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OBJECTIVE To study the effects of the curcumin derivative bisdemethoxycurcumin （BC） promoting neuronal differentiation of neuroblastoma cells Neuro-2a （N2a） in mice and its mechanism. METHODS The effects of BC （1， 2， 4， 6， 8， 10 μmol/L） on the viability of N2a cells were detected by MTT assay to determine the concentration range of drug treatment. The control group， retinoic acid （RA） group （10 μmol/L） and BC groups （1， 2 and 4 μmol/L） were set up， and the length of neural protrusions of the differentiated cells was measured and the cell differentiation rate was calculated after 48 h and 72 h of culture. Compared with 0 min group， Western blot was used to detect the phosphorylation levels of protein kinase B （Akt）， extracellular- signal regulated kinase 1/2 （ERK1/2）， and p38 mitogen-activated protein kinase （p38） proteins in cells treated by 4 μmol/L BC for 5， 15， 30， 60， 120 min. After intervention with inhibitors LY294002 （LY） and PD98059 （PD）， the effects of BC on Akt and ERK1/2 protein phosphorylation levels and promoting neural differentiation were further validated. RESULTS According to the MTT experiment， the BC concentrations for subsequent induction of cell differentiation were determined to be 1， 2， and 4 μmol/L. After 48 hours of differentiation， compared with the control group， the cell differentiation rate in RA group and BC 1， 2 and 4 μmol/L groups， the length of cellular neural processes wjxhhxx413@163.com in the BC 4 μmol/L group significantly increased （P＜0.05 or P＜0.01）；after inducing differentiation of BC for 72 hours，compared with the control group， the cell differentiation rate and the length of cellular neural processes in the RA group， the cell differentiation rate in the BC 4 μmol/L group， and the length of cellular neural processes in the BC 2 μmol/L group all significantly increased （P＜0.05 or P＜0.01）.Compared with the 0 min group， the phosphorylation levels of Akt， ERK1/2， and p38 proteins in cells of the 5， 15， 30， 60 and 120 min groups increased to varying degrees after treated by 4 μmol/L BC， and some differences were statistically significant （P＜0.05 or P＜0.01）. After adding the inhibitor LY/PD， compared with the BC group， the phosphorylation level of ERK1/2 protein in the PD+BC group cells were significantly reduced （P＜0.01）， and the cell differentiation rates in the LY group， LY+BC group， PD group， and PD+BC group was significantly reduced （P＜0.01）. CONCLUSIONS BC promotes N2a cell differentiation mainly by increasing cell differentiation rate and neural protrusion length. The mechanism may be related to the activation of mitogen-activated protein kinase/ ERK and PI3K/Akt signaling pathways.
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Curcuma longa, a well-known traditional Chinese medicine, which is warm in nature, acrid and bitter in taste. It has the effects of supplementing qi and activating blood circulation, treating amenorrhea, and pain relief. It was first collected in the Annotation of Materia Medica with long medication history. In this paper, chemical composition and main pharmacological activities of C. longa were summarized, and the quality markers of C. longa were predicted and analyzed based on traditional efficacy and modern research. It is suggested that the identification and quantification of ar-turmerone, α-turmerone, β-turmerone, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and flavonoids should be carried out and the further research of the chemical group of terpenoids and sterols from C. longa should be focused, which could provide scientific basis for clarifying the quality marker (Q-marker) and quality evaluation research of C. longa.
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Objective To optimize the processing technology of stir-frying with vinegar of Curcuma Longa Radix (CLR) by orthogonal design and Box-Behnken design-respanse surface method (BBD-RSM) based on entropy method. Methods As comprehensive evaluation indexes, the contents of curcumin, demethoxycurcumin, and bisdemethoxycurcumin in CLR processed by traditional method were determined by HPLC. The orthogonal test was adapted to examine the influence of the amount of vinegar, the moistening time, parching time, and parching temperature on processing technology of stir-frying with vinegar. Based on the results above, BBD-RSM was adopted to optimize the processing technology further using the moistening time, parching time and parching temperature as factors. Results The optimum processing technology of the orthogonal test was covered the amount of vinegar of 15%, moistening time of 10 min, parching temperature of 130 ℃, and parching time of 10 min. The optimum processing technology by BBD-RSM was covered moistening time of 12 min, parching temperature of 150 ℃, and parching time of 8 min. The verification esting indicates that the process conditions are reasonable and feasible with good reproducibility. Conclusion The method and data are precise and reliable. Besides, it established the processing technology of vinegar CLR and provided a theoretical basis for the processing technology of stir-frying with vinegar of CLR.
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Objective To establish an effective UHPLC-ESI-MS/MS method for the simultaneous determination of 19 active components (ginsenoside Rg1, Rb1, Rd, berberine, epiberberine, jatrorrhizine, palmatine, columbamine, coptisine, evodiamine, rutaecarpine, dehydroevodiamine, limonin, hyperin, curcumin, demethoxycurcumin, bisdemethoxycurcumin, echinacoside, and verbascoside) of different types in Xintiantai I (XI), and provide a comprehensive and efficient quality control method for traditional Chinese medicine (TCM). Methods The analysis was performed on an Agilent 1290 system with a Agilent Zorbax Eclipse Plus C18 column (150 mm × 4.6 mm, 3.5 μm) at a flow rate of 0.4 mL/min using acetonitrile and 0.1% formic acid aqueous solution as mobile phase. Mass spectrometric detection was performed on multiple reaction monitoring (MRM) in positive and negative ionization mode. The contents of 19 active components in XI were determined by monitoring the specific ions of each component. Results The 19 active components were accurately determined in 15 min and had the good linearity (r2 > 0.999) within the linear ranges. The average recovery rates of ginsenoside Rg1, Rb1, Rd, berberine, epiberberine, jatrorrhizine, palmatine, columbamine, coptisine, evodiamine, rutaecarpine, dehydroevodiamine, limonin, hyperin, curcumin, demethoxycurcumin, bisdemethoxycurcumin, echinacoside, and verbascoside were 94.80%, 96.78%, 95.59%, 96.88%, 97.74%, 100.08%, 96.27%, 100.25%, 98.32%, 97.16%, 95.60%, 95.28%, 96.81%, 95.22%, 96.85%, 95.31%, 93.86%, 94.79%, and 95.20%, respectively; The contents of three batches XI of the 19 components were in the ranges of 2.28-2.49, 0.82-0.90, 1.22-1.32, 14.44-15.50, 3.71-3.99, 3.26-3.49, 3.09-3.33, 4.39-4.72, 4.56-4.92, 0.52-0.57, 0.30-0.33, 4.46-4.76, 3.02-3.24, 2.59-2.76, 6.03-6.38, 1.47-1.58, 1.90-2.08, 3.40-3.88, and 1.53-1.74 mg/g, respectively. Conclusion The developed UHPLC-ESI-MS/MS-MRM method is fast, sensitive, and reproducible for TCM quality control. It can be used for the quality control of XI, which also provides reference for TCM quality research.
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Objective The research is about the correlation of the color values of Curcuma longa in Sichuan and the content of the main composition (curcumin, demethoxycurcumin, bisdemethoxycurcumin, and curcuminoids). Methods Based on the theory of “distinguish quality by the appearance of medicine”, CM-5 spectro-colorimeter was used to measure the color values of slices and powders of C. longa in Sichuan, and combining to the content of the main composition of these medicines to analyze the correlation between them. Results It showed that there was a significant negative correlation between the color values of powders of C. longa in Sichuan (L*, b*, and ΔE*ab) and the content of the main component of medicines. The correlation coefficients were all around 0.4; Meanwhile, there was a significant positive correlation between the color value a* of C. longa in Sichuan and its main composition content, and the correlation coefficients were all around 0.7. Conclusion The color value a* of C. longa powders produced in Sichuan has higher correlation than other color values. It prompted that we can predict and judge the quality of C. longa in Sichuan by color value a* of C. longa powders, thereby verifying the scientificity of “distinguish quality by the appearance of medicine” in the identification of C. longa. The research can lay the foundation of establishing the evaluation system of C. longa, which can rapidly identify the quality of C. longa.
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Objective To investigate the effect of bisdemethoxycurcumin on the proliferation and apoptosis of melanoma B16-F10 cells. Methods The B16-F10 cells were incubated with bisdemethoxycurcumin for 24 h, and MTT assay was used to detect the proliferation of B16-F10 cell. Flow cytometry was used to detect cell cycle and cell apoptosis. A C57BL/6 mouse melanoma model was established to investigate the effect of bisdemethoxycurcumin on the proliferation of melanoma. Expression of BCL-1 in B16-F10 cells and tissues was detected by western blotting assay. Results bisdemethoxycurcumin could significantly inhibit B16-F10 cell proliferation, induce B16-F10 cell apoptosis and block the cell cycle at S phase. The intravenous dosing of bisdemethoxycurcumin could inhibit the growth of melanoma. Bisdemethoxycurcumin could inhibit the expression of BCL-1. Conclusion Bisdemethoxycurcumin can inhibit the proliferation of B16-F10 cell, resulting from its role in promoting cell apoptosis.
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<p><b>OBJECTIVE</b>To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells.</p><p><b>METHODS</b>CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells.</p><p><b>RESULTS</b>BDMC inhibited the viability of NSCLC cells, but had no cytotoxic effects on lung small airway epithelial cells (SAECs). The apoptotic cell death induced by BDMC was accompanied with the induction of autophagy in NSCLC cells. Blockage of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) repressed the growth inhibitory effects and induction of apoptosis by BDMC. In addition, BDMC treatment significantly decreased smoothened (SMO) and the transcription factor glioma-associated oncogene 1 (Gli1) expression. Furthermore, depletion of Gli1 by siRNA and cyclopamine (a specific SMO inhibitor) induced autophagy.</p><p><b>CONCLUSION</b>Aberrant activation of Hedgehog (Hh) signaling has been implicated in several human cancers, including lung cancers. The present findings provide direct evidence that BDMC-induced autophagy plays a pro-death role in NSCLC, in part, by inhibiting Hedgehog signaling.</p>
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Autophagy , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Cell Line, Tumor , Curcumin , Chemistry , Pharmacology , Down-Regulation , Gene Expression Regulation, Neoplastic , Hedgehog Proteins , Genetics , Metabolism , Kruppel-Like Transcription Factors , Genetics , Metabolism , Signal Transduction , Zinc Finger Protein GLI1ABSTRACT
Objective: To explore the feasibility of self-emulsifying drug delivery system (SEDDS) for multicomponents simuitaneous solubilization. Methods: The curcumin (Cur) components were used as model drug, D-optimal mixture design was used to optimize SEDDS prescription, and the contents of bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC), and Cur, SEDDS particle size, and emulsifying time were made as indicators to select and evaluate SEDDS, so as to explore the feasibility of SEDDS for the multicomponents simuitaneous solubilization. Results: The optimal SEDDS prescription was Obleique CC497-Tween 20-Transcutol P (0.21:0.50:0.29), SEDDS particle size was (248.8 ± 3.4) nm, and emulsifying time was (70 ± 1) s. At 37°C, the maximum loading capacities of SEDDS for BDMC, DMC, and Cur were 2.998, 12.220, and 52.561 mg/g, respectively, and the solubilities in water were 0.107, 0.661, and 1.648 mg/mL. Conclusion: SEDDS can realize the solubilization of multicomponent simultaneously.
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Objective: To study the photostability of curcumin (Cur), demethoxycurcumin (DMCur), and bisdemethoxycurcumin (BDMCur) in the rhizomes of Curcuma longa, and to investigate the photochemical conversion product of BDMCur. Methods: The stock solution of the extracts from the rhizomes of C. longa was kept in brown volumetric flasks. Then the absorbances of Cur, DMCur, and BDMCur were determined by HPLC analysis, and the solutions were placed in the daylight or daylight/dark conditions for 0, 1, 2, 4, 6, and 8 h. The photochemical conversion products of BCMCur were detected by LC-MS analysis. Results: Both Cur and DMCur were stable in the daylight and daylight/dark conditions. BDMCur was liable to photochemical reaction in the daylight condition. Conclusion: Both Cur and DMCur have good photostabilities, but BDMCur is not stable in daylight condition. As a result, the sample solution of the rhizomes of C. longa should be conserved in dark.
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OBJECTIVE:To investigate the effect of liposome-encapsulated demethoxycurcumin on the proliferation of human lung adenocarcinoma cell line A549.METHODS:The in vitro cultured human lung adenocarcinoma cell line A549 was treated with liposome-encapsulated Bisdemethoxycurcumin.The bionomics including morphology and cell cycle of cell line A549 were observed by morphological analysis,MTT assay and flow cytometry assay.RESULTS:Marked morphological changes were noted in cell line A549 under microscope.Liposome-encapsulated Bisdemethoxycurcumin showed inhibitory action on the growth of A549 cell lines,with IC50 at 12.108?g/mL.The progression of cell cycle was arrested in S phase.CONCLUSION:Liposome-encapsulated Bisdemethoxycurcumin can inhibit the growth of human lung adenocarcinoma cell line A549,which has a promising future in the treatment of adenocarcinoma of lung.
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AIM:To evaluate the therapeutic effects of bisdemethoxycurcumin liposome in mice with CCl4-induced acute liver injury model and its mechanism.METHODS:40 ICR mice were randomly divided into 4 groups:control group,model group,bisdemethoxycurcumin injection group and demethoxycurcumin liposome group(n=10).The liver injury model was made by injecting CCl4 in mouse's abdomen.The activities of ALT,AST in serum,the contents of MDA in liver and the pathological changes of hepatic tissue were investigated.RESULTS:Compared with those in control group,the serum ALT,AST activities and liver MDA contents of model group were highly increased,but those in bisdemethoxycurcumin injection group and bisdemethoxycurcumin liposome group were reduced significantly.The liver lobules were ameliorated obviously too,especially in bisdemethoxycurcumin liposome group.The pharmacodynamic action of liposome was better than that of the injection.CONCLUSION:Bisdemethoxycurcumin liposome has significantly protective effects on CCl4-induced acute chemical liver injury by reducing peroxidation of lipid in endotheliocyte of the liver.