<i>In-silico</i> and <i>In-vivo</i> Long-term Safety Studies of Mangosteen Rind Ethanol Extract (Garcinia mangostana Linn.)



  • Rifa’atul Mahmudah Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, West Java, Indonesia
  • Elin Y. Sukandar Pharmacy, Faculty of Science and Technology, Mandala Waluya University, Kendari, Southeast Sulawesi, Indonesia
  • I. K. Adnyana Pharmacy, Faculty of Science and Technology, Mandala Waluya University, Kendari, Southeast Sulawesi, Indonesia


safety, in vivo, in silico, Ethanol extract of mangosteen rind


Mangosteen rind has been used extensively to treat a variety of diseases. However, research on the use of mangosteen, especially over the long-term, remains limited. The aim of this study was to evaluate the toxicity of ethanol extract of mangosteen rind (EEMR) to ensure its safety. The in silico method used the Protox-II web server to test the safety of marker compounds found in EEMR (xanthones, alpha-mangostin and gamma-mangostin). The in vivo method involved the oral feeding of EEMR to rats at doses of 100, 200 and 400 mg/kg bw. The researchers observed signs of toxicity and mortality over a period of six months. The study showed a high degree of organ safety, with a safety class of 4 for xanthone and alpha-mangostin and 5 for gamma-mangostin. In addition, consumption of any dose of EEMR to rats showed no toxic effect on body weight, haematology or relative organ weight, nor was it the cause of mortality in the animal model. However, its use at 200 and 400 mg/kg bw influenced triglyceride, GOT and creatinine levels and caused liver cell abnormalities in rats. EEMR 400 mg/kg bw also showed adverse effects on the kidneys. Based on these findings, it can be concluded that the gamma-mangostin compound in mangosteen rind is safer than xanthones and alpha-mangostin, while EMMR at a dose of 100 mg/kg bw is relatively safe for long-term use. However, doses of 200 mg/kg bw and 400 mg/kg bw require further evaluation.


The Food and Drug Supervisory Agency. Regulation of The Head of the Food and Drug Supervisory Agency of the Republic of Indonesia Number 7 of 2014 Concerning Guidelines for In Vivo Non-Clinical Toxicity Testing. Jakarta: The Food and Drug Supervisory Agency. 2014. p. 46-52.

Raies AB, Bajic VB. In Silico Toxicology: Computational Methods for The Prediction of Chemical Toxicity. Wiley Interdiscip Rev. Comput. Mol. Sci. 2016; 6(2): 147-172.

Zhao YL, Su M, Shang JH. Acute and Chronic Toxicity of Indole Alkaloids From Leaves of Alstonia scholaris (L.) R. Br. In Mice and Rats. Nat. Prod. Bioprospect.. 2020; 10(2): 77-88.

Manimekalai I, Sivakumari K, Ashok K, Rajesh S. Phytochemical Profiling of Mangosteen Fruit, Garcinia mangostana. World J. Pharm. Pharm. Sci., 2016; 5(2): 221-52.

Ovalle-Magallanes B, Eugenio-Pérez D, Pedraza-Chaverri J. Medicinal Properties of Mangosteen (Garcinia mangostana L.): a Comprehensive Update. Food Chem. Toxicol. 2017; 109: 102-122.

Tousian SH, Razavi BM, Hosseinzadeh H. Review of Garcinia mangostana and Its Xanthones in Metabolic Syndrome and Related Complications. Phyther. Res. 2017; 31: 1173-1182.

Godavari A, Amutha K. In vitro Antidiabetic Activity of Garcinia mangostana by Enzymatic Inhibition Assay. Research J. Pharm. and Tech. 2017; 10(2): 508-512.

Warditiani NK, Astuti KW, Sari PMNA, Wirasuta IMAG. Antidyslipidemic Activity of Methanol, Ethanol and Ethyl Acetate Mangosteen rind (Garcinia mangostana L). Research J. Pharm. and Tech. 2020; 13(1): 261-264.

Abuzaid AS, Sukandar EY, Kurniati NF, Adnyana IK. Prevention of Obesity and Development of Metabolic Syndrome by Mangosteen (Garcinia Mangostana L.) Pericarp Ethanolic Extract in Male Wistar Rats Fed with High-Fat Diet. Int. J. Pharm. Pharm. Sci. 2016; 8(5): 372-378.

Muchtaridi M, Afiranti FS, Puspasari PW, Subarnas A, Susilawati Y. Cytotoxicity of Garcinia mangostana L. Pericarp Extract, Fraction, and Isolate on Hela Cervical Cancer Cells. Int. J. Pharm. Sci. Res. 2018; 10(2): 348-351.

Ansori ANM, Fadholly A, Hayaza S, Susilo RJK, Inayatillah B, Winarni D, Husen SA. A Review on Medicinal Properties of Mangosteen (Garcinia mangostana L.). Research J. Pharm. and Tech. 2020; 13(2): 974-982.

Ashton MM, Dean OM, Walker AJ, Bortolasci CC, Chee HN, Hopwood M, Harvey BH, Möller M, McGrath JJ, Marx W, Turner A, Dodd S, Scott JG, Khoo J, Walder K, Sarris J, Berk M. The Therapeutic Potential of Mangosteen Pericarp as an Adjunctive Therapy for Bipolar Disorder and Schizophrenia. Front. Psychiatry. 2019; 10(115): 1-17.

Fu T, Wang S, Liu J, Cai E, Li H, Li P, Zhao Y. Protective Effects Of α-Mangostin Against Acetaminophen-Induced Acute Liver Injury in Mice. Eur. J. Pharmacol. 2018; 173-180.

Fan JB, Florenly F, Liena L, Fioni F. Exploration of the Analgesic and Antipyretic Effects of Mangosteen Peel Methanol Extract (Garcinia mangostana L.) in Male Wistar Rats. BirEx-Journal. 2021; 3(4): 261-273.

Sugita P, Arya S, Ilmiawati A, Arifin B. Characterization, Antibacterial and Antioxidant Activity of Mangosteen (Garcinia mangostana L.) Pericarp Nanosized Extract. Rasayan J. Chem. 2017; 10(3): 707-715.

Vien LC, Chinnappan S, R Mogana. Antioxidant activity of Garcinia mangostana L and alpha mangostin: A Review. Research J. Pharm. and Tech. 2021; 14(8): 4466-0.

Anam K, Munandar R, Wulandari ON, Lestari AB, Farada RE, Hudiyanti D, Aminin AL. Chemical Composition, Antioxidant Activities, and Total Phenolic Content of Combination of Mangosteen (Garcinia mangostana L.) Peel-Kodavan (Centella asiatica L. Urban) Fractions. Trop. J. Nat. Prod. Res. 2023; 7(1): 2222-2228.

Zhang S, Li Z, Wang X, An L, Bao J, Zhang J, Cui J, Li Y, Jin DQ, Tuerhong M, Abudukeremu M, Ohizumi Y, Xu J, Guo Y. Isolation, Structural Elucidation, and Immunoregulation Properties Of An Arabinofuranan from The Rinds of Garcinia mangostana. Carbohydr Polym. 2020; 246(2): 116567.

Ansori ANM, Susilo RJK, Hayaza S, Winarni D, Husen SA. Renoprotection by Garcinia mangostana L. Pericarp Extract in Streptozotocin-Induced Diabetic Mice. Iraqi J. Vet. Sci. 2019; 33(1): 13-19.

Lee Y, Kim S, Oh Y, Kim YM, Chin YW, Cho J. Inhibition of Oxidative Neurotoxicity and ScopolamineInduced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence. Oxid. Med. Cell. Longev. 2019; 1-14.

Putri NO, Mujiono KR, Rizqiawan A. Mangosteen Peel Extract Increases Transforming Growth Factor-Beta in the Wound Healing Process. Trop. J. Nat. Prod. Res. 2022; 6(10): 1660-1662.

Widyaningsih I, Santoso S, Hidayati DYN, Djajalaksana S. The Effect of Ethanolic Extract of Mangosteen Peel to Malondialdehyde Level, Colony Number, and Pulmonary Damage Level Score of Tuberculosis Model Rats. Research J. Pharm. and Tech. 2021; 14(12): 6710-4.

Amnuaikit T, Phadungkarn T, Wattanapiromsakul C, Boonme P. Formulation Development of Antibacterial Films Containing Mangosteen Peel Extract. Research J. Pharm. and Tech. 2012; 5(8): 1058-1065.

Swastini DA, Udayana, INK, Arisanti C. Cold cream combination of Garcinia mangostana L., Anredera cordifolia (Ten.) and Centella asiatica Extracts on Burn Healing Activity Test. Research J. Pharm. and Tech. 2021; 14(5): 2483-6.

Saptarini NM, Hadisoebroto G. Formulation and Evaluation of Lotion and Cream of Nanosized Chitosan-Mangosteen (Garcinia mangostana L.) Pericarp Extract. Rasayan J. Chem. 2020; 13(2): 789-795.

Cosyns JP. Aristolochic Acid and Chinese Herbs Nephropathy: A Review of The Evidence to Date. Drug Saf. 2003; 26(1): 33-48.

Nigatu TA, Afework M, Urga K, Ergete W, Makonnen E. Toxicological Investigation of Acute and Chronic Treatment with Gnidia stenophylla gilg Root Extract on Some Blood Parameters and Histopathology of Spleen, Liver and Kidney in Mice. BMC Res. Notes. 2017; 10(1): 1-13.

Abood WN, Bradosty SW, Shaikh FK, Salehen N, Farghadani R, Agha NFS, Al-Medhtiy MH, Kamil TDA, Agha AS, Abdulla MA. Garcinia mangostana Peel Extracts Exhibit Hepatoprotective Activity Against Thioacetamide-Induced Liver Cirrhosis in Rats. J. Funct. Foods. 2020; 74: 104200.

Chayaburakul K, Sukplang P, Pinpart T, Kengkoom K. Acute and Subchronic Oral Toxicity of Xanthones Extracted from The Pericarp of Garcinia mangostana Linn. in Rat. Asian Arch. Pathol. 2015; 11(3): 57-70.

Hutadilok-Towatana N, Reanmongkol W, Chatchai W, Bunkrongcheap R. Acute and Subchronic Toxicity Evaluation of The Hydroethanolic Extract of Mangosteen Pericarp. J. Med. Plant Res. 2010; 4(10): 969-974.

Chivapat S, Chavalittumrong P, Wongsinkongman P, Phisalpong C, Phisalpong A. Chronic Toxicity Study of Garcinia mangostana Linn. Pericarp Extract. Thai J. Vet. Med. 2011; 41(1): 45-53.

Ministry of Health of the Republic of Indonesia. Indonesian Herbal Pharmacopoeia Edition II. Jakarta: Ministry of Health of the Republic of Indonesia. 2017. p. 307-310.

Bryda EC. The Mighty Mouse: the impact of rodents on advances in biomedical research. Mo Med. 2013;110(3): 207-11.

AVMA (American Veterinary Medical Association). AVMA guidelines for the euthanasia of animals. Schaumburg: Illinois. 2020. p. 28.

Raies AB, Bajic VB. In Silico Toxicology: Computational Methods for The Prediction of Chemical Toxicity. Wiley Interdiscip Rev Comput Mol Sci. 2016; 6(2): 147-172.

Makiyah SNN, Usman S, Dwijayanti DR. In Silico Toxicity Prediction of Bioactive Compounds of Dioscorea alata L. Trop. J. Nat. Prod. Res. 2022; 6(10): 1587-1596.

Ta GC, Mokhtar MB, Peterson PJ, Yahaya NB. A Comparison of Mandatory and Voluntary Approaches to The Implementation of Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in The Management of Hazardous Chemicals. Ind. Health. 2011; 49(6): 765-73.

Dubey SK, Batra A. Acute and Sub Acute Toxicity Studies on Ethanolic Fraction of Thuja occidentalis Linn. Research J. Pharm. and Tech. 2008; 1(3): 245-248.

Mahmudah R, Adnyana IK, Sukandar EY. Pharmacological effects of Garcinia mangostana L.: An Update Review. Research J. Pharm. and Tech. 2020; 13(11): 5471-5476.

Yadav T, Rohane S. Acute Toxicity Study of Synthesized Drug and Herbal Product. Asian J. Pharm. Res. Dev. 2021; 11(4): 251-6.

Aizat WM, Jamil IN, Ahmad-Hashim FH, Noor NM. Recent Updates on Metabolite Composition and Medicinal Benefits of Mangosteen Plant. PeerJ. 2019; 7:e6324.

Yulianti R, Simanjuntak P, Purba AV. Development of Antidiabetic Powder Preparations from The Combination of Mangosteen Peel Extract (Garcinia mangostana L.) and Bay Leaf Extract (Syzygium polyanthum (Wight) Walp.). JFFI. 2020; 7(1): 22-26.

Adriani L, Widjastuti T, Nurdianti RR, Wiradimadja R. Effects of Mangosteen Peel Extract (Garcinia mangostana L.) on Blood Lipid of Sentul Chicken Growth Phase. Proceeding of the 3rd ICONIC. 2018; p. 1-5.

Abuzaid AS, Sukandar EY, Kurniati NF, Adnyana IK. Antihyperlidemic Effects of Mangosteen (Garcinia mangostana L.) Pericarp Ethanolic Extract in High-Carbohydrate Wistar Rats. J. Nat. Remedies. 2017; 17(4): 165-173.

John OD, Mouatt P, Panchal SK, Brown L. Rind from Purple Mangosteen (Garcinia mangostana) Attenuates Diet-Induced Physiological and Metabolic Changes in Obese Rats. Nutrients. 2021; 13(2): 319.

Lala V, Goyal A, Minter DA. Liver Function Tests. StatPearls Publishing, 2020; p. 1-12.

Widyastuti E, Maharani N, Utomo AW. Effect of Mangosteen Peel Extract on SGOT and SGPT in Rats Fed Reused Cooking Oil. SainsMed. 2018; 9(2): 45-49.

Hosten AO. BUN and Creatinine. [Online]. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. [cited 2023 Oct 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK201/

Arika WM , Nyamai DW, Musila MN, Ngugi MP, Njagi ENM. Hematological Markers of In Vivo Toxicity. J. Hematol. Thrombo. Dis. 2016; 4(2): 1000236.



How to Cite

Mahmudah, R., Sukandar, E. Y., & Adnyana, I. K. (2024). <i>In-silico</i> and <i>In-vivo</i> Long-term Safety Studies of Mangosteen Rind Ethanol Extract (Garcinia mangostana Linn.): http://www.doi.org/10.26538/tjnpr/v8i1.38. Tropical Journal of Natural Product Research (TJNPR), 8(1), 5980–5986. Retrieved from https://tjnpr.org/index.php/home/article/view/3409