Antioxidant Activity and Neuroprotective Effect of Garcinia mangostana Pericarp Extracts on N1E–115 Cells
Article Sidebar
Main Article Content
Abstract
Abstract
Introduction and Objective: Oxidative stress plays a vital role in the pathophysiology of neurodegenerative diseases. Mangosteen (Garcinia mangostana L.) pericarp is rich in phenolic compounds, particularly xanthones, which possess potent antioxidant activities and may alleviate or delay neuronal degeneration. This study aimed to investigate the antioxidant and neuroprotective activities of G mangostana pericarp extracts against hydrogen peroxide (H2O2)–and glutamate–induced neurotoxicity in N1E–115 cells.
Methods: G. mangostana pericarp water extract (GM–W) and ethanol extract (GM–E), were evaluated for their antioxidant activity using a superoxide scavenging assay. Neuroprotective effects against H2O2 –and glutamate–induced injury were assessed using the 3–[4,5–dimethylthiazol–2–yl]–2,5–diphenyltetrazolium bromide (MTT) reduction assay. Furthermore, the underlying neuroprotective mechanisms were investigated by using specific inhibitors of the mitogen–activated protein kinase (MAPK) and phosphatidylinositol 3–kinase (PI3K) signaling pathways.
Results: GM–W and GM–E showed strong antioxidant activities with IC50 29.11 + 3.88 and 14.49 + 1.66 µg/mL, respectively. Co–exposure or pre–exposure to GM–E significantly reduced H2O2 –induced cell death, whereas GM–W showed no protective effect. For glutamate toxicity, only co–exposure with GM–E demonstrated neuroprotection. Additionally, the presence of MAPK and PI3K inhibitors significantly antagonized the neuroprotective effects of GM–E against both H2O2 –and glutamate–induced neurotoxicity.
Discussion: GM–E protected neuronal cells from H2O2 –and glutamate–induced toxicity. This neuroprotection is likely mediated through both direct antioxidant properties and the modulation of MAPK and PI3K signaling pathways. Study results indicate that natural antioxidants effectively reduce free radical–induced cellular damage, making them a promising alternative for preventing and delaying neurodegeneration.
Conclusion and Recommendation: These findings support the potential of mangosteen pericarp extract in protecting against H2O2 –and glutamate–induced neurotoxicity, suggesting their therapeutic role in preventing or delaying the progression of neurodegenerative diseases. Further studies in in vitro degenerative models with specific pathology and animal models on bioactive compound from mangosteen pericarp extracts and xanthone derivatives are required to clarify its activity and molecular mechanisms, as well as herbal product development into herbal medicinal products or herbal health products using nanotechnology.
Keywords : Garcinia mangostana L., antioxidant activity, neuroprotective activity, hydrogen peroxide, glutamate
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017; 2017:8416763. https://doi.org/10.1155/2017/8416763.
Rudrapal M, Khairnar SJ, Khan J, Dukhyil AB, Ansari MA, Alomary MN, Alshabrmi FM, Palai S, Deb PK, Devi R. Dietary polyphenols and their role in oxidative stress–induced human diseases: Insights into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 2022;13:806470. https://doi:10.3389/fphar.2022.806470.
Feng J, Zheng Y, Guo M, Ares I, Martínez M, Lopez–Torres B, Martínez–Larrañaga MR, Wang X, Anadón A, Martínez MA. Oxidative stress, the blood–brain barrier and neurodegenerative diseases: The critical beneficial role of dietary antioxidants. Acta Pharm Sin B. 2023;13(10):3988-4024.
Forest Botany Division, Forest and Plant Conservation Research Office, Department of National Parks, Wildlife and Plant. Thai Plant Names. [Internet]. 2557 [cited 2024 May 30]. Available from: https://www.dnp.go.th/Botany/mplant/index.html.
Plants of the World Online, Facilitated by the Royal Botanic Gardens, Kew. [Internet]. [cited 2024 May 30]. Available from: https://www.plantsoftheworldonline.org/.
National List of Essential Medicines (No. 2) B.E. 2555 (2012). Published in Government Gazette on 21 August B.E. 2555 (2012). (in Thai).
Alam M, Summya Rashid S, Fatima K, Adnan M, Shafie A, Akhtar MS, Ganie AH, Sayed M. Eldin SM, Islam A, Khan I, Hassan MI. Biochemical features and therapeutic potential of –Mangostin: Mechanism of action, medicinal values, and health benefits. Biomed Pharmacother. 2023;163:114710. https://doi.org/10.1016/j.biopha.2023.114710.
Ghasemzadeh A, Jaafar HZE, Baghdadi A, Tayebi–Meigooni A. Alpha–mangostin–rich extracts from mangosteen pericarp: Optimization of green extraction protocol and evaluation of biological activity. Molecules. 2018;23(8):1852. https://doi:10.3390/molecules23081852.
Zonouz AM, Rahbardar MG, Hosseinzadeh H. Antidotal and protective effects of mangosteen (Garcinia mangostana) against natural and chemical toxicities: A review. Iran J Basic Med Sci. 2023;26:492-503. https://dx.doi.org/10.22038/IJBMS.2023.66900.14674
Ansori ANM, Fadholly A, Hayaza S, Susilo RJK, Inayatillah B,Winarni D, Husen SA. A review on medicinal properties of mangosteen (Garcinia mangostana L.). Res J Pharm Technol. 2020;13(2):974-82.
Weecharangsan W, Opanasopit P, Sukma M, Ngawhirunpat T, Sotanaphun U, Siripong P. Antioxidative and neuroprotective activities of extracts from the fruit hull of mangosteen (Garcinia mangostana Linn.). Med Princ Pract. 2006;15;281-7.
Moongkarndi P, Srisawat C, Saetun P, Jantaravinid J, Peerapittayamongkol C, Soi–ampornkul R, Junnu S, Sinchaikul S, Chen ST, Charoensilp P, Thongboonkerd V, Neungton N. Protective effect of mangosteen extract against beta–amyloid–induced cytotoxicity, oxidative stress and altered proteome in SK–N–SH cells. J Proteome Res. 2010;9:2076-86. (in Thai)
Lee Y, Kim S, Kim Y, Chin Y, Cho J. Inhibition of excitotoxic and Aβ(25-35)–induced neuronal damage by fractions prepared from mangosteen pericarp in primary cultured rat cortical cells. Proceedings of the 2012 Fall International Convention of The Pharmaceutical Society of Korea, Seoul, Korea; 2012 Oct 23-24; Seoul, Korea.
Cho J, Chin Y–W. Neuroprotective and memory–enhancing effects of the water extract from pericarp of mangosteen. Fruit Clin Ther. 2016;38(10S):e31. https://doi.org/10.1016/j.clinthera.2016.07.163.
Sattayasai J, Chaonapan P, Arkaravichie T, Soi–ampornkul R, Junnu S, Charoensilp P, Samer J, Jantaravinid J, Masaratana P, Suktitipat B, Manissorn J, Thongboonkerd V, Neungton N, Moongkarndi P. 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(12):e85053. https://doi.org/10.1371/journal.pone.0085053. (in Thai)
Avinash P, Reddy A, Begum N, Bakshi V. Neuroprotective effect of Garcinia mangostana on streptozotocin induced sporadic type Alzheimer’s disease in mice. Int J Appl Pharm Sci Res. 2016;1:8-15.
Murugaiyah V, Jayadhisan M, Majid ASA, Majid AMSA. Neuroprotective effect of Garcinia mangostana extract, xanthone–enriched fraction and –mangostin on amyloid ß, hydrogen peroxide, ischemia, hypoxia and glutamate–induced neurotoxicity in SH–SY5Y cells. Front cell Neurosci. 2016;10. https://doi:10.3389/conf.fncel.2016.36.00100.
eFloras (2008). Missouri Botanical Garden, St. Louis, MO & Harvard University Herbaria, Cambridge, MA. [Internet]. [cited 2024 May 30]. Available from: http://www.efloras.org
Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun. 1972;46(2):849-54.
Amano T, Richelson E, Nirenberg M. Neurotransmitter synthesis by neuroblastoma clones. Proc Natl Acad Sci USA. 1972;69:258-63.
Kimhi Y, Parfrey C, Spector I, Barak Y, Littauer UZ. Maturation of neuroblastoma cells in the presence of dimethylsulfoxide. Biochemistry. 1976;73:462-6.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
Rizaldy D, Ramadhita NK, Nadhifa T, Fidrianny I. Mangosteen (Garcinia mangostana L.): Evaluation of in vitro antioxidant activities. Pharmacogn J. 2022;14(3):633-40.
Suttirak W, Manurakchinakorn S. In vitro antioxidant properties of mangosteen peel extract. J Food Sci Technol. 2014;51(12):3546-58.
Lewerenz J, Maher P. (2015). Chronic glutamate toxicity in neurodegenerative diseases–What is the evidence? Front Neurosci. 2015;9:469. https://doi:10.3389/fnins.2015.00469.
Walker CL, Liu NK, Xu XM. PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries. Front Biol (Beijing). 2013;8(4). https://doi:10.1007/s11515–013–1255–1.
Rai SN, Dilnashin H, Birla H, Singh SS, Zahra W, Rathore AS, Singh BK, Singh SP. The role of PI3K/Akt and ERK in neurodegenerative disorders. Neurotox Res. 2019;35:775-95.
Long HZ, Cheng Y, Zhou ZW, Luo HY, Dan–Dan Wen DD, Li–Chen Gao LC. PI3K/AKT signal pathway: A target of natural products in the prevention and treatment of Alzheimer’s disease and Parkinson’s disease. Front Pharmacol. 2021;12:648636. https://doi.org/10.3389/fphar.2021.648636.
Li Q, Rubin L, Silva M, Li S, Yang C, Lazarovici P, Zheng W. Current progress on neuroprotection Induced by Artemisia, Ginseng, Astragalus, and Ginkgo traditional chinese medicines for the therapy of alzheimer’s disease. Oxid Med Cell Longev. 2022;2022:3777021. 21 pages https://doi.org/10.1155/2022/3777021.
Kondo M, Zhang L, Ji H, Kou Y, Ou B. Bioavailability and antioxidant effects of a xanthone-rich mangosteen (Garcinia mangostana) product in humans. J. Agric Food Chem. 2009;57(19):8788-92. https://doi:10.1021/jf901012
