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Process Biochemistry
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a
Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
b
Supercritical Fluid Centre (SFC), Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia
c
Research Center of Supercritical Fluid Technology, Tohoku University, Aramaki Aza Aoba, 6-6-11-403, Aoba-ku, Sendai, 980-8579, Japan
d
School of Science, Monash University Malaysia, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
Keywords: This work aims to develop a method for producing α-mangostin that has high bio-accessibility through the use of
Supercritical fluid extraction supercritical carbon dioxide (scCO2) extraction of mangosteen pericarp extract (MPE) with virgin coconut oil
Xanthone (VCO) as co-extractant. Extractions with scCO2 were carried out at 30 MPa to 40 MPa, 60 °C, CO2 flow rate of
Garcinia mangostana Linn 1.7 g/min and co-extractant VCO (0% to 20%). MPE yield and extraction yield increased with the amount of co-
Virgin coconut oil
extractant added. The highest yield of MPE obtained was 17% at conditions of 35 MPa with 20% of VCO. The
Co-extractant
Bio-accessibility
scCO2 MPE had higher bio-accessibility for α-mangostin (91%) than α-mangostin obtained by extraction with
ethanol (30%) or hexane (50%). Thus, supercritical CO2 extraction used with virgin coconut oil co-extractant
provides a method for producing high bio-accessible α-mangostin from mangosteen pericarp extract.
⁎
Corresponding author at: Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, Serdang, Selangor,
Malaysia.
E-mail address: gunhean@upm.edu.my (G.H. Chong).
https://doi.org/10.1016/j.procbio.2019.09.009
Received 19 June 2019; Received in revised form 23 August 2019; Accepted 7 September 2019
1359-5113/ © 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: Wan Jun Lee, et al., Process Biochemistry, https://doi.org/10.1016/j.procbio.2019.09.009
W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
Fig. 1. Overview of experimental design. Assessment of vegetable oil for extraction of mangosteen pericarp extract, extraction steps and bio-accessibility tests.
bioactive compounds and to increase their extraction yield. ground into powder form (RT-CR30S 3HP, Rong Tsong precision
It has been reported that α-mangostin has restricted bioavailability technology CO, Taiwan) with measured particle size of < 2 mm, cor-
[24,25]. Presence of oil as co-extractant potentially enhances the bio- responding to 18 mesh.
accessibility of α-mangostin from the MPE since the oil could act as a
carrier lipid for lipophilic bioactive components [26]. The role of oil co- 2.3. Soxhlet extraction
extractant in both influencing the scCO2 extraction yield and bio-ac-
cessibility of α-mangostin has not been reported. MP powder (20 g) was extracted with hexane (ca. 68 °C), ethanol
In this work, virgin coconut oil was used as co-extractant to increase (ca. 78 °C) and ethyl acetate (ca. 77 °C) for 6 h using a Soxhlet appa-
the extraction yield of mangosteen pericarp extract (MPE) and α-man- ratus. The solvent was evaporated at 40 °C and the extract was flushed
gostin. The objectives of this study were to determine effective con- with nitrogen and sealed before being kept in the dark at −18 °C. The
centrations of co-extractant and extraction conditions for separating results from solvent extraction are used as controls in the assessment of
MPE and α-mangostin and to investigate the effect of co-extractant on the experiments.
the in-vitro bio-accessibility of α-mangostin.
2.4. Dissolution of MPE in solvents and vegetable oils
2. Materials and method
2.4.1. Solubility of MPE in different solvents
2.1. Materials Dissolution experiments of MPE in ethanol, ethyl acetate and
hexane were performed as follows. MPE (0.05 g to 0.2 g) was mixed
Dried MP and virgin coconut oil (VCO) were supplied by with 4 mL of solvent in a test tube. The dissolution of MPE was visually
Adirondack (M) Sdn. Bhd (Selangor, Malaysia), and liquid CO2 (purity: observed under different temperatures (30 to 70) °C with continuous
99.99%) was purchased from NIG Gases (M) Sdn Bhd. (Selangor, stirring.
Malaysia). Rice bran oil (RBO), palm kernel oil (PKO), grape seed oil
(GSO), canola oil (CO), sunflower oil (SO) and olive oil (OO) were 2.4.2. Suitability of different vegetable oils as co-extractant
purchased from AEON CO. (M) BHD (Selangor, Malaysia). HPLC grade To determine a suitable type of vegetable oil as co-extractant for
solvents (ethanol, methanol, acetonitrile, orthophosphoric acid), hy- scCO2 extraction, the ability of the MPE to dissolve in the oil was de-
drochloric acid, sodium chloride, sodium hydroxide, ethyl acetate were termined. The dissolution of MPE in VCO, RBO, PKO, GSO, CO, SO and
purchased from Thermo Fisher Scientific (New Hampshire, United OO were studied. MPE (0.025 g to 0.2 g) was mixed with oil (4 g) in a
States). Enzymes pepsin (P-7000), pancreatin (P-1750) and bile extract test tube before subjecting the mixture to different temperatures (ca.
(B-8631) from porcine source and α-mangostin analytical standard 50 °C, 60 °C, 70 °C, 80 °C, 90 °C and 98 °C) using a water bath with
(purity ≥98%) were purchased from Wuhan ChemFaces Biochemical continuous stirring for 5 min. The oils that allowed for the highest MPE
Co. (Hubei, China). dissolution by visual observation at the lowest possible temperature
were selected as the co-extractant for the subsequent scCO2 extraction.
2.2. Sample preparation Extractions with scCO2 were carried out at moderate temperatures (ca.
60 °C) and 35 MPa to select the most suitable type of vegetable oil based
Prior to extraction, the dried MP (moisture content of 8%) was on the extraction yield. Experiments were conducted in triplicate.
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W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
An overview on the experimental design for this work is shown in and small intestinal digestion model for the extracted MPE were carried
Fig. 1. out using the methods adapted from Bumrungpert et al. [29] and Goh
et al. [30]. The MPE solution was prepared by mixing 32 mL of 0.9%
2.5. scCO2 extraction NaCl to 0.2 g of MPE, followed by homogenisation and acidification to
pH 2.0 with HCl. Simulation of the gastric digestion was carried out by
A laboratory scale system as described by Lee et al. [27] was used adding pepsin into the MPE solution followed by incubation for 1 h at
for the extraction of MPE with scCO2. The system consisted of an ex- 37 °C. Simulation of intestinal digestion was done by adding pan-
traction vessel (110 mL), an oven (UFE 600, Memmert, Germany), a creatin/bile extract solution and bile extract to the MPE solution (ad-
CO2 pump (P-2024SFC, ChromTech, USA) and a CO2 measuring flow justed to pH 5.3). The pH of the mixture was further adjusted to 7.5 and
metre (#20136, Restek, USA). VCO was selected as the co-extractant for incubated for 2 h at 37 °C. Micellar fraction was obtained from the su-
the scCO2 extraction (discussed in Section 3.1). MP powder (5 g) was pernatant after the digesta was centrifuged (×5000g, 4 °C, and 45 min)
mixed with different amounts of VCO (5, 10, and 20% w/w) before and filtered (0.22 μm). Extraction of α-mangostin from the micellar
being loaded into the extraction vessel in which it was preliminary fraction was done by adding in 1.5 mL of ethyl acetate followed by
determined that the addition of VCO above 20% caused powder ag- centrifugation at ×2000g for 5 min. The organic layer was collected
glomeration. Hence the maximum co-extractant amount was set to and the extraction step with ethyl acetate was repeated for another
20%. A control sample without the addition of VCO was also prepared time. The solvent was then evaporated under reduced pressure at 40 °C
for the scCO2 extraction. Glass wool (#20411, Supelco, USA) was to obtain α-mangostin. Concentration of α-mangostin was then quan-
placed at both ends of the extraction vessel to hold the MP powder in tified with HPLC as in Section 2.6.
place. The scCO2 extractions were conducted at 30 MPa, 35 MPa and The bio-accessibility of α-mangostin was calculated from Eq. (5):
40 MPa, ca. 60 °C and CO2 flow rate of 1.7 g/min for 4 h. The weight of
Bio-accessibility = (BCdialysed/ BCnon-digested) × 100% (5)
collected MPE was recorded and the samples were flushed with ni-
trogen and sealed before being kept in the dark at −18 °C. The ex- where, BCdialysed and BCnon-digested correspond to the α-mangostin con-
periments were conducted in triplicate. centration (mg/g) in the micellar fraction and non-digested MPE, re-
The extraction yield was calculated from Eq. (1) spectively.
Extraction yield = mMPE /(mmp + moil) × 100% (1)
2.8. Statistical analysis
where, mMPE is the mass of mangosteen pericarp extract collected from
scCO2 extraction and mmp is the total mass of mangosteen pericarp Analysis of variance (ANOVA) was performed followed by Tukey
powder and moil is the amount of VCO loaded into the extraction vessel. HSD post hoc test using Minitab 16 statistical software (Minitab Inc.,
Pennsylvania). The limit of probability of significance was fixed at
2.6. α-mangostin with HPLC p < 0.05.
The α-mangostin was quantified with an HPLC system (Agilent 3. Results and discussion
Technologies 1200). The HPLC system was equipped with two precision
pumps and the chromatographic separations were performed using a 3.1. Dissolution tests with solvents and oils
SGE RP-18 (146 × 4.6 mm, 5 μm) with UV–vis detector. Samples
(20 μL) of α-mangostin were analysed at wavelengths of 245 nm and Table 1 shows results of the dissolution tests of MPE for ethyl
319 nm, with mobile phase of (A) 0.03% orthophosphoric acid in water acetate, ethanol and n-hexane. MPE was highly-soluble in both ethyl
and (B) acetonitrile/methanol (75:25 v/v), being delivered at 0.8 mL/ acetate (instantaneous dissolution) and in ethanol at 30 °C whereas the
min with gradient elution [28]. The gradient elution was as follows: MPE had very low solubility in n-hexane at 30 °C and only slightly
0 min, 25% A and 75% B; 0–15 min, 10% A and 90% B; (15 to 30) min, dissolved in n-hexane at higher temperatures of 60 °C and 70 °C.
100% B; (30 to 35) min, 25% A and 75% B. The α-mangostin present in Kamlet-Taft parameters can be used to explain the mechanism of dis-
samples was calculated on the basis of a calibration curve using α- solution of MPE in different solvents, expressed as dipolarity/polariz-
mangostin standard that had a correlation coefficient of R2 = 0.9994 ability (π*), hydrogen-bond acidity (α) and hydrogen-bond basicity (β)
(Supplementary Materials, Fig. S1). as presented in Table 1. It can be suggested that the hydrogen-bond
The α-mangostin yield and selectivity were calculated from the basicity (β) and dipolarity/polarizability (π*) are able to be used to
following equations:
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W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
Table 3
Yields of α-mangostin obtained from mangosteen pericarp extract (MPE) using supercritical carbon dioxide extraction (60 °C, 1.7 g/min flow rate) and virgin coconut
oil (VCO) co-extractant. Results obtained from MPE for organic solvent extraction are shown for comparison.
Runa Pressure VCO (%, MPE (g) Extraction α-mangostin α-mangostin α-mangostin
(MPa) w/w) yield (%) (mg/g pericarp) yield (%) selectivity (%)
1 30 0 – – – – –
2 5 0.29 ± 0.03 5.56 ± 0.50 6.12 ± 0.14 0.61 ± 0.01 2.14 ± 0.15
3 10 0.34 ± 0.06 6.12 ± 1.01 9.41 ± 0.22 0.94 ± 0.02 2.87 ± 0.43
4 20 0.69 ± 0.03 11.45 ± 0.51 15.60 ± 0.87 1.56 ± 0.09 2.32 ± 0.18
5 35 0 – – – – –
6 5 0.27 ± 0.01 5.16 ± 0.22 20.86 ± 0.94 2.09 ± 0.09 8.35 ± 0.22
7 10 0.63 ± 0.14 11.49 ± 2.47 35.16 ± 0.75 3.52 ± 0.08 5.89 ± 1.10
8 20 1.05 ± 0.15 17.55 ± 2.55 92.49 ± 2.09 9.25 ± 0.21 9.63 ± 1.39
9 40 0 0.05 ± 0.01 1.09 ± 0.20 – – –
10 5 0.23 ± 0.01 4.30 ± 0.11 16.11 ± 0.81 1.61 ± 0.08 7.69 ± 0.36
11 10 0.38 ± 0.02 6.84 ± 0.31 22.83 ± 0.20 2.28 ± 0.02 6.46 ± 0.38
12 20 0.88 ± 0.11 14.63 ± 1.84 34.02 ± 1.07 3.40 ± 0.11 4.03 ± 0.68
Hexane extraction (at 68 °C) 0.15 ± 0.04 3.05 ± 0.72 11.53 ± 0.75 1.15 ± 0.08 8.18 ± 1.97
Ethanol extraction (at 78 °C) 1.90 ± 0.12 38.09 ± 2.30 21.75 ± 0.40 2.18 ± 0.04 1.16 ± 0.05
Ethyl acetate extraction (at 77 °C) 2.02 ± 0.08 40.36 ± 1.67 36.65 ± 0.86 3.66 ± 0.09 1.85 ± 0.04
a
Total extractable α-mangostin was taken to be 121 mg/g pericarp (Source: Ghasemzadeh et al. [50]).
4
W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
done by Zarena et al. [3] which employed ethanol (5% w/w) as co- isomangostin hydrate, γ-mangostin, 8-deoxygartanin, gartanin, and α-
solvent in scCO2 extraction, recording xanthone yields of 14.8%. De- mangostin; and hexane-extracted MPE could contain γ-mangostin, 8-
spite the lower extraction yields, VCO as co-extractant is still a great deoxygartanin, gartanin and α-mangostin. Ethyl acetate was not con-
alternative to using ethanol from the point of food processing, since it sidered since MPE had high solubility in the solvent and many peaks
avoids contamination issues. VCO can have desirable properties to the would appear. Further work could be carried out to identify the pre-
end product such as enhancing the bio-accessibility of α-mangostin sence of bioactive components in each of the extracts.
(Section 3.4) and does not have to be removed from the extract.
Ethanol, when used as co-solvent, must be removed from the final 3.4. In-vitro bio-accessibility of α-mangostin
product, which increases production cost.
Although ethyl acetate had favorable extraction characteristics for
3.3.1. Co-extractant MPE, the in-vitro bio-accessibility study using ethyl acetate extracted
Without co-extractant (VCO = 0%), the MPE yield was below the MPE was not performed due to consideration of the Globally
weighable limit (Run 1 and 5) and the concentration of α-mangostin Harmonized System (GHS) and its compatibility with functional food
was below detection limit (Run 1, 5 and 9). Table 2 shows by increasing products.
the amount of VCO from 0% to 20%, the extraction yield of MPE in- The in-vitro bio-accessibility of α-mangostin obtained from scCO2
creased for the pressures of 30 MPa, 35 MPa and 40 MPa. The increment extraction (Run 8) and the solvent extraction are shown in Fig. 3. The α-
in the yield was contributed by the higher available amount of VCO to mangostin from scCO2 extracted MPE showed the highest bio-accessi-
be co-extracted during the extraction process. The extraction yield of α- bility (91%) followed by α-mangostin from ethanol-extracted MPE
mangostin also increased with high amount of VCO. Similar observa- (47%) and α-mangostin from hexane-extracted MPE (5%). The α-man-
tions were made by Shi et al. [20] whereby the extraction yield of gostin in scCO2 extract could be considered almost fully digested and
carotenoid increased from 4.2 mmol/kg to 4.73 mmol/kg (∼10% in- reached a complete bio-accessibility through in-vitro gastrointestinal
crement) with increasing olive oil concentration of 5% to 15%. digestion as it reached more than 90% bio-accessibility of the amount
ingested. Hexane-extracted MPE mainly contained non-polar hydro-
3.3.2. Effect of pressure phobic compounds that were lipophilic, thus it had low solubility in the
The concentration of α-mangostin increased when the operating aqueous solution and remained intact that caused low bio-accessibility.
pressure was raised from 30 MPa to 35 MPa, however, at 40 MPa, the As for scCO2 extracted MPE, the high bio-accessibility could be due to
concentration decreased. The increased in solvation power when the the scCO2 affecting the molecular properties of compounds and directly
density of scCO2 increased at high pressures allowed for high solubility affecting the release of bioactive compounds and its bio-accessibility
of solute. For the case of α-mangostin, it was postulated that the re- through gastrointestinal digestion. A recent study disclosed that lipo-
pulsive solute–solvent interactions became large which lowered the philic compounds (terpenes) in marigold supercritical extracts showed
solubility in scCO2 [21] and thus, lower concentration was obtained at high bio-accessibility (> 75%) due to the significant correlation be-
40 MPa. This observation is consistent to the reported findings by Ma tween molecular properties of compounds, such as molecular flexibility
et al. [21], whereby the extraction yield of lutein esters started to de- and lipophilicity with their bio-accessibility [38].
cline beyond pressure of 30 MPa. To demonstrate the importance of VCO in enhancing the bio-ac-
cessibility of α-mangostin, the bio-accessibilities of α-mangostin from
3.3.3. Comparison with solvent extraction ethanol-extracted MPE and hexane-extracted MPE in the presence of
Table 2 shows a comparison between the extraction yield obtained 20% VCO were tested, recording values of 67% and 11% (Fig. 2), re-
from scCO2 extraction (Table 2, Run 8) (scCO2 extracted MPE) and from spectively. It was evident that with the addition of VCO, the bio-ac-
solvent extraction; ethanol-extracted MPE, hexane-extracted MPE and cessibilities of α-mangostin from ethanol-extracted MPE and hexane-
ethyl acetate-extracted MPE. The yield of ethyl acetate-extracted MPE extracted MPE increased significantly. The capability of α-mangostin to
was the highest (40.4%), followed by ethanol-extracted MPE (38%), be taken up during digestion is hindered due to the lipophilic molecular
scCO2-extracted MPE (17%) and lastly, hexane-extracted MPE (3%). It structure which has limited solubility in an aqueous micelle [39,40].
was postulated that one of the main reasons that affect extraction yield The VCO acts as a key positive effector by promoting the formation and
of MPE was solvent polarity according to the β and π* Kamlet-Taft incorporation of the α-mangostin into micelles before absorption
parameters as discussed in Section 3.1. Ethyl acetate had the highest β [41,42]. Similar observations on enhanced bio-accessibility and bioa-
and π* values followed by ethanol, hence, high extraction yields were vailability of α-mangostin or xanthone in the presence of lipid have
recorded for those two solvents. As for the scCO2, it was reported in the been reported [29,43,44].
literature that it had α value of 0, β value of 0.01, and π* of −0.03
(100 MPa, 60 °C) [37]. With the aid of VCO as co-extractant, it was 3.4.1. Effect of consumption quantities
postulated that the β and π* of scCO2 was modified and recorded a The influence of consumption quantities of the scCO2-extracted MPE
higher extraction yield compared with that of hexane extraction. in the gastrointestinal digestion was investigated. From previous
Therefore, the importance of addition of VCO as co-extractant was Section 3.4, the consumption of 0.2 g of scCO2-extracted MPE showed
demonstrated. Although both ethyl acetate and ethanol showed higher high bio-accessibility of α-mangostin (91%). As the consumption
MPE yield than scCO2, the selectivity of α-mangostin was lower for li- quantity increased to 0.5 g, 1.0 g and 3.0 g, the bio-accessibility of α-
quid solvents compared with that of scCO2-MPE. Solvent extracts often mangostin decreased to 66%, 27% and 18%, respectively. Beyond
contain large quantities of matrix organics that act as product im- consumption of 0.2 g of extracts, the α-mangostin was postulated to
purities that may or may not affect bioactivity. remain intact and dissolve only within the undigested oil (upper phase)
Fig. 2 shows HPLC chromatograms of the extracts obtained from after the in-vitro gastrointestinal digestion steps. The absorption of
scCO2 extraction and solvent extractions. Original HPLC chromato- scCO2-extracted MPE was substantially related to the lipid digestion
grams are provided in supplementary materials (Fig. S2). As shown mechanism, whereby the rate and extent of digestion were affected by
(Fig. 2), α-mangostin was the main peak in all the MPE analyses, ap- the decrease in the (1) ratio of lipase: oil in the digesta and (2) the ratio
pearing at a retention time of around 2.9 min. A comparison of the of bile salt: oil. The decrease in lipase and bile salt or the increment of
chromatogram obtained in this work with the work by Zarena et al. [28] oil content slows down the dissolution of fatty acid released during
was carried out to define the unidentified peaks in the chromatograms. digestion which inhibits the process of lipid lipolysis [45,46]. Results
Other than α-mangostin, the scCO2-extracted MPE potentially contains were supported by previous studies on the bioactive components re-
8-deoxygartanin and gartanin; ethanol-extracted MPE could contain 3- lease and lipid hydrolysis of the lipophilic bioactive compounds such as
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W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
Fig. 2. Analyses of co-extractant, raw materials, and extracts made with high performance liquid chromatography (HPLC). Panels (A): virgin coconut oil (VCO), (B):
α-mangostin standard (retention time at 2.9 min), (C): mangosteen pericarp extract (MPE) extracted using supercritical carbon dioxide with VCO as co-extractant,
(D): ethanol-extracted MPE and (E): hexane-extracted MPE.
β-carotene, phytosterols, vitamin D3, curcumin and coenzyme Q10 α-mangostin had high bio-accessibility (91%). The presence of VCO
[47,48]. enhanced the bio-accessibility of α-mangostin by 30% in ethanolic MPE
and by 50% in hexane-extracted MPE. The use of VCO has the potential
to replace organic solvents (i.e. ethanol) in extracting xanthones or
4. Conclusions specifically α-mangostin from mangosteen pericarp. Future work in
determining the application of VCO in SFE to other types of xanthones
The extraction yield of α-mangostin from mangosteen pericarp ex- is of interest, because many of these compounds have valuable phar-
tract (MPE) with supercritical CO2 was enhanced with the addition of macological properties.
virgin coconut oil (VCO) as co-extractant to MPE. At extraction con-
ditions of 35 MPa, 60 °C, and VCO concentration of 20% (w/w), high
yields of α-mangostin were obtained and the supercritical CO2 extracted
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W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
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W.J. Lee, et al. Process Biochemistry xxx (xxxx) xxx–xxx
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