This study sought to clarify the molecular location and the interaction between mitoxantrone and mitoxantrone transforsomes. The anthraquinone of mitoxantrone, a heterocyclic ring that intercalates in the lipid of bilayer, was determined by UV-spectrophotometry and electron probes scan microscopy. Two aminoethylamino side-chains of the drugs fit to the phosphates of lecithin were determined by 8-value, thus the interaction with lecithin was substantiated. Differential scanning calorimetry confirmed that mitoxantrone has remarkable stabilizing effect on the mitoxantrone transforsomes membrane. The mitoxantrone binds tightly to lecithin. So a high degree of encapsulation efficiency and the sustained-release character of mitoxantrone transforsomes are verified.
Anthraquinones ; chemistry ; Calorimetry, Differential Scanning ; Delayed-Action Preparations ; chemistry ; Lecithins ; chemistry ; Mitoxantrone ; chemistry ; Spectrophotometry

PURPOSE: This study was designed to pursue the basic relationship between MMP-2 and ligament injury via ex vivo stretching of the anterior cruciate ligament (ACL) and its changes by signal transduction pathway. MATERIALS AND METHODS: After femur-ACL-tibia complex was harvested from rats, release of MMP-2 in stretch group and non-stretch group was checked using gelatin zymography. Firstly, authors investigated whether MMP-2 was released from the ligament or not and if so, how long it was released. In addition, the complexes were divided into two groups. In group I, 5 and 12N weights were used to stretch the complex for 10, 30, and 60-minute. In group II, after the ligament complexes were stretched by 15N for 30 minutes, various signal pathway inhibitors such as pertusis toxin, SP600125, PD98059, KT5720, curcumin, and Bay11-7082 were added to their supernatants. MMP-2 activity was evaluated. RESULTS: MMP-2 was immediately released after ligament injury and its activity was increased in proportion to stretching duration and magnitude. As for the signal pathways, inhibition of JNK, ERK, AP-1, and NF-k beta pathways caused MMP-2 expression to be decreased. CONCLUSION: It is considered that the release of MMP-2 plays an important role in remodeling process after ACL injury.
Animals ; Anterior Cruciate Ligament ; Anthracenes ; Carbazoles ; Curcumin ; Flavonoids ; Gelatin ; Knee ; Ligaments ; Matrix Metalloproteinase 2 ; Nitriles ; Pyrroles ; Rats ; Signal Transduction ; Sulfones ; Transcription Factor AP-1 ; Weights and Measures

OBJECTIVE: Triptolide (TP) has been reported to suppress the expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), of which main function is to inactivate the extracellular signal-regulated kinase-1/2 (ERK-1/2), the p38 MAPK and the c-Jun N-terminal kinase-1/2 (JNK-1/2), and to exert antiproliferative and pro-apoptotic activities. However, the mechanisms underlying antiproliferative and pro-apoptotic activities of TP are not fully understood. The purpose of this study was to examine whether the down-regulation of MKP-1 expression by TP would account for antiproliferative activity of TP in immortalized HT22 hippocampal cells. METHODS: MKP-1 expression and MAPK phosphorylation were analyzed by Western blot. Cell proliferation was assessed by 3H-thymidine incorporation. Small interfering RNA (siRNA) against MKP-1, vanadate (a phosphatase inhibitor), U0126 (a specific inhibitor for ERK-1/2), SB203580 (a specific inhibitor for p38 MAPK), and SP600125 (a specific inhibitor for JNK-1/2) were employed to evaluate a possible mechanism of antiproliferative action of TP. RESULTS: At its non-cytotoxic dose, TP suppressed MKP-1 expression, reduced cell growth, and induced persistent ERK-1/2 activation. Similar growth inhibition and ERK-1/2 activation were observed when MKP-1 expression was blocked by MKP-1 siRNA and its activity was inhibited by vanadate. The antiproliferative effects of TP, MKP-1 siRNA, and vanadate were significantly abolished by U0126, but not by SB203580 or SP600125. CONCLUSION: Our findings suggest that TP inhibits the growth of immortalized HT22 hippocampal cells via persistent ERK-1/2 activation by suppressing MKP-1 expression. Additionally, this study provides evidence supporting that MKP-1 may play an important role in regulation of neuronal cell growth.
Anthracenes ; Blotting, Western ; Butadienes ; Cell Proliferation ; Diterpenes ; Down-Regulation ; Epoxy Compounds ; Imidazoles ; Neurons ; Nitriles ; p38 Mitogen-Activated Protein Kinases ; Phenanthrenes ; Phosphorylation ; Protein Kinases ; Pyridines ; RNA, Small Interfering ; Vanadates

OBJECTIVE: It is well established that manganese neurotoxicity is associated with clinical symptoms similar to those of idiopathic Parkinson's disease. Recent research has shown that the exposure to manganese (MnCl2) leads to induction of iNOS in BV2 microglial cells via iNOS transcriptional up-regulation and activation of both MAPKs and PI3K/Akt signaling pathways. Here, we further investigated the effect and the action mechanism of MnCl2 on iNOS expression in C6 glioma cells. METHODS: Western blot analyses demonstrated that treatment with MnCl2 at 250 micronmeter was sufficient to induce iNOS at both the protein and mRNA levels in C6 cells. RESULTS: These studies demonstrated that the induction of iNOS protein and mRNA was visible after 4h- and 2 h-treatment with MnCl2, respectively. MnCl2 treatment led to strong phosphorylation of JNKs and ERKs, members of MAP kinases (MAPKs), and Akt, a PI3-kinase (PI3K) downstream effector, in C6 cells. MnCl2 treatment had no effect on I kappa B-alpha in C6 cells. Notably, pretreatment with LY294002 (a PI3K inhibitor), which inhibited phosphorylation of Akt by MnCl2, caused strong suppression of MnCl2- induced iNOS protein and mRNA expression in C6 cells. Moreover, pretreatment with SP600125 (an inhibitor of JNKs) and PD98050 (an inhibitor of ERKs), which respectively interfered with MnCl2-mediated phosphorylation of JNKs and ERKs, led to the partial suppression of MnCl2-induced iNOS protein. Interestingly, pretreatment with LY294002 inhibited phosphorylation of not only Akt, but also ERKs and JNKs, in response to MnCl2. Moreover, there was an effective suppression of MnCl2-mediated phosphorylation of AKT by SP600125. CONCLUSION: These results collectively suggest that MnCl2 induces iNOS expression in C6 glioma cells via activation of PI3K/Akt and JNK-ERK MAPK signaling proteins, whose activations seem to be mutually interconnected in response to MnCl2.
Anthracenes ; Blotting, Western ; Chlorides ; Chromones ; Glioma ; Manganese ; Manganese Compounds ; Morpholines ; Nitric Oxide Synthase Type II ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Phosphotransferases ; Proteins ; RNA, Messenger ; Up-Regulation

OBJECTIVETo study and compare the therapeutic effects of electroacupuncture and probiotics combine Deanxit in treating diarrhea predominant irritable bowel syndrome (D-IBS).

METHODSTotally 64 D-IBS patients accompanied with anxiety and/or depression were randomly assigned to the Western medicine group (Group A) and the electroacupuncture (EA) group (Group B), 30 patients in Group A and 34 patients in Group B. Patients in Group A took Bacillus licheniformis and Deanxit, while those in Group B received EA. Four weeks consisted of one therapeutic course. Three-month follow-up was carried out. The scoring for the digestive tract symptoms, HAMA score, and HAMD score were evaluated before and after treatment. The recurrence in the 3-month follow-up was also observed.

RESULTSThe total effect rate was 86.67% in Group A and 88.24% in Group B with no statistical difference between the two groups (P > 0.05). There was statistical difference in the scoring for the digestive tract symptoms, HAMA score, and HAMD score (P < 0.05, P < 0.01). There was no statistical difference in the improvement of defecation frequency score, HAMA score, HAMD score between the two groups after treatment (P > 0.05). Better effects on improving abdominal pain score and abdominal distention score was obtained in Group B (P < 0.01), while better effects on improving the stool form score and mucus score were obtained in Group A (P < 0.01). There was no statistical difference in the recurrence rate between the two groups within the two-month follow-up (P > 0.05). The recurrence rate within the 3-month follow-up was obviously lower in Group B than in Group A (P < 0.05).

CONCLUSIONSEA and Western medicine (probiotics combined Deanxit) could effectively treat D-IBS patients accompanied with anxiety and/or depression. Both of them had different superiorities in improving symptoms. But EA had better long-term therapeutic effects.

Adult ; Anthracenes ; therapeutic use ; Diarrhea ; therapy ; Drug Combinations ; Electroacupuncture ; Female ; Flupenthixol ; therapeutic use ; Humans ; Irritable Bowel Syndrome ; therapy ; Male ; Middle Aged ; Probiotics ; therapeutic use ; Treatment Outcome

OBJECTIVETo observe the therapeutic effects between abdominal acupuncture and Deanxit for treatment of menopause depressive disorder, and to explore the efficacy and safety of abdominal acupuncture.

METHODSSixty cases were randomly divided into an observation group and a control group, 30 cases in each. The observation group was treated with abdominal acupuncture at Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4), etc. The control group was treated with oral administration of Deanxit. The patients in both groups were treated for 4 weeks and followed up for another 4 weeks, and they were evaluated by Hamilton Depression Scale (HAMD) every couple weeks.

RESULTSThe total HAMD scores of 2 and 4 weeks treatments and 2 and 4 weeks follow-up were all reduced in both groups (all P < 0.01). The total scores of 2 and 4 weeks follow-up in observation group were lower than those in control group, with significant differences in statistical analysis (both P < 0.05). Compared with the clinical therapeutic effect of both groups after 4 weeks treatment, there was no significant difference (P > 0.05), however, after 4 weeks follow-up, the therapeutic effect in observation group was superior to that in control group, with significant difference in statistical analysis (P < 0.05). The safety indexes before and after treatment of both groups were normal, and the adverse reaction rate in observation group was much lower than that in control group (P < 0.05).

CONCLUSIONAbdominal acupuncture is an effective and safe method for menopause depressive disorder, it improves the menopause depressive symptoms with persistent action, less symptoms relapse and adverse reactions.

Abdomen ; Acupuncture Therapy ; Adult ; Anthracenes ; therapeutic use ; Depressive Disorder ; drug therapy ; therapy ; Drug Combinations ; Female ; Flupenthixol ; therapeutic use ; Humans ; Menopause ; drug effects ; psychology ; Middle Aged

OBJECTIVETo study the effect and potential mechanism of expression of c-jun N-terminal kinase (JNK) signal pathway on neuron autophagy after diffuse brain injury (DBI).

METHODSMale Sprague Dawley rats (n = 216) were randomly divided into four groups: DBI group (n = 54), SP600125 intervene group (n = 54), DMSO group (n = 54) and sham operation group (n = 54). DBI rat model was established according to the description of Marmarou DBI. At different time points (1, 6, 12, 24, 48 and 72 h) after operation, the histopathologic changes of neurons in cortex were observed by HE staining method; The expression of p-JNK, p-P53, DRAM and Beclin-1 were detected by Western blot and immunohistochemistry.

RESULTSThe results showed that under light microscope degenerated and necrotic neurons were observed to be scattered in cortex at 6 h after operation in DBI group, but these changes were low in SP600125 intervene group. Compared with SP600125 intervene group, the expression of p-JNK in DBI group were enhanced obviously at 6, 12 and 24 h (F = 17.902, P < 0.05); the expression of p-P53 in DBI group were enhanced obviously at 12, 24, 48 and 72 h (F = 7.107, P < 0.05); the expression of DRAM in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 15.455, P < 0.05); the expression of Beclin-1 in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 11.517, P < 0.05). Compared with DBI group, the expression of p-JNK, p-P53, DRAM and Beclin-1 in DMSO group were similar at 1, 6, 12, 24, 48 and 72 h (F = 1.509, P > 0.05).

CONCLUSIONSThe present results indicate that SP600125 can dramatically improve trauma brain injury from autophagy after DBI and the molecular mechanism is related to the modulation of JNK signal pathway following DBI, while it measures the neuron autophagy by means of intervening JNK signal pathway.

Animals ; Anthracenes ; pharmacology ; Autophagy ; Brain Injuries ; metabolism ; pathology ; Disease Models, Animal ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Male ; Neurons ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE3-Bromobenzanthrone (3-BBA), an anthraquinone intermediate dye, is extensively used in textile industry. Since, our prior studies have shown that 3-BBA caused significant depletion of ascorbic acid (AsA) levels, the effect of exogenous supplementation of AsA on the urinary elimination of 3-BBA metabolites was investigated.

METHODGuinea pigs were treated with single oral dose of 3-BBA (50 mg/kg b. wt.) in groundnut oil while another group was treated with single oral dose of 3-BBA (50 mg/kg b. wt.) along with 3 day prior and post oral supplementation of AsA. Control groups were either treated with groundnut oil or AsA alone. Urine from individual animals was collected, extracted and analysed on HPTLC.

RESULTSThe highest elimination of 3-BBA (75 microg) was found to be in 0-24 h urine fraction which decreased to 18 microg and 5 microg in the two subsequent 24 hourly fractions of urine. Exogenous supplementation of AsA increased the total urinary elimination of 3-BBA by almost 77%. A total of 10 fluorescent metabolites excluding the parent compound were eliminated in the urine of guinea pigs treated with 3-BBA. Densitometric scanning of chromatogram showed different peaks at Rf 0.18, 0.22, 0.27, 0.34, 0.40, 0.48, 0.56, 0.66, 0.72, 0.80, and 0.95 which were eliminated and marked as urinary metabolite 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 respectively. AsA not only significantly enhanced the elimination of 3-BBA metabolites but also modified the pattern of metabolites drastically in 0-6 h, 6-24 h and 24-48 h urine fractions.

CONCLUSIONThese results indicate that AsA may be useful in protecting the toxicity of 3-BBA by fascilitating the urinary metabolite(s) excretion of 3-BBA.

Administration, Oral ; Animals ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; urine ; Benz(a)Anthracenes ; analysis ; metabolism ; Chromatography, High Pressure Liquid ; Guinea Pigs ; Lipid Peroxidation ; drug effects ; Plant Oils ; metabolism ; Time Factors

Study a method for the detemination of the content of polysaccharides in Gentiana farreri, and analysis of the content of polysaccharides from different producing areas. The results showed that using the anthrone-sulfuric acid method, simple operation, accurate result. Sample was measured at 620 nm absorbance after anthrone-sulfuric acid color, at this wavelength, solution absorption and glucose showed a good linear relationship; The linearity was in the range of 0.01-0.07 g x L(-1) (r = 0.996 7). The recovery rate was 99.41%, with RSD of 2.0%. Considering the experimental conditions, to determine the solid-liquid ratio 1:60, extracting time 50 min, concentration of ethanol 80%. The mass fraction of polysaccharides was the highest to reached 0.743% in G. farreri from Gansu Xiahe. This experiment has laid a good foundation for further study on G. farreri.
Anthracenes ; chemistry ; Chemistry Techniques, Analytical ; methods ; Gentiana ; chemistry ; growth & development ; Geography ; Linear Models ; Polysaccharides ; analysis ; Reproducibility of Results ; Sulfuric Acids ; chemistry ; Time Factors

OBJECTIVETo investigate the potential of Gomphidius viscidus, a kind of ectomycorrhizal fungi, for phytoremediation of anthracene in soil.

METHODSAbsorptioe changes of micro-habitat were studied in detail.

CONCLUSIONEctomycorrhizal plants have a strong potential for remediation of polycyclic aromatic hydrocarn characteristics of both active and inactivated mycelia.

RESULTSA high calculated adsorption capacity of 1,886.79 mg/g and 1,515.15 mg/g at 25 °C, pH 6.0 for active and inactivated mycelia respectively, was obtained based on Langmuir model. The ANT biosorption was more ideally characterized by the Langmuir model than by the Freundlich model. The biosorption of anthracene to biomass was extremely fast and could be modeled with pseudo-second order adsorption kinetics. Moreover, ectomycorrhizal mycelia demonstrated a strong ability to adjust the physiological process to get adapted to the change of micro-habitat.

Adsorption ; Anthracenes ; analysis ; Basidiomycota ; growth & development ; Biodegradation, Environmental ; China ; Chromatography, High Pressure Liquid ; Hydrogen-Ion Concentration ; Mycelium ; growth & development ; Mycorrhizae ; growth & development ; Soil Pollutants ; analysis ; Temperature