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ABSTRACT: An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol-an extract from Formosan soft coral-has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases.
Marine Drugs 01/2013; 11(1):99-113. · 3.85 Impact Factor
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ABSTRACT: In order to search for new bioactive substances from marine organisms, we have investigated the acetone extracts of the soft coral Sarcophyton ehrenbergi collected at San-Hsian-Tai, Taitong County, Taiwan. Chromatographic fractionation of the extracts of the octocoral S. ehrenbergi led to the isolation of three new cembranoids, (+)-12-ethoxycarbonyl-11Z-sarcophine (1), ehrenbergol A and B (2 and 3). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, metabolites 1-3 were evaluated in vitro for their cytotoxicity towards selected cancer cell lines and antiviral activity against human cytomegalovirus (HCMV).
Marine Drugs 07/2012; 10(7):1433-44. · 3.85 Impact Factor
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ABSTRACT: Paralemnolide A (1), possessing an unprecedented bisnorsesquiterpene skeleton, was isolated from the soft coral Paralemnalia thyrsoides. The structure of paralemnolide A was elucidated by extensive analysis of spectroscopic data. The anti-HCMV (human cytomegalovirus) activity of 1 and its cytotoxicity against selected cell lines were evaluated.
Marine Drugs 07/2012; 10(7):1528-35. · 3.85 Impact Factor
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ABSTRACT: In order to search for novel bioactive substances from marine organisms, we investigated the acetone extract of the soft coral Nephthea chabrolii collected at San-Hsian-Tai, Taitong County, Taiwan. From this extract three new 19-oxygenated steroids, nebrosteroids N-P (1-3) were isolated. The structures of these compounds were elucidated by extensive spectroscopic analyses.
Marine Drugs 06/2012; 10(6):1288-96. · 3.85 Impact Factor
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ABSTRACT: Chemical investigations on the EtOAc-soluble fractions from the EtOH extract of Formosa soft coral afforded a new 9,11-secosteroid, 8αH-3β,11-dihydroxy-5α,6α-expoxy-24-methylene-9,11-secocholestan-9-one (1), along with one known steroid 3β,11-dihydroxy-5β,6β-expoxy-24-methylene-9,11-secocholestan-9-one (2) from Sinularia granosa. The structure of the new metabolite was elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with the known compounds, including 2. Both 1 and 2 were shown to significantly inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase protein, and 1 also was found to effectively reduce the level of cyclooxygenase-2 protein, in lipopolysaccharide-stimulated RAW264.7 macrophage cells at 10 μM. Furthermore, cytotoxic activity of 1 and 2 toward a limited panel of cancer cell lines was also discovered.
Bioorganic & medicinal chemistry letters 05/2012; 22(13):4373-6. · 2.65 Impact Factor
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ABSTRACT: In order to search for novel bioactive substances from marine organisms, we have investigated the organic extracts of the Taiwanese octocoral Briareumexcavatum collected at Orchid Island. Three new briarane-type diterpenoids, briacavatolides A-C (1-3) as well as two known briaranes, briaexcavatolide U (4) and briaexcavatin L (5) were isolated from the acetone extract. The structures of these compounds were elucidated by extensive NMR spectroscopic analysis and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-5 and their cytotoxicity against selected cancer cell lines were evaluated.
Marine Drugs 05/2012; 10(5):1019-26. · 3.85 Impact Factor
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ABSTRACT: Six new cembranolides, michaolides L-Q (1-6), and a known cembranolide, lobomichaolide (7) were isolated from the CH₂Cl₂ extract of the soft coral Lobophytum michaelae. Their structures were established by extensive spectral analysis. The anti-HCMV (human cytomegalovirus) activity of 1-7 and their cytotoxicity against selected cell lines were evaluated.
Marine Drugs 02/2012; 10(2):306-18. · 3.85 Impact Factor
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ABSTRACT: The investigators previously found that the administration of lemnalol, a natural marine compound isolated from the Formosan soft coral Lemnalia cervicorni, produced anti-inflammatory and analgesic effects in carrageenan-injected rats. Recently, several studies have demonstrated that the development and maintenance of neuropathic pain are accompanied by releasing of proinflammatory mediators from activated glial cells in the spinal cord. In this study, we investigated the antinociceptive properties of lemnalol, a potential anti-inflammatory compound, on chronic constriction injury (CCI) in a well-established rat model of neuropathic pain. Our results demonstrated that a single intrathecal administration of lemnalol (0.05-10 μg) significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia, 14 days postsurgery. Furthermore, immunohistofluorescence analyses showed that lemnalol (10 μg) also significantly inhibits CCI-induced upregulation of microglial and astrocytic immunohistochemical activation markers in the dorsal horn of the lumbar spinal cord. Double immunofluorescent staining demonstrated that intrathecal injection of lemnalol (10 μg) markedly inhibited spinal proinflammatory mediator tumor necrosis factor-α expression in microglial cells and astrocytes in neuropathic rats. Collectively, our results indicate that lemnalol is a potential therapeutic agent for neuropathic pain, and that further exploration of the effects of lemnalol on glial proinflammatory responses is warranted.
Behavioural pharmacology 12/2011; 22(8):739-50. · 2.85 Impact Factor
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ABSTRACT: Chemical investigation of the Dongsha Atoll soft coral Lobophytum crassum has afforded four new cembranoids, crassumols A-C (1-3) and 13-acetoxysarcophytoxide (4). The structures of these isolated compounds were elucidated by extensive NMR and HRESIMS experiments. The cytotoxicity and anti-HCMV (Human cytomegalovirus) activities of 1-4 were evaluated in vitro. Compound 4 exhibited cytotoxicity against A-549 (human lung carcinoma) cell line with an ED(50) of 3.6 μg/mL.
Marine Drugs 12/2011; 9(12):2705-16. · 3.85 Impact Factor
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ABSTRACT: Capilloquinol (1), possessing an unprecedented farnesyl quinoid skeleton, was isolated from the Dongsha Atoll soft coral Sinularia capillosa. The structure of capilloquinol was elucidated by extensive analysis of spectroscopic data. The cytotoxicity and antiviral activity against human cytomegalovirus of 1 was evaluated in vitro.
Marine Drugs 01/2011; 9(9):1469-76. · 3.85 Impact Factor
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ABSTRACT: Chemical investigations of the Dongsha Atoll soft coral Lobophytum durum resulted in the isolation of five new cembranolides, durumolides M-Q (1-5). The structures of compounds 1-5 were characterized by the interpretation of extensive spectroscopic analysis. Compound 4 exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED₅₀ of 3.8 μg/mL. Moreover, compound 5 showed significant antiviral activity against human cytomegalovirus with an IC₅₀ of 5.2 μg/mL.
Marine Drugs 01/2011; 9(8):1307-18. · 3.85 Impact Factor
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ABSTRACT: In previous studies on the secondary metabolites of the Taiwanese octocoral Isis hippuris, specimens have always been collected at Green Island. In the course of our studies on bioactive compounds from marine organisms, the acetone-solubles of the Taiwanese octocoral I. hippuris collected at Orchid Island have led to the isolation of five new polyoxygenated steroids: hipposterone M-O (1-3), hipposterol G (4) and hippuristeroketal A (5). The structures of these compounds were determined on the basis of their spectroscopic and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-5 and their cytotoxicity against selected cell lines were evaluated. Compound 2 exhibited inhibitory activity against HCMV, with an EC(50) value of 6.0 μg/mL.
Marine Drugs 01/2011; 9(10):1829-39. · 3.85 Impact Factor
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ABSTRACT: Chemical investigation of the soft coral Sinularia gyrosa led to the purification of three new diterpenoids, designated as gyrosanols A-C (1-3). The structures of 1-3 were elucidated through extensive spectroscopic analyses. Compounds 1 and 2 exhibited antiviral activity against HCMV with IC(50)'s of 2.6 and 3.7 microM, respectively. In addition, compounds 1 and 2 showed significant anti-inflammatory activity by reducing the levels of the COX-2 protein (19.6 + or - 3.9% and 29.1 + or - 9.6%, respectively) in RAW 264.7 macrophages.
Journal of Natural Products 06/2010; 73(6):1184-7. · 3.13 Impact Factor
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ABSTRACT: Chemical investigations of the Formosan soft coral Cespitularia hypotentaculata ROXAS led to the isolation of two new verticillane diterpenoids, cespitularins R and S (1, 2), along with seven known compounds (3-9). The structures of these isolated compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison with those of reported in literature. The anti-inflammatory activity using RAW 264.7 macrophages of compounds 1-9 were evaluated in vitro.
Chemical & pharmaceutical bulletin 06/2010; 58(6):848-51. · 1.70 Impact Factor
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ABSTRACT: Chemical investigations of the soft coral Sinularia gyrosa resulted in the isolation of six new norcembranolides, gyrosanolides A-F (1-6), a new norcembrane, gyrosanin A (7), and 11 known norditerpenoids 8-18. The structures of the isolated compounds were elucidated through extensive spectroscopic data and by comparison with reported data in the literature. Compounds 1-3, 7-9, 12, and 13 at concentration of 10microM did not inhibit the COX-2 protein expression, but significantly reduced the levels of the iNOS protein (55.2+/-14.6%, 18.6+/-6.7%, 10.6+/-4.6%, 66.9+/-5.2%, 10.2+/-5.1%, 17.4+/-7.2%, 47.2+/-11.9%, and 56.3+/-5.1%, respectively) by LPS stimulation. Compound 8 showed significant antiviral activity against HCMV (human cytomegalovirus) cells with an IC(50) of 1.9microg/mL.
Bioorganic & medicinal chemistry 05/2010; 18(10):3379-86. · 2.82 Impact Factor
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ABSTRACT: Chemical investigation of the octocoral Sarcophyton ehrenbergi led to the isolation of six new cembranoids, (+)-12-carboxy-11Z-sarcophytoxide (1), (+)-12-methoxycarbonyl-11Z-sarcophine (3), ehrenberoxides A-C (4-6), and lobophynin C (2), along with two known compounds, (+)-sarcophytoxide (7) and (+)-sarcophine (8). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses, while the relative configuration of 1 was confirmed by X-ray diffraction analyses. The chemical evidence combined with spectroscopic and physical data suggested that the locations of the epoxide and the methyl carboxylate for lobophynin C should be exchanged. Moreover, metabolites 1-6 were evaluated in vitro for their cytotoxicity against selected cancer and normal cells lines, antiviral activity against human cytomegalovirus, and antibacterial activity against Salmonella enteritidis.
Journal of Natural Products 02/2010; 73(2):197-203. · 3.13 Impact Factor
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ABSTRACT: Chemical investigations of the soft coral Sinularia capillosa resulted in the isolation of one new tetraprenylbenzoquinone, capilloquinone (1), two new furanobenzosesquiterpenoids, capillobenzopyranol (2) and capillobenzofuranol (3), one new furanosesquiterpenoid, capillofuranocarboxylate (4), and five previously characterized metabolites, comprising (E)-5-(2,6-dimethylocta-5,7-dienyl)furan-3-carboxylic acid (5), 2-[(2E,6E)-3,7-dimethyl-8-(4-methylfuran-2-yl)octa-2,6-dienyl]-5-methylcyclohexa-2,5-diene-1,4-dione (6), 2-[(2E,6E)-3,7-dimethyl-8-(4-methylfuran-2-yl)octa-2,6-dienyl]-5-methylbenzene-1,4-diol (7), (−)-loliolide (8), and 3,4,11-trimethyl-7-methylenebicyclo[6.3.0]undec-2-en-11α-ol (9). The structures of 1−4 were elucidated through extensive spectroscopic analysis. The cytotoxicity, anti-HCMV (human cytomegalovirus) activity, antibacterial activity, and anti-inflammatory effects of 1−9 were evaluated in vitro.
Journal of Natural Products 02/2010; 73(4). · 3.13 Impact Factor
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ABSTRACT: Chemical investigations of the Formosan soft coral Lemnalia flava have obtained a new ylangene-type sesquiterpenoid, (1S,2S,4R,6S,7R,8S)-4alpha-formyloxy-beta-ylangene (1), along with two known sesquiterpenoids, lemnalol (2) and isolemnalol (3). Three new nardosinane-type sesquiterpenoids, designated as paralemnolins J-L (4-6), and five known sesquiterpenoids (7-11), were isolated from the other soft coral Paralemnalia thyrsoides. The structures of metabolites 1 and 4-6 were elucidated through extensive spectroscopic analysis and chemical methods. Moreover, the anti-inflammatory activity of metabolites 1-7 and 11 was evaluated in vitro.
Chemical & pharmaceutical bulletin 01/2010; 58(3):381-5. · 1.70 Impact Factor
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ABSTRACT: Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells.
To examine chromosomal integrity and the DNA damage signal gamma-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76.
We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal gamma-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels.
Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations.
Journal of Biomedical Science 11/2009; 16:107. · 2.01 Impact Factor
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ABSTRACT: Chemical investigations on the organic extract of the Formosan soft coral Nephthea erecta led to the isolation of two new eudesmanoids, (4R*,5S*,6Z,10R*)-8-oxo-eudesm-6-en-5alpha,11-diol (1) and (6E,10R)-4,5-dioxo-11-methoxy-eudesm-6-ene (2), together with one new tri-nor-eudesmane sesquiterpenoid, (4S*,5E,10R*)-7-oxo-tri-nor-eudesm-5-en-4beta-ol (3). The structures of metabolites 1-3 were elucidated through extensive spectroscopic analyses and by comparison with those reported in the literature. The anti-inflammatory activity using RAW 264.7 macrophages and their cytotoxicity against selected cancer cells of 1-3 were evaluated in vitro.
Journal of Asian natural products research 11/2009; 11(11):967-73. · 0.61 Impact Factor
