In-vitro, In-vivo, and In-silico Studies of Insulinotropic Activity and Cytotoxicity of Mahagony Seed Extracts and Its Nanophytosome
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Keywords:
BRIN-BD11 cell lines; diabetic mouse models; liquid chromatography with tandem mass spectrometry (LCMS); molecular docking
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Abstract
This present study set out with the objective of evaluating the effect of ethanol–water solvent composition on extraction yield, insulinotropic activity (IA), cytotoxicity, and phytochemical profile (PP) of mahogany (Swietenia mahagoni) seed (MS) extracts. It also sought to study in silico and encapsulate the best extract, and to assay the antidiabetic of the extract and its nanophytosome. The extraction of MSs was achieved through the utilization of ethanol, ethanol–water (1:1), and water through ultrasound–assisted extraction. The extracts of IA and cytotoxicity were assayed in vitro using BRIN–BD11 cell lines and analyzed using LC-MS. The most effective extract was identified for its active compounds using molecular docking, encapsulation, characterization, and testing for its antidiabetic properties in vivo. The highest yield was observed in the water extract (MW), followed by the ethanol–water extract (MEW) and the ethanol extract (ME). MEW and MW demonstrated low level of cytotoxicity, with MEW exhibiting the highest level of IA. An in silico study identified four key antidiabetic compounds through the IA mechanism. The study demonstrated that MEW and its nanophytosome (250 mg/kg mouse weight) effectively reduced blood glucose level, and enhanced both erythrocyte function, and insulin secretion. This finding provides a new perspective in the development of natural-based antidiabetic agents through the nanophytosome formulation of mahogany seed extract.
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Hamidi, Z., Sari, R. K., Prayogo, Y. H., Syafii, W., Kasmi, A. Z. M., Prasetyo, B. F., … Wahyudi, S. T. (2025). In-vitro, In-vivo, and In-silico Studies of Insulinotropic Activity and Cytotoxicity of Mahagony Seed Extracts and Its Nanophytosome . Communications in Science and Technology, 10(2), 234–247. https://doi.org/10.21924/cst.10.2.2025.1676
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9. Ahmad AR, Malik A, Handayani V. In Vivo and In Vitro Antidiabetic Assay of Purified Mahoni Seeds Extract (Swietenia mahagoni (L.) Jacq). Biomedical and Pharmacology Journal. (2023);16:1701–6.
10. Wresdiyati T, Sa’diah Siti, Winarto Adi, Febriyani V. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract. Hayati. (2015);22:73–8.
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13. Ahmadi A, Khalili M, Margedari S, Nahri-Niknafs B. The Effects of Solvent Polarity on Hypoglycemic and Hypolipidemic Activities of Securigera Securidaca (L) Seeds. Drug Res. (2015);66:130–5.
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15. Carreira-Casais A, Otero P, Garcia-Perez P, Garcia-Oliveira P, Pereira AG, Carpena M, Benefits and drawbacks of ultrasound-assisted extraction for the recovery of bioactive compounds from marine algae. Int J Environ Res Public Health. (2021);18.
16. Sari RK, Prayogo YH, Rozan SA, Rafi M, Wientarsih I. Antioxidant Activity, Sun Protection Activity, and Phytochemical Profile of Ethanolic Extracts of Daemonorops acehensis Resin and Its Phytosomes. Sci Pharm. (2022);90.
17. Taiyeb M, Hartati H, Arwansyah A, Dahlia, Muis A, Mu’nisa A, Self-Nanoemulsifying Drug Delivery System (SNEDDS) formulation and molecular docking of mahogany seed extract (Swietenia mahagoni) as anti-hyperglycemic. Inform Med Unlocked. (2024);47.
18. Sukardiman, Ervina M. The recent use of Swietenia mahagoni (L.) Jacq. as antidiabetes type 2 phytomedicine: A systematic review. Heliyon. Elsevier Ltd; (2020) 89-95.
19. McClenaghan NH, Barnett CR, Ah–Sing E, Abdel–Wahab YHA, O’Harte FPM, Yoon T–W, Swanston–Flatt SK, Flatt PR. Characterization of a
Novel Glucose–Responsive Insulin–Secreting Cell Line, BRIN–BD11, Produced by Electrofusion. J. Diabetes. (1996) 45:1132–40.
20. Freimoser FM, Jakob CA, Aebi M, Tuor U. The MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] Assay Is a Fast and Reliable Method for Colorimetric Determination of Fungal Cell Densities. Appl Environ Microbiol. (1999).
21. Shekoohi N, Harnedy-Rothwell P, Sharkey S, Lafferty R, Khatib N, O’ Harte F, Purification and characterization of multifunctional peptides with in situ insulinotropic and antioxidative activity from a blue whiting (Micromesistius poutassou) protein hydrolysate. J Funct Foods. (2024);116.
22. Zhao S, Kanno Y, Li W. Molecular mechanism of the effect of gegen qinlian decoction on type 2 diabetes mellitus based on network pharmacology and molecular docking. Pharmacological Research - Modern Chinese Medicine. (2022);3.
23. Kusunoki M, Hirota K, Shoji T, Uba T, Matsuo Y, Hayashi M. Dexmedetomidine suppresses glucose-stimulated insulin secretion in pancreatic ?-cells. FEBS Open Bio . (2024) 63-68
24. Suba Zsuzsanna. Recent avenue to cancer prevention. Nova Science Publishers; (2014) 51-55.
25. Le HT, Yu J, Ahn HS, Kim MJ, Chae IG, Cho HN, eIF2? phosphorylation-ATF4 axis-mediated transcriptional reprogramming mitigates mitochondrial impairment during ER stress. Mol Cells. (2025);48.
26. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An Open chemical toolbox. J Cheminform. (2011);33-39.
27. Sari Rk, Syafii W, Prayogo Yh, Carolina A, Familasari S, Cahyaningsih U, In Vitro and Molecular Docking Studies of the Antimalarial Activities of Strychnos ligustrina Extracts from Different Parts of the Woody Stem. Journal of the Korean Wood Science and Technology. (2025);53:89–104.
28. Fazni Nengsih R, Widi L, Yendri H, Subangkit M, Tarigan E, Irarang Y, Efikasi Pemberian Maserasi Kemangi sebagai Antifertilitas terhadap Profil Hematologi dan Biokimia Darah Tikus Betina (Eficacy of Holy Basil Maseration Administration as Antifertility to Hematology and Blood Biochemistry of Female Rats). J Pharmac (2022) 86-90.
29. O’Harte FPM, Parthsarathy V, Hogg C, Flatt PR. Apelin-13 analogues show potent in vitro and in vivo insulinotropic and glucose lowering actions. Peptides (NY). (2018);100:219–28.
30. Mcclung JP, Roneker CA, Mu W, Lisk DJ, Langlais P, Liu F, et al. Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase. Molecules (2004) 121-125.
31. Laila SR, Sukmawinata E, Putri FMK, Akbar I, Zahra LF, Agungpriyono S, Cahyaningsih U, Wresdiyati T. Ampiang–Dadih: A Combination of Indonesian Traditional Fermented Buffalo Milk and Black Glutinous Rice – Prevents Hypercholesterolemia and Liver Cell Degeneration In Vivo. J Adv Vet Anim Res. 2024; 11(2):275–283.
32. Sasidharan S, Chen Y, Saravanan D, Sundram KM, Latha LY. Extraction, Isolation And Characterization Of Bioactive Compounds From Plants’ Extracts. Afr J Tradit Complement Altern Med. (2011) 63-67.
33. Meregalli MM, Puton BMS, Camera FDM, Amaral AU, Zeni J, Cansian RL, Conventional and ultrasound-assisted methods for extraction of bioactive compounds from red araçá peel (Psidium cattleianum Sabine). Arabian Journal of Chemistry. (2020);13:5800–9.
34. Arisandi R, Takahashi K, Nirsatmanto A, Sunarti S, Rimbawanto A, Putri AI, Analysis of Lipophilic Constituents Related to Heartwood Formation in Young Swietenia mahagoni (L.) Jacq Trees. Journal of the Korean Wood Science and Technology. (2024);52:13–30.
35. Romano E, Domínguez-Rodríguez G, Mannina L, Cifuentes A, Ibáñez E. Characterization of Non-Polar and Polar Bioactive Compounds Obtained by Pressurized Biobased Solvents from Different Arctium lappa L. Root Ecotypes. Applied Sciences. (2025);15:2491.
36. Gaik M, Khoo H, Abdullah Z, Hani Badron U, Abdullah F, Kasim N,. In Vitro Toxicity Assessment of Swietenia macrophylla King Extracts Using a Cell-Based Assay. Malaysian Journal of Medicine and Health Sciences. (2023).
37. Borah A, Selvaraj S, Holla SR, De S. Extraction and characterization of total phenolic and flavonoid contents from bark of Swietenia macrophylla and their antimicrobial and antioxidant properties. Arabian Journal of Chemistry.( 2022);15.
38. Shahneh FZ, Valiyari S, Azadmehr A, Hajiaghaee R, Yaripour S, Bandehagh A, Inhibition of growth and induction of apoptosis in fibrosarcoma cell lines by echinophora platyloba DC: In vitro analysis. Adv Pharmacol Sci. (2013) 67-72.
39. Canga I, Vita P, Oliveira AI, Castro MÁ, Pinho C. In Vitro Cytotoxic Activity of African Plants: A Review. Molecules. MDPI; (2022).
40. Khotimah H, Wulandari AM, Ainiyati SO, Wiyasa WA. A Systematic Review on the Hypoglycemic Potentials of Mahogany (Swietenia spp.) Seeds as Antioxidants in the Management of Gestational Diabetes Mellitus. Tropical Journal of Natural Product Research. (2024) 6472.
41. Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY, Sasidharan S. Acute oral toxicity of methanolic seed extract of Cassia fistula in mice. Molecules. (2011);16:5268–82.
42. Sukardiman, Ervina M. The recent use of Swietenia mahagoni (L.) Jacq. as antidiabetes type 2 phytomedicine: A systematic review. Heliyon. Elsevier Ltd; (2020).
43. Rappold BA. Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II-Operations. Ann Lab Med. Cognitive Science; (2022) 531–57.
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