Evaluation of antioxidant and hypoglycemic activities and metabolite profiles of the fractionated extract of the Crescentia cujete Linn. fruit
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Published
May 19, 2025
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Jan Edward S. Bautista
Camille Angela D. Bolaños
Kim Andrew A. Macatangay
Daniel Edward Paje
Rogie Royce Carandang
Kevin Jace Miranda
Abstract
Diabetes mellitus (DM) is a prevalent disease that is the sixth leading cause of death in the Philippines. The fruit juice of Crescentia cujete Linn, or “miracle fruit”, is utilized by locals from Agusan del Sur, Zamboanga del Sur, and Zamboanga Sibugay in the Philippines as an anti-diabetic and antioxidant treatment alternative or additive due to the high costs of their current prescriptions. Phytochemical screening of the fruit extract indicated the presence of alkaloids and reducing sugars with trace amounts of saponins, volatile oil, tannins, and polyphenols. Hypoglycemic and antioxidant assays were utilized to determine the potential activity. Alpha-glucosidase inhibition at 10 ppm of the fruit exhibited low enzyme inhibition activity. Methanol/H2O solvent fraction showed notable antioxidant activity in the 2,2-Diphenyl-1-PicrylHydrazyl (DPPH) assay, averaging 55.69% inhibition. For more comprehensive bioactivity comparison of C. cujete, the half-maximal inhibitory concentration (IC50) of α-glucosidase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) should be identified and various concentration screening protocols for the assays should be conducted to help identify the effective enzyme inhibitory effects of the sample. Mass Spectral Library included 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine, 15(S)-15-Methyl Prostaglandin E1, and 5,6-Dihydroxy-8Z,11Z,14Z-eicosatrienoic acid.
How to Cite
Bautista JES, Bolaños CAD, Macatangay KAA, Paje DE, Carandang RR, Miranda KJ. 2025. Evaluation of antioxidant and hypoglycemic activities and metabolite profiles of the fractionated extract of the Crescentia cujete Linn. fruit. The Palawan Scientist. 17(2):23–32. https://doi.org/10.69721/TPS.J.2025.17.2.03.
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Keywords
2,2-diphenyl-1-picrylhydrazyl, α-glucosidase, GNPS, miracle fluit, phytochemical screening
References
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Saxena M, Saxena J, Nema R, Singh D and Gupta. 2013. Phytochemistry of Medicinal Plants. Journal of Pharmacognosy and Phytochemistry, 1(6): 168-182.
Shaikh S, Lee E-J, Ahmad K, Ahmad S-S, Lim J-H and Choi I. 2021. A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes. Pharmaceuticals, 14(6): 591. https://doi.org/10.3390/ph140605
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StataCorp. 2023. Stata Statistical Software: Release 13. College Station, TX: StataCorp LLC.
Tai Z, Cai L, Dai L, Dong L, Wang M, Yang Y, Cao Q and Ding Z. 2011. Antioxidant activity and chemical constituents of edible flower of Sophora viciifolia. Food Chemistry, 126(4): 1648–1654. https://doi.org/10.1016/j.foodchem.2010.12.048
Tupas GD, Rañeses GMM, Guarino DV, Martinez C, Marundan JA, Mascardo K, Melanio A, Meling RK, Mendez M, Monteverde KA and Montojo MD. 2018. Effect of ED90 dose of Calabash (Crescentia cujete) Decoction on the Blood Sugar Levels of Pre-Diabetic Individuals. DMSFI Research Journal, 3: 21-26.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M and Telser J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology, 39(1): 44–84. https://doi.org/10.1016/j.biocel.2006.07.001
Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Nguyen DD, Watrous J, Kapono CA, Luzzatto-Knaan T et al. 2016. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology, 34: 828-837. https://doi.org/10.1038/nbt.3597
Ambhore JP, Laddha PR, Nandedkar A, Ajmire PV, Chumbhale D, Navghare AB, Kuchake V, Chaudhari P and Adhao VS. 2023. Medicinal chemistry of non-peptidomimetic dipeptidyl peptidase IV (DPP IV) inhibitors for treatment of Type-2 diabetes mellitus: Insights on recent development. Journal of Molecular Structure, 1284: 135249 https://doi.org/10.1016/j.molstruc.2023.135249
Arquion RD, Galanida CC, Villamor B and Aguilar HT. 2015. Ethnobotanical study of indigenous plants used by local people of Agusan del Sur, Philippines. Asia Pacific Higher Education Research Journal, 2(2). https://doi.org/10.56278/apherj.v2i2.102
Bakker R, Pierce S and Myers D. 2017. The role of prostaglandins E1 and E2, dinoprostone, and misoprostol in cervical ripening and the induction of labor: a mechanistic approach. Archives of Gynecology and Obstetrics, 296(2): 167–179. https://doi.org/10.1007/s00404-017-4418-5
Billacura MP and Laciapag GCR. 2017. Phytochemical Screening, Cytotoxicity, Antioxidant, and Anthelmintic Property of the Various Extracts from Crescentia cujete Linn. Fruit. Science International-Lahore, 29(2): 31-35.
Clarke G, Ting KN, Wiart C and Fry J. 2013. High Correlation of 2,2-diphenyl-1-picrylhydrazyl (DPPH) Radical Scavenging, Ferric Reducing Activity Potential and Total Phenolics Content Indicates Redundancy in Use of All Three Assays to Screen for Antioxidant Activity of Extracts of Plants from the Malaysian Rainforest. Antioxidants, 2(1): 1–10. https://doi.org/10.3390/antiox2010001
Das N, Islam ME, Jahan N, Islam MS, Khan A, Islam MR and Parvin MS. 2014. Antioxidant activities of ethanol extracts and fractions of Crescentia cujete leaves and stem bark and the involvement of phenolic compounds. BMC Complementary and Alternative Medicine, 14: 45. https://doi.org/10.1186/1472-6882-14-45
De Guzman AAD, Jamanulla CEVA, Sabturani AM and Madjos GG. 2020. Ethnobotany and physiological review on folkloric medicinal plants of the Visayans in Ipil and Siay, Zamboanga Sibugay, Philippines. International Journal of Herbal Medicine, 8(3): 08-16.
Feng Y, Nan H, Zhou H, Xi P and Li B. 2022. Mechanism of inhibition of α-glucosidase activity by bavachalcone. Food Science and Technology, 42: e123421 https://doi.org/10.1590/fst.123421
Gilbert MP and Pratley RE. 2020. GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials. Frontier in Endocrinology, 11: 178. https://doi.org/10.3389/fendo.2020.00178
Glaudson FGP, de Oliveira AP, Maria CSS, De Gonçalves ROJ, Miranda IMP, Pereira X, Delange DM and Roberto JAS. 2016. Phytochemical screening and antioxidant activity of methanolic fraction from the leaves of Crescentia cujete L. (Bignoniaceae). Journal of Chemical and Pharmaceutical Research, 8(2): 231-236.
Gonzales AL, Sevilla UTA, Tsai PW and Huang SKH. 2022. Antioxidant and anti-inflammatory activities of bioactive compounds from Crescentia cujete L. leaves and fruit–A review. International Journal of Advanced and Applied Sciences, 9(11): 64-70. https://doi:10.21833/ijaas.2022.11.007
Han AR, Park HR, Kim GJ, Kim BR, Kim YR, Park HH, Park J, Jin CH, Kim JM, Kwon SJ et al. 2021. 18:0 Lyso PC Derived by Bioactivity-Based Molecular Networking from Lentil Mutant Lines and Its Effects on High-Fat Diet-Induced Obese Mice. Molecules, 26(24): 7547. https://doi.org/10.3390/molecules26247547
Kushwaha V, Agrawal P, Vekaria H, Das A, Shoraisham BK and Pathak B. 2023. Prostaglandins: An overview. European Journal of Pharmaceutical and Medical Research, 11(1): 130-139.
Lim TK. 2012. Crescentia cujete. In: Lim TK (eds). Edible Medicinal and Non-Medicinal Plants. Springer Netherlands, pp. 480–485pp. https://doi.org/10.1007/978-90-481-8661-7_64
Lobo V, Patil A, Phatak A and Chandra N. 2010. Free radicals, Antioxidants and Functional foods: Impact on Human Health. Pharmacognosy Reviews, 4(8): 118–126. https://doi.org/10.4103/0973-7847.70902
Morilla LJG and Demayo CG. 2019. Medicinal plants used by traditional practitioners in two selected villages of Ramon Magsaysay, Zamboanga Del Sur. Pharmacophore, 10(1): 84-89.
Mukherjee PK. 2019. Chapter 6 - Extraction and Other Downstream Procedures for Evaluation of Herbal Drugs. Quality Control and Evaluation of Herbal Drugs. 195-236pp. https://doi.org/10.1016/B978-0-12-813374-3.00006-5
Naing MD, Yerro JZ, Fernandez PL and Amor E. 2019. a-Glucosidase Inhibition Assay. In: Guevarra A and Alvero R (eds). Tuklas Lunas® Protocols for Drug Discovery and Development Volume IIB: Primary Bioactivity Assays. Taguig: Philippine Council for Health Research and Development.
Peng L, Sun B, Liu Y, Huang J, Chen G, Zhang X, Chen C, Wang DW and Wang G. 2021. Increased lipoxygenase and decreased cytochrome P450s metabolites correlated with the incidence of diabetic nephropathy: Potential role of eicosanoids from metabolomics in type 2 diabetic patients. Clinical and Experimental Pharmacology and Physiology, 48(5): 679-685. https://doi.org/10.1111/1440-1681.13471
Rellin KFB, Dasmariñas DD and Junio HA. 2018. Untargeted Metabolite Profiling of Philippine-grown Crescentia cujete and its Commercial Fruit Juice using GC-MS and UPLC-HRMS. Philippine Journal of Science, 147(4): 647-658.
Saxena M, Saxena J, Nema R, Singh D and Gupta. 2013. Phytochemistry of Medicinal Plants. Journal of Pharmacognosy and Phytochemistry, 1(6): 168-182.
Shaikh S, Lee E-J, Ahmad K, Ahmad S-S, Lim J-H and Choi I. 2021. A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes. Pharmaceuticals, 14(6): 591. https://doi.org/10.3390/ph140605
Shekhar TC and Anju G. 2014. Antioxidant Activity by DPPH Radical Scavenging Method of Ageratum conyzoides Linn. Leaves. American Journal of Ethnomedicine, 1(4): 244-249.
StataCorp. 2023. Stata Statistical Software: Release 13. College Station, TX: StataCorp LLC.
Tai Z, Cai L, Dai L, Dong L, Wang M, Yang Y, Cao Q and Ding Z. 2011. Antioxidant activity and chemical constituents of edible flower of Sophora viciifolia. Food Chemistry, 126(4): 1648–1654. https://doi.org/10.1016/j.foodchem.2010.12.048
Tupas GD, Rañeses GMM, Guarino DV, Martinez C, Marundan JA, Mascardo K, Melanio A, Meling RK, Mendez M, Monteverde KA and Montojo MD. 2018. Effect of ED90 dose of Calabash (Crescentia cujete) Decoction on the Blood Sugar Levels of Pre-Diabetic Individuals. DMSFI Research Journal, 3: 21-26.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M and Telser J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology, 39(1): 44–84. https://doi.org/10.1016/j.biocel.2006.07.001
Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, Nguyen DD, Watrous J, Kapono CA, Luzzatto-Knaan T et al. 2016. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nature Biotechnology, 34: 828-837. https://doi.org/10.1038/nbt.3597
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