Cytotoxic activity of Secondary Metabolites from Marine-derived Fungus Neosartorya siamensis in Human Cancer Cells.

Compounds isolated from the marine sea fan-derived fungus Neosartorya siamensis (KUFA 0017), namely, 2,4-dihydroxy-3-methylacetophenon (1), chevalone C (2), nortryptoquivaline (4), tryptoquivaline H (6), tryptoquivaline F (7), fiscalin A (8), epi-fiscalin A (9), epi-neofiscalin A (11) and epi-fiscalin C (13) were tested for anti-proliferative activity by MTT assay, DNA damage induction by comet assay, and induction of cell death by nuclear condensation assay on colon HCT116, liver HepG2 and melanoma A375 cancer cell lines. Compounds 2, 4, 8, 9, 11 and 13 presented IC50 values ranging from 24 to 153 µM in the selected cell lines. Cell death was induced in HCT116 by compounds 2, 4 and 8. In HepG2, compounds 4, 8, 9 and 11 were able to induce significant cell death. This induction of cell death is possibly not related to genotoxicity because none of the compounds induced significant DNA damage. These results suggest that selected compounds present an interesting anti-proliferative activity and cell death induction, consequently showing potential (specifically epi-fiscalin C) as future leads for chemotherapeutic agents. Further studies on mechanisms of action should ensue. Copyright © 2016 John Wiley & Sons, Ltd.

The perception of the benefits of herbal medicine consumption among the Thai elderly.

OBJECTIVES: To determine how the Thai elderly perceived the benefits of herbal medicine consumption and to study related variables influencing their perception. DESIGN: A cross-sectional study was used. PARTICIPANTS/SETTINGS: 419 participants were chosen by systematic stratified sampling; people between 60-96 years of age (mean age 70.2 years); 68.3 % female, and 31.7% male of Chonburi Province (Thailand). MEASUREMENTS: To determine the elderly perception about the benefits of herbal medicine consumption, a scale from one to four based upon 12 simply worded item check lists was used among the others. The questionnaires were conducted in June to August 2008 in 3 different regions (urban, suburban and rural areas). RESULTS: 97.4% having used herbal medicines in many ways. Most of the elderly used the local herbals together with conventional medicines. They believed that herbals could reduce expenses (51%), cure diseases (41.9%), relieve symptoms (35.4%), and provide good health (33.6%). A 16.7% of the elderly had the strongest opinion regarding the use of herbal medicines as substitutes for conventional medicines. They also strongly agreed on using them as nutrients (39.8%). The study found significant correlation among levels of education, stress levels, happiness levels, and perception of benefits of herbal medicine consumption. CONCLUSIONS: This study indicated that levels of education, happiness, and stress could influence the perception of herbal medicine consumption. Knowing how people perceive herbal medicine, its use, and local culture can help practicing health professionals, among other things, to avoid side effects from prescriptions and so maintain or promote the elderly health status.

The natural prenylated flavone artelastin is an inhibitor of ROS and NO production.

Artelastin, a prenylated flavone previously isolated from Artocarpus elasticus, was evaluated for its effect on the production of reactive oxygen species (ROS) by human polymorphonuclear neutrophils (PMNs) and nitric oxide (NO) by J774 murine macrophage cell line. Artelastin showed to be an inhibitor of ROS production due to a strong O2- scavenging activity. No effect was observed on the activity of myeloperoxidase (MPO). Artelastin showed also to be an inhibitor of NO production without NO scavenging activity. This flavone seems to interfere with the expression of the inducible nitric oxide synthase (iNOS) immediately after LPS-IFNgamma-macrophage stimulation.

Naturally-occurring xanthones: recent developments.

A literature survey covering the report of naturally occurring xanthones from January 2000 to December 2004, with 219 references, is presented in this review. Among 515 xanthones reported in this period, 278 were new natural xanthones. These xanthones have been identified from 20 families of higher plants (122 species in 44 genera), fungi (19 species) and lichens (3 species). The structural formulas of 368 identified xanthones, their distribution and a brief mention of their biological properties are also included.

Free Radical Scavenging Activity of Extracts from Thai Plants in Guttiferae and Schisandraceae Families.

Five Thai plants from the Guttiferae (Hypericum hookerianum. Wight & Arn, Garcinia speciosa. Wall, Garcinia xanthochymus. Hook f. ex. T. Anderson, Cratoxylum formosum. ssp. pruniflorum. (Kurz) Gogel, and Calophyllum polyanthum. Wall ex Choisy) and one from the Schisandraceae (Schisandra verruculosa.) were extracted by methanol and chloroform. The extracts were screened for free radical scavenging activity using the DPPH assay. All extracts showed a dose-dependent antioxidant activity. The most potent with the lowest IC50 values were observed in the methanol extracts from the wood of G. speciosa., which were 2.5- and 5.3-fold more potent than the two standard antioxidants, ascorbic acid and α.-tocopherol, respectively. Free radical scavenging activities ranging from moderate to high were observed in both methanol and chloroform extracts from H. hookerianum., C. formosum. ssp. pruniflorum., G. xanthochymus., S. verruculosa. and C. polyanthum.. The information from this study can explain the traditional use and the further development of these extracts into new pharmaceuticals.

Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor.

Eight natural prenylated flavones, previously isolated from Artocarpus elasticus, were evaluated for their effect on the mitogenic response of human lymphocytes to PHA. They all exhibited a dose-dependent suppression effect. An interesting relationship was observed between their antiproliferative activity and their chemical structure. Indeed, the most potent flavones possessed a 3,3-dymethylallyl group (prenyl) at C-8, such as artelastin, which exhibited the highest antiproliferative activity. Studies of the mechanism underlying its effect revealed that artelastin had an irreversible inhibitory effect on the PHA-induced lymphocyte proliferation and could affect the course of the ongoing mitogenic response either at the initial induction phase or at the late phase of proliferation. This prenylated flavone was also shown to be a potent inhibitor of both T- and B-lymphocyte mitogen induced proliferation although B-mitogenic response was the more sensitive one. Artelastin did not affect either the basal levels of the early marker of activation CD69 on non-stimulated splenocytes or its expression on ConA- or LPS-stimulated splenocytes. However, it decreased the production of IFN-gamma, IL-2, IL-4 and IL-10 in ConA-stimulated splenocytes. Furthermore, artelastin had no effect on apoptosis of splenocytes.

Artelastocarpin and carpelastofuran, two new flavones, and cytotoxicities of prenyl flavonoids from Artocarpus elasticus against three cancer cell lines.

Further study of one of the fractions from the wood of Artocarpus elasticus furnished two new prenylated flavonoids artelastocarpin and carpelastofuran as well as ethyl 2,4-dihydroxybenzoate. The two flavonoids and the prenylated flavonoids artelastin, artelastochromene, artelasticin, artocarpesin, and cyclocommunin isolated earlier from this species were tested for cytotoxicity in vitro against three human cell lines. All seven flavonoids were active, the cytotoxic effect varying from strong to moderate and with artelastin showing the most potent activity.

Naturally occurring 1,2,8-trimethoxyxanthone and biphenyl ether intermediates leading to 1,2-dimethoxyxanthone.

In order to study structure-activity relationships, a series of mono-, di- and trioxygenated xanthones has been synthesized and the structures of methyl 2-(3,4-dimethoxyphenoxy)benzoate, C(16)H(16)O(5), 2-(3,4-dimethoxyphenoxy)benzoic acid, C(15)H(14)O(5), 1,2-dimethoxy-9H-xanthen-9-one, C(15)H(12)O(4), and 1,2,8-trimethoxy-9H-xanthen-9-one, C(16)H(14)O(5), have been determined. The first two compounds both assume skew conformations, the dihedral angles between the two phenyl rings being 80.04 (8) and 83.0 (1) degrees, respectively. The latter two compounds are essentially planar and their methoxy substituents assume orientations consistent with minimum steric interactions.

Tetillapyrone and nortetillapyrone, two unusual hydroxypyran-2-ones from the marine sponge Tetilla japonica.

Extraction of the marine sponge Tetilla japonica from the Bay of Thailand furnished tetillapyrone and nortetillapyrone, two unusual tetrahydrofurylhydroxypyran-2-ones, whose structures were established by NMR spectrometry and an X-ray analysis of tetillapyrone.

11,17-dideoxyagelorin A and B, new bromotyrosine derivatives and analogs from the marine sponge Suberea aff. praetensa.

A collection of the marine sponge Suberea aff. praetensa from the Gulf of Thailand furnished the bromotyrosine derivatives fistularin-3, agelorins A and B and the new desoxyagelorins A and B.

Xanthones from Calophyllum teysmannii var. inophylloide.

Further study of the wood of Calophyllum teysmannii Miq. var. inophylloide from Thailand yielded the xanthones 1,2,8-trimethoxyxanthone, 6-hydroxy-1,2,5,7-tetramethoxyxanthone and 3-(3'-carboxybutyl)-4-methoxyxanthone (teysmannic acid) in addition to scriblitifolic acid, 1,7-dihydroxyxanthone and the benzoic acid derivative leiocarpic acid.

Xanthones from Calophyllum teysmannii var. inophylloide.

Further study of the wood of Calophyllum teysmannii Miq. var. inophylloide yielded xanthones 7-hydroxy-1,2,8-trimethoxyxanthone, 6-hydroxy-1,2,5-trimethoxyxanthone, and 2-carbomethoxy-6-methoxyxanthone in addition to 3,8-dihydroxy-1,2,4-trimethoxyxanthone, 3-hydroxy-2,4-dimethoxyxanthone, 1,7-dihydroxy-3-methoxyanthone (gentisin) and 2-hydroxyxanthone.

Immunomodulatory Activity of Xanthones from Calophyllum teysmannii var. inuphylloide.

Nine xanthones, including 3-(4-hydroxy-3-metnylbutyl)-4,8-dihydroxyxanthone, were isolated from the wood of a Thai collection of CALOPHYLLUM TEYSMANNII Miq. var. INUPHYLLOIDE (King) P. Stephen. Immunomodulatory activities of eight of these have been investigated.

Inhibition of inflammatory responses by a series of novel dolabrane derivatives.

Four dolabrane derivatives isolated from Endospermum diadenum have been studied for their inhibitory effects on murine models of inflammation and human neutrophil functions in vitro. After topical application, akendo 1, akendo 2 and akendo 3 potently inhibited the mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) with a striking effect on myeloperoxidase levels. After oral administration, akendo 2 and akendo 3 inhibited mouse paw oedema induced by carrageenan, with a significant reduction in myeloperoxidase levels. In contrast to indomethacin, they did not modify the prostaglandin E2 content of the inflammed paw. None of the compounds affected superoxide generation by human neutrophils. On the contrary, they inhibited degranulation induced by different stimuli. The most effective compounds were akendo 2 and akendo 3, which also inhibited myeloperoxidase activity. All compounds were weak inhibitors of leukotriene B4 synthesis and release by human neutrophils, whereas only akendo 3 decreased 5-lipoxygenase activity. Cyclo-oxygenase-1 from human platelets was inhibited mainly by akendo 2 and akendo 3, although with a low potency. The latter compound also reduced weakly the synthesis of prostaglandin E2 by cyclo-oxygenase-2. The anti-inflammatory activity of these dolabrane derivatives was not related to arachidonic acid mobilization or metabolism.

HIV-1 gp120 and NMDA induce protein kinase C translocation differentially in rat primary neuronal cultures.

Exposure of rat cortical neurons to the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 in vitro causes a rise in the intracellular Ca2+ level and a subsequent translocation of protein kinase C (PKC) from the cytosol to the membrane. Such a translocation persists for at least 2 h, but only in cultures with media not depleted of endogenous glutamate. Enzymatic degradation of glutamate in the medium by the enzyme glutamate-pyruvate transaminase (GPT) abolishes the long-lasting effect of gp120 on the association state of PKC; under this incubation condition the translocation period is < 1 h. Memantine and the ganglioside GM1 prevent N-methyl D-aspartate receptor-mediated long-term translocation of PKC and gp120-mediated neurotoxicity (in the absence of GPT); they have no effect on short-term translocation of PKC. We suggest that gp120-caused neuronal death involves an indirect sensitization step of the NMDA receptors, which ultimately induces neuronal death.

Constituents of Knema laurina and Knema tenuinervia ssp. setosa.

Extraction of the stem bark of KNEMA LAURINA Warb. and KNEMA TENUINERVIA W. J. J. O. de Wilde ssp. SETOSA de Wilde furnished 3-(12-phenyl-8 Z-dodecenyl)-phenol and 3-(8 Z-pentadecenyl)-phenol together with 8-hydroxy-6-methoxy-3- N-pentylisocoumarin, respectively. 2-Carboxy-3-(12-phenyldodecyl)-phenol) and 2,4-dihydroxy-6-(10-phenyldecyl)-acetophenone were common to both extracts.

Lignans and Other Constituents of Centaurea sphaerocephala ssp. polyacantha.

Extraction of the aerial parts of CENTAUREA SPHAEROCEPHALA L. ssp. POLYACANTHA (Willd.) Dostal furnished the lignans (-)-matairesinol, (-)-arctigenin, and (-)-arctiin, two sesquilignans lappaol A and a stereo- or structural isomer of lappaol A, and a new dithienylacetylene.

A New Linalool Derivative and Other Constituents from Piper ribesoides.

Extraction of PIPER RIBESOIDES Wall, furnished the new linalool derivative (+)-3,7-dimethyl-3-hydroxy-4-( P-coumaryloxy)-1,6-octadiene, the lignans (-)-hinokinin and (-)-cubebin, N-isobutyl-2 E,4 E-deca-2,4-dienamide, methyl piperate, methyl 2 E,4 E,6 E-7-phenyl-2,4,6-heptatrienoate, palmitic acid, stearic acid, and beta-sitosterol.