Antioxidant and  In Vitro  Antidiabetic Properties of  Lansium domesticum  Leaves Extracted with Solvents of Varying Polarity

Jiro Hasegawa Situmorang; Ana Yulyana; Ririn Astyka; Hafid Syahputra; Muhammad Fauzan Lubis

doi:10.22146/ijc.110695

Antioxidant and In Vitro Antidiabetic Properties of Lansium domesticum Leaves Extracted with Solvents of Varying Polarity

https://doi.org/10.22146/ijc.110695

Jiro Hasegawa Situmorang⁽¹⁾, Ana Yulyana⁽²⁾, Ririn Astyka⁽³⁾, Hafid Syahputra⁽⁴⁾, Muhammad Fauzan Lubis^(5*)

(1) Center for Biomedical Research, National Research and Innovation Agency (BRIN), KST Soekarno, Jl. Raya Bogor No. 970, Cibinong 16915, Indonesia
(2) Department of Pharmacy, Faculty of Pharmacy, Universitas Pancasila, Jl. Srengseng Sawah, Jakarta Selatan 12640, Indonesia
(3) Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Jl. Tri Dharma, Padang Bulan, Medan 20155, Indonesia
(4) Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Sriwijaya, Jl. Palembang Prabumulih Km. 32, Indralaya 30862, Indonesia
(5) Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Jl. Tri Dharma, Padang Bulan, Medan 20155, Indonesia
(*) Corresponding Author

Abstract

Conventional therapies for diabetes mellitus, such as oral hypoglycemic agents, are often limited by side effects and incomplete glycemic control, highlighting the need for safer alternatives. Exploring natural remedies, such as Lansium domesticum, is compelling, as this plant has been traditionally used for diabetes therapy. This study aimed to investigate how solvent polarity and affinity influence phytochemical content, antioxidant activity, and enzyme inhibitory potential of L. domesticum leaf extracts. Extraction was conducted using methanol, ethanol, and acetone (50%, 75%, 100%), and distilled water. Total phenolic content (TPC) and total flavonoid content (TFC) were quantified, and antioxidant activities were assessed via total antioxidant activity (TAA), DPPH, and FRAP assays. Antidiabetic activity was evaluated in vitro through α-glucosidase and α-amylase inhibition assays. The results indicated that 100% ethanol extract exhibited the highest TPC and TFC, correlating strongly with superior antioxidant and enzyme inhibitory activities. The extract has also demonstrated the most potent inhibition of α-glucosidase and α-amylase, with IC₅₀ values of 70.64 and 105.13 µg/mL, respectively. Pearson correlation analysis revealed strong negative correlations between phytochemical contents and IC₅₀ values. Overall, ethanol proved to be the most effective solvent for extracting bioactive compounds from L. domesticum leaves, underscoring its potential as a natural antioxidant and antidiabetic agent.

Keywords

Lansium domesticum; antioxidant; antidiabetic; solvent polarity

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References

[1] Mohan, S., and Egan, A.M., 2024, Diagnosis and treatment of hyperglycemia in pregnancy: Type 2 diabetes mellitus and gestational diabetes, Endocrinol. Metab. Clin. North Am., 53 (3), 335–347.

[2] Husna, F., Marisa, M., Suryawati, S., Suyatna, F.D., Husnah, H., Hakim, R.W., Aulia, M.I., and Dasopang, E.A., 2025, Traditional remedies from Aceh for diabetes mellitus treatment: Patterns of use in rural-urban areas in Aceh, Clin. Epidemiol. Global Health, 34, 102079.

[3] Yang, Y., Chen, Z., Zhao, X., Xie, H., Du, L., Gao, H., and Xie, C., 2022, Mechanisms of kaempferol in the treatment of diabetes: A comprehensive and latest review, Front. Endocrinol., 13, 990299.

[4] Tangvarasittichai, S., 2015, Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus, World J. Diabetes, 6 (3), 456–480.

[5] Gong, L., Feng, D., Wang, T., Ren, Y., Liu, Y., and Wang, J., 2020, Inhibitors of α-amylase and α-glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia, Food Sci. Nutr., 8 (12), 6320–6337.

[6] Chokki, M., Cudălbeanu, M., Zongo, C., Dah-Nouvlessounon, D., Ghinea, I.O., Furdui, B., Raclea, R., Savadogo, A., Baba-Moussa, L., Avamescu, S.M., Dinica, R.M., and Baba-Moussa, F., 2020, Exploring antioxidant and enzymes (A-amylase and B-glucosidase) inhibitory activity of Morinda lucida and Momordica charantia leaves from Benin, Foods, 9 (4), 434.

[7] Abdallah, H.M., Mohamed, G.A., and Ibrahim, S.R.M., 2022, Lansium domesticum—A fruit with multi-benefits: Traditional uses, phytochemicals, nutritional value, and bioactivities, Nutrients, 14 (7), 1531.

[8] Febriani, H., Lubis, M.F., Sumaiyah, S., Hasibuan, P.A.Z., Syahputra, R.A., Astyka, R., and Juwita, N.A., 2025, Optimization of microwave-assisted extraction to obtain a polyphenol-rich crude extract from duku (Lansium domesticum Corr.) leaf and the correlation with antioxidant and cytotoxic activities, Kuwait J. Sci., 52 (1), 100315.

[9] Asem, N., Abdul Gapar, N.A., Abd Hapit, N.H., and Omar, E.A., 2020, Correlation between total phenolic and flavonoid contents with antioxidant activity of Malaysian stingless bee propolis extract, J. Apic. Res., 59 (4), 437–442.

[10] Dudoit, A., Benbouguerra, N., Richard, T., Hornedo-Ortega, R., Valls-Onayet, J., Coussot, G., and Saucier, C., 2020, α-Glucosidase inhibitory activity of Tannat grape phenolic extracts in relation to their ripening stages, Biomolecules, 10 (8), 1088.

[11] Olennikov, D.N., Chirikova, N.K., Kashchenko, N.I., Nikolaev, V.M., Kim, S.W., and Vennos, C., 2018, Bioactive phenolics of the genus Artemisia (Asteraceae): HPLC-DAD-ESI-TQ-MS/MS profile of the Siberian species and their inhibitory potential against α-amylase and α-glucosidase, Front. Pharmacol., 9, 756.

[12] Mokrani, A., and Madani, K., 2016, Effect of solvent, time and temperature on the extraction of phenolic compounds and antioxidant capacity of peach (Prunus persica L.) fruit, Sep. Purif. Technol., 162, 68–76.

[13] Venkatachalam, R., Kalimuthu, K., Chinnadurai, V., Saravanan, M., Radhakrishnan, R., Shanmuganathan, R., and Pugazhendhi, A., 2020, Various solvent effects on phytochemical constituent profiles, analysis of antioxidant and antidiabetic activities of Hopea parviflora, Process Biochem., 89, 227–232.

[14] Atanu, F.O., Ikeojukwu, A., Owolabi, P.A., and Avwioroko, O.J., 2022, Evaluation of chemical composition, in vitro antioxidant, and antidiabetic activities of solvent extracts of Irvingia gabonensis leaves, Heliyon, 8 (7), e09922.

[15] Al-Hamdany, I.Y.A., Mohammed, M.J., and Al-Taei, S.M.S., 2025, Exploring the antimicrobial and antioxidant properties of Silybum marianum tissue-cultured phenolic extracts, J. Multidiscip. Appl. Nat. Sci., 5 (2), 429–445.

[16] Lestari, S., Husni, A., Nurjanah, N., and Firdaus, M., 2025, Chemical characteristic, antioxidant activity, and consumer acceptance level of kombucha from Sargassum cristaefolium seaweed tea, J. Multidiscip. Appl. Nat. Sci., 5 (3), 949–968.

[17] Hasibuan, P.A.Z., Keliat, J.M., and Lubis, M.F., 2024, Combination of cisplatin and ethyl acetate extract of Vernonia amygdalina Delile induces cell cycle arrest and apoptosis on PANC-1 cells via PI3K/mTOR, J. Pharm. Pharmacogn. Res., 12 (5), 870–880.

[18] Sumaiyah, S., Murwanti, R., Illian, D.N., Lubis, M.F., and Tampubolon, K., 2024, New insights of response surface methodology approach in optimizing total phenolic content of Zanthoxylum acanthopodium DC. fruit extracted using microwave-assisted extraction and the impact to antioxidant activity, Indones. J. Chem., 24 (6), 1743–1759.

[19] Nasution, H.M., Yulyana, A., Utama, R.F., Bangar, R.I., Kaban, V.E., Daulay, W., Astyka, R., and Lubis, M.F., 2025, Synergistic mechanism of Phyllanthus emblica extract and tetracycline against multidrug-resistant Acinetobacter baumannii, Narra J, 5 (1), e1939.

[20] Astyka, R., Hasibuan, P.A.Z., Sumaiyah, S., Juwita, N.A. and Lubis, M.F., 2024, Optimization of microwave-assisted extraction of total flavonoid content from red betel leaf (Piper crocatum Ruiz and Pav) and its correlation with antioxidant and antibacterial activities using response surface methodology, J. Appl. Pharm. Sci., 14 (8), 150–159.

[21] Mansoori, A., Singh, N., Dubey, S.K., Thakur, T.K., Alkan, N., Das, S.N., and Kumar, A., 2020, Phytochemical characterization and assessment of crude extracts from Latana camara L. for antioxidant and antimicrobial activity, Front. Agron., 2, 582268.

[22] Lubis, M.F., Syahputra, H., Illian, D.N. and Kaban, V.E., 2022, Antioxidant activity and nephroprotective effect of Lansium parasiticum leaves in doxorubicin-induced rats, J. Res. Pharm., 26 (3), 565–573.

[23] Kiss, A., Papp, V.A., Pál, A., Prokisch, J., Mirani, S., Toth, B.E., and Alshaal, T., 2025, Comparative study on antioxidant capacity of diverse food matrices: Applicability, suitability, and inter-correlation of multiple assays to assess polyphenol and antioxidant status, Antioxidant, 14 (3), 317.

[24] Yulyana, A., Amin, C., Simanjuntak, P., Abdillah, S., Rohman, A., and Mugiyanto, E., 2023, Assessing the antimetabolite activity of anthocyanins in Cantigi fruits from two conservation sites in Indonesia, Indones. J. Pharm., 34 (3), 450–459.

[25] Yulyana, A., Chaidir, C., Simanjuntak, P., Sulastri, L., and Abdillah, S., 2023, The water fraction of Cantigi (Vaccinium variegatum Bl. Miq.) fruits demonstrate the highest antimetabolic syndrome properties on enzyme assay, Pharmacia, 70 (3), 587–594.

[26] Suryani, M., Yulyana, A., Sumaiyah, S., Fitri, K., Lubis, L.D., Daulay, W., Surbakti, C., Astyka, R., and Lubis, M.F., 2025, Microwave-assisted extraction enhances the antioxidant and anti-diabetic activities of polyphenol-rich Phyllanthus emblica fruit extract, Discover Food, 5 (1), 244.

[27] Al-Mansoub, M.A., Asmawi, M.Z., and Murugaiyah, V., 2014, Effect of extraction solvents and plant parts used on the antihyperlipidemic and antioxidant effects of Garcinia atroviridis: A comparative study, J. Sci. Food Agric., 94 (8), 1552–1558.

[28] Dong, J., Zhou, K., Ge, X., Xu, N., Wang, X., He, Q., Zhang, C., Chu, J., and Li, Q., 2022, Effects of extraction technique on the content and antioxidant activity of flavonoids from Gossypium hirsutum Linn. flowers, Molecules, 27 (17), 5627.

[29] Sepahpour, S., Selamat, J., Abdul Manap, M.Y., Khatib, A., and Abdull Razis, A.F., 2018, Comparative analysis of chemical composition, antioxidant activity and quantitative characterization of some phenolic compounds in selected herbs and spices in different solvent extraction systems, Molecules, 23 (2), 402.

[30] Chatepa, L.E.C., Mwamatope, B., Chikowe, I., and Masamba, K.G., 2024, Effects of solvent extraction on the phytoconstituents and in vitro antioxidant activity properties of leaf extracts of the two selected medicinal plants from Malawi, BMC Complementary Med. Ther., 24 (1), 317.

[31] Ghasemzadeh, A., Jaafar, H.Z.E., Juraimi, A.S., and Tayebi-Meigooni, A., 2015, Comparative evaluation of different extraction techniques and solvents for the assay of phytochemicals and antioxidant activity of Hashemi rice bran, Molecules, 20 (6), 10822–10838.

[32] Gil-Martín, E., Forbes-Hernández, T., Romero, A., Cianciosi, D., Giampieri, F., and Battino, M., 2022, Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products, Food Chem., 378, 131918.

[33] Méndez, D.A., Fabra, M.J., Odriozola-Serrano, I., Martín-Belloso, O., Salvia-Trujillo, L., López-Rubio, A., and Martínez-Abad, A., 2022, Influence of the extraction conditions on the carbohydrate and phenolic composition of functional pectin from persimmon waste streams, Food Hydrocolloids, 123, 107066.

[34] El Mannoubi, I., 2023, Impact of different solvents on extraction yield, phenolic composition, in vitro antioxidant and antibacterial activities of deseeded Opuntia stricta fruit, J. Umm Al-Qura Univ. Appl. Sci., 9 (2), 176–184.

[35] Kaplan, M., Yilmaz, M.M., Say, R., Köprü, S., and Karaman, K., 2020, Bioactive properties of hydroalcoholic extract from Origanum onites L. as affected by glycerol incorporation, Saudi J. Biol. Sci., 27 (8), 1938–1946.

[36] Santana, Á.L., and Macedo, G.A., 2019, Effects of hydroalcoholic and enzyme-assisted extraction processes on the recovery of catechins and methylxanthines from crude and waste seeds of guarana (Paullinia cupana), Food Chem., 281, 222–230.

[37] Chaves, J.O., de Souza, M.C., da Silva, L.C., Lachos-Perez, D., Torres-Mayanga, P.C., Machado, A.P.F., Forster-Carneiro, T., Vázquez-Espinosa, M., González-de-Peredo, A.V., Barbero, G.F., and Rostagno, M.A., 2020, Extraction of flavonoids from natural sources using modern techniques, Front. Chem., 8, 507887.

[38] Liu, X., Liu, Y., Shan, C., Yang, X., Zhang, Q., Xu, N., Xu, L., and Song, W., 2022, Effects of five extraction methods on total content, composition, and stability of flavonoids in jujube, Food Chem.: X, 14, 100287.

[39] Dirar, A.I., Alsaadi, D.H.M., Wada, M., Mohamed, M.A., Watanabe, T., and Devkota, H.P., 2019, Effects of extraction solvents on total phenolic and flavonoid contents and biological activities of extracts from Sudanese medicinal plants, S. Afr. J. Bot., 120, 261–267.

[40] Do, Q.D., Angkawijaya, A.E., Tran-Nguyen, P.L., Huynh, L.H., Soetaredjo, F.E., Ismadji, S., and Ju, Y.H., 2014, Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of Limnophila aromatica, J. Food Drug Anal., 22 (3), 296–302.

[41] Ojha, S., Raj, A., Roy, A., and Roy, S., 2018, Extraction of total phenolics, flavonoids and tannins from Paederia foetida L. leaves and their relation with antioxidant activity, Pharmacogn. J., 10 (3), 541–547.

[42] Bakhouche, K., Dhaouadi, Z., Jaidane, N., and Hammoutène, D., 2015, Comparative antioxidant potency and solvent polarity effects on HAT mechanisms of tocopherols, Comput. Theor. Chem., 1060, 58–65.

[43] Herrera-Pool, E., Ramos-Díaz, A.L., Lizardi-Jiménez, M.A., Pech-Cohuo, S., Ayora-Talavera, T., Cuevas-Bernardino, J.C., García-Cruz, U., and Pacheco, N., 2021, Effect of solvent polarity on the Ultrasound Assisted extraction and antioxidant activity of phenolic compounds from habanero pepper leaves (Capsicum chinense) and its identification by UPLC-PDA-ESI-MS/MS, Ultrason. Sonochem., 76, 105658.

[44] Abolmaesoomi, M., Abdul Aziz, A., Mat Junit, S., and Mohd Ali, J., 2019, Ficus deltoidea: Effects of solvent polarity on antioxidant and anti-proliferative activities in breast and colon cancer cells, Eur. J. Integr. Med., 28, 57–67.

[45] Ye, F., Liang, Q., Li, H., and Zhao, G., 2015, Solvent effects on phenolic content, composition, and antioxidant activity of extracts from florets of sunflower (Helianthus annuus L.), Ind. Crops Prod., 76, 574–581.

[46] Lubis, M.F., Sumaiyah, S., Lubis, L.D., Fitri, K., and Astyka, R., 2024, Application of Box-Behnken design for optimization of Vernonia amygdalina stem bark extract in relation to its antioxidant and anti-colon cancer activity, Arabian J. Chem., 17 (4), 105702.

[47] Akullo, J.O., Kiage-Mokua, B.N., Nakimbugwe, D., Ng’ang’a, J., and Kinyuru, J., 2023, Phytochemical profile and antioxidant activity of various solvent extracts of two varieties of ginger and garlic, Heliyon, 9 (8), e18806.

[48] Mohammed, E.A., Abdalla, I.G., Alfawaz, M.A., Mohammed, M.A., Al Maiman, S.A., Osman, M.A., Yagoub, A.E.A., and Hassan, A.B., 2022, Effects of extraction solvents on the total phenolic content, total flavonoid content, and antioxidant activity in the aerial part of root vegetables, Agriculture, 12 (11), 1820.

[49] Adebiyi, O.E., Olayemi, F.O., Ning-Hua, T., and Guang-Zhi, Z., 2017, In vitro antioxidant activity, total phenolic and flavonoid contents of ethanol extract of stem and leaf of Grewia carpinifolia, Beni-Suef Univ. J. Basic Appl. Sci., 6 (1), 10–14.

[50] Maser, W.H., Maiyah, N., Nagarajan, M., Kingwasharapong, P., Senphan, T., Ali, A.M.M., and Bavisetty, S.C.B., 2023, Effect of different extraction solvents on the yield and enzyme inhibition (α-amylase, α-glucosidase, and lipase) activity of some vegetables, Biodiversitas, 24 (6), 3320–3331.

[51] Hossain, M.A., Arafat, M.Y., Alam, M., and Hossain, M.M., 2021, Effect of solvent types on the antioxidant activity and total flavonoids of some Bangladeshi legumes, Food Res., 5 (4), 329–335.

[52] Yeasmen, N., and Islam, M.N., 2015, Ethanol as a solvent and hot extraction technique preserved the antioxidant properties of tamarind (Tamarindus indica) seed, J. Adv. Vet. Anim. Res., 2 (3), 332–337.

[53] Lin, Y.T., Lin, H.R., Yang, C.S., Liaw, C.C., Sung, P.J., Kuo, Y.H., Cheng, M.J., and Chen, J.J., 2022, Antioxidant and anti-α-glucosidase activities of various solvent extracts and major bioactive components from the fruits of Crataegus pinnatifida, Antioxidants, 11 (2), 320.

[54] Ervina, M., Diva, J., Caroline, C., and Soewandi, A., 2023, The solvents influence in the continuous extraction to antioxidant and α-glucosidase inhibition of Cinnamomum burmannii bark, Food Res., 7 (4), 258–264.

[55] Li, C.W., Chu, Y.C., Huang, C.Y., Fu, S.L., and Chen, J.J., 2020, Evaluation of antioxidant and anti-α-glucosidase activities of various solvent extracts and major bioactive components from the seeds of Myristica fragrans, Molecules, 25 (21), 5198.

[56] Saltos, M.B.V., Puente, B.F.N., Faraone, I., Milella, L., De Tommasi, N., and Braca, A., 2015, Inhibitors of α-amylase and α-glucosidase from Andromachia igniaria Humb. & Bonpl, Phytochem. Lett., 14, 45–50.

[57] Khan, S.A., Al Kiyumi, A.R., Al Sheidi, M.S., Al Khusaibi, T.S., Al Shehhi, N.M., and Alam, T., 2016, In vitro inhibitory effects on α-glucosidase and α-amylase level and antioxidant potential of seeds of Phoenix dactylifera L., Asian Pac. J. Trop. Biomed., 6 (4), 322–329.

[58] Wibowo, S., Wardhani, S.K., Hidayati, L., Wijayanti, N., Matsuo, K., Costa, J., Nugraha, Y., Siregar, J.E., and Nuringtyas, T.R., 2024, Investigation of α-glucosidase and α-amylase inhibition for antidiabetic potential of agarwood (Aquilaria malaccensis) leaves extract, Biocatal. Agric. Biotechnol., 58, 103152.

[59] Jaber, S.A., 2023, In vitro alpha-amylase and alpha-glucosidase inhibitory activity and in vivo antidiabetic activity of Quercus coccifera (Oak tree) leaves extracts, Saudi J. Biol. Sci., 30 (7), 103688.

[60] Gazali, M., Jolanda, O., Husni, A., Nurjanah, N., Abd Majid, F.A., Zuriat, Z., and Syafitri, R., 2023, In vitro α-amylase and α-glucosidase inhibitory activity of green seaweed Halimeda tuna extract from coast of Lhok Bubon, Aceh, Plants, 12 (2), 393.

[61] Magaji, U.F., Sacan, O., and Yanardag, R., 2020, Alpha amylase, alpha glucosidase and glycation inhibitory activity of Moringa oleifera extracts, S. Afr. J. Bot., 128, 225–230.

[62] Ambarwati, Y., Nurhasanah, N., Karima, N., and Purnomo, H., 2025, Antidiabetic activity test of Fe(III) complex compound with arginine ligand in male mice (Mus musculus L.), J. Multidiscip. Appl. Nat. Sci., 5 (1), 141–157.

[63] Mardani-Ghahfarokhi, A., and Farhoosh, R., 2020, Antioxidant activity and mechanism of inhibitory action of gentisic and α-resorcylic acids, Sci. Rep., 10 (1), 19487.

[64] Magiera, A., Kołodziejczyk-Czepas, J., and Olszewska, M.A., 2025, Antioxidant and anti-inflammatory effects of vanillic acid in human plasma, human neutrophils, and non-cellular models in vitro, Molecules, 30 (3), 467.

[65] Liu, H., Huang, P., Wang, X., Ma, Y., Tong, J., Li, J., and Ding, H., 2024, Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity, Bioorg. Chem., 143, 107059.

[66] Hendra, R., Army, M.K., Frimayanti, N., Teruna, H.Y., Abdulah, R., and Nugraha, A.S., 2024, α-Glucosidase and α-amylase inhibitory activity of flavonols from Stenochlaena palustris (Burm.f.) Bedd, Saudi Pharm. J., 32 (2), 101940.

[67] Jia, J., Dou, B., Gao, M., Zhang, C., Liu, Y., and Zhang, N., 2024, Effect of genistein on starch digestion in vitro and its mechanism of action, Foods, 13 (17), 2809.

[68] Fan, W., Fan, L., Wang, Z., and Yang, L., 2021, Limonoids from the genus Melia (Meliaceae): Phytochemistry, synthesis, bioactivities, pharmacokinetics, and toxicology, Front. Pharmacol., 12, 795565.

[69] Hilmayanti, E., Nurlelasari, N., Supratman, U., Kabayama, K., Shimoyama, A., and Fukase, K., 2022, Limonoids with anti-inflammatory activity: A review, Phytochemistry, 204, 113469.

DOI: https://doi.org/10.22146/ijc.110695