Protective Effect of α-Mangostin on High Glucose Induced Endothelial Cell Apoptosis


  • Kanjana JITTIPORN Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000
  • Primchanien MOONGKARNDI Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400
  • Jutima SAMER Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400
  • Wisuda SUVITAYAVAT Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400



α-mangostin, high glucose, oxidative stress, apoptosis


α-mangostin is a phenolic compound from pericarp of mangosteen. It has prominent anti-oxidant properties. Oxidative stress has been shown to be a major factor that disrupts cell functions including endothelium. High glucose (HG) induced ROS production plays a key role in endothelial cell apoptosis. However, the effect of α-mangostin on HG induced apoptosis has not been studied yet. This study demonstrates the effect of α-mangostin in HG induced human umbilical vein endothelial cells (HUVECs) apoptosis. The non-toxic dose of α-mangostin was determined using a MTT assay. Intracellular reactive oxygen species (ROS) and cell apoptosis were evaluated using DCF-DA and TUNEL assays, respectively. The signaling of α-mangostin was elucidated by western blotting. α-mangostin significantly and, dose-dependently, decreased HG induced ROS formation. Also, α-mangostin significantly attenuated HG induced endothelial cell apoptosis. In addition, α-mangostin suppressed HG induced apoptosis via JNK and p38-MAPK. According to our results, α-mangostin attenuated HG induced endothelial cell apoptosis through inhibition of phosphorylation of JNK and p38-MAPK.


Download data is not yet available.


Metrics Loading ...


MM Kockx and MW Knaapen. The role of apoptosis in vascular disease. J. Pathol. 2000; 190, 267-80.

CK Ho, YL Huang and CC Chen. Garcinone E, a xanthone derivative, has potent cytotoxic effect against hepatocellular carcinoma cell lines. Planta Med. 2002; 68, 975-9.

HA Jung, BN Su, WJ Keller, RG Mehta and AD Kinghorn. Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J. Agric. Food Chem. 2006; 54, 2077-82.

K Matsumoto, Y Akao, E Kobayashi, K Ohguchi, T Ito, T Tanaka, M Iinuma and Y Nozawa. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J. Nat. Prod. 2003; 66, 1124-7.

K Matsumoto, Y Akao, K Ohguchi, T Ito, T Tanaka, M Iinuma and Y Nozawa. Xanthones induce cell-cycle arrest and apoptosis in human colon cancer DLD-1 cells. Bioorg. Med. Chem. 2005; 13, 6064-9.

P Moongkarndi, N Kosem, S Kaslungka, O Luanratana, N Pongpan and N Neungton. Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J. Ethnopharmacol. 2004; 90, 161-6.

P Moongkarndi, N Kosem, O Luanratana, S Jongsomboonkusol and N Pongpan. Antiproliferative activity of Thai medicinal plant extracts on human breast adenocarcinoma cell line. Fitoterapia 2004; 75, 375-7.

S Suksamrarn, O Komutiban, P Ratananukul, N Chimnoi, N Lartpornmatulee and A Suksamrarn. Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. Chem. Pharm. Bull. 2006; 54, 301-5.

YW Chin, HA Jung, H Chai, WJ Keller and AD Kinghorn. Xanthones with quinone reductase-inducing activity from the fruits of Garcinia mangostana (Mangosteen). Phytochemistry 2008; 69, 754-8.

L Yu, M Zhao, B Yang, Q Zhao and Y Jiang. Phenolics from hull of Garcinia mangostana fruit and their antioxidant activities. Food Chem. 2007; 104, 176-81.

M Buelna-Chontal, F Correa, S Hernandez-Resendiz, C Zazueta and J Pedraza-Chaverri. Protective effect of alpha-mangostin on cardiac reperfusion damage by attenuation of oxidative stress. J. Med. Food 2011; 14, 1370-4.

PD Sampath and K Vijayaraghavan. Cardioprotective effect of alpha-mangostin, a xanthone derivative from mangosteen on tissue defense system against isoproterenol-induced myocardial infarction in rats. J. Biochem. Mol. Toxicol. 2007; 21, 336-9.

K Jittiporn, J Suwanpradid, C Patel, M Rojas, S Thirawarapan, P Moongkarndi, W Suvitayavat and RB Caldwell. Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative α-mangostin. Microvas. Res. 2014; 93, 72-9.

Y Fang, T Su, X Qiu, P Mao, Y Xu, Z Hu, Y Zhang, X Zheng, P Xie and Q Liu. Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death. Sci. Rep. 2016; 6, 21018.

T Wada and JM Penninger. Mitogen-activated protein kinases in apoptosis regulation. Oncogene 2004; 23, 2838-49.

P Moongkarndi, N Jaisupa, J Samer, N Kosem, J Konlata, E Rodpai and N Pongpan. Comparison of the biological activity of two different isolates from mangosteen. J. Pharm. Pharmacol. 2014; 66, 1171-9.

T Yu, BS Jhun and Y Yoon. High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid. Redox Signal. 2011; 14, 425-37.

F Chen, LH Qian, B Deng, ZM Liu, Y Zhao and YY Le. Resveratrol protects vascular endothelial cells from high glucose-induced apoptosis through inhibition of NADPH oxidase activation-driven oxidative stress. CNS Neurosci. Ther. 2013; 19, 675-81.

JM Perez-Rojas, C Cruz, P Garcia-Lopez, DJ Sanchez-Gonzalez, CM Martinez-Martinez, G Ceballos, M Espinosa, J Melendez-Zajgla and J Pedraza-Chaverri. Renoprotection by alpha-Mangostin is related to the attenuation in renal oxidative/nitrosative stress induced by cisplatin nephrotoxicity. Free Radic. Res. 2009; 43, 1122-32.

B Marquez-Valadez, R Lugo-Huitron, V Valdivia-Cerda, LR Miranda-Ramirez, V Perez-De La Cruz, O Gonzalez-Cuahutencos, I Rivero-Cruz, R Mata, A Santamaria and J Pedraza-Chaverri. The natural xanthone alpha-mangostin reduces oxidative damage in rat brain tissue. Nutr. Neurosci. 2009; 12, 35-42.

HH Kwak, IR Kim, HJ Kim, BS Park and SB Yu. Alpha-mangostin induces apoptosis and cell cycle Arrest in oral squamous cell carcinoma cell. Evid. Based Complement. Alternat. Med. 2016; 2016, 5352412.

HN Lee, HY Jang, HJ Kim, SA Shin, GS Choo, YS Park, SK Kim and JY Jung. Antitumor and apoptosis-inducing effects of alpha-mangostin extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.) in YD-15 tongue mucoepidermoid carcinoma cells. Int. J. Mol. Med. 2016; 37, 939-48.

S Kritsanawong, S Innajak, M Imoto and R Watanapokasin. Antiproliferative and apoptosis induction of alpha-mangostin in T47D breast cancer cells. Int. J. Oncol. 2016; 48, 2155-65.

P Li, W Tian and X Ma. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol. Cancer 2014; 13, 138.

R Watanapokasin, F Jarinthanan, Y Nakamura, N Sawasjirakij, A Jaratrungtawee and S Suksamrarn. Effects of alpha-mangostin on apoptosis induction of human colon cancer. World J. Gastroenterol. 2011; 17, 2086-95.

Y Nakagawa, M Iinuma, T Naoe, Y Nozawa and Y Akao. Characterized mechanism of alpha-mangostin-induced cell death: Caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg. Med. Chem. 2007; 15, 5620-8.

K Matsumoto, Y Akao, H Yi, K Ohguchi, T Ito, T Tanaka, E Kobayashi, M Iinuma and Y Nozawa. Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg. Med. Chem. 2004; 12, 5799-806.

SY Tsai, PC Chung, EE Owaga, IJ Tsai, PY Wang, JI Tsai, TS Yeh and RH Hsieh. Alpha-mangostin from mangosteen (Garcinia mangostana Linn.) pericarp extract reduces high fat-diet induced hepatic steatosis in rats by regulating mitochondria function and apoptosis. Nutr. Metab. 2016; 13, 88.

FM Ho, SH Liu, CS Liau, PJ Huang and SY Lin-Shiau. High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH2-terminal kinase and Caspase-3. Circulation 2000; 101, 2618-24.

H Nakagami, R Morishita, K Yamamoto, SI Yoshimura, Y Taniyama, M Aoki, H Matsubara, S Kim, Y Kaneda and T Ogihara. Phosphorylation of p38 mitogen-activated protein kinase downstream of bax-caspase-3 pathway leads to cell death induced by high D-glucose in human endothelial cells. Diabetes 2001; 50, 1472-81.

Z Yang, X Mo, Q Gong, Q Pan, X Yang, W Cai, C Li, JX Ma, Y He and G Gao. Critical effect of VEGF in the process of endothelial cell apoptosis induced by high glucose. Apoptosis 2008; 13, 1331-43.

L Meng and L Cui. Inhibitory effects of crocetin on high glucose-induced apoptosis in cultured human umbilical vein endothelial cells and its mechanism. Arch. Pharm. Res. 2008; 31, 357-63.




How to Cite

JITTIPORN, K., MOONGKARNDI, P., SAMER, J., & SUVITAYAVAT, W. (2017). Protective Effect of α-Mangostin on High Glucose Induced Endothelial Cell Apoptosis. Walailak Journal of Science and Technology (WJST), 15(8), 579–587.