A Synergistic Effect of Free Radical Scavenging Activity of the Combination of Mangifera indica and Euphorbia hirta Extracts
I Made Wisnu Adhi Putra(1*), Nyoman Suarjana(2), Mahfur Mahfur(3), Hasnawati Hasnawati(4)
(1) Department of Biology, Faculty of Health and Science, Universitas Dhyana Pura, Jl. Raya Padang Luwih, Badung 80361, Bali, Indonesia
(2) Department of Public Health, Faculty of Health and Science, Universitas Dhyana Pura, Jl. Raya Padang Luwih, Badung 80361, Bali, Indonesia
(3) Department of Pharmacy, Faculty of Pharmacy, Universitas Pekalongan, Jl. Sriwijaya No. 3, Bendan, Pekalongan 51119, Indonesia
(4) Department of Pharmacy, Faculty of Pharmacy, Universitas Halu Oleo, Jl. H.E.A. Mokodompit, Kendari 93232, Indonesia
(*) Corresponding Author
Abstract
Due to its synergistic effect, the extract-extract combination is essential in traditional medicine formulation. The combination of Mangifera indica and Euphorbia hirta extracts can produce a synergistic effect if combined in a proper ratio. This investigation reported the synergistic antioxidant effect of M. indica and E. hirta. The ethanolic extracts of M. indica leaf (MILE) and E. hirta aerial part (EHAE) were acquired by the maceration method, followed by evaporation to remove the solvent. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) tests were used to assess the extracts' capacity to scavenge radicals. MILE and EHAE were combined with a ratio of 1:3 (comb. 1), 1:1 (comb. 2), and 3:1 (comb. 3). This work disclosed that the extract combinations showed all types of interactions. However, of all combinations, only comb. 3 depicted the synergistic interaction caused by the regeneration effect of EHAE on MILE. This finding has important implications for health, particularly disease prevention. M. indica and E. hirta extracts with high phenolic and flavonoid contents can work together to reduce oxidative stress and protect the body from a variety of diseases.
Keywords
Full Text:
Full Text PDFReferences
[1] Reddy, V.P., 2023, Oxidative stress in health and disease, Biomedicines, 11 (11), 2925.
[2] Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., and Bitto, A., 2017, Oxidative stress: Harms and benefits for human health, Oxid. Med. Cell. Longevity, 2017 (1), 8416763.
[3] Itoh, K., Matsukawa, T., Okamoto, M., Minami, K., Tomohiro, N., Shimizu, K., Kajiyama, S., Endo, Y., Matsuda, H., and Shigeoka, S., 2020, In vitro antioxidant activity of Mangifera indica leaf extracts, J. Plant Stud., 9 (2), 39–45.
[4] Khumpook, T., Saenphet, S., Tragoolpua, Y., and Saenphet, K., 2019, Anti-inflammatory and antioxidant activity of Thai mango (Mangifera indica Linn.) leaf extracts, Comp. Clin. Pathol., 28 (1), 157–164.
[5] Kingne, F.K., Djikeng, F.T., Tsafack, H.D., Karuna, M.S.L., and Womeni, H.M., 2019, Phenolic content and antioxidant activity of young and mature mango (Mangifera indica) and avocado (Persea americana) leave extracts, Int. J. Phytomed., 10 (4), 181–190.
[6] Mistry, J., Biswas, M., Sarkar, S., and Ghosh, S., 2023, Antidiabetic activity of mango peel extract and mangiferin in alloxan-induced diabetic rats, Future J. Pharm. Sci., 9 (1), 22.
[7] Sekar, V., Chakraborty, S., Mani, S., Sali, V.K., and Vasanthi, H.R., 2019, Mangiferin from Mangifera indica fruits reduces post-prandial glucose level by inhibiting α-glucosidase and α-amylase activity, S. Afr. J. Bot., 120, 129–134.
[8] Sferrazzo, G., Palmeri, R., Restuccia, C., Parafati, L., Siracusa, L., Spampinato, M., Carota, G., Distefano, A., Di Rosa, M., Tomasello, B., Costantino, A., Gulisano, M., Li Volti, G., and Barbagallo, I., 2022, Mangifera indica L. leaves as a potential food source of phenolic compounds with biological activity, Antioxidants, 11 (7), 1313.
[9] Ekor, M., 2014, The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety, Front. Pharmacol., 4, 177.
[10] Bommakanti, V., Puthenparambil Ajikumar, A., Sivi, C.M., Prakash, G., Mundanat, A.S., Ahmad, F., Haque, S., Prieto, M.A., and Rana, S.S., 2023, An overview of herbal nutraceuticals, their extraction, formulation, therapeutic effects and potential toxicity, Separations, 10 (3), 177.
[11] Khursheed, A., Jain, V., and Wani, A.R., 2022, Euphorbia hirta as a gold mine of high-value phytochemicals: A comprehensive review of its pharmacological activities and possible role against SARS-CoV-2, Biomed. Res. Ther., 9 (2), 4930–4949.
[12] Gupta, S.S., Azmi, L., Mohapatra, P.K., and Rao, C.V., 2017, Flavonoids from whole plant of Euphorbia hirta and their evaluation against experimentally induced gastroesophageal reflux disease in rats, Pharmacogn. Mag., 13 (Suppl. 1), S127–S134.
[13] Wu, Y., Qu, W., Geng, D., Liang, J.Y., and Luo, Y.L., 2012, Phenols and flavonoids from the aerial part of Euphorbia hirta, Chin. J. Nat. Med., 10 (1), 40–42.
[14] Perumal, S., Mahmud, R., and Ismail, S., 2017, Mechanism of action of isolated caffeic acid and epicatechin 3-gallate from Euphorbia hirta against Pseudomonas aeruginosa, Pharmacogn. Mag., 13 (Suppl. 2), S311–S315.
[15] Meda, R.N.T., Kam, S.E., Kagambega, W., Zongo, E., Ouedraogo, C., Segda, A., Koama, B.K., Somda, F.T., Zongo, E., and Ouedraogo, G.A., 2023, A review on bioactive compounds isolated from Euphorbia hirta L., Am. J. Plant Sci., 14 (6), 710–726.
[16] Basyal, D., Neupane, A., Pandey, D.P., and Pandeya, S., 2021, Phytochemical screening and in vitro antioxidant and anti-inflammatory activities of aerial parts of Euphorbia hirta L., J. Nepal Chem. Soc., 42 (1), 115–124.
[17] Indriyanti, R.A., Kharisma, Y., and Damayanti, M.M., 2024. Mangifera indica Linn. waste peel ethanol extract on inducing Citrus amblycarpa Hassk. Ochese antioxidant activity, Pharmacogn J., 16 (5), 1010–1014.
[18] Utami, Y.P., Yulianty, R., Djabir, Y.Y., and Alam, G., 2024, Antioxidant activity, total phenolic and total flavonoid contents of Etlingera elatior (Jack) R.M. Smith from North Luwu, Indonesia, Trop. J. Nat. Prod. Res., 8 (1), 5955–5961.
[19] Hussen, E.M., and Endalew, S.A., 2023, In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of Vernonia amygdalina, BMC Complementary Med. Ther., 23 (1), 146.
[20] Lee, K.J., Oh, Y.C., Cho, W.K., and Ma, J.Y., 2015, Antioxidant and anti-inflammatory activity determination of one hundred kinds of pure chemical compounds using offline and online screening HPLC assay, Evidence-Based Complementary Altern. Med., 2015 (1), 165457.
[21] Nutmakul, T., and Chewchinda, S., 2023, Synergistic effect of Trikatuk, a traditional Thai formulation, on antioxidant and alpha-glucosidase inhibitory activities, Heliyon, 9 (1), e13063.
[22] Valle Ortiz, D.J., Aguila Muñoz, D.G., Cruz López, M.D., Cortés Espinosa, D.V., Rosales Castro, M., and Jiménez Montejo, F.E., 2024, Comparison of secondary metabolite extraction methods in Hamelia patens Jacq. and their inhibitory effect on Fusarium oxysporum f. sp. radicis-lycopersici, Metabolites, 15 (1), 23.
[23] Ghaffar, N., and Perveen, A., 2025, Solvent polarity effects on extraction yield, phenolic content, and antioxidant properties of Malvaceae family seeds: A comparative study, N. Z. J. Bot., 63 (4), 627–637.
[24] Loan, N.T.T., Long, D.T., Yen, P.N.D., Hanh, T.T.M., Pham, T.N., and Pham, D.T.N., 2021, Purification process of mangiferin from Mangifera indica L. leaves and evaluation of its bioactivities, Processes, 9 (5), 852.
[25] Phuong, N.T.N., Ha, M.T., Nguyen, D.X.T., Nguyen, N.Y., Huynh, H.A.T., Hau, T.P., Quyen, T.T.B., Nguyen, M.Q., Nguyen, A.T., and Pham, D.T., 2024, Development and antioxidant evaluation of mango leaf (Mangifera indica L.) extract loaded silk fibroin nanoparticles, Front Mater., 11, 1419697.
[26] Mekam, P.N., Martini, S., Nguefack, J., Tagliazucchi, D., and Stefani, E., 2019, Phenolic compounds profile of water and ethanol extracts of Euphorbia hirta L. leaves showing antioxidant and antifungal properties, S. Afr. J. Bot., 127, 319–332.
[27] Sharma, N., Samarakoon, K.W., Gyawali, R., Park, Y.H., Lee, S.J., Oh, S.J., Lee, T.H., and Jeong, D.K., 2014, Evaluation of the antioxidant, anti-inflammatory, and anticancer activities of Euphorbia hirta ethanolic extract, Molecules, 19 (9), 14567–14581.
[28] Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., and Zhao, L., 2017, Inflammatory responses and inflammation-associated diseases in organs, Oncotarget, 9 (6), 7204–7218.
[29] Labarrere, B., Prinzing, A., Dorey, T., Chesneau, E., and Hennion, F., 2019, Variations of secondary metabolites among natural populations of sub-Antarctic Ranunculus species suggest functional redundancy and versatility, Plants, 8 (7), 234.
[30] Sulistyarsi, A., Rahayu, T., Primiani, C.N., and Pujiati, P., 2023, Phytochemical analysis of Indonesian gadung mango leaf (Mangifera indica L. var. gadung) and their antibacterial activity, Biodiversitas, 24 (11), 6295–6304.
[31] Das, K., Asdaq, S.M.B., Khan, M.S., Amrutha, S., Alamri, A., Alhomrani, M., Alsanie, W.F., Bhaskar, A., Chandana Shree, G., and Harshitha, P., 2022, Phytochemical investigation and evaluation of in vitro anti-inflammatory activity of Euphorbia hirta ethanol leaf and root extracts: A comparative study, J. King Saud Univ., Sci., 34 (7), 102261.
[32] Durazzo, A., Lucarini, M., Souto, E.B., Cicala, C., Caiazzo, E., Izzo, A.A., Novellino, E., and Santini, A., 2019, Polyphenols: A concise overview on the chemistry, occurrence, and human health, Phytother. Res., 33 (9), 2221–2243.
[33] Teshika, J.D., Zakariyyah, A.M., Zaynab, T., Zengin, G., Rengasamy, K.R.R., Pandian, S.K., and Fawzi, M.M., 2019, Traditional and modern uses of onion bulb (Allium cepa L.): A systematic review, Crit. Rev. Food Sci. Nutr., 59 (Suppl. 1), S39–S70.
[34] Zhang, H., and Tsao, R., 2016, Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects, Curr. Opin. Food Sci., 8, 33–42.
[35] Zeinali, M., Rezaee, S.A., and Hosseinzadeh, H., 2017, An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances, Biomed. Pharmacother., 92, 998–1009.
[36] Bibi, N., Shah, M.H., Khan, N., Al-Hashimi, A., Elshikh, M.S., Iqbal, A., Ahmad, S., and Abbasi, A.M., 2022, Variations in total phenolic, total flavonoid contents, and free radicals’ scavenging potential of onion varieties planted under diverse environmental conditions, Plants, 11 (7), 950.
[37] Gulcin, İ., and Alwasel, S.H., 2023, DPPH radical scavenging assay, Processes, 11 (8), 2248.
[38] Mishra, S.B., Verma, A., and Vijayakumar, M., 2013, Preclinical valuation of anti-hyperglycemic and antioxidant action of Nirmali (Strychnos potatorum) seeds in streptozotocin-nicotinamide-induced diabetic Wistar rats: A histopathological investigation, Biomarkers Genomic Med., 5 (4), 157–163.
[39] Ulfa, A.M., Lukman, I.R., Widiyanti, B.L., Hartini, H., Hilmi, A., and Darmawan, M.I., 2021, Antioxidant activity of seaweed (Eucheuma cottonii) and coconut (Cocos nucifera) masks, IOP Conf. Ser.: Earth Environ. Sci., 712 (1), 012041.
[40] Shin, H.Y., Kim, H., Jung, S., Jeong, E.J., Lee, K.H., Bae, Y.J., Suh, H.J., Jang, K.I., and Yu, K.W., 2021, Interrelationship between secondary metabolites and antioxidant capacities of Centella asiatica using bivariate and multivariate correlation analyses, Appl. Biol. Chem., 64 (1), 82.
[41] Duresa, L.W., and Manaye, D., 2017, Phytochemical screening and antioxidant activity of selected mango (Mangifera indica L.) and avocado (Persea americana) fruits in Illu Ababor zone, Oromia regional state, Ethiopia, Indo Am. J. Pharm. Res., 7 (9), 252–257.
[42] Lavanya, R., Monisha, M., Narmatha, M., Fouzeeya Begum, S.R., and Savithri, J.S., 2022, Phytochemical screening of Euphorbia hirta L and antioxidant properties, Int. J. Bot. Stud., 7 (3), 228–234.
[43] Abidin, R.K.S., and Arsianti, A., 2023, Phytochemical screening, antioxidant activity, and cytotoxicity of ethanol, ethyl acetate, and n-hexane kluwak (Pangium edule) extract on MCF-7 breast cancer cells, IJMCB, 2 (2), 1–12.
[44] Aghababaei, F., and Hadidi, M., 2023, Recent advances in potential health benefits of quercetin, Pharmaceuticals, 16 (7), 1020.
[45] Zheng, Y.Z., Deng, G., Liang, Q., Chen, D.F., Guo, R., and Lai, R.C., 2017, Antioxidant activity of quercetin and Its glucosides from propolis: A theoretical study, Sci. Rep., 7 (1), 7543.
[46] Czigle, S., Nagy, M., Mladěnka, P., and Tóth, J., 2023, Pharmacokinetic and pharmacodynamic herb-drug interactions—part I. Herbal medicines of the central nervous system, PeerJ, 11, e16149.
[47] Caesar, L.K., and Cech, N.B., 2019, Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2, Nat. Prod. Rep., 36, 869–888.
[48] Fong, C.R., Bittick, S.J., and Fong, P., 2018, Simultaneous synergist, antagonistic and additive interactions between multiple local stressors all degrade algal turf communities on coral reefs, J. Ecol., 106 (4), 1390–1400.
[49] Fabre, G., Bayach, I., Berka, K., Paloncýová, M., Starok, M., Rossi, C., Duroux, J.L., Otyepka, M., and Trouillas, P., 2015, Synergism of antioxidant action of vitamins E, C and quercetin is related to formation of molecular associations in biomembranes, Chem. Commun., 51 (36), 7713–7716.
[50] Sazhina, N.N., 2017, Determination of antioxidant activity of various bioantioxidants and their mixtures by the amperometric method, Russ. J. Bioorg. Chem., 43 (7), 771–775.
[51] Rúa, J., de Arriaga, D., García-Armesto, M.R., Busto, F., and del Valle, P., 2017, Binary combinations of natural phenolic compounds with gallic acid or with its alkyl esters: An approach to understand the antioxidant interactions, Eur. Food Res. Technol., 243 (7), 1211–1217.
[52] Crespo, Y.A., Bravo Sánchez, L.R., Quintana, Y.G., Cabrera, A.S.T., Bermúdez del Sol, A., and Mayancha, D.M.G., 2019, Evaluation of the synergistic effects of antioxidant activity on mixtures of the essential oil from Apium graveolens L., Thymus vulgaris L. and Coriandrum sativum L. using simplex-lattice design, Heliyon, 5 (6), e01942.
[53] Putra, I.M.W.A., Fakhrudin, N., Kusumawati, I.G.A.W., Nurrochmad, A., and Wahyuono, S., 2021, Antioxidant properties of extract combination of Coccinia grandis and Blumea balsamifera: An in vitro synergistic effect, J. HerbMed Pharmacol., 11 (1), 55–62.
[54] Villanueva-Bermejo, D., Siles-Sánchez, M.D.L.N., Martín Hernández, D., Rodríguez García-Risco, M., Jaime, L., Santoyo, S., and Fornari, T., 2024, Theoretical framework to evaluate antioxidant synergistic effects from the coextraction of marjoram, rosemary and parsley, Food Chem., 437, 137919.
Article Metrics
Copyright (c) 2025 Indonesian Journal of Chemistry

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.











