ABSTRACT
Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 µM K2Cr2O7, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 µg/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 µg/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function.
ABSTRACT
This study was designed to determine the complement activation effects of carotenoid-derived aldehydes (CDA) on cultured human umbilical vein endothelial cells (HUVEC). A dose-dependent complement activation upon incubation of HUVEC with CDA was observed. Interestingly, the data showed that the alternative pathway was not activated. In addition, upon CDA treatment a significant number of apoptotic cells was also observed. The results revealed that CDA could activate the complement by way of the classical pathway. The study suggests that high carotenoid supplementation for the treatment of coronary heart disease should be used cautiously.
Subject(s)
Aldehydes/pharmacology , Carotenoids/pharmacology , Complement Activation/drug effects , Endothelial Cells/metabolism , Apoptosis/drug effects , Cell Survival , Cells, Cultured , Complement Pathway, Alternative/drug effects , Complement Pathway, Classical/drug effects , Dose-Response Relationship, Drug , Humans , Umbilical Veins/cytologyABSTRACT
Bioassay-guided chromatographic separation of the cytotoxic MeOH extract of Phaius mishmensis led to the isolation of two known and six new indoloquinazolinones, phaitanthrins A-E (1-5) and methylisatoid (6). The structures of the new compounds were elucidated by spectroscopic analysis. Phaitanthrin A (1) and tryptanthrin (7) showed moderate cytotoxicity against MCF-7, NCI-H460, and SF-268 cell lines. A series of ketone adducts of tryptanthrin were prepared and tested initially for anticancer activity in vitro against MCF-7, NCI-H460, and SF-268 human cancer cell lines. The 3-pentanone adduct 13 showed activity similar to tryptanthrin.
Subject(s)
Antineoplastic Agents, Phytogenic , Orchidaceae/chemistry , Plants, Medicinal/chemistry , Quinazolines , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Molecular Conformation , Molecular Structure , Quinazolines/chemistry , Quinazolines/isolation & purification , Quinazolines/pharmacology , TaiwanABSTRACT
Bioassay-guided fractionation of the MeOH extract of the leaves of Grevillea robusta led to the isolation of six new 5-alkylresorcinols, gravicycle (1), dehydrogravicycle (2), bisgravillol (3), dehydrobisgravillol (4), dehydrograviphane (5), and methyldehydrograviphane (6), as well as eight known compounds. The structures of these compounds were determined by spectroscopic and chemical methods. Graviphane (7) and methylgraviphane (8) were isolated in the pure form for the first time from a natural source. The compounds all showed marginal cytotoxicity against MCF-7, NCI-H460, and SF-268 cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic , Plants, Medicinal/chemistry , Proteaceae/chemistry , Resorcinols , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Inhibitory Concentration 50 , Molecular Structure , Plant Leaves/chemistry , Resorcinols/chemistry , Resorcinols/isolation & purification , Resorcinols/pharmacology , TaiwanABSTRACT
UNLABELLED: Peanut is a potent plant to be induced to synthesize bioactive stilbenoids. Bioactivities of those stilbenoids except resveratrol have been meagerly investigated. When peanut kernels (Tainan 14, a Spanish cultivar) were imbibed, incubated 3 days for germination, sliced, incubated with artificial aeration, periodically sampled, lyophilized, extracted with methanol, and subjected to reverse-phase HPLC analysis, four major fractionations were detected and identified as trans-resveratrol (Res), trans-arachidin-1 (Ara-1), trans-arachidin-3 (Ara-3), and trans-isopentadienylresveratrol (IPD). During incubation of the peanut slices, contents of Res, Ara-1, and Ara-3 increased tremendously from initially trace or not detectable amounts up to 147.3, 495.7, and 2414.8 microg/g, corresponding to 20, 16, and 24 h of incubation, while IPD contents continued to increase up to 28 h (4474.4 microg/g). When the four stilbenoids and butylated hydroxytoluene (BHT) were subjected to antioxidant characterization by various measures, all have exhibited varied potencies of antioxidant activity. In particular, retardation of absorbance increase at 234 nm as formation of the conjugated diene hydroperoxides in a real pork oil system stored at 60 degrees C, supplement of Ara-1 at 100 microM has shown equivalent or even greater activity than did BHT. When the media were supplemented with Res, Ara-1, Ara-3, and IPD at 15 microM for cultivation of mouse macrophage RAW 264.7 cells activated by lipopolysaccharide (LPS), the LPS-induced extracellular production of prostaglandin E2 (PGE2) and nitric oxide (NO) was significantly inhibited by Ara-1 (p < 0.001), Res (p < 0.001), Ara-3 (p < 0.01), and IPD (p < 0.01). It is noteworthy and of merit that all test stilbenoids have exhibited potent antioxidant and anti-inflammatory activities and varied as affected by number of hydroxyl groups and isopentenyl or isopentadienyl moiety. KEYWORDS: Arachis hypogaea L.; peanut; groundnut; resveratrol; stilbenoids; arachidin; antioxidant; anti-inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Arachis/chemistry , Stilbenes/metabolism , Stilbenes/pharmacology , Animals , Cell Line , Hemiterpenes , Macrophages/drug effects , Mice , Plant Extracts/pharmacology , Seeds/chemistry , Seeds/growth & development , Stilbenes/analysisABSTRACT
Purification of CHCl3 and EtOAc solubles of the MeOH extract of Cephalanceropsis gracilis afforded seven new indole alkaloids, cephalinones A (1), B (2), C (3), and D (4) and cephalandoles A (5), B (6), and C (7), besides eight known compounds. The structures of the new compounds were determined by spectroscopic analysis. All 15 indole alkaloids were evaluated for their cytotoxic effects on MCF-7, NCI-H460, and SF-268 cell lines by the MTT method. Only cephalinone-F (6) showed significant cytotoxicity.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Indole Alkaloids/isolation & purification , Orchidaceae/chemistry , Plants, Medicinal/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indole Alkaloids/chemistry , Indole Alkaloids/pharmacology , Molecular Structure , Taiwan , Tumor Cells, CulturedABSTRACT
Twelve new compounds, vittarin-A (1), -B (2), -C (3), -D (4), -E (5), -F (6), 3-O-acetylniduloic acid (7), ethyl 3-O-acetylniduloate (8), methyl 4-O-coumaroylquinate (9), vittarilide-A (10), and -B (11), and vittariflavone (12), as well as 20 known compounds have been isolated from the whole plant of Vittaria anguste-elongata. The structures of these compounds were determined by spectroscopic and chemical transformation methods. 5,7-Dihydroxy-3',4',5'-trimethoxyflavone (18) displayed moderate cytotoxicity against human lung carcinoma and central nervous system carcinoma cell lines with inhibition of 89 and 61% at a concentration of 58 microM, respectively. Vittarilide-A (10) and -B (11) and ethyl 4-O-caffeoylquinate (14) exhibited moderate DPPH radical scavenging activity with IC50 values of 91, 290, and 234 microM, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Ferns/chemistry , Free Radical Scavengers/isolation & purification , Phenols/isolation & purification , Plants, Medicinal/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Biphenyl Compounds , Drug Screening Assays, Antitumor , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Humans , Inhibitory Concentration 50 , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phenols/chemistry , Phenols/pharmacology , Picrates/pharmacology , Taiwan , Tumor Cells, CulturedABSTRACT
In addition to six known phenanthroindolizidine alkaloids, eight new alkaloids, namely, ficuseptines B-D (1-3), 10R,13aR-tylophorine N-oxide (4), 10R,13aR-tylocrebrine N-oxide (5), 10S,13aR-tylocrebrine N-oxide (6), 10S,13aR-isotylocrebrine N-oxide (7), and 10S,13aS-isotylocrebrine N-oxide (8), were isolated from a methanol extract of the stems of Ficus septica. The structures of the new compounds were elucidated by means of spectroscopic data interpretation. Cytotoxicity of some of these alkaloids was assessed in vitro using the HONE-1 and NUGC cell lines.
Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Ficus/chemistry , Indolizines/isolation & purification , Phenanthrenes/isolation & purification , Plants, Medicinal/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Indolizines/chemistry , Indolizines/pharmacology , Molecular Structure , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , Plant Stems/chemistry , Tumor Cells, CulturedABSTRACT
Five new compounds, hibicuslide A (1), hibicuslide B (2), hibicuslide C (3), hibicutaiwanin (4), hibicusin (5), and fifty-one known compounds have been isolated from the stems of Hibiscus taiwanensis. The structures of these compounds were determined by spectroscopic and chemical transformation methods. Among them, mansonone H (19) and uncarinic acid A (30) inhibited HIV replication in H9 lymphocyte cells. The 9,9'-O-feruloyl-(-)-secoisolaricinresinol (12), myriceric acid C (29), and uncarinic acid A (30) showed cytotoxic activity against human lung carcinoma and breast carcinoma.
Subject(s)
Hibiscus , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Cell Line, Tumor , HIV-1/drug effects , HIV-1/physiology , Humans , Lymphocytes/drug effects , Lymphocytes/virology , Plant Extracts/pharmacology , Plant StemsABSTRACT
Three new compounds: begonanline (1). nantoamide (2). and methyl (S)-glycerate (3). as well as forty-four known compounds have been isolated and characterized from the rhizomes of Begonia nantoensis. The structures of these compounds were determined by spectral analyses and/or X-ray crystallography. Among them, cucurbitacin B (4). dihydrocucurbitacin B (5). cucurbitacin E (6). dihydrocucurbitacin E (7). cucurbitacin I (8). and (-)-auranamide (9). showed cytotoxicity against four human cancer cell lines. 3beta,22alpha-Dihydroxyolean-12-en-29-oic acid (10), indole-3-carboxylic acid (11), 5,7-dihydroxychromone (12), and (-)-catechin (13) demonstrated significant activity against HIV replication in H9 lymphocyte cells.
Subject(s)
Anti-HIV Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Begoniaceae/chemistry , Benzamides/isolation & purification , Carbolines/isolation & purification , Glyceric Acids/isolation & purification , Plants, Medicinal/chemistry , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Benzamides/chemistry , Benzamides/pharmacology , Carbolines/chemistry , Carbolines/pharmacology , China , Crystallography, X-Ray , Glyceric Acids/chemistry , Glyceric Acids/pharmacology , Humans , Lymphocytes/drug effects , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Rhizome/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Tumor Cells, CulturedABSTRACT
In a continuing search for bioactive compounds from Aristolochia species, 28 compounds, including three new constituents, demethylaristofolin E (1), aristomanoside (2), and dehydrooxoperezinone (3), were isolated from an extract of the stems of Aristolochia manshuriensis. The structures of these compounds were established by extensive 1D and 2D NMR spectral studies. Among these compounds, dehydrooxoperezinone (3) was found to inhibit the replication of HIV, with an EC(50) value of 17.5 microg/mL and a therapeutic index of 1.43.
Subject(s)
Anti-HIV Agents/isolation & purification , Aristolochia/chemistry , Dopamine/isolation & purification , Furans/isolation & purification , Glucosides/isolation & purification , Naphthoquinones/isolation & purification , Phenanthrenes/isolation & purification , Plants, Medicinal/chemistry , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Dopamine/analogs & derivatives , Dopamine/chemistry , Dopamine/pharmacology , Furans/chemistry , Furans/pharmacology , Glucosides/chemistry , Glucosides/pharmacology , Inhibitory Concentration 50 , Molecular Structure , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Nuclear Magnetic Resonance, Biomolecular , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , Plant Stems/chemistry , TaiwanABSTRACT
Two new antioxidative and cytotoxic compounds, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone (1) and 10'(Z),13'(E)-heptadecadienylhydroquinone (2), as well as the known 10'(Z)-heptadecenylhydroquinone (3), were isolated from an EtOH extract of the sap of Rhus succedanea. The structures were elucidated by spectral analyses. These compounds showed antioxidative and cytotoxic activities against five cancer cell lines.