Qualitative and quantitative analysis of trace element of terpenoid conjugated curcuminoid and curcuminoids in herbal medicine derived from different Curcuma species / 中草药

Objective: To qualitatively and quantitatively analyze the terpene-conjugated curcuminoid compound- Bisabolocurcumin ether (BCE) in Curcuma species. Methods: UPLC-Q-TOF-MS/MS was used to establish a qualitative analysis of BCE, and its distribution in Curcuma species was studied. UPLC was used to establish quantitative analysis of BCE and three main curcuminoids in three Curcuma species (Rhizoma Curcumae Longae, HuangsiYujin, Curcuma phaeocaulis), in order to study the difference of BCE content in different Curcuma species and its content difference with other curcuminoids. Results: In the qualitative analysis, by analyzing the primary, secondary pyrolysis fragments and the cracking law of BCE, it was found that only Jianghuang and HuangsiYujin contained it, but BCE could not be detected in the PengEzhu. In the quantitative analysis, BCE and the three main curcuminoids had good linear relationship in their linear range (r ≥ 0.999 3); The average recovery rates were in range of 99.407%-113.631%, and RSD < 4%. It was found that the content of three curcuminoids in Jianghuang were significantly higher than the other two herbs, and the content of BCE in the three herbs was very different. The BCE content in Jianghuang was four times than that of HuangsiYujin. Conclusion: The qualitative and quantitative analysis methods established in this study can provide reference for the discovery and analysis of more novel BCE structure’s compounds, and provide a basis for improving the quality standards of Curcuma species.

Analysis of Curcuma longa Q-markers based on traditional efficacy and modern research / 中草药

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.

Optimization of processing technology of stir-frying with vinegar of Curcuma Longa Radix by orthogonal design and Box-Behnken design-response surface based on entropy method / 中草药

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.

Correlation study of color of Curcuma longa in Sichuan and content of main composition based on theory of “distinguish quality by appearance of medicine” / 中草药

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.

Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

Intestinal absorption characteristics of demethoxycurcumin hydroxypropyl-β-cyclodextrin in rats / 第二军医大学学报

Objective To study the intestinal absorption characteristics of demethoxycurcumin hydroxypropyl/β cyclodcxtrin (DECD) and demethoxycurcumin (DE) in rats. Methods DECD was prepared by cyclodcxtrin inclusion technique and characterized by spectroscopic method. The morphology of DECD was observed by microphotograph and zeta potential was examined by Malvern laser particle sizer. In vivo single-pass intestinal perfusion rat model was adopted; the absorption rate constant (Ka), effective permeability (Papp) and percent absorption of DECD and DE were determined using the ultraviolet spectrophotometry. Results DECD was successfully prepared, with a solubility of 2. 30 g/L, which was 38. 33 times that of DE. Zeta potential of DECD was —32. 2 mV. The results of intestinal absorption experiment showed that the Ka and Papp values of DECD decreased in order in the ileum, duodenum, jejunum, and colon. In addition, the Ka, Papp values and percent absorption of DECD were higher than that of DE. Conclusion DECD can markedly improve the intestinal absorption of DE in rats.

Optimization of the Formula and Preparation Technology of Demethoxycurcumin Nano-structured Lipid Carriers / 中国药师

Objective:To screen the optimal formula and technology of demethoxycurcumin nano-structured lipid carriers. Meth-ods:The encapsulation efficiency as the main investigation index, the single factor exploration and orthogonal design were used to study the main factors affecting the quality of the nanoparticles. The optimal formula and technology were obtained. Results:The optimized parameters were as follows:the ratio of drug to lipid materials was 1 ∶40, the ratio of liquid lipid to total lipid materials was 10%, the amount of surfactants was 4% and the amount of lecithin was 2%. The prepared nanoparticles were spheric and regular. The size dis-tribution of the nanoparticles was narrow with the average particle size of 110nm and PDI of 0. 199. Conclusion:The optimized formula and technology of demethoxycurcumin nano-structured lipid carriers are stable and practicable,which provide reference for the further research of demethoxycurcumin.

Pharmacokinetics study of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex in rats / 第二军医大学学报

Objective To compare the pharmacokinetics of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex, deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, deme-thoxycurcumin phospholipid complex and deme-thoxycurcumin in rats in vivo, so as to discuss the advantages of hydroxypropyl-β-cyclodextrin phospholipid complex as drug carrier. Methods SD rats were gavaged with the preparations and free drug at 50 mg/mL (dose according to deme-thoxycurcumin). Then, blood samples were drawn from rat retinal venous plexus at 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 1 d, 2 d and 3 d. And the deme-thoxycurcumin concentrations in blood were determined by HPLC. Results The AUC0-∞ of deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex was (1 424.87±258.62) μg•L-1•h, which was higher than that of deme-thoxycurcumin (370.58±2.76) μg•L-1•h, deme-thoxycurcumin phospholipid complex (716.17±123.18) μg•L-1•h and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin (1 009.35±138.64) μg•L-1•h, being 3.84, 1.98, and 1.41 folds of deme-thoxycurcumin, deme-thoxycurcumin phospholipid complex and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, respectively (P<.01 or P<.05). Conclusion The deme-thoxycurcumin hydroxypropyl-β-cyclodextrin phospholipid complex has a better absorption property than deme-thoxycurcumin phospholipid complex and deme-thoxycurcumin hydroxypropyl-β-cyclodextrin, which can help to improve the bioavailability.

Solubilization of self-emulsifying drug delivery system (SEDDS) for curcumin components / 中草药

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.

Photostability of curcumine, demethoxycurcumin, and bisdemethoxycurcumin in rhizomes of Curcuma longa / 中草药

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.

Comparative effects of curcuminoids on endothelial heme oxygenase-1 expression: ortho-methoxy groups are essential to enhance heme oxygenase activity and protection

Recently, it has been reported that curcumin, which is known as a potent antioxidant, acts as a non-stressful and non-cytotoxic inducer of the cytoprotective heme oxygenase (HO)-1. In this study, naturally occurring curcuminoids, such as pure curcumin, demethoxycurcumin (DMC) and bis-demethoxycurcumin (BDMC), were compared for their potential ability to modulate HO-1 expression and cytoprotective activity in human endothelial cells. All three curcuminoids could induce HO-1 expression and HO activity with differential levels. The rank order of HO activity was curcumin, DMC and BDMC. In comparison with endothelial protection against H2O2-induced cellular injury, cytoprotective capacity was found to be highest with curcumin, followed by DMC and BDMC. Interestingly, cytoprotective effects afforded by curcuminoids were considerably associated with their abilities to enhance HO activity. Considering that the main difference among the three curcuminoids is the number of methoxy groups (none for BDMC, one for DMC, and two for curcumin), the presence of methoxy groups in the ortho position on the aromatic ring was suggested to be essential to enhance HO-1 expression and cytoprotection in human endothelial cells. Our results may be useful in designing more efficacious HO-1 inducers which could be considered as promising pharmacological agents in the development of therapeutic approaches for the prevention or treatment of endothelial diseases caused by oxidative damages.