Cytoprotective and Anti-genotoxic Effects of Xanthone Derivatives from Garcinia mangostana Against H2O2 Induced PBMC Cell and Blood Leukocytes Damage of Normal and Type 2 Diabetes Volunteers

Naymul KARIM, Lanchakon CHANUDOM, Jitbanjong TANGPONG


Hyperglycemia is well-known for inducing cellular oxidative damage in type II diabetes (T2D) patients. This research addressed the cytoprotective and anti-genotoxic effect of xanthone derivatives from Garcinia mangostana against hydrogen peroxide (H2O2)-induced human peripheral blood mononuclear cell (PBMC) and blood leukocytes damage of the normal and T2D volunteers. The cytoprotective effects of an aqueous extract of xanthone (100 and 200 µg/mL) was assessed on cell viability and free radical scavenging activity using the trypan blue exclusion method on PBMC cells. Malondialdehyde (MDA) levels and lactate dehydrogenase (LDH) activity were measured as cellular oxidative damage markers and estimated from culture medium of PBMCs of normal and T2D volunteers. The anti-genotoxicity was assessed as the protective effect of xanthone against H2O2-induce DNA damage of blood leukocytes of the normal volunteers following comet assay technique. Xanthone and Gallic acid (control) concentrations 100, 200 and 100 µg/mL significantly (P < 0.05) protected from H2O2 (20 mM)-induced oxidative damage of PBMCs. It was confirmed by increased cell viability and free radical scavenging activity coupled with the decreased MDA and LDH levels in cell culture medium compared to H2O2 (20 mM)-treated group. In H2O2 (40 mM)-induced blood leukocytes of normal volunteers, different concentration xanthone (50 - 500 µg/mL) significantly (P < 0.05) improved the anti-genotoxicity effect compared to negative/positive control group by lowering comet formation. Xanthone treatments on PBMCs and blood leukocytes of the normal and T2D volunteers could attenuate the H2O2-induced cellular oxidative damage and cell death via exhibiting antioxidant and free radical scavenging activities.


Xanthone, Garcinia mangostana, cytoprotective activity, anti-genotoxicity, type II diabetes

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CD Mathers and D Loncar. Projections of global mortality and burden of disease from 2002 to 2030. Plos Med. 2006; 3, e442.

American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. Diabet Care 2010; 33, 62-9.

J Bhutani AND S Bhutani. Worldwide burden of diabetes. Indian J. Endocrinol. Metab. 2014; 18, 868-70.

S Wild, G Roglic, A Green, R Sicree and H King. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabet Care 2004; 27, 1047-53.

U Asmat, K Abad and K Ismail. Diabetes mellitus and oxidative stress: A concise review. Saudi. Pharm. J. 2016; 24, 547-53.

AC Maritim, RA Sanders, JB Watkins. Diabetes, oxidative stress, and antioxidants: A review. J. Biochem. Mol. Toxicol. 2003; 17, 24-38.

OR Ayepola, NL Brooks and OO Oguntibeju. Oxidative Stress and Diabetic Complications: The Role of Antioxidant Vitamins and Flavonoids. In: O Oguntibeju (Ed.). Antioxidant-Antidiabetic Agents and Human Health. Rijeka, InTech, 2014.

F Ke, PK Yadav and LZ Ju. Herbal medicine in the treatment of ulcerative colitis. Saudi. J. Gastroenterol. 2012; 18, 3-10.

N Karim, N Jeenduang and J Tangpong. Anti-Glycemic and anti-hepatotoxic effects of mangosteen vinegar rind from Garcinia mangostana against HFD/STZ-Induced type II diabetes in mice. Polish J. Food Nutr. Sci. 2018; 68, 163-9.

N Karim, N Jeenduang and J Tangpong. Renoprotective effects of xanthone derivatives from Garcinia mangostana against high fat diet and streptozotocin-induced type II diabetes in mice. Walailak J. Sci. Tech. 2018; 15, 107-16.

YW Chin and AD Kinghorn. Structural characterization, biological effects, and synthetic studies on xanthones from mangosteen (Garcinia mangostana), a popular botanical dietary supplement. Mini Rev. Org. Chem. 2008; 5, 355-64.

K Nuttavut, H Youn-Hee and M Primchanien. Antioxidant and cytoprotective activities of methanolic extract from Garcinia mangostana Hulls. Sci. Asia 2007; 33, 283-92.

G Momekov, PT Nedialkov, GM Kitanov, DZ Zheleva-Dimitrova, T Tzanova, U Girreser and M Karaivanova. Cytoprotective effects of 5 benzophenones and a xanthone from Hypericum annulatum in models of epirubicin-induced cytotoxicity: SAR-analysis and mechanistic investigations. Med. Chem. 2006; 2, 377-84.

O Kaisoon, S Siriamornpun, N Weerapreeyakul and N Meeso. Phenolic compounds and antioxidant activities of edible flowers from Thailand. J. Funct. Foods 2011; 3, 88-99.

R Re, N Pellegrini, A Proteggente, A Pannala, M Yang and C Rice-Evans. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999; 26, 1231-7.

L He, CK Wong, KK Cheung, HC Yau, A Fu, HL Zhao, KM Leung, AP Kong, GW Wong, PK Chan, G Xu and JC Chan. Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes. J. Diabetes Investig. 2013; 4, 382-92.

UR Kuppusamy, YL Chong, AA Mahmood, M Indran, N Abdullah and S Vikineswary. Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicity in peripheral blood mononuclear cells. Indian J. Biochem. Biophys. 2009; 46, 161-5.

R Ceci, MR Beltran Valls, G Duranti, I Dimauro, F Quaranta, M Pittaluga, S Sabatini, P Caserotti, P Parisi, A Parisi and D Caporossi. Oxidative stress responses to a graded maximal exercise test in older adults following explosive-type resistance training. Redox Biol. 2014; 2, 65-72.

G Holmgren, J Synnergren, Y Bogestal, C Ameen, K Akesson, S Holmgren, A Lindahl and P Sartipy. Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology 2015; 328, 102-11.

MN Rana and J Tangpong. In vitro free radical scavenging and anti-genotoxic activities of Thunbergia laurifolia aqueous leaf extract. J. Health Res. 2017; 31, 127-33.

RH Liu. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am. J. Clin. Nutr. 2003; 78, 517-20.

S Tjahjani, W Widowati, K Khiong, A Suhendra and R Tjokropranoto. Antioxidant properties of Garcinia mangostana L (Mangosteen) rind. Proc. Chem. 2014; 13, 198-203.

MP Phyu and J Tangpong. Neuroprotective effects of xanthone derivative of Garcinia mangostana against lead-induced acetylcholinesterase dysfunction and cognitive impairment. Food Chem. Toxicol. 2014; 70, 151-6.

L Chanudom and J Tangpong. Scavenging activities and protective effects of Syzygium cumini (L.) Skeels on H2O2 induce oxidative stress in normal human peripheral blood mononuclear cells. J. Health Res. 2015; 29, 315-22.

J Sattayasai, P Chaonapan, T Arkaravichie, R Soi-Ampornkul, S Junnu, P Charoensilp, J Samer, J Jantaravinid, P Masaratana, B Suktitipat, J Manissorn, V Thongboonkerd, N Neungton and P Moongkarndi. Protective effects of mangosteen extract on H2O2-induced cytotoxicity in SK-N-SH cells and scopolamine-induced memory impairment in mice. PLoS One 2013; 8, e85053.

SS Beevi, LN Mangamoori and LV Reddy. Protective effect of Raphanus sativus on H2O2 induced oxidative damage in human lymphocytes. World J. Microbiol. Biotechnol. 2010; 26, 1519-25.

S Petrovic, A Leskovac and G Joksic. Radioprotective properties of Gentiana dinarica polyphenols on human lymphocytes in vitro. Curr. Sci. 2008; 95, 1035-41.

GC Jagetia and VA Venkatesha. Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytes. Environ. Mol. Mutagen. 2005; 46, 12-21.

S Pal, PB Pal, J Das and PC Sil. Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro. Toxicology 2011; 283, 129-39.

NP Singh, CE Ogburn, NS Wolf, G van Belle and GM Martin. DNA double-strand breaks in mouse kidney cells with age. Biogerontology 2001; 2, 261-70.

R Carvalho-Silva, ACF Pereira, RPS Alves, TN Guecheva, JAP Henriques, M Brendel, C Pungartnik and F Rios-Santos. DNA protection against oxidative damage using the hydroalcoholic extract of Garcinia mangostana and alpha-mangostin. Evid Based Compl. Alternat. Med. 2016; 2016, 8.

C Martin-Cordero, AJ Leon-Gonzalez, JM Calderon-Montano, E Burgos-Moron, M Lopez-Lazaro. Pro-oxidant natural products as anticancer agents. Curr. Drug Targets 2012; 13, 1006-28.

MG Erdem, N Cinkilic, O Vatan, D Yilmaz, D Bagdas and R Bilaloglu. Genotoxic and anti-genotoxic effects of vanillic acid against mitomycin C-induced genomic damage in human lymphocytes in vitro. Asian Pac. J. Cancer Prev. 2012; 13, 4993-8.


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