Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC₅₀ values of 10.2 and 8.6 μmol·L^-1, respectively.
Animals ; Dysidea/chemistry* ; Porifera ; Quinones/pharmacology* ; Sesquiterpenes/pharmacology* ; Skeleton

The effect of amygdalin joint hydroxysafflor yellow A (HSYA) on the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and the possible mechanism were studied and explored. Chondrocytes were obtained from endplate of one-month SD rat intervertebral discs and cultured primary endplate chondrocytes. After identification, they were divided into normal group, induced group, amygdalin group, HSYA group and combined group. CCK-8 kit was adopted to detect the proliferation of the endplate chondrocytes. FCM was measured to detect the apoptosis. Real-time PCR method was adopted to observe the mRNA expression of Aggrecan, Col 2 alpha1, Col 10 alpha1, MMP-13 and the inflammatory cytokines IL-1beta. The protein expression of Col II, Col X was tested through immunofluorescence. Compared with the normal group, the proliferation of the endplate chondrocytes decreased while the apoptosis increased (P < 0.05). With down regulation of the mRNA expressions of Aggrecan, Col 2 alpha1 and up regulation of the mRNA expressions of Col 10 alpha1, MMP-13, IL-1beta (P < 0.05), the protein expression of Col II decreased while the protein expression of Col X increased. Compared with the induced group, amygdalin group, HSYA group, the combined group could inhibit the apoptosis and promote the proliferation (P < 0.05). They could increase the mRNA expressions of Aggrecan and Col 2 alpha1 while decrease the mRNA expressions of Col 10 alpha1, MMP-13 and IL-1beta (P < 0.05). They could also enhance the protein expression of Col II while reduce the protein expression of Col X. The effect of the combined group was significantly better than that of amygdalin and HSYA. Amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of amygdalin or HSYA.
Amygdalin ; pharmacology ; Animals ; Apoptosis ; Cells, Cultured ; Chalcone ; analogs & derivatives ; pharmacology ; Chondrocytes ; drug effects ; Collagen ; metabolism ; Drug Synergism ; Interleukin-1beta ; Intervertebral Disc ; cytology ; Quinones ; pharmacology ; Rats

OBJECTIVETo screen out the main components with no significant difference with Salvia miltiorrhiza diterpene quinones pharmacological action, in order to determine the compatible form of representative components that can describe the overall property of S. miltiorrhiza diterpene quinones.

METHODAccording to the results of the in vitro pharmacological experiment, the myocardial ischemia model of rats was induced through intraperitoneal injection of isoproterenol. The pharmacologic effects of S. miltiorrhiza diterpene quinones, combination with principal component A and combination with principal component B were compared in electrocardiogram (changes in J point), enzymology indicators (SOD, MDA, CK, LDH) and pathology (myocardial histological changes), so as to screen out the compatible form of representative components that can describe the overall property of S. miltiorrhiza diterpene quinones.

RESULTThe S. miltiorrhiza diterpenoid quinone high-dose group and the B high-dose group were similar in all pharmacological effects, with equal efficacy but no significant difference.

CONCLUSIONThe S. miltiorrhiza diterpenoid quinone high-dose group and the B high-dose group showed a certain therapeutic effect on ISO-induced myocardial ischemia. Therefore, the four components in the B high-dose group can be used as representative components of S. miltiorrhiza diterpene quinones.

Animals ; Diterpenes ; pharmacology ; Drug Evaluation, Preclinical ; Isoproterenol ; pharmacology ; Male ; Myocardial Ischemia ; drug therapy ; Quinones ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine, have been isolated from various marine organisms. A class of pyrroloiminoquinone-related alkaloids, known as bispyrroloquinones, is the focus of this review article. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B, and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogs show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogs that has been discovered recently is through the inhibition of indoleamine 2, 3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids and their analogs.
Alkaloids ; chemistry ; pharmacology ; Animals ; Anti-Infective Agents ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Humans ; Indole Alkaloids ; chemistry ; pharmacology ; Indoles ; chemistry ; pharmacology ; Pyrroles ; chemistry ; pharmacology ; Quinolines ; chemistry ; pharmacology ; Quinones ; chemistry ; pharmacology

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 micrometer) was inhibited by PAF receptor blocker (WEB 2086, IC50=0.65 micrometer) and calcium channel blockers, diltiazem (IC50=13 micrometer) and verapamil (IC50=18 micrometer). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 micrometer), a cyclooxygenase inhibitor (indomethacin; IC50=0.2 micrometer) and inhibitor of TLCK, herbimycin A with IC50 value of 5 micrometer. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 micrometer. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways.
Blood Platelets/*drug effects ; Calcimycin/*pharmacology ; Humans ; Indomethacin/pharmacology ; Ionophores/pharmacology ; Platelet Activating Factor/metabolism/*pharmacology ; Platelet Aggregation/*physiology ; Protein-Tyrosine Kinase/antagonists & inhibitors/*physiology ; Quinones/pharmacology ; Research Support, Non-U.S. Gov't ; Thromboxane A2/*physiology ; Verapamil/pharmacology

The chronic myelogenous leukemic K562 cell line carrying Bcr-Abl tyrosine kinase is considered as pluripotent hematopoietic progenitor cells expressing markers for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Here we investigated the signaling modulations required for induction of erythroid differentiation of K562 cells. When the K562 cells were treated with herbimycin A (an inhibitor of protein tyrosine kinase), ras antisense oligonucleotide, and PD98059 (a specific inhibitor of MEK), inhibition of ERK/MAPK activity and cell growth, and induction of erythroid differentiation were observed. The ras mutant, pZIPRas61leu-transfected cells, K562-Ras61leu, have shown a markedly decreased cell proliferation rate with approximately 2-fold doubling time, compared with the parental K562 cells, and about 60% of these cells have shown the phenotype of erythroid differentiation. In addition, herbimycin A inhibited the growth rate and increased the erythroid differentiation, but did not affect the elevated activity of ERK/MAPK in the K562-Ras61leu cells. On the other hand, effects of PD98059 on the growth and differentiation of K562-Ras61leu cells were biphasic. At low concentration of PD98059, which inhibited the elevated activity of ERK/MAPK to the level of parental cells, the growth rate increased and the erythroid differentiation decreased slightly, and at high concentration of PD98059, which inhibited the elevated activity of ERK/MAPK below that of the parental cells, the growth rate turned down and the erythroid differentiation was restored to the untreated control level. Taken together, these results suggest that an appropriate activity of ERK/MAPK is required to maintain the rapid growth and transformed phenotype of K562 cells.
Androstadienes/pharmacology ; Ca(2+)-Calmodulin Dependent Protein Kinase ; Cell Differentiation/drug effects ; Enzyme Inhibitors/pharmacology ; Erythroid Progenitor Cells/physiology* ; Erythroid Progenitor Cells/cytology ; Erythropoiesis* ; Flavones/pharmacology ; Human ; K562 Cells ; Leukemia, Myeloid/pathology ; Oligonucleotides, Antisense/pharmacology ; Quinones/pharmacology ; ras Proteins/metabolism*

AIMTo study the effects of hydroxysafflor yellow A (HSYA) on the mitochondrial function of cortex mitochondrial during cerebral ischemia in rats.

METHODSRat focal cerebral ischemia model in rats was established by ligation of middle cerebral central artery. Cortex mitochondria were isolated and prepared for the measurement of membrane fluidity, swelling, respiratory function, activities of mitochondrial respiratory enzymes and superoxide dismutase (SOD), contents of phospholipid, malondial dehyde (MDA) and Ca2+ to evaluate the function of mitochondria.

RESULTSFocal cerebral ischemia resulted in severe neuronal mitochondrial injuries, which could be alleviated by i.v. HSYA (10, 20 mg x kg(-1)), and nimodipine (Nim, 1.0 mg x kg(-1)). The swelling of mitochondria was ameliorated, the decomposability of membrane phospholipid was decreased, the membrane fluidity of mitochondria was increased, HSYA also significantly inhibited the decrease in the activities of respiratory enzymes and SOD of mitochondria, and the increase in MDA and Ca2+ levels caused by cerebral ischemia in rats.

CONCLUSIONHSYA showed a protective action against the cortex mitochondrial injuries in rats induced by cerebral ischemia. The mechanisms may be derived from reducing lipid peroxides, inhibiting Ca2+ overload, scavenging free radicals and improving the energy metabolism.

Animals ; Brain Ischemia ; metabolism ; pathology ; Calcium ; metabolism ; Chalcone ; analogs & derivatives ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Membrane Fluidity ; drug effects ; Mitochondria ; metabolism ; pathology ; Mitochondrial Swelling ; drug effects ; NAD ; metabolism ; Neuroprotective Agents ; pharmacology ; Quinones ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the possible mechanism of apoptosis induced by photodynamic therapy (PDT) in human pancreatic cancer cells Capan-1 with 2-butylamino-2-demethoxy-hypocrellin B (BAHB) as photosensitizer.

METHODSThe localization of BAHB in Capan-1 cells was studied, apoptosis was determined by DNA gel electrophoresis after PDT. The mitochondria membrane potential (DYm) and cytochrome C release were observed by laser scan confocal microscopy and Western blotting.

RESULTSThe low concentration photosensitizer was mainly localized in mitochondria and also in lysosomes when the concentration is high. DNA ladder analysis showed characteristic of apoptosis. The mitochondria membrane potential (DYm) showed a loss of 30% around, after 6 hours by PDT under laser scan confocal microscopy, which is caused by a sudden increase in the permeability of mitochondria membrane accompanied with apoptosis. In Western blotting, cytochrome C release was observed from the mitochondria into the cytoplasm during BAHB-induced apoptosis.

CONCLUSIONThe research suggests that BAHB-induced apoptosis is related to photosensitization of mitochondria.

Apoptosis ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Pancreatic Neoplasms ; drug therapy ; pathology ; Perylene ; administration & dosage ; analogs & derivatives ; pharmacology ; Photochemotherapy ; Photosensitizing Agents ; administration & dosage ; pharmacology ; Quinones ; administration & dosage ; pharmacology ; Tumor Cells, Cultured

OBJECTIVE: To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines. METHODS: Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively. RESULTS: MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC₅₀) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC₅₀ values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC₅₀ values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G₁ phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells. CONCLUSION Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.
Humans ; beta Catenin/metabolism* ; Caco-2 Cells ; Quinones/pharmacology* ; Glycogen Synthase Kinase 3 beta/metabolism* ; Cell Proliferation ; Colorectal Neoplasms/metabolism* ; Cell Line, Tumor ; Apoptosis ; Benzoquinones/pharmacology* ; RNA, Messenger ; Wnt Signaling Pathway

Bio-active components from Carthamus tinctorius were separated on the basis of antioxidant capacities in vitro. The antioxidant capacity was investigated on the basis of the ability to scavenge DPPH radical, ABTS radical and reduce Fe3+ of different polar fractions. Furthermore, the chemical compounds were isolated from bio-active fraction, and were evaluated for the antioxidative effects. Five major components were isolated and identified from water extract as 6-hydroxykaempferol 3,6,7-tri-O-β-D-glucoside(1), 6-hydroxykaempferol 3-O-β-rutinoside-6-O-β-D-glucoside (2), 6-hydroxykaempferol 3-O-β-D-glucoside (3), hydroxysafflor yellow A (4) and anhydrosafflor yellow B (5). By evaluating and comparing the antioxidative effects of different fractions and obtained compounds, the results showed that water extract displayed significantly high antioxidative activities and 6-hydroxykaempferol glycosides and quinochalcone C-glycosides were found as main contribution for antioxidant property.
Antioxidants ; isolation & purification ; metabolism ; pharmacology ; Benzothiazoles ; metabolism ; Biphenyl Compounds ; metabolism ; Carthamus tinctorius ; chemistry ; Chalcone ; analogs & derivatives ; isolation & purification ; metabolism ; pharmacology ; Ferric Compounds ; metabolism ; Free Radicals ; metabolism ; Kaempferols ; isolation & purification ; metabolism ; pharmacology ; Oxidation-Reduction ; drug effects ; Picrates ; metabolism ; Plant Extracts ; isolation & purification ; metabolism ; pharmacology ; Plants, Medicinal ; chemistry ; Quinones ; isolation & purification ; metabolism ; pharmacology ; Sulfonic Acids ; metabolism ; Water ; chemistry