Abstract
Background:
The pericarp of Garcinia mangostana (mangosteen) has been used as a medicinal agent by Southeast Asians for centuries in the treatment of skin infections and wounds. Its main active constituents were xanthones and phenolic compounds. The plant and its metabolites possessed diverse bioactivities.
Methods:
A methanolic extract of G. mangostana pericarp was subjected to solvent partitioning and chromatographic purification to isolate α-mangostin (1), β-mangostin (2), gartanin (3), garcinone C (4), garcinone D (5), and (+)-2R,3R-taxifolin-3-O-α-L-rhamnoside (astilbin) (6) that were identified by NMR spectral data, as well as comparing with literature data. These compounds were assessed for their in vitro cytotoxic effect against ovarian adenocarcinoma cell line (SKOV-3), hepatic cell line (HepG-2), and colorectal cancer (HCT-116) cell lines using sulforhdamine B (SRB) assay. Doxorubicin was used as a positive control.
Results:
All compounds exhibited varying degrees of cytotoxic activity. Garcinone D demonstrated significant cytotoxic potential (IC50 27.27 ± 2.41 µM) against SKOV-3 cells. While α-mangostin and β-mangostin exhibited cytotoxic activity (IC50 values of 28.1 ± 1.1 µM and 31.9 ± 10.7 µM, respectively) towards HepG-2 cells. Also, β-mangostin and garcinone D demonstrated cytotoxic effects with IC50 values of 56.1 ± 2.5 µM and 44.3 ± 2.5 µM, respectively against HCT-116.
Conclusion:
The study highlights the cytotoxic potential of xanthones derived from Garcinia mangostana pericarp. Among the isolated metabolites, garcinone D and α-mangostin emerged as promising lead compounds for further anticancer drug development due to their significant in vitro cytotoxic effects.
Keywords: clusiaceae, cytotoxicity, flavonoid, Garcinia mangostana, health and well-being health and wellbeing, peels, xanthones
INTRODUCTION
Mangosteen (G. mangostana) is known as “the queen of fruits” because it is one of the best-tasting tropical fruits. The pericarp of mangosteen fruit has been used as a medicinal agent by Southeast Asians for centuries in the treatment of skin infections and wounds.[1] The main active constituents isolated from G. mangostana pericarps were xanthones[2,3,4,5,6,7,8,9,10,11,12,13,14] and phenolic compounds.[15,16,17,18] The plant and its metabolites possessed diverse bioactivities such as anticancer,[4,5,6,7] antidiabetic,[8,15,16] α-amylase inhibitory,[9,10,11,17,18] hepatoprotective,[12] antioxidant,[13] and antibacterial activities.[14]
The current work reported the isolation and characterization of six known metabolites (1–6) from G. mangostana pericarps EtOAc fraction. Moreover, the cytotoxic potential of the isolated compounds was assessed toward different cancer cell lines using sulforhodamine B (SRB-U) assay.
MATERIALS AND METHOD
Plant materials
The fruits of Garcinia mangostana L. were purchased from the local market in Riyadh and identified by the staff members at the Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University. A herbarium specimen (No. GM-2022-1) was deposited at the Faculty of Pharmacy Herbarium, King Abdulaziz University.
General experimental procedures
NMR spectra were recorded on Bruker Avance DR × 500 MHz spectrometer (Bruker BioSpin, Billerica, MA, USA). Silica gel 60 (0.04–0.063 mm, Merck, Darmstadt, Germany) and Sephadex LH-20 (0.25–0.1 mm, Merck, Darmstadt, Germany) were used for column chromatography. Precoated silica gel plates Kieselgel 60 F254 (0.25 mm, Merck, Darmstadt, Germany) were used for thin-layer chromatographic (TLC) analysis. The compounds were detected by UV absorption at λma × 255 and 366 nm, followed by spraying with a p-anisaldehyde: H2SO4 spray reagent and then heating at 110°C for 1–2 min.
Cytotoxicity assay
The cytotoxicity of the isolated compounds was tested against human hepatocellular carcinoma (HepG-2), colorectal adenocarcinoma (HCT-116), and breast adenocarcinoma MCF-7 cell lines that were obtained from the American Type of Culture Collection (ATCC) using sulforhodamine B assay (SRB) according to previous work.[19,20] Doxorubicin was used as a positive control. The linear relation between viability percentage of each tumor cell line and compounds concentrations was analyzed to get the IC50 (dose of the drug which reduces survival to 50%) using SigmaPlot® 12.0 software.
RESULTS AND DISCUSSION
The MeOH extract of G. mangostana was subjected to solvent/solvent partition between CHCl3, EtOAc, and H2O. The EtOAc fraction was successively chromatographed over normal silica gel column (SiO2) and Sephadex LH-20 column chromatography (CC) to afford five known xanthone derivatives and one flavonoid (1–6) [Figure 1].
Figure 1.
Extraction and isolation procedure of compounds 1–6
These compounds were identified by analysis of their spectroscopic data and comparison with literature as: α-mangostin (1),[21] β-mangostin (2),[21] gartanin (3),[22] garcinone C (4),[23] garcinone D (5),[24] and (+)-2R,3R-taxifolin-3-O-α-L-rhamnoside (astilbin) (6)[25] [Figure 2; Table 1].
Figure 2.
Chemical structures of the isolated compounds (1–6)
Table 1.
NMR spectral data of compounds 1–6 (500 and 125 MHz)
| No. | 1a |
2a |
3a |
4b |
5b |
6b |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| δH [mult., J (Hz)] | δC (mult.) | δH [mult., J (Hz)] | δC (mult.) | δH [mult., J (Hz)] | δC (mult.) | δH [mult., J (Hz)] | δC (mult.) | δH [mult., J (Hz)] | δC (mult.) | No. | δH [mult., J (Hz)] | δC (mult.) | |
| 1 | – | 160.4 | – | 159.6 | – | 157.9 | – | 160.3 | – | 160.4 | 2 | 5.21 d (10.0) |
82.0 |
| 2 | – | 108.6 | – | 111.3 | – | 109.3 | – | 109.7 | – | 110.1 | 3 | 4.65 d (10.0) |
76.1 |
| 3 | – | 161.4 | – | 163.3 | – | 161.5 | – | 162.4 | – | 162.7 | 4 | – | 195.0 |
| 4 | 6.26 s | 93.0 | 6.32 s | 88.6 | – | 105.6 | 6.32 s | 92.4 | 6.34 s | 92.7 | 5 | – | 163.9 |
| 4a | – | 154.8 | – | 155.5 | – | 152.3 | – | 153.6 | – | 155.1 | 6 | 5.89 brs | 96.5 |
| 4b | – | 155.5 | – | 155.1 | – | 142.7 | – | 152.6 | – | 154.6 | 7 | – | 167.4 |
| 5 | 6.78 s | 101.4 | 6.81 s | 101.3 | – | 135.5 | 6.71 s | 100.3 | 6.78 s | 102.0 | 8 | 5.91 brs | 95.5 |
| 6 | – | 154.5 | – | 154.2 | 7.21 d (10.0) |
122.7 | – | 154.6 | – | 157.3 | 9 | – | 162.6 |
| 7 | – | 142.4 | – | 142.4 | 6.63 d (10.0) |
109.6 | – | 141.4 | – | 143.8 | 10 | – | 101.5 |
| 8 | – | 136.9 | – | 136.9 | – | 153.6 | – | 130.8 | – | 139.0 | 1' | – | 127.4 |
| 8a | – | 112.0 | – | 112.2 | – | 107.0 | – | 110.2 | – | 110.5 | 2' | 6.89 brs | 115.2 |
| 8b | – | 103.4 | – | 103.7 | – | 102.0 | – | 102.4 | – | 102.3 | 3' | – | 145.6 |
| 9 | – | 181.8 | – | 181.8 | – | 184.5 | – | 181.9 | – | 181.7 | 4' | – | 146.3 |
| 1' | 3.41 d (10.0) |
21.3 | 3.33 d (10.0) |
21.2 | 3.44 d (10.0) |
21.4 | 3.22 d (10.0) |
21.4 | 3.21 d (10.0) |
21.4 | 5' | 6.74 brs | 115.8 |
| 2' | 5.24 t (10.0) |
123.0 | 5.22 t (10.0) |
123.0 | 5.21 t (10.0) | 120.8 | 5.18 t (10.0) |
123.0 | 5.17 t (10.0) |
122.9 | 6' | 6.74 brs | 119.4 |
| 3' | – | 134.9 | – | 131.9 | – | 133.8 | – | 129.8 | – | 130.9 | 1'' | 4.04 brs | 100.5 |
| 4' | 1.73 s | 17.8 | 1.66 s | 17.6 | 1.73 s | 17.8 | 1.62 | 26.0 | 1.72 s | 25.9 | 2'' | 3.11–3.90 m | 70.6 |
| 5' | 1.80 s | 25.6 | 1.77 s | 25.6 | 1.83 s | 25.2 | 1.73 | 18.1 | 1.61 s | 18.1 | 3'' | 70.9 | |
| 1'' | 4.06 d (10.0) |
26.4 | 4.07 d (10.0) |
26.4 | 3.52 d (10.0) |
21.8 | 3.31 d (10.0) |
22.4 | 3.29 d (10.0) |
22.7 | 4'' | 72.1 | |
| 2'' | 5.24 t (10.0) |
121.4 | 5.25 t (10.0) |
122.1 | 5.25 t (10.0) |
121.6 | 1.61 m | 44.2 | 1.56 | 45.3 | 5'' | 69.5 | |
| 3'' | – | 131.9 | – | 131.5 | – | 136.1 | – | 69.8 | – | 69.8 | 6'' | 1.05 d (5.0) | 18.2 |
| 4'' | 1.66 s | 18.0 | 1.67 s | 18.0 | 1.76 s | 17.8 | 1.21 s | 29.5 | 1.21 s | 29.4 | 4-OH | 11.79 s | – |
| 5'' | 1.80 s | 25.7 | 1.81 s | 25.6 | 1.83 s | 25.7 | 1.21 s | 29.5 | 1.21 s | 29.4 | 7-OH | 11.00 s | – |
| 3-OCH3 | – | – | 3.88 s | 55.7 | – | – | – | – | 4'-OH | 9.17 s | – | ||
| 7-OCH3 | 3.77 s | 61.8 | 3.79 2 | 61.9 | – | – | – | – | 3.73 | 61.0 | 3'-OH | 9.11 s | – |
| 1-OH | 13.72 s | 13.40 s | – | 12.31 s | – | 14.03 s | – | 13.84 | |||||
| 8-OH | – | – | – | – | 11.23 s | – | – | – | – | – | |||
aMeasured in CDCl3; bMeasured in DMSO-d6
In the cytotoxicity assay conducted on SKOV-3, HepG-2, and HCT-116 cancer cell lines, the isolated compounds exhibited varying degrees of cytotoxic activity. In SKOV-3 human ovarian cancer cells, garcinone D demonstrated the most potent cytotoxic efficacy, with an IC50 of 27.27 ± 2.41 µM. Both α-mangostin and gartanin displayed moderate cytotoxicity, with IC50 values of 43.6 ± 4.5 µM and 40.7 ± 6.4 µM, respectively. Garcinone C exhibited a promising effect, with an IC50 of 37.9 ± 2.5 µM, whereas β-mangostin and astilbin had weak effects compared with the other compounds. In HepG-2 human hepatocellular carcinoma cells, α-mangostin and β-mangostin showed significant cytotoxic activity, with IC50 values of 28.1 ± 1.1 µM and 31.9 ± 10.7 µM, respectively. The cytotoxic effects of gartanin, garcinone C, and garcinone D were also noteworthy, with IC50 values of 55.5 ± 23.5 µM, 49.3 ± 7.8 µM, and 43.2 ± 8.49 µM, respectively. In HCT-116 human colon cancer cells, β-mangostin and garcinone D demonstrated cytotoxic effects with IC50 values of 56.1 ± 2.5 µM and 44.3 ± 2.5 µM, respectively. Garcinone C showed low cytotoxicity with an IC50 of 65.2 ± 6.4 µM, while the astilbin had a minimal effect, with an IC50 greater than 100 µM [Table 2].
Table 2.
Cytotoxic activity of isolated compounds (1–6)
| Compounds | IC50 (μM) |
||
|---|---|---|---|
| SKOV-3 | HepG2 | HCT-116 | |
| α-Mangostin (1) | 43.6±4.5 μM | 28.1±1.1 μM | 39.8±10.6 μM |
| β-Mangostin (2) | ≥100 μM | 31.9±10.7 μM | 56.1±2.5 μM |
| Gartanin (3) | 40.7±6.4 μM | 55.5±23.5 μM | ≥100 μM |
| Garcinone C (4) | 37.9±2.5 μM | 49.3±7.8 μM | 65.2±6.4 μM |
| Garcinone D (5) | 27.27±2.41 μM | 43.2±8.49 μM | 44.3±2.5 μM |
| (+)-2R,3R-Taxifolin-3-O-α-L-rhamnoside (Astilbin) (6) | ≥100 μM | ≥100 μM | ≥100 μM |
CONCLUSION
In this study, six known compounds were successfully isolated and characterized from the ethyl acetate fraction of the methanolic extract of Garcinia mangostana pericarp, including five xanthones and one flavonoid. These compounds demonstrated varying levels of cytotoxic activity against SKOV-3 (ovarian), HepG-2 (hepatic), and HCT-116 (colorectal) cancer cell lines. Among the isolated metabolites, garcinone D exhibited the most potent cytotoxic effect against SKOV-3 cells, while α-mangostin and β-mangostin also exhibited significant activity against HepG-2 cells. These findings highlight the promising cytotoxic potential of xanthones derived from G. mangostana, particularly garcinone D and α-mangostin, as lead compounds for further development of anticancer agents.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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