 2 (50 to 100 microM) showed decrease motor activity with tegumental alterations, while 3 (100 microM) and 4 (10 to 100 microM) showed decrease motor activity without tegumental alterations. Desaspidinol (5) and filicinic acid (6), at the tested concentrations (10 to 100 microM), did not show activity against adult worms of S. mansoni. Praziquantel (10 microM), used as positive control, caused death of the parasites and tegumental alterations without separation of worms. In the groups treated with 100 microM of compounds 1-4, the viability of the adult worms was similar to the positive control group, in which the worms were dead. Also, both the egg productions and the development of eggs produced by the adult worms were inhibited by the incubation with compounds 1-4 (10 and 100 microM) in comparison with the negative control (RPMI 1640 medium). It is suggested that the in vitro schistosomicidal effects of phloroglucinols derivatives 1, 2, 3, and 4 may be related to the inhibition of oxidative phosphorylation pathway in S. mansoni. The present results confirmed the traditional indications of rhizomes from Dryopteris species, which possess phloroglucinol compounds, in the treatment of tapeworm infections.

Fructus Psoraleae and Folium Eucalypti Globuli have long been used as Chinese medicines to treat various ailments such as asthma, eczema and dermatomycosis. In previous studies, their antifungal activities were demonstrated. The aim of the present study was to isolate active antidermatophytic compounds from their ethanolic extracts by means of bioassay-guided purification. Guided by the inhibitory activities on Trichophyton mentagrophytes, Trichophyton rubrum and Paecilomyces variotii, bakuchiol was isolated from the n-hexane fraction of Fructus Psoraleae whilst macrocarpal C was isolated from the n-hexane fraction of Folium Eucalypti Globuli. Both pure compounds could effectively inhibit the growth of dermatophytes in vitro. This is the first paper to report the isolation and identification of active antidermatophytic compounds from Fructus Psoraleae and Folium Eucalypti Globuli by the bioassay-guided purification.

From the ethyl acetate soluble fraction of an acetone-water extract of the aerial parts of Rumex acetosa L. (Polygonaceae), a variety of monomeric flavan-3-ols (catechin, epicatechin, epicatechin-3-O-gallate), A- and B-type procyanidins and propelargonidins (15 dimers, 7 trimers, 2 tetramers) were isolated with 5 so far unknown natural products. Dimers: procyanidin B1, B2, B3, B4, B5, B7, A2, epiafzelechin-(4beta-->8)-epicatechin, epiafzelechin-(4beta-->8)-epicatechin-3-O-gallate (new natural product), epiafzelechin-(4beta-->6)-epicatechin-3-O-gallate (new natural product), epiafzelechin-3-O-gallate-(4beta-->8)-epicatechin-3-O-gallate, B2-3'-O-gallate, B2-3,3'-di-O-gallate, B5-3'-O-gallate, and B5-3,3'-di-O-gallate. Trimers: procyanidin C1, epiafzelechin-(4beta-->8)-epicatechin-(4beta-->8)-epicatechin (new natural product), epicatechin-(4beta-->8)-epicatechin-(4beta-->8)-catechin, cinnamtannin B1, cinnamtannin B1-3-O-gallate (new natural product), tentatively epicatechin-(2beta-->7, 4beta-->8)-epiafzelechin-(4alpha-->8)-epicatechin (new natural product), and epicatechin-3-O-gallate-(4beta-->8)-epicatechin-3-O-gallate-(4beta-->8)-epicatechin-3-O-gallate. Tetramers: procyanidin D1 and parameritannin A1. All compounds were elucidated by ESI-MS, CD spectra, 1D- and 2D-NMR experiments as free phenols or peracetylated derivatives and, in part, after partial acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin polymer was also isolated, purified and its chemical composition studied by (13)C NMR. In addition a so far unknown phloroglucinolglycoside (1-O-beta-D-(2,4-dihydroxy-6-methoxyphenyl)-6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-glucopyranoside) was isolated.

Three acylphloroglucinol derivatives have been isolated from the hexane and acetone extracts of the aerial parts of Hypericum densiflorum Pursch. The compounds were characterized by NMR spectroscopy and mass spectrometry and identified as 4-geranyloxy-2,6-dihydroxybenzophenone (1), 4-geranyloxy-1-(2-methylpropanoyl)- phloroglucinol (2) and 4-geranyloxy-1-(2-methylbutanoyl)-phloroglucinol (3). Compounds 1-3 were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF-7), lung (NCI H460), CNS (SF-268), stomach (AGS) and colon (HCT-116) tumor cell lines; antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); inhibition of cyclooxygenase (COX-1 and -2) enzymes; and antioxidant activity in the lipid peroxidation (LPO) assay. All three compounds showed moderate to strong antitumor, antibacterial, antioxidant and inhibition of COX-2 activities. Also, this is the first reported occurrence of compound 3 in the Hypericum genus., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Four new benzophenone-O-rhamnosides, petiolins F-I (1-4), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum, and the structures were elucidated by spectroscopic data and chemical means.

Two bioactive phloroglucinol derivatives, dioxinodehydroeckol (DHE) and phlorofucofuroeckol A (PFF-A) were isolated from edible marine brown alga, Ecklonia stolonifera, and evaluated for effects on cell surface Fc(epsilon)RI expression in KU812F cells. DHE and PFF-A were found to reduce the cell surface expression, and total cellular protein and mRNA levels for the Fc(epsilon)RI alpha chain. Moreover, both compounds exerted inhibitory effects against the elevation of intracellular calcium concentration [Ca(2+)](i) and histamine release from anti-Fc(epsilon)RI alpha chain antibody (CRA-1)-stimulated cells. These inhibitory effects were stronger for PFF-A than for DHE. These results show that two phloroglucinol derivatives, DHE and PFF-A, may exert anti-allergic effects via the inhibition of Fc(epsilon)RI expression, calcium influx, and degranulation in basophils, and contributes to the pharmacological activities of marine brown alga, including E. stolonifera.

The phloroglucinol glucoside derivative [2,4-dihydroxy-6-(beta-D-glucopyranosyloxy)phenyl]-butan-1-one (1), roseoside (2), and kaempferol-3-O-beta-D-glucopyranoside (3) were isolated from the aerial parts of Conyza aegyptiaca (L.). To the best of our knowledge, this is the first isolation of compounds 1-3 from C. aegyptiaca. Their structures were determined by spectroscopic techniques including, IR, HR-EIMS, and extensive 500 MHz 1D- and 2D-NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC and HMBC experiments). The antioxidant activity of 1, using the DPPH assay, was investigated; in addition, 1 was investigated against different types of cell lines, including Hep-G2, HCT-116, and RAW 264.7 for its cytotoxic effects. Also, this is the first report on the activity of 1.

Within the framework of our continuous efforts to explore Hypericum species from Jordan, we report the analysis of the major active metabolites, naphthodianthrones and phloroglucinols, in the methanolic extracts of two under-explored Hypericum species; H. empetrifolium Willd. and H. sinaicum Hochst. & Steud. ex Boiss., using LC-(+,-)-ESI-MS (TIC and SIM) and LC-UV/Vis spectroscopy. Based on their LC-UV/Vis profiles, retention times and (+,-)-ESI-MS (TIC and SIM) spectral data, hypericin, protohypericin and pseudohypericin were identified in both of the investigated species. In addition adhyperfirin was only detected in H. empetrifolium, while hyperforin and protopseudohypericin were only detected in H. sinaicum. This is the first report documenting the presence of hypericin, protohypericin, pseudohypericin, protopseudohypericin, and hyperforin in H. sinaicum, and adhyperfirin in H. empetrifolium.

Phloroglucinol derivatives, dioxinodehydroeckol (1) and 1-(3',5'-dihydroxyphenoxy)-7-(2'',4'',6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin (2), were isolated from Ecklonia Cava. Their ability to inhibit the proliferation of human breast cancer cells were evaluated by measuring cell death via induction of apoptosis. Compound 1 exerted a higher anti-proliferative activity in human breast cancer cells compared with compound 2. Furthermore, compound 1 induced a significant proliferative inhibition and apoptosis in a dose-dependent manner on MCF-7 human cancer cells. Treatment with compound 1 also induced the increase in caspase (-3 and -9) activity, DNA repair enzyme poly-(ADP-ribose) polymerase (PARP) cleavage, and pro-apoptotic gene and the decrease in anti-apoptotic gene. In addition, NF-kappaB family and -dependent activated genes were down-regulated by compound 1. These results indicated that the potential inhibitory effect of compound 1 against growth of MCF-7 human breast cancer cells might be associated with induction of apoptosis through NF-kappaB family and NF-kappaB dependent pathway. The present results suggest that compound 1 has a promising potential to be used as a valuable chemopreventive agent.

Arthritis is one of the most prevalent chronic inflammatory diseases, and it is characterized by structural and biochemical changes in major tissues of the joint, including degradation of the cartilage matrix, insufficient synthesis of extracellular matrix (ECM). Ecklonia cava (EC) is a member of the family of Laminariaceae, which is an edible marine brown alga with various bioactivities. In this study of the methanol extract of brown alga EC, the dieckol (1) and 1-(3',5'-dihydroxyphenoxy)-7-(2'',4'',6''-trihydroxyphenoxy) 2,4,9-trihydroxydibenzo-1,4,-dioxin (2) were isolated and characterized by NMR techniques with high yield. Phlorotannin derivatives (1, 2) promoted osteosarcoma differentiation by increasing alkaline phosphatase (ALP) activity, mineralization, total protein and collagen synthesis in human osteosarcoma cell (MG-63 cells), respectively. Furthermore, these phlorotannin derivatives (1, 2) inhibited mRNA gene and protein levels of matrix metalloproteinase (MMP-1, MMP-3, and MMP-13), iNOS and COX-2 in casein zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. In addition, it was observed that the phlorotannins inhibited phosphorylation of JNK and p38 MAPK in human osteosarcoma cell. These results suggested the phlorotannin derivatives (1, 2) could promote cell differentiation, attenuate MMP-1, MMP-3, MMP-13 expressions, and inflammatory response via MAPK pathway in chronic articular diseases.

The pericarp and seeds from fruits of Garcinia brasiliensis were subjected to extraction with hexane and ethanol. The pericarp hexane extract (PHE) and seed ethanol extract (SEE) were purified by silica gel column chromatography, which permitted isolation of the prenylated benzophenones 7-epiclusianone (1) and guttiferone-A (2), respectively. The antimicrobial activity of PHE, SEE, and compounds 1 and 2 were evaluated against Candida albicans, Staphylococcus aureus, Escherichia coli, and Bacillus cereus cultures. The minimum inhibitory concentration and minimum bactericidal concentration were established. The substances presented activity against S. aureus and B. cereus as follows: PHE, 4.0 microg/mL and 2.4 microg/mL; SEE, 10.0 microg/mL and 12.6 microg/mL; 7-epiclusianone, 1.2 microg/mL and 0.6 microg/mL; and guttiferone-A, 2.4 microg/mL and 2.4 microg/mL, respectively. The direct relationship between the lipophilic character of the structure and activity in Gram-positive bacteria was specifically observed. Therefore these extracts and prenylated benzophenones represent an interesting topic for further studies and open possibilities for an alternative control of diseases associated with Gram-positive bacteria.

Myrtucommulone (MC), a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor-alpha and interleukin-1beta) in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B(4), but not prostaglandin E(2), levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation.

Two new bicyclic phloroglucinols were isolated from the diethyl ether extract of an Argentine collection of the fern Elaphoglossum piloselloides. Structures were established by analysis of their spectroscopic data ((1)H NMR, HRMS, IR) and chemical derivatization. Both compounds show an acute molluscicidal activity against the schistosomiasis vector snail Biomphalaria peregrina.

High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin-releasing hormone (TRH) receptor-2 binding affinity led to the isolation of four new, myrtucommulones F-I (3-6), and two known, myrtucommulones A (1) and D (2), active acylphloroglucinols from the seeds of the Queensland tree Corymbia scabrida. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The relative configuration of the stereogenic centers for all six compounds was deduced from ROESY correlations. This is the first time that myrtucommulone A (1) has been isolated as a single pure compound. The structure of myrtucommulone D (2) has been revised. Myrtucommulones A, D, and F-I showed rat TRH receptor-2 binding affinity with IC50 values of 39, 11, 16, 24, 31, and 16 microM, respectively.

Three phlorotannins, including phloroglucinol, diphlorethohydroxycarmalol, and 6,6'-bieckol, were isolated from Ishige okamurae by column chromatography. The structures of the phlorotannins were determined on the basis of spectroscopic analysis, including NMR and mass spectrometry (MS) techniques. Antioxidant effects of phlorotannins were measured by direct free radical scavenging activities using the electron spin resonance spectrometry (ESR) technique and cellular systems in vitro. The results indicated that diphlorethohydroxycarmalol and 6,6'-bieckol showed potential radical scavenging activities against the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, alkyl, and superoxide radicals. Moreover, no cytotoxicities of the phlorotannins on human fetal lung fibroblasts cell line (MRC-5), mouse macrophages cell line (RAW264.7), and human leukemic cell line (HL-60) were observed. In addition, diphlorethohydroxycarmalol and 6,6'-bieckol significantly reduced the intracellular reactive oxygen species level assessed by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay in RAW264.7 cells, and myeloperoxide (MPO) activity in HL-60 cells and radical-mediated oxidation of cell membrane proteins in RAW264.7 cells were dose-dependently inhibited in the presence of diphlorethohydroxycarmalol and 6,6'-bieckol. In conclusion, these results suggested that phlorotannins could be used as novel functional foodstuffs or antioxidants in the cosmetic and drug industries.

Two new prenylated phloroglucinol derivatives and 15 known compounds were isolated from the aerial parts of Hypericum perforatum var. angustifolium. Their structures were determined on the basis of spectroscopic evidence.

A new phloroglucinol, hyperielliptone HA (1/1a), a new spirophloroglucinol possessing an unprecedented skeleton, hyperielliptone HB (2/2a), and two new xanthonolignoids, hyperielliptones HC (3) and HD (4), were isolated from the heartwood of Hypericum geminiflorum. Compounds 1/1a and 2/2a were obtained as tautomeric pairs. The structures and relative configurations of these compounds were elucidated by spectroscopic methods. In biological testing, compound 2/ 2a revealed significant inhibition of oxidative DNA damage and an inhibitory effect on xanthine oxidase.

The synthesis of a series of modularized porphyrins bearing bioactive molecule is described. Starting with meso-tetraphenylporphyrin, the compounds with two nitro functional groups were synthesized via regiospecific nitration reaction. After reduction to the amino group and subsequent coupling with l-phenylalanine or 1-carboxylmethyl-5-fluorouracil (5-Fu acid), the functionalized porphyrins were metallized with Co(II) or Mn(II) to form miscellaneous porphyrins in good yields. The spectra of all the porphyrins were furnished. In vitro photodynamic therapy of the porphyrins against Ec9706 cell line was evaluated by standard cytotoxicity assays.

Two new phloroglucinol derivatives possessing chromane skeleton, petiolins A (1) and B (2), and a new phloroglucinol derivative containing a dihydrofuran ring, petiolin C (3), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum. The gross structures of 1-3 were elucidated by spectroscopic data, and the relative stereochemistry of 3 was elucidated by NOESY data. Petiolins A-C (1-3) showed modest cytotoxicity, while petiolin C (3) exhibited antifungal activity.

High-throughput screeing of a plant and marine invertebrate extract library to find natural products with rat thytotropin releasing hormone receptor 2 binding affinity led to the isolation of two new active acylphloroglucinols, corymbones A and B (1 and 2) from flowers of the Queensland tree Corymbia peltata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 showed rat TRH receptor 2 binding affinity with IC 50 values of 23 and 19 microM, respectively.

A new phloroglucinol, garcinielliptone HF ( 1), possessing an unprecedented skeleton, and the tautomeric pair of garcinielliptone FC ( 2/ 2a) were isolated from the heartwood and pericarp of Garcinia subelliptica, respectively. Their structures, including relative configurations, were elucidated by means of spectroscopic methods. The ability of compounds 1 and 2/ 2a to induce DNA-cleavage activity was examined using supercoiled plasmid pBR322 DNA. In the presence of Cu(II), compounds 1 and 2/ 2a caused significant breakage of pBR322 DNA. The involvement of H2O2 and O2 (*-), and H2O2, O2 (*-), and OH (*) in 1- and 2/ 2a-mediated scission, respectively, was established by inhibition or no protection of DNA breakage by various oxygen radical scavengers. Thus, in the presence Cu(II), 1 and 2/ 2a may show a prooxidant effect on DNA and induce cell death.

Five 2,4,6-prenylated phloroglucinols, garcinielliptones HA (1), HB (2), HC (3), HD (4) and HE (5), were isolated from the heartwood of Garcinia subelliptica Merr. Their structures, including relative configurations, were elucidated by means of spectroscopic data analysis. The ability of phloroglucinols, 1-5 and lignans, tuberculatin (8), justicidin A (9), procumbenoside A (10) and ciliatosides A (11) and B (12), isolated from Justicia ciliata and Justicia procumbens, to induce DNA-cleavage activity was examined using pBR322, a supercoiled, covalently closed circular DNA, and it was analyzed by agarose gel electrophoresis. In the presence of Cu (II), compounds 3, 8, 10 and 11 caused significant breakage of supercoiled plasmid pBR322. The products were relaxed circles with no detectable linear forms. In the Cu(II)-mediated DNA damage of 3 and selective compound 8, Cu(I) was shown not to be an essential intermediate by using the Cu(I)-specific sequestering reagent neocuproine.

Hypericum montbretii, a perennial herbaceous plant from Turkish flora has a great pharmaceutical potential with its well-documented chemical content. In the present study, morphogenetic and phenological variations of hyperforin were investigated in this species for the first time. Wild growing plants were harvested at vegetative, floral budding, full flowering, fresh fruiting, and mature fruiting stages and dissected into stem, leaf and reproductive tissues and assayed for hyperforin by HPLC method. Phenological changes in hyperforin content were found to be significant. After decreasing at floral budding slightly, hyperforin concentration in whole shoots increased with advancing of plant development and the highest level was reached at fresh fruiting. Among different parts of the plant, reproductive tissues namely green capsules and full opened flowers accumulated significantly higher amount of hyperforin when compared to stems and leaves. Such kind of data could be useful for elucidation of the chemotaxonomical significance of hyperforin and phytochemical evaluation of H. montbretii.

Bioassay-directed fractionation using multidrug-resistant (MDR) Staphylococcus aureus resulted in the isolation of four new polyprenylated benzophloroglucinol derivatives, sampsoniones N-Q (1-4), and four known compounds, 7-epiclusianone (5) and sampsoniones B, L, and R, from the roots of Hypericum sampsonii. The structures of these compounds were established by analysis of spectroscopic data, and the structures of 4 and 5 were determined by single-crystal X-ray diffraction crystallography. In the bioassay, 7-epiclusianone (5) showed promising activity with a minimum inhibitory concentration (MIC) of 7.3 microM against the NorA overexpressing MDR S. aureus strain SA-1199B; the positive control antibiotic norfloxacin showed activity at MIC 100 microM.

The removal of small trihalomethane precursors (THMPs) from aqueous solution by two commercial nanofiltration membranes (NF70 and NF270) was investigated. Resorcinol, phloroglucinol, and 3-hydroxybenzoic acid were selected as model compounds of small THMPs, while tannic acid was chosen as a medium molecular disinfection by-product (DBP) precursor for comparison. The performance of nanofiltration membranes were evaluated by introducing polyethylene glycol (PEG) solutions and uncharged saccharides to estimate molecular weight cut-off (MWCO) and membrane pore radii, respectively. The streaming potential was measured to estimate the membrane surface charge at different pH values, which reveals that the NF270 membrane is more pH-sensitive than the NF70 membrane. The rejections of the above selected THMPs were assessed under various pH values, and the removal efficiencies of THMPs for both membranes at high pH values are reasonably well. Charge exclusion is the prevailing mechanism for the selected small model compounds retended by the negatively charged nanofiltration membranes, while size exclusion and adsorption are controlled mechanisms but not sufficient for the rejection of unionized small organic molecules. In general, the NF270 membrane exhibits the superior permeation rate value, which takes an advantage over the NF70 membrane from the aspect of energy conservation.

Three preparations of Hypericum perforatum L. (a hydroalcoholic extract, a lipophilic extract and an ethylacetic fraction) and the pure compounds hypericin, adhyperforin, amentoflavone, hyperoside, isoquercitrin, hyperforin dicyclohexylammonium (DHCA) salt and dicyclohexylamine were evaluated for their topical anti-inflammatory activity. H. perforatum preparations provoked a dose-dependent reduction of Croton-oil-induced ear oedema in mice, showing the following rank order of activity: lipophilic extract > ethylacetic fraction > hydroalcoholic extract (ID50 (dose that inhibited oedema by 50%) 220, 267 and >1000 microg cm(-2), respectively). Amentoflavone (ID50 0.16 micromol cm(-2)), hypericin (ID50 0.25 micromol cm(-2)), hyperforin DHCA salt (ID50 0.25 micromol cm(-2)) and adhyperofrin (ID50 0.30 micromol cm(-2)) had anti-inflammatory activity that was more potent or comparable to that of indometacin (ID50 0.26 micromol cm(-2)), whereas isoquercitrin and hyperoside were less active (ID50 about 1 micromol cm(-2)). As dicyclohexylamine alone was inactive, the effect of hyperforin DHCA salt can be attributed completely to the phloroglucinol moiety. The pharmacological activity and phytochemical profile of the tested extracts and fraction suggest that different constituents are involved in the topical antiphlogistic property of H. perforatum in-vivo.

Two new compounds, lysidicin D (1) and lysidicin E (2), were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by means of spectroscopic methods. Among them compound 1 showed potent anti-oxidant activity on in vitro.

St. John's Wort (Hypericum perforatum L.) is commonly accepted as a medicinal plant. The data on the physiological activities of the individual substances that are produced in different organs of H. perforatum are well known at present. The highest attention is focused on the characterization and phytochemical properties of hypericin and hyperforin. These organic compounds are used as antidepressant, anticarcinogenic (photodynamic), antimicrobial and virostatic agents. The review paper surveys the present knowledge of chemical and analytical methods for their identification and quantification, physiological activity, and pharmacological and biomedical applications of hypericin and hyperforin.

An acetone extract of Helichrysum italicum ssp. microphyllum afforded the phloroglucinol alpha-pyrone arzanol (1a) as a potent NF-kappaB inhibitor. Arzanol is identical with homoarenol (2a), whose structure should be revised. The phloroglucinol-type structure of arzanol and the 1,2,4-trihydroxyphenyl-type structure of the base-induced fragmentation product of homoarenol could be reconciled in light of a retro-Fries-type fragmentation that triggers a change of the hydroxylation pattern of the aromatic moiety. On the basis of these findings, the structure of arenol, the major constituent of the clinically useful antibiotic arenarin, should be revised from 2b to 1b, solving a long-standing puzzle over its biogenetic derivation. An alpha-pyrone (micropyrone, 7), the monoterpene rac-E-omega-oleoyloxylinalol (10), four known tremetones (9a-d), and the dimeric pyrone helipyrone (8) were also obtained. Arzanol inhibited HIV-1 replication in T cells and the release of pro-inflammatory cytokines in LPS-stimulated primary monocytes, qualifying as a novel plant-derived anti-inflammatory and antiviral chemotype worth further investigation.

The antifungal compound 2,4-diacetylphloroglucinol-producing bacterium, Pseudomonas fluorescens strain LRB3W1, inhibits the growth of Fusarium oxysporum f. sp. lycopersici, and controls Fusarium wilt of tomato caused by F. oxysporum f. sp. lycopersici. On the other hand, Serratia marcescens strain B2, which produces cell wall-degrading enzyme chitinases, did not inhibit fungal growth and the suppressive effect of strain B2 against tomato Fusarium wilt was less than that of strain LRB3W1. Combined inoculation of strain LRB3W1 with strain B2 was more effective than treatment with strain LRB3W1 alone. When 2,4-diacetylphloroglucinol and the chitinolytic enzymes were applied in combination, a synergistic inhibitory effect against the pathogen was observed. It was possible that bacteria which produce cell wall-degrading enzymes enhanced the biocontrol effect of the antibiotic-producing bacterium against tomato Fusarium wilt.

Objective: To study the chemical constituents in the fruits of Eucalyptus globulus Labill., Method: The chemical constituents were isolated by various column chromatographic methods and structurally elucidated by IR, NMR and MS evidences., Result: Fifteen compounds were obtained and identified as beta-sitosterol (1), betulinic acid (2), stigmasterol (3), euscaphic acid (4), 2a-Hydroxybetulinic acid (5), macrocarpal B (6), macrocarpal A (7), oleanolic acid (8), 3,4,3'-O-trimethylellagic acid (9), 3-O-methylellagic acid 4'-O-(2"-O-acetyl )-alpha-L-rhamnopyranoside (10), camaldulenside (cypellocarpin C, 11), 3-O-methylellagic acid 4'-O-alpha-L-rhamnopyranoside (12), 3-O-methylellagic acid (13), ellagic acid (14), and gallic acid (15)., Conclusion: Compounds 4 and 5 from genera Eucalyptus, 1, 3 and 11 from plant E. globulus, and 6, 7, 9 and 15 from the fruits of E. globulus were isolated for the first time.

Two new phloroglucinol glycosides, lysidisides C (1) and D (2), together with two new resveratrol glycosides, lysidisides E (3) and F (4), were isolated from the n-BuOH extract of the roots of Lysidice rhodostegia. The structures were elucidated on the basis of spectroscopic and chemical evidence. The antioxidant activity of the isolates was also investigated

Literature indicates that herb-drug interaction of St. John's wort is largely due to increased metabolism of the co-administered drugs that are the substrates of cytochrome P450 (CYP) 3A4 enzyme, alteration of the activity and/or expression of the enzyme. The major St. John's wort constituents, acylphloroglucinols, were evaluated for their effects on CYP3A4 enzyme activity to investigate their roles in herb-drug interaction. Hyperforin and four oxidized analogues were isolated from the plant and fully characterized by mass spectral and NMR analysis. These acylphloroglucinols inhibited activity of CYP3A4 enzyme potently in the fluorometric assay using the recombinant enzyme. Furoadhyperforin (IC(50) 0.072 microM) was found to be the most potent inhibitor of CYP3A4 enzyme activity, followed by furohyperforin isomer 1 (IC(50) 0.079 microM), furohyperforin isomer 2 (IC(50) 0.23 microM), hyperforin (IC(50) 0.63 microM) and furohyperforin (IC(50) 1.3 microM). As the acylphloroglucinols are potent inhibitors of the CYP3A4 enzyme, their modulation of the enzyme activity is unlikely to be involved in increased drug metabolism by St. John's wort.

Three new acylphloroglucinol derivatives have been isolated from the hexane extract of the aerial parts of Hypericum prolificum L.: prolificin A (1), prolifenone A (2), and prolifenone B (3). The structures were elucidated on the basis of extensive 2D NMR and MS data. All three compounds were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF-7), lung (NCI-H460), CNS (SF-268), stomach (AGS), and colon (HCT-116) tumor cell lines. Prolificin A showed growth inhibition of all cell lines with IC50 values ranging from 23 to 36 microM. Prolifenones A and B were inactive at the concentrations tested.