Lemnalol attenuates mast cell activation and osteoclast activity in a gouty arthritis model.

OBJECTIVES: In this study, we investigated the effects of a soft coral-derived anti-inflammatory compound, lemnalol, on mast cell (MC) function and osteoclast activity in rats with monosodium urate (MSU) crystal-induced gouty arthritis. METHODS: In this study, we examined the therapeutic effects of lemnalol on intra-articular injection of MSU induces gouty arthritis with the measurement of ankle oedema. Toluidine blue staining were used to analyse the infiltration and the percentage degranulation MCs. Immunohistochemical analysis showed CD117, transforming growth factor beta 1 (TGF-ß1), matrix metalloproteinase 9 (MMP-9), the osteoclast markers cathepsin K and tartrate-resistant acid phosphatase (TRAP) protein expression in ankle tissue. KEY FINDINGS: We found that both infiltration and degranulation of MCs increased at 24 h after MSU injection in the ankle joint. Immunohistochemical analysis showed that MSU induced upregulation of TGF-ß1, MMP-9, the osteoclast markers cathepsin K and TRAP in ankle tissues. Administration of lemnalol ameliorated MSU-induced TGF-ß1, MMP-9, cathepsin K and TRAP protein expression. CONCLUSIONS: Taken together, our results show that MSU-induced gouty arthritis is accompanied by osteoclast-related protein upregulation and that lemnalol treatment may be beneficial for the attenuation of MC infiltration and degranulation and for suppressing osteoclast activation in gouty arthritis.

Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats.

BACKGROUND AND PURPOSE: Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coral Capnella imbricate, 4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[]pentalene-2,3a-diol (GB9) exhibited anti-inflammatory actions on activated macrophages in vitro. Here we have assessed the anti-neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a-hydroxy-4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[]pentalen-2-yl ester (GB10). EXPERIMENTAL APPROACH: Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in interferon-gamma (IFN-gamma)-stimulated mouse microglial BV2 cells were measured by Western blot. The in vivo effects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX-2 protein in lumbar spinal cord, by immunohistochemistry. KEY RESULTS: In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX-2, stimulated by IFN-gamma. Intrathecal administration of GB9 and GB10 inhibited CCI-induced nociceptive sensitization and thermal hyperalgesia in a dose-dependent manner. Intraperitoneal injection of GB9 inhibited CCI-induced thermal hyperalgesia and also inhibited CCI-induced activation of microglial cells and up-regulation of COX-2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury. CONCLUSION AND IMPLICATIONS: Taken together, these data indicate that the marine-derived capnellenes, GB9 and GB10, had anti-neuroinflammatory and anti-nociceptive properties in IFN-gamma-stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.

A new cytotoxic amide from the stem wood of Hibiscus tiliaceus.

A new coumarin, hibiscusin, and a new amide, hibiscusamide, together with eleven known compounds including vanillic acid, P-hydroxybenzoic acid, syringic acid, P-hydroxybenzaldehyde, scopoletin, N- trans-feruloyltyramine, N-cis-feruloyltyramine, a mixture of beta-sitosterol and stigmasterol, a mixture of beta-sitostenone and stigmasta-4,22-dien-3-one were isolated from the stem wood of Hibiscus tiliaceus. The structures of these new compounds were determined through spectral analyses. Among the isolates, three compounds exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

Cytotoxic dihydroagarofuranoid sesquiterpenes from the stem of Microtropis fokienensis.

Four dihydroagarofuran sesquiterpene polyesters (1-4) have been isolated from the stem of Microtropis fokienensis. The structures of these new compounds were determined through spectroscopic analyses. Compound 1, 2, 3, and 4 exhibited cytotoxicities (IC(50) values < 0.1 microg/mL) against P-388 and HT-29 cell lines in vitro.

New cytotoxic tetrahydrofuran- and dihydrofuran-type lignans from the stem of Beilschmiedia tsangii.

Five new compounds including two tetrahydrofuran-type lignans, beilschmin A and beilschmin B, a dihydrofuran-type lignan, beilschmin C, and two 1-phenylbutyl benzoates, tsangin A and tsangin B, together with thirteen known compounds have been isolated from the stem of Beilschmiedia tsangii. The structures of these new compounds were determined through spectral analyses. Among the isolates, beilschmin A (1), beilschmin B (2), beilschmin C (3), tsangin A (4), tsangin B (5), 2,6,11-trimethyldodeca-2,6,10-triene (14), alpha-tocopherylquinone (17), and alpha-tocospiro B (18) were cytotoxic (IC (50) values < 4 microg/mL) in P-388 and/or HT-29 cell lines in vitro.

Cytotoxic and anti-platelet aggregation constituents from the root wood of Melicope semecarpifolia.

A new acetophenone derivative, melicopone, along with twenty-nine known compounds has been isolated from the root wood of Melicope semecarpifolia. The structure of this new compound was determined using spectral analyses. The compound oxynitidine isolated in this study adds the Melicope genus to the benzo[c]phenanthridine-containing members chemotaxonomically. Three isolates were cytotoxic in P-388 and HT-29 cell lines, and anti-platelet aggregation activities were shown for 10 known compounds.

Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura.

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

New cytotoxic biflavonoids from Selaginella delicatula.

Five new biflavonoids, robustaflavone 7,4',4'''-trimethyl ether, robustaflavone 4',4'''-dimethyl ether, 2,3-dihydroamentoflavone 7,4',7''-trimethyl ether, 2,3-dihydroamentoflavone 7,4'-dimethyl ether, and 2'',3''-dihydroisocryptomerin 7-methyl ether, together with six known compounds have been isolated from the aerial parts of Selaginella delicatula. The structures of these new compounds were determined through spectral analyses. Among the isolates, robustaflavone 4',4'''-dimethyl ether, 2,3-dihydroamentoflavone 7,4'-dimethyl ether, and alpha-tocopheryl quinone exhibited cytotoxicities (ED50 values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.

New cytotoxic cyclobutanoid amides, a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens.

Three new cyclobutanoid amides with trans-trans-trans configurations, piperarborenine C, piperarborenine D and piperarborenine E, and a new furanoid lignan, (+)-arborone, together with twelve known compounds, were isolated from the stems of Piper arborescens. The structures of these new compounds were determined by means of spectral analyses. Piperarborenine C, (+)-diayangambin, piplartine, piperolactam B, piperolactam C, aristolactam BIII, goniothalactam, and methyl trans-3,4,5-trimethoxycinnamate possessed anti-platelet aggregation activity in vitro. Among them, piplartine showed the most potent anti-platelet aggregation activity induced by collagen and showed an IC50 value of 21.5 microM. Piperarborenines A - E, piperarborenine, aristololactam BIII and goniothalactam showed significant cytotoxic activity (IC50 values < 4 microg/mL) against P-388, HT-29 and A549 cell lines in vitro.

New indolopyridoquinazoline, benzo[c]phenanthridines and cytotoxic constituents from Zanthoxylum integrifoliolum.

Three new alkaloids, 7,8-dehydro-1-methoxyrutaecarpine, isodecarine, and 8-demethyloxychelerythrine, together with sixteen known compounds, norchelerythrine, oxychelerythrine, decarine, dihydrocherythrinylacetaldehyde, 6-acetonyldihydrochelerythrine, rutaecarpine, 1-hydroxyrutaecarpine, gamma-fagarine, skimmianine, (-)-matairesinol, (-)-isoarctigenin, (+)-epipinoresinol, d-sesamin, lupeol, canthin-6-one, and arnottianamide have been isolated from the root bark of Zanthoxylum integrifoliolum. The structures of these new compounds were determined through spectral analyses. Among the isolates, 7,8-dehydro-1-methoxyrutaecarpine, norchelerythrine, oxychelerythrine, dihydrocherythrinylacetaldehyde, 6-acetonyldihydrochelerythrine, 1-hydroxyrutaecarpine, gamma-fagarine, skimmianine, (-)-matairesinol, and canthin-6-one exhibited cytotoxicities (ED50 values < 4 microg/mL) against P-388 or HT-29 cell lines in vitro.

Cytotoxic chromenes from Myriactis humilis.

Two new chromenes, myriachromene and 2,2-dimethyl-6,7-methylenedioxy-2H-chromene, together with ten known compounds including alpha-tocopherylquinone, alpha-tocopherol acetate, diphenyl sulfone, beta-carotene, chondrillasterol, beta-sitosterol, beta-sitostenone, vanillin, and vanillic acid were isolated from the whole plant of Myriactis humilis. The structures of these new compounds were determined through spectral analyses. Among the isolates, four compounds exhibited cytotoxicity (ED50 values < 4 microg/mL) against P-388 or HT-29 cell lines in vitro.

New lignans and cytotoxic constituents from Wikstroemia lanceolata.

Two new lignans, (-)-aptosimon ( 1) and (-)-diasesamin-di-gamma-lactone ( 2), together with twenty-two known compounds, have been isolated from the stems and roots of Wikstroemia lanceolata. The structures of the new compounds were determined through spectral analyses. The proton and carbon assignments of the known sesquiterpenoid, 1alpha,7alpha,10alpha H-guaia-4,11-dien-3-one ( 24) were revised by 2D NMR techniques. Among the isolates, three compounds, (+)-hinokinin ( 6), 2,6-dimethoxy- p-benzoquinone ( 17), and 1alpha,7alpha,10alpha H-guaia-4,11-dien-3-one ( 24) exhibited effective cytotoxicities (ED50 values < 4.0 microg mL-1) against P-388 and HT-29 tumor cell lines.

New diterpenoids from Viburnum awabuki.

Eight new vibsane-type diterpenoids, vibsanins P-W (1-8), were isolated from the methanol extracts of the leaves and twigs of Viburnum awabuki. The structures were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.

Cytotoxic xanthones and biphenyls from the root of Garcinia linii.

Three new xanthones, linixanthones A-C, two new biphenyls, garcibiphenyls A and B, and a new benzopyran, garcibenzopyran, together with twelve known xanthones and a known biphenyl have been isolated from the root of Garcinia linii. The structures of these new compounds were determined through spectral analyses. Among the isolates, five compounds exhibited cytotoxicities (ED50 values < 4 microg/mL) against P-388 and HT-29 cell lines in vitro.

A cytotoxic butenolide, two new dolabellane diterpenoids, a chroman and a benzoquinol derivative formosan Casearia membranacea.

Investigation of a cytotoxic chloroform-soluble fraction of the stem of Casearia membranacea (Flacourtiaceae) led to the isolation of five new compounds, including one butenolide, casealactone (1), one chroman, caseamemin (2), two dolabellane diterpenoids, casearimene A (3) and casearimene B (4), one benzoquinol ether, casearinone (5), together with fifteen known compounds, including two amides, N- trans-feruloyltyramine (6) and N- cis-feruloyltyramine (7), six steroids, beta-sitosterol (8), stigmast-5-ene-3beta,7alpha-diol (9), stigmast-5-ene-3beta,7beta-diol (10), stigmastane-3beta,5alpha,6beta-triol (11), beta-sitostenone (12), beta-sitosterol 3- O-beta-glucoside (13), two triterpenoids, squalene (14) and friedelin (15), one lignan, (+/-)-syringaresinol (16), two benzenoids, syringaldehyde (17) and vanillic acid (18), one ester, methyl hexadecanoate (19), and anthraquinone (20), respectively. Among these isolates, 1 showed cytotoxicity against P-388 and HT-29 cancer cell lines in vitro, and 6 and 7 showed cytotoxicity against the P-388 cancer cell line. The structures of these compounds were determined by means of spectroscopic techniques, and the structure of 3 was confirmed by X-ray crystallographic analysis.

Furoquinoline alkaloids and cytotoxic constituents from the leaves of Melicope semecarpifolia.

Three new furoquinoline alkaloids, melicarpine, semecarpine, and (+/-)-8-methoxyplatydesmine, together with a known flavone, ayanin, were isolated from the leaves of Melicope semecarpifolia. The structures of the three alkaloids were determined through spectral analyses. Of the nineteen isolates obtained here and during earlier work, twelve exhibited cytotoxic activity against P-388, HT-29, or A549 cell lines in vitro. Among them, confusameline is the most cytotoxic isolate, and exhibited more potent cytotoxicity (ED 50 value = 0.03 microgram/mL) against the P-388 cell line than the reference compound mithramycin (ED 50 value = 0.06 microgram/mL).

Cytotoxic butanolides and secobutanolides from the stem wood of Formosan Lindera communis.

Bioassay-guided fractionation of the chloroform-soluble fraction from the stem wood of Formosan Lindera communis led to the isolation of two new cytotoxic butanolides, lincomolide C (1), lincomolide D (2), as well as two new secobutanolides, secolincomolide A (3), secolincomolide B (4), together with four known compounds, including one butanolide, isoobtusilactone A (5), and one secobutanolide, secoisolancifolide (6), one sesquiterpene, epi-cubenol (7), one steroid: beta-sitosterol (8). Compound 4 existed in enol [(2E)-2-[(1R)-1-hydroxy-2-oxo-propyl]-6,9-dimethyl-8-hydroxy-hexadec-2,7-dienoic acid methyl ester] (4a) and keto [(2E)-2-[(1R)-1-hydroxy-2-oxo-propyl]-6,9-dimethyl-8-oxo-hexadec-2-enoic acid methyl ester] (4b) tautomers. Compound 2 showed significant cytotoxicity against P-388 and HT-29 cancer cell lines. Also, 2 exhibited marginal activity against A549, 5 against P-388, and 1 against P-388, A549 and HT-29 cancer cell lines. Their structures were determined by spectroscopic analyses.