Industrial Crops and Products 76 (2015) 487–493
Contents lists available at ScienceDirect
Industrial Crops and Products journal homepage: www.elsevier.com/locate/indcrop
Optimization of ionic liquid based ultrasonic assisted extraction of antioxidant compounds from Curcuma longa L. using response surface methodology Jialin Xu a , Wenchao Wang b , Hui Liang a , Qing Zhang b , Qingyong Li a,b,∗ a b
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China Collaborative Innovation Center of Yangtze River Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China
a r t i c l e
i n f o
Article history: Received 7 April 2015 Received in revised form 11 June 2015 Accepted 15 July 2015 Keywords: Ionic liquid Ultrasonic assisted extraction Radical scavenging capacity Curcuma longa L. Response surface methodology
a b s t r a c t In this paper, response surface methodology was employed to optimize experimental process for ionic liquid based ultrasonic assisted extraction of curcuminoids compounds from rhizomes of Curcuma longa L. The Box–Behnken design on three factors and ﬁve levels together with response surface methodology were used to optimize experimental conditions for total curcuminoids content and radical scavenging capacity. The radical scavenging capacity was determined by ABTS and TRAP methods. For the ionic liquid based ultrasonic assisted extraction, optimum process was set as below: [Omim]Br concentration, 4.2 mol/L; liquid-raw ratio, 30 mL/g; extraction time, 90 min; ultrasonic power, 250 W. © 2015 Elsevier B.V. All rights reserved.
1. Introduction As a favorite and widely used medical herb in traditional Chinese medicine, Curcuma longa L. attracts a growing interest among scholars because of its potential biological activities. Curcumin (Cur), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) known as curcuminoids, are active phytochemicals derived from turmeric, the rhizomes of C. longa L. (Miquel et al., 2002). Curcuminoids have been used as food additives: coloring, ﬂavoring substance and food preservative, with its wide spectrum of biological activity (Kong et al., 2009). Recent study has also been focused on its pharmaceutical functions, such as antioxidant (Gazal et al., 2014), anti-inﬂammatory (Kant et al., 2014), anticancer (Riela et al., 2014), anti-ageing (Lima et al., 2011), anti-depressant (Jiang et al., 2013), and other functions (Mourtas et al., 2014; Prasad et al., 2014; Sukandar et al., 2014). Although curcuminoids can be chemically synthesized, application of synthetic curcuminoids for healthcare and prevention of diseases apparently is not an optimum choice as nowadays ´ 2007). Developing curcuminoids nature is advocated (Pokorny, from natural sources is the need of pharmaceutical and health-
∗ Corresponding author at: College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China. Fax: +86 571 88320984. E-mail address: li [email protected]
(Q. Li). http://dx.doi.org/10.1016/j.indcrop.2015.07.025 0926-6690/© 2015 Elsevier B.V. All rights reserved.
care. Conventional methods of extracting curcuminoids turmeric generally involve large amount of organic solvents, and can be timeconsuming, low extraction efﬁciency, not environmentally friendly. Recently environment friendly techniques, such as microwave assisted extraction (Aoki et al., 2005; Mandal et al., 2008; Wakte et al., 2011), ultrasonic assisted extraction (UAE)(Li et al., 2014; Wakte et al., 2011), and supercritical ﬂuid (SCF)(Chang et al., 2006; Zabihi et al., 2014) have been reported. Among these methods, UAE has been widely used to extract phytochemicals from many matrixes as an efﬁcient, energy-saving, environmental friendly extraction technique. It offers short extraction time, high extraction efﬁciency, low solvent consumption and energy input and is suitable for the extraction of heat sensitive material (Afshari et al., 2014; Asfaw et al., 2005; Fang et al., 2014; Zhang et al., 2011). Ionic liquids (ILs) have been proposed as green solvents, due to their unique chemical and physical properties, such as negligible vapor pressure, good thermal stability, tunable viscosity, wide liquid range, and extractability for various organic compounds (Bucar et al., 2013; Pandey, 2006; Passos et al., 2014), despite of their unknown toxicity and potentially hazardous properties to environment. Based on its unique properties, ILs have been used extensively in areas of synthesis (Hernández-Fernández et al., 2010), catalysis (Zhang, 2013), analysis (Sun and Armstrong, 2010), and separation (Blahuˇsiak et al., 2011; Chowdhury et al., 2010; Han and Armstrong, 2007). Furthermore, ILs are regarded as “designer solvents” as their polarity, viscosity, hydrophobicity, selectivity
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493
Fig. 1. Chemical structures for ILs(a). HPLC chromatogram of raw extract of Curcumalonga L. (b).
toward target compounds can be changed by combining different anions and cations (Huddleston et al., 2001; Larsen et al., 2000; Sosnowska et al., 2014), so they have been successfully applied for extraction of alkaloids (Cao et al., 2009), terpenoids (Lin et al., 2013), ﬂavonoids (Bi et al., 2013), phenolic acids (Du et al., 2009) and other value-added compounds (Liu et al., 2012; Ma et al., 2011; Severa et al., 2013) from natural sources. During last few years, ILs-based extraction methods have been developed, among which ILs-based MAE and UAE seem to be superior in the view of experimental operation, economic expense, and extraction efﬁciency (Li et al., 2009). The purpose of this work was to employ response surface methodology (RSM) to optimize the extraction parameters for turmeric based on curcuminoids recovery yield and radical scavenging capacity, in order to develop an effective and environmentally friendly ILs-based UAE method. In this study, a three-variable (IL’s concentration, extraction time and ultrasonic power), ﬁve–level Box–Behnken design (BBD) was adopted to get the maximal curcuminoids recovery yield and radical scavenging capacity from turmeric.
China) and degassed by ultrasound before use. C. longa L. was purchased from local medicinal market, Hangzhou, Zhejiang Province, China, and was pulverized to powder, then sieved (60–80 mesh).
2. Material and methods
2.3. Determination of curcuminoids content
An HPLC system consisted of a SHIMADZU manual sample handling system series equipped LC-20AT Bin pump, CTO-10AS VP automatic column temperature control box and SPD-20A UV-detector (SHIMADZU, Japan), was employed to determinate curcuminoids in turmeric extract. Chromatographic separation was performed on a Sino Chrom ODS-BP C18 reversed-phase column (4.6 mm × 250 mm, 5 m, Elite-AAA, Dalian, China). Mobile phase was acetonitrile-water (60:40, v/v, glacial acetic acid 0.5%). Flow rate was 0.9 mL/min, injection volume was 20 L and the column temperature was maintained 25 ◦ C. The monitoring wavelength was 420 nm. The calibration curves for three targeted components were: YB = 169829X − 547018 (r = 0.9999) for DBMC, YD = 170449X − 108892 (r = 0.9998) for DMC and YC = 179295X − 831890 (r = 0.9994) for Cur (50–250 g/mL). Peaks of raw extract chromatogram were identiﬁed by retention times of standards of BDMC, DMC, Cur, which were 7.2, 7.9, and 8.5 min, respectively (Fig. 1b). And total curcuminoids content was obtained
Cur, DMC, and BDMC standards (98% purity) were purchased from Shanghai ShiFeng Biological Technology Co., Ltd. (Shanghai, China). ABTS [2,2 -azino-bis-(3-ethylbenzthiazoline-6sulphonic acid)], AAPH [2,2 -azobis(2-methylpropionamidine) dihydrochloride], Trolox [(±)-6-hydroxy-2,5,7,8tetramethylchroman-2-carboxylic acid], K2 S2 O8 of analytical grade, acetonitrile, and methanol of HPLC grade were purchased from J&K Chemical Ltd., All ILs (1-butyl-3-methylimidazolium bromide ([Bmim]Br), 1-hexyl-3-methylimidazolium bromide ([Hmim]Br), 1-octyl-3-methylimidazolium bromide ([Omim]Br), ([Omim][BF4 ]), 1-octyl-3-methylimidazoliumtetraﬂuoroborate whose structures were shown in Fig. 1a were bought from Chengjie Chemical Co., Ltd., (Shanghai, China) and are of 99% purity. All of the solvents prepared for HPLC were ﬁltered through 0.45 m microporous membrane (GuangFu Chemical Reagents Co., Tianjin,
2.2. ILs-based ultrasonic-assisted extraction An ultrasonic bath (KQ-250 DB, Kunshan ultrasonic Co., Ltd., China), as a rectangular container (300 × 240 × 150 mm), was used to extract curcuminoids as an ultrasonic source. The bath power rating was 250 W on the scale of 0–100%. Curcuminoids were extracted by adding 0.5 g of turmeric to conical ﬂask with 15 mL IL aqueous (concentration 0.1–0.5 mol/L). Then the ﬂask was immersed in the ultrasonic bath after quick shake. The extraction was performed under different ultrasonic powder level (100–250 W) for certain irradiation time (10–90 min). During the ultrasonication, water in the bath was kept at room temperature by controlling the outlet and inlet water ﬂow rate. The extract was centrifuged for 5 min, and supernatant was diluted 50 and 10 times with absolute EtOH for HPLC analysis and for total curcuminoids yield and radical scavenging capacity analysis, respectively.
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493
Table 1 Experimental parameters of Box–Benhnken design and total curcuminoids content and total antioxidant capacity for ILs-based ultrasonic-assisted extraction. Run
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
0.1 (−1) 0.5 (1) 0.1 (−1) 0.1 (−1) 0.3 (0) 0.1 (−1) 0.3 (0) 0.3 (0) 0.3 (0) 0.3 (0) 0.5 (1) 0.3 (0) 0.3 (0) 0.3 (0) 0.5 (1) 0.3 (0) 0.5 (1)
50(0) 50(0) 50(0) 90(1) 50(0) 10(−1) 50(0) 10(−1) 10(−1) 50(0) 50(0) 50(0) 90(1) 50(0) 90(1) 90(1) 10(−1)
100(−1) 250(1) 250(1) 175(0) 175(0) 175(0) 175(0) 250(1) 100(−1) 175(0) 100(−1) 175(0) 100(−1) 175(0) 175(0) 250(1) 175(0)
Total curcuminoids content (g/100 g turmeric)
Total antioxidant capacity
ABTS (mg TE/g turmeric) Experimental (predicted)
TRAP (mg TE/g turmeric) Experimental (predicted)
1.53(1.39) 5.51(5.65) 1.42(1.53) 1.35(1.43) 5.37(5.31) 1.63(1.58) 5.22(5.31) 5.43(5.38) 5.07(5.26) 5.25(5.31) 5.48(5.37) 5.21(5.31) 5.18(5.24) 5.50(5.31) 5.65(5.70) 5.72(5.53) 5.49(5.41)
7.48(6.07) 55.29(56.70) 6.65(7.43) 6.09(6.75) 53.63(53.42) 5.55(5.52) 52.98(53.42) 53.61(52.86) 50.32(51.77) 52.55(53.42) 54.94(54.15) 52.35(53.42) 51.99(52.74) 55.58(53.42) 55.99(56.02) 56.99(55.55) 54.25(53.59)
8.12(7.17) 56.58(57.53) 9.55(8.35) 6.58(7.92) 59.44(58.54) 6.69(7.5) 59.10(58.54) 58.49(58.87) 58.02(58.15) 58.49(58.54) 55.26(56.46) 56.82(58.54) 58.75(58.37) 58.84(58.54) 58.17(57.36) 60.05(59.91) 57.85(56.52)
t–extraction time and P–ultrasonic power. a C-concentration of ILs aqueous solution.
from the following formula:
Total curcuminoids content g/100g =
(Cur amount + BDMC amount + DMC amount) × 100 Initial sample amount
2.4. Determination of radical scavenging capacity An inﬁnite 200 pro multimode reader (Tecan, Swizerland) was employed to determinate the absorbance of working solutions of ABTS and TRAP methods. Major radical scavenging capacity assays can be roughly divided into single electron transfer reaction-based assays (such as TEAC (also for ABTS), short for Trolox equivalence antioxidant capacity) and hydrogen atom transfer reaction-based assays (such as TRAP, short for total radical trapping antioxidant parameter) (Huang et al., 2005). The ABTS assay was carried out according to the method • reported by Sahin et al. (2013). ABTS + was generated by combining 20 mM ABTS aqueous solution and 2.45 mM potassium persulphate solution and incubating at room temperature in the dark for 12–16 h. Then this solution was diluted with ethanol to the absorbance of 0.7 ± 0.02 at 734 nm to give working solution. 100 L of sample was mixed with 4 mL working solution. The absorbance was read at 734 nm after 6 min. The results were expressed as mg of trolox equivalent (TE) per g turmeric. For TRAP assay, 0.02 g ABTS and 0.27 g AAPH was dissolved in acetate buffer (pH 4.3) and diluted to 500 mL. Such solution was allowed to react for 1 h in 45 ◦ C water bath, and cool to room temperature to get the stock solution. The mixture of 100 L sample solution and 4 mL stock solution was shaken vigorously and incubated for 15 min at 25 ◦ C. The absorbance of the reaction solution was recorded at 734 nm and the results were expressed as mg of trolox equivalent (TE) per gram turmeric. 2.5. Optimization ILs-based UAE by response surface methodology (RSM) Response surface methodology (RSM) is an empirical statistical technique, which can be employed to study the interactions
between factors and optimize operating parameters. In this work, a three-factor-ﬁve-level Box–Benhnken design (BBD) was applied, requiring 17 experiments (Table 1) for the optimization of extraction parameters. The independent variables were concentration of ILs (X1 , 0.1–0.5 mol/L), extraction time (X2 , 10–90 min) and ultrasonic power (X3 , 100–250 W), and total curcurminoids content (Y1 ), ABTS value (Y2 ) and TRAP value (Y3 ) were chosen as the response values. 2.6. Conventional reference extraction methods Extraction methods determine extraction ﬁeld, cost and complexity to a large extent. In order to investigate the effect of ILs, ILs based UAE, heat-reﬂux extraction and organic solvent UAE were compared for their efﬁciency in the extraction of curcuminoids from C. longa L. The extraction experiment for ILs-based UAE was operated at optimum conditions optimized by our work. 85% ethanol based heat-reﬂux extraction (4 h, 75 ◦ C, 10 mL/g) and 85% ethanol-based UAE (90 min, room temperature, 250 W, 30 mL/g) were carried out simultaneously. 3. Results and discussion 3.1. Screening different ILs The structure of ILs has signiﬁcant inﬂuence on its physicochemical properties, which might affect the extraction efﬁciency of curcuminoids. Four kinds of ILs water aqueous solution were chosen to compare different structure on the inﬂuence of extraction result in Fig. 2a. Here, four types of imidazolium based ILs were screened, which had different carbon chain lengths (C-4–C-8) in the cation and two kinds of anions(BF4 − , Br− ). As [Omin][BF4 ] is hydrophobic, it can not disperse in aqueous solution homogeneously, which can not accelerate curcuminoids dissolving in solvent adequately. The three ILs based Br− , are all water-soluble, although the lipophilicity of these ILs increases with increasing alkyl chain length (Yang et al., 2011). The alkyl chain length of cation can also decide ILs’ extraction efﬁciency towards target components. Our results showed that the extraction efﬁciency of curcuminoids increased signiﬁcantly when the alkyl chain was
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493
Fig. 2. Effect of types of ILs (a). Extraction parameters were as follows: 0.5 g turmeric, IL concentration of 0.3 mol/L, ratio of solution to raw was 30 mL/g, ultrasonic power of 40 W and extraction time was 30 min. Effect of ratio of solvent to raw on the extraction efﬁciency (b). Extraction expriments were performed with ultrasonic power of 40 W for 30 min. 0.5 g turmeric was mixed with different volume (10, 15, 20, 25, 30, 35, and 40 mL/g, ratio of liquid to raw) of 0.3 mol/L [Bmim]Br.
changed from butyl to octyl. Curcuminoids are of poor water solution, and nearly unextracted by water, but ILs aqueous solution with longer alkyl chains showed good extraction efﬁciency for curcuminoids. Thus, [Omin]Br had extraordinary extraction efﬁciency toward target compounds among these four ILs. 3.2. Effect of ratio of liquid to raw on the extraction efﬁciency Ratio of liquid to raw is an important factor in inﬂuencing extraction efﬁciency as it concerns the contact area between raw and solvent. Generally, large solvent volume will lead to high extraction efﬁciency, but on the other side, it may cause unnecessary wasting. While a low solid–liquid ratio will result in the incomplete extraction, subsequently leading to low extraction efﬁciency. The effect of ratio of liquid to raw material (10, 15, 20, 25, 30, 35, and 40 mL/g, respectively) on extraction yield of curcuminoids was shown in Fig. 2b. The result indicated that the extraction efﬁciency increased signiﬁcantly when the liquid–solid ratio was increased up to 30 mL/g. However, only slight improvements were observed when liquid raw ratio was increased from 30 to 40 mL/g. Considering larger liquid to raw ratio will result in more unnecessary wasting, 30 mL/g was selected for further experiments. 3.3. Optimization of single factor extraction condition The extraction procedures were carried out in [Omin]Br aqueous solutions of different concentrations (0.1, 0.2, 0.3, 0.4, and
0.5 mol/L, respectively). Fig. 3a shows the extraction efﬁciency of curcuminoids increased obviously following with increasing the IL concentration before it reached 0.4 mol/L, and then the efﬁciency decreased slightly by further increasing the IL concentration. With increasing of the IL aqueous solution concentration, it was easier to disrupt cellulose structure and facilitate dissolving the solute in cell, thus promoting extraction efﬁciency of curcuminoids, while the concentration was over 0.4 mol/L, the viscosity of the solution increased continuously and inﬂuenced the mass transfer of target component and decreased the extraction efﬁciency. Therefore, [Omin]Br aqueous solution concentration of 0.1–0.5 mol/L was used to in further optimization study. To examine the effect of extraction time on extraction efﬁciency, extractions of different radiation time (10, 30, 50, 70, and 90 min, respectively) was examined. Fig. 3b listed the effect of extraction time on the yield of curcuminoids. It was found that the extraction yield of curcuminoids increased with increasing extraction time. Thus, ultrasonic time of 10–90 min was used in the present optimization study. Optimization of the ultrasonic power is essential in ultrasonic assisted extraction. Extractions were carried out at 100, 150, 200, 225, and 250 W, respectively. Fig. 3c indicated the effect of ultrasonic power on the yield of curcuminoids. It showed that the extraction yield of curcuminoids was continuously increased with increasing ultrasonic power. Therefore, ultrasonic power of 100, 150, 200, 225, and 250 W were used in the further optimization study.
Fig. 3. Effects of the concentration of [Omim]Br (a), extraction time (b), and ultrasonic power (c) on the extraction efﬁciency with 0.3 mol/L [Omim]Br. Dried powder: 0.5 g, ratio of liquid to raw: 30 mL/g.
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493 Table 2 Analysis of variance (ANOVA) of the ﬁtted second-order polynomial model for total curcuminoids content, ABTS, and TRAP value. Sum of squares Total curcuminoids contenta Model 47.04 Residual 0.22 0.16 Lack of ﬁt 0.061 Pure error 47.26 Total b ABTS value Model 6909.15 18.18 Residual 11.35 Lack of ﬁt Pure error 6.83 6927.33 Total TRAP valuec Model 7784.27 14.00 Residual 9.84 Lack of ﬁt 4.16 Pure error Total 7798.27 a b c
DF 9 7 3 4 16
Mean square 5.23 0.031 0.053 0.015
9 7 3 4 16
767.68 2.60 3.78 1.71
9 7 3 4 16
864.92 2.00 3.28 1.04
The R2 and Adj R2 of the model were 0.995 and 0.989, respectively. The R2 and Adj R2 of the model were 0.997 and 0.994, respectively. The R2 and Adj R2 of the model were 0.998 and 0.996, respectively.
3.4. Optimization parameters by response surface methodology 3.4.1. Statistical analysis and the model ﬁtting It was necessary to investigate the interactions between the extraction variables to optimize operating parameters, so a 17-run BBD containing 5 replicates at center point was utilized to optimize the three independent variables. Single factor trials enabled the range of IL concentration (X1 , 0.1–0.5 mol/L), extraction time (X2 , 10–90 min), ultrasonic power (X3 , 100–250 W), Y representing target content and radical scavenging capacity. Table 1 showed the experimental and predicted data in terms of curcuminoids content and radical scavenging capacity. Among the 17 runs, experiment 16 (0.3 mol/L [Omin]Br, 90 min extraction time, 250 W ultrasonic power) produced the highest total curcuminoinds content(5.72 g /100 g turmeric) and experiment 4 (0.1 mol/L [Omin]Br, 90 min extraction time, 175 W ultrasonic power) produced the lowest total curcuminoids content (1.35 g /100 g turmeric). Experiment 16 for ABTS and TRAP both produced the highest radical scavenging capacity (56.99 mg TE/g turmeric for ABTS and 60.05 mg TE/g turmeric for TRAP). Experiment 6 for ABTS (0.1 mol/L [Omin]Br, 10 min extraction time, 175 W ultrasonic power) and experiment 4 for TRAP produced the lowest radical scavenging capacity (5.55 mg TE/g turmeric for ABTS and 6.58 mg TE/g turmeric for TRAP). Fitting the data with various model, and the ANOVA showed that the curcuminoids content and radical scavenging capacity were described in quadratic polynomial models. The ANOVA (Table 2) showed that large model F-value implied the models were signiﬁcant at 95% conﬁdence level. All the models were highly signiﬁcant as their “Prob > F” less than 0.0001. Lack of Fit p-value was large than 0.05, meaning it was not signiﬁcant relative to the pure error. So, non-signiﬁcant Lack of Fit was good. Furthermore the low values of pure error indicated good reproducibility of the data. “R-squared” and “Adj R-squared” also revealed excellent correlations between
the independent variables. Table 3 demonstrated the relationship between independent variables and target content, radical scavenging capacity in second-order polynomial models. The effects of independent factors and their interactions on total curcuminoids content, ABTS value and TRAP value were calculated by response surface plots. Fig. 4 showed IL concentration had extremely comparable inﬂuence on response value among three variables. Fig. 4a, d, and g reﬂected concentration of IL aqueous solution had high effect on response values at 0.4 mol/L approximately, which was similar to the coefﬁcient of IL concentration and ultrasonic power in Fig. 4b, e, and h. The effects of extraction time and ultrasonic power shown in Fig. 4c, f, and i demonstrated that a highest response values was observed at a longer extraction time and higher ultrasonic power. It can approximately attribute the main activity to curcuminoids as the total curcuminoids yield was positively associated with radical scavenging capacity, but the effect of other phenolic compounds also can not be excluded.
3.5. Veriﬁcation tests The optimum ILs-based UAE condition for the response variables from turmeric obtained by RSM were presented in Table 4. The veriﬁcation tests were operated under the optimum conditions (0.42 mol/L [Omin]Br at 250 W for 90 min extraction time). The actual extraction efﬁciency was 6.1386 ± 0.4171 g total curcuminoids/100 g turmeric, 0.6227 ± 0.0470 mg TE/g turmeric and 0.6521 ± 0.0397 mg TE/g turmeric for actual ABTS value and TRAP value, respectively. Under these conditions, the biggest total curcuminoids content and radical scavenging capacity were obtained. These experimental results matched the predicted results, which indicated the polynomial models with good correlations.
3.6. Comparison of different methods for extraction of curcuminoids from C. longa L. The ILs-based UAE was compared to organic solvent-based UAE and heat-reﬂux extraction, and the extraction yields of total curcumioids obtained by ILs and 85% ethanol-based UAE, and 85% ethanol based heat-reﬂux extraction were 6.1386 ± 0.4171, 4.3960 ± 0.4342, and 5.1218 ± 0.4686 g/100 g, respectively. The extraction results indicated the efﬁciency of ethanol was statistically lower than that of ILs at the same UAE conditions. Such difference in efﬁciency can be mainly caused by ILs, as ILs can form stronger binding energy with cellulose than ethanol. Such acting force indicated that ILs in water solution would have higher afﬁnity to interact with cellulose active sites, which may disrupt the hydrogen-bonding network of cellulose so that disrupted cellulose structure and facilitated dissolving the solute in cell (Bogdanov and Svinyarov, 2013). Moreover, ILs were supposed be a better choice for extraction of curcuminoids, for nitrogen atom in imidazolium based ILs can form hydrogen bond with hydroxyl radicals in Cur, DMC and BDMC. Furthermore, the ultrasonic power was a driving force for the complete dispersion and access of ILs into medical materials (Passos et al., 2014). Therefore, ILs based ultrasonic procedure is a new, effective method for extraction of curcuminoids from C. longa L.
Table 3 Second-order polynomial equations for investigated response variables. Response
Second-order polynomial model equation
Total curcuminoids Y1 = −1.61816 + 36.38598X1 − 0.00855X2 + 0.00066X3 + 0.01368X1 X2 + 0.00576X1 X3 + 0.0000366X2 X3 − 45.5718X1 2 − 0.0000275X2 2 − 0.00000539X3 2 content ABTS value Y2 = −33.85537 + 454.5241X1 − 0.01195X2 − 0.03327X3 + 0.03736X1 X2 + 0.04926X1 X3 + 0.000357X2 X3 − 563.597X1 2 − 0.000252X2 2 − 0.000237X3 2 TRAP value Y3 = −37.51833 + 517.6873X1 − 0.01552X2 − 0.01508X3 + 0.01322X1 X2 + 0.004409X1 X3 + 0.000171X2 X3 − 658.261X1 2 − 0.0000741X2 2 − 0.00019X3 2
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493
Fig. 4. Response surface for the interactions of independent variables on extraction efﬁciency of total curcuminoids content, ABTS value and TRAP value.
Table 4 Predicted and experimental values of responses under optimum conditions. Response
Optimum extraction conditions [Omim]Br concentration (mol/L)
Total curcuminoids content(g/100 g turmeric) ABTS (mg TE/g turmeric) TRAP (mg TE/g turmeric)
Maximum values Extraction time (min) 90
Ultrasonic power (W) 250
Predicted 6.18 62.40 65.28
Experimental 6.14 61.57 63.96
ILs-based UAE method was employed in order to obtain a novel and green extraction process towards curcuminoids from turmeric, the rhizomes of C. longa L. RSM was successfully applied to optimize conditions for maximum total curcuminoids content and radical scavenging capacity. Among the three dependent variables, IL concentration was the most signiﬁcant parameter with its p-value less than 0.001. Optimum process was set as below: [Omim]Br aqueous solution concentration, 4.2 mol/L; liquid–solid ratio, 30 mL/g; extraction time, 90 min; ultrasonic power, 250 W. This Optimized conditions produced total curcuminoids 6.1773 g/100 g turmeric, 0.6244 mg TE/g turmeric for ABTS value and 0.6546 mg TE/g turmeric for TRAP value.
Afshari, K., Samavati, V., Shahidi, S.-A., 2014. Ultrasonic-assisted extraction and in-vitro antioxidant activity of polysaccharide from Hibiscus leaf. Int. J. Biol. Macromol. 74, 558–567. Aoki, F., Nakagawa, K., Tanaka, A., Matsuzaki, K., Arai, N., Mae, T., 2005. Determination of glabridin in human plasma by solid-phase extraction and LC–MS/MS. J. Chromatogr. B 828, 70–74. Asfaw, N., Licence, P., Novitskii, A.A., Poliakoff, M., 2005. Green chemistry in Ethiopia: the cleaner extraction of essential oils from Artemisia afra: a comparison of clean technology with conventional methodology. Green Chem. 7, 352–356. Bi, W.T., Tian, M.L., Row, K.H., 2013. Evaluation of molecularly imprinted anion-functionalized poly(ionic liquid) s by multi-phase dispersive extraction of ﬂavonoids from plant. J. Chromatogr. B 913–914, 61–68. ˇ Marták, J., 2011. Extraction of butyric acid by a solvent Blahuˇsiak, M., Schlosser, S., impregnated resin containing ionic liquid. React. Funct. Polym. 71, 736–744. Bogdanov, M.G., Svinyarov, I., 2013. Ionic liquid-supported solid–liquid extraction of bioactive alkaloids. II. Kinetics, modeling and mechanism of glaucine extraction from Glaucium ﬂavum Cr. (Papaveraceae). Sep. Purif. Technol. 103, 279–288. Bucar, F., Wube, A., Schmid, M., 2013. Natural product isolation – how to get from biological material to pure compounds. Nat. Prod. Rep. 30, 525–545. Cao, X.J., Ye, X.M., Lu, Y.B., Yu, Y., Mo, W.M., 2009. Ionic liquid-based ultrasonic-assisted extraction of piperine from white pepper. Anal. Chim. Acta 640, 47–51.
Acknowledgments This work was ﬁnancially supported by Qianjiang talents project in Zhejiang province.
J. Xu et al. / Industrial Crops and Products 76 (2015) 487–493 Chang, L.H., Jong, T.T., Huang, H.S., Nien, Y.F., Chang, C.M.J., 2006. Supercritical carbon dioxide extraction of turmeric oil from Curcuma longa Linn and puriﬁcation of turmerones. Sep. Purif. Technol. 47, 119–125. Chowdhury, S.A., Vijayaraghavan, R., MacFarlane, D.R., 2010. Distillable ionic liquid extraction of tannins from plant materials. Green Chem. 12, 1023–1028. Du, F.Y., Xiao, X.H., Luo, X.J., Li, G.K., 2009. Application of ionic liquids in the microwave-assisted extraction of polyphenolic compounds from medicinal plants. Talanta 78, 1177–1184. Fang, X.S., Wang, J.H., Wang, Y.Z., Li, X.K., Zhou, H.Y., Zhu, L.X., 2014. Optimization of ultrasonic-assisted extraction of wedelolactone and antioxidant polyphenols from Eclipta prostrate L. using response surface methodology. Sep. Purif. Technol. 138, 55–64. Gazal, M., Valente, M.R., Acosta, B.A., Kaufmann, F., Braganhol, E., Lencina, C.L., Stefanello, F.M., Ghisleni, G., Kaster, M.P., 2014. Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats. Eur. J. Pharmacol. 724, 132–139. Han, X.X., Armstrong, D.W., 2007. Ionic liquids in separations. Acc. Chem. Res. 40, 1079–1086. Hernández-Fernández, F.J., de los Ríos, A.P., Lozano-Blanco, L.J., Godínez, C., 2010. Biocatalytic ester synthesis in ionic liquid media. J. Chem. Technol. Biotechnol. 85, 1423–1435. Huang, D.J., Ou, B.X., Prior, R.L., 2005. The chemistry behind antioxidant capacity assays. J. Agric. Food Chem. 53, 1841–1856. Huddleston, J.G., Visser, A.E., Reichert, W.M., Willauer, H.D., Broker, G.A., Rogers, R.D., 2001. Characterization and comparison of hydrophilic and hydrophobic room temperature ionic liquids incorporating the imidazolium cation. Green Chem. 3, 156–164. Jiang, H., Wang, Z., Wang, Y.H., Xie, K., Zhang, Q.R., Luan, Q.S., Chen, W.Q., Liu, D.X., 2013. Antidepressant-like effects of curcumin in chronic mild stress of rats: involvement of its anti-inﬂammatory action. Prog. Neuropsychopharmacol. Biol. Psychiatry 47, 33–39. Kant, V., Gopal, A., Pathak, N.N., Kumar, P., Tandan, S.K., Kumar, D., 2014. Antioxidant and anti-inﬂammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int. Immunopharmacol. 20, 322–330. Kong, Y., Ma, W., Liu, X., Zu, Y.G., Fu, Y.J., Wu, N., Liang, L., Yao, L.P., Efferth, T., 2009. Cytotoxic activity of curcumin towards CCRF-CEM leukemia cells and its effect on DNA damage. Molecules 14, 5328–5338. Larsen, A.S., Holbrey, J.D., Tham, F.S., Reed, C.A., 2000. Designing ionic liquids: imidazolium melts with inert carborane anions. J. Am. Chem. Soc. 122, 7264–7272. Li, M., Ngadi, M.O., Ma, Y., 2014. Optimisation of pulsed ultrasonic and microwave-assisted extraction for curcuminoids by response surface methodology and kinetic study. Food Chem. 165, 29–34. Li, S.Q., Cai, S., Hu, W., Chen, H., Liu, H.L., 2009. Ionic liquid-based ultrasound-assisted dispersive liquid–liquid microextraction combined with electrothermal atomic absorption spectrometry for a sensitive determination of cadmium in water samples. Spectrochim. Acta Part B 64, 666–671. Lima, C.F., Pereira-Wilson, C., Rattan, S.I., 2011. Curcumin induces heme oxygenase-1 in normal human skin ﬁbroblasts through redox signaling: relevance for anti-aging intervention. Mol. Nutr. Food Res. 55, 430–442. Lin, H.M., Zhang, Y.G., Han, M., Yang, L.M., 2013. Aqueous ionic liquid based ultrasonic assisted extraction of eight ginsenosides from ginseng root. Ultrason. Sonochem. 20, 680–684. Liu, Y., Yang, L., Zu, Y.G., Zhao, C.J., Zhang, L., Zhang, Y., Zhang, Z.H., Wang, W.J., 2012. Development of an ionic liquid-based microwave-assisted method for simultaneous extraction and distillation for determination of proanthocyanidins and essential oil in Cortex cinnamomi. Food Chem. 135, 2514–2521.
Ma, C.H., Liu, T.T., Yang, L., Zu, Y.G., Wang, S.Y., Zhang, R.R., 2011. Study on ionic liquid-based ultrasonic-assisted extraction of biphenyl cyclooctene lignans from the fruit of Schisandra chinensis Baill. Anal. Chim. Acta 689, 110–116. Mandal, V., Mohan, Y., Hemalatha, S., 2008. Microwave assisted extraction of curcumin by sample-solvent dual heating mechanism using Taguchi L9 orthogonal design. J. Pharm. Biomed. Anal. 46, 322–327. Miquel, J., Bernd, A., Sempere, J.M., Dı´ıaz-Alperi, J., Ramı´ırez, A., 2002. The Curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review. Arch. Gerontol. Geriatr. 34, 37–46. Mourtas, S., Lazar, A.N., Markoutsa, E., Duyckaerts, C., Antimisiaris, S.G., 2014. Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease. Eur. J. Med. Chem. 80, 175–183. Pandey, S., 2006. Analytical applications of room-temperature ionic liquids: a review of recent efforts. Anal. Chim. Acta 556, 38–45. Passos, H., Freire, M.G., Coutinho, J.A., 2014. Ionic liquid solutions as extractive solvents for value-added compounds from biomass. Green Chem. 16, 4786–4815. ´ J., 2007. Are natural antioxidants better – and safer – than synthetic Pokorny, antioxidants? Eur. J. Lipid Sci. Technol. 109, 629–642. Prasad, S., Gupta, S.C., Tyagi, A.K., Aggarwal, B.B., 2014. Curcumin, a component of golden spice: from bedside to bench and back. Biotechnol. Adv. 32, 1053–1064. Riela, S., Massaro, M., Colletti, C.G., Bommarito, A., Giordano, C., Milioto, S., Noto, R., Poma, P., Lazzara, G., 2014. Development and characterization of co-loaded curcumin/triazole-halloysite systems and evaluation of their potential anticancer activity. Int. J. Pharm. 475, 613–623. Sahin, S., Aybastier, O., Isik, E., 2013. Optimisation of ultrasonic-assisted extraction of antioxidant compounds from Artemisia absinthium using response surface methodology. Food Chem. 141, 1361–1368. Severa, G., Kumar, G., Troung, M., Young, G., Cooney, M.J., 2013. Simultaneous extraction and separation of phorbol esters and bio-oil from Jatropha biomass using ionic liquid–methanol co-solvents. Sep. Purif. Technol. 116, 265–270. Sosnowska, A., Barycki, M., Zaborowska, M., Rybinska, A., Puzyn, T., 2014. Towards designing environmentally safe ionic liquids: the inﬂuence of the cation structure. Green Chem. 16, 4749–4757. Sukandar, E.Y., Sudjana, P., Adnyana, I.K., Setiawan, A.S., Yuniarni, U., 2014. Recent study of turmeric in combination with garlic as antidiabetic agent. Procedia Chem. 13, 44–56. Sun, P., Armstrong, D.W., 2010. Ionic liquids in analytical chemistry. Anal. Chim. Acta 661, 1–16. Wakte, P.S., Sachin, B.S., Patil, A.A., Mohato, D.M., Band, T.H., Shinde, D.B., 2011. Optimization of microwave, ultra-sonic and supercritical carbon dioxide assisted extraction techniques for curcumin from Curcuma longa. Sep. Purif. Technol. 79, 50–55. Yang, L., Wang, H., Zu, Y.-g., Zhao, C., Zhang, L., Chen, X., Zhang, Z., 2011. Ultrasound-assisted extraction of the three terpenoid indole alkaloids vindoline, catharanthine and vinblastine from Catharanthus roseus using ionic liquid aqueous solutions. Chem. Eng. J. 172, 705–712. Zabihi, F., Xin, N., Li, S.N., Jia, J.F., Cheng, T., Zhao, Y.P., 2014. Polymeric coating of ﬂuidizing nano-curcumin via anti-solvent supercritical method for sustained release. J. Supercrit. Fluids 89, 99–105. Zhang, G.W., He, L., Hu, M.M., 2011. Optimized ultrasonic-assisted extraction of ﬂavonoids from Prunella vulgaris L. and evaluation of antioxidant activities in vitro. Innov. Food Sci. Emerg. Technol. 12, 18–25. Zhang, Z.C., 2013. Catalytic transformation of carbohydrates and lignin in ionic liquids. WIREs Energy Environ. 2, 655–672.