Journal of Ethnopharmacology and Toxicology, Volume 2, Issue 2 : 27-43. Doi : 10.37446/jet/rsa/2.2.2024.27-43
Research Article

OPEN ACCESS | Published on : 31-Dec-2024

Evaluation of antioxidant, antidiabetic and bioactive compounds in polyphenol-rich stem bark extract and fractions of Averrhoa carambola

  • Godwin Ndarake Enin
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Uduak Nicholas Umanah
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Basil Nse Ita
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Ubong Okon Jeremiah
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Oguche Anne Divine
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Bassey Sunday Antia
  • Department of Chemistry, Faculty of Physical Sciences, University of Uyo, Nigeria.
  • Paul Sunday Thomas
  • Department of Pharmacognosy and Natural Medicine, Faculty of Pharmacy, University of Uyo, Nigeria.
  • Jude Efiom Okokon
  • Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Nigeria.

Abstract

Averrhoa carambola is employed traditionally in Nigeria to treat diabetes, vomiting, cough, chickenpox, ringworm, aphthous stomatitis, high blood pressure, eczema, diarrhea, and kidney dysfunction.. This study investigated the bioactive compounds, antioxidant and antidiabetic activities of the stem bark of Averrhoa carambola using standard methods. The antioxidant properties were assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing power (FRAP) assay and the metal chelating (MC) activity. The phytochemical analysis of the extract indicated the presence of flavonoids, saponins, alkaloids, tannins, and cardiac glycosides. The total phenolic and flavonoid content ranged from 4.46 ± 0.19 to 51.25 ± 0.52 mg of GAE/g and from 441.00 ± 5.98 to 2285.00 ± 11.13 mg of QE/g, respectively. Antioxidant study revealed IC50 range for DPPH (26.47 to 29.64 µg/mL), FRAP (26.51 to 51.30 µg/mL) and MC (69.53 to 60.66 µg/mL). The acute toxicity test of Averrhoa carambola stem bark extract showed a mean lethal dose (LD50) of 3872.98 mg/kg. The extract’s effect on α-amylase and α-glucosidase enzymes in rats, at doses of 155, 310 and 6200 mg/kg showed a significant reduction in blood glucose levels (p < 0.05). Gas chromatography-mass spectrometry (GC-MS) analysis of ethyl acetate fraction indicated several compounds, including 5-(2-Amino-phenyl)-[1,3,4]thiadiazo-2-yl-p-tolyl-amine, 2-hydroxymethoxybenzaldehyde, tert-butyldimethylsilyl ether, phenol, 4-[2,3-dihydro-7-methoxy-3-methyl-5-(1-propenyl)-2-benzofuranyl]-2-methoxy, thiazolo[3,2-a]2enzimidazole-3(2H)-one,2-(2-fflorobenzylideno)-7,8-dimethyl, squalene, phenol 2-methoxy-4-(2-propenyl)-, acetate, 2-(2,5-dimethoxy-4-propylphenyl) ethanamine, isoquinoline,1,2,3,4-tetrahydro-8-amino-2-methyl-4-phenyl-, phenol, 2,6-dimethoxy-4-(2-propenyl)-. This research suggests that Averrhoa carambola stem bark possesses antioxidative activity and inhibits the enzymes α-amylase and α-glucosidase in rats, probably due to the presence of its bioactive constituents.

Keywords

Averrhoa carambola, stem bark extract, antioxidant activity, diabetes, bioactive compounds

References

  • Aba, P. E., & Asuzu, I. U. (2018). Mechanisms of actions of some bioactive anti-diabetic principles from phytochemicals of medicinal plants: A review. Indian Journal of Natural Products and Resources (IJNPR)[Formerly Natural Product Radiance (NPR)]9(2), 85-96.

    Abduh, M. S., Saghir, S. A., Al Hroob, A. M., Bin-Ammar, A., Al-Tarawni, A. H., Murugaiyah, V., & Mahmoud, A. M. (2023). Averrhoa carambola leaves prevent dyslipidemia and oxidative stress in a rat model of poloxamer-407-induced acute hyperlipidemia. Frontiers in Pharmacology, 14, 1134812.

    Aguirre, L., Arias, N., Macarulla, M. T., Gracia, A., & Portillo, M. (2014). Beneficial effects of quercetin on obesity and diabetes. Open Nutraceuticals Journal, 4, 189–198.

    Ali, B. M., & Boothapandi, M., & Nasar, A. S. (2020). Nitric oxide, DPPH and hydrogen peroxide radical scavenging activity of TEMPO terminated polyurethane dendrimers: Data supporting antioxidant activity of radical dendrimers. Data in Brief, 28, 104972. https://doi.org/10.1016/j.dib.2019.104972.

    Alkhalidy, H., Wang, Y., & Liu, D. (2018). Dietary flavonoids in the prevention of T2D: An overview. Nutrients10(4), 438.

    Al-Rashood, K. A, Abdel-Aziz, H. A. (2010). Thiazolo [3, 2-a] benzimidazoles: synthetic strategies, chemical transformations and biological activities. Molecules, 15(6), 3775-815.

    Asika, A. O., Adeyemi, O. T., Anyasor, G. S. N., Gisarin, O., & Osilesi, O. (2016). GC-MS Determination of bioactive compounds and nutrient composition of Myristica fragrans Seeds. Journal of Herbs, Spices & Medicinal Plants, 22(4), 337-347.

    Awah, F. M., Uzoegwu, P. N., Ifeonu, P., Oyugi, J. O., Rutherford, J., Yao, X., Fehrmann, F., Fowke, K. R., Eze, M.O. (2012). Free radical scavenging activity, phenolic contents and cytotoxicity of selected Nigerian medicinal plants. Food Chemistry131(4), 1279-1286.

    Babu, P. V. A., Liu, D., & Gilbert, E. R. (2013). Recent advances in understanding the anti-diabetic actions of dietary flavonoids. The Journal of Nutritional Biochemistry24(11), 1777-1789.

    Beas-Guzmán, O. F., Cabrera-Licona, A., Hernández-Fuentes, G. A., Ceballos-Magaña, S. G., Guzmán-Esquivel, J., De-León-Zaragoza, L., Ramírez-Flores, M., Diaz-Martinez, J., Garza-Veloz, I., Martínez-Fierro, M. L. & Rodríguez-Sanchez, I. P. (2024). Ethanolic Extract of Averrhoa carambola Leaf Has an Anticancer Activity on Triple-Negative Breast Cancer Cells: An In vitro Study. Pharmaceutics17(1), 2.

    Bnouham, M., Ziyyat, A., Mekhfi, H., Tahri, A., & Legssyer, A. (2006). Medicinal plants with potential antidiabetic activity-A review of ten years of herbal medicine research (1990-2000). International Journal of Diabetes and Metabolism, 14(1), 1-25. https://doi.org/10.1159/000497588.

    Bogle, I. D. L., & Mendes, M. F. (2015). Evaluation of the effects and mechanisms of bioactive components present in hypoglycemic plants. International Journal of Chemical and Biomolecular Science, 1(3), 167-178.

    de Melo, E. B., da Silveira Gomes, A., & Carvalho, I. (2006). α-and β-Glucosidase inhibitors: chemical structure and biological activity. Tetrahedron62(44), 10277-10302.

    de Sousa, E., Zanatta, L., Seifriz, I., Creczynski-Pasa, T. B., Pizzolatti, M. G., Szpoganicz, B., & Silva, F. R. (2004). Hypoglycemic Effect and Antioxidant Potential of Kaempferol-3, 7-O-(α)-dirhamnoside from Bauhinia forficata Leaves. Journal of Natural Products, 67(5), 829-32.

    Dembinska-Kiec, A., Mykkänen, O., Kiec-Wilk, B., & Mykkänen, H. (2008). Antioxidant phytochemicals against type 2 diabetes. British Journal of Nutrition, 9, 109–117. https://doi. org/10.1017/S000711450896579X.

    Egbuna, C., Awuchi, C. G., Kushwaha, G., Rudrapal, M., Patrick-Iwuanyanwu, K. C., Singh, O., Odoh, U. E., Khan, J., Jeevanandam, J., Kumarasamy, S., & Chukwube, V. O. (2021). Bioactive compounds effective against type 2 diabetes mellitus: a systematic review. Current Topics in Medicinal Chemistry, 21(12), 1067-1095.

    Gidado, A., Watafua, M., Sa'ad, R. S., Tagi, H. S., Abdullahi, S. (2019). Alpha-amylase, maltase and sucrase inhibitions by aqueous leaf extracts of Anacardium occidentale (Anacardiacea) and Piliostigma reticulatum (Caesalpiniaceae) in rats. Tropical Journal of Natural Product Research, 3(6), 210-215.

    Gowrishankar, N. L., Farsena, A., Mubashireen, R., Rameesa, K., VP, S.S. & Sinara, N. S. (2018). A complete review on: Averrhoa carambola. Journal of Pharmacognosy and Phytochemistry7(3), 595-599.

    Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of Toxicology94(3), 651-715.

    GUSMAILINA, G., & KOMARAYATI, S. (2015). Exploration of organic compounds strychnine bush (Strychnos lucida) as source of medicines. In Prosiding Seminar Nasional Masyarakat Biodiversitas Indonesia, 1(7), 1741-1746.

    Halliwell, B., & Gutteridge, J. (1984). Oxygen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal, 219(1), 1.

    Hanamura, T., Hagiwara, T., & Kawagishi, H. (2005). Structural and functional characterization of polyphenols isolated from acerola (Malpighia emarginata DC.) fruit. Bioscience, Biotechnology, and Biochemistry, 69(2), 280-6.

    He, J. H., Chen, L. X., & Li, H. (2019). Progress in the discovery of naturally occurring anti-diabetic drugs and in the identification of their molecular targets. Fitoterapia, 134, 270-289.

    Hiyoshi, T., Fujiwara, M., & Yao, Z. (2017). Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes. Journal of Biomedical Research, 33(1), 1

    Jaydeokar, A. V., Bandawane, D. D., Nipate, S. S., & Chaudhari, P. D. (2012). Natural antioxidants: a review on therapeutic applications. Research Journal of Pharmacology and Pharmacodynamics4(1), 55-61.

    Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023). Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging. Archives of Toxicology97(10), 2499-2574.

    Kadhim, M. J., Mohammed, G. J., & Hussein, H. (2016). Analysis of bioactive metabolites from Candida albicans using (GC-MS) and evaluation of antibacterial activity. International Journal of Pharmaceutical and Clinical Research, 8(7), 655-670.

    Kalra, S. (2014). Alpha Glucosidase Inhibitors. The Journal of Pakistan Medical Association, 64(4), 474-476.

    Khoo, H. E., Azlan, A., Tang, S. T. & Lim, S. M. (2017). Anthocyanidins and anthocyanins: Colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food & Nutrition Research61(1), 1361779.

    Khoo, N. K., White, C. R., Pozzo-Miller, L., Zhou, F., Constance, C., Inoue, T., Patel, R. P., & Parks, D.A. (2010). Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels. Free Radical Biology and Medicine49(3), 339-347.

    Kim, D. O, Jeong, S. W., & Lee, C. Y. (2003). Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chemistry, 81(3), 321-326. https://doi.org/10.1016/S0308-8146(02)00423-5.

    Köksal, E., Gülçin, I., Beyza, S., Sarikaya, O., & Bursal, E. (2009). In vitro antioxidant activity of silymarin. Journal of Enzyme Inhibition and Medicinal Chemistry, 24(2), 395-405.

    Kumar, A., Aswal, S., Semwal, R. B., Chauhan, A., Joshi, S. K. & Semwal, D. K. (2019). Role of plant-derived alkaloids against diabetes and diabetes-related complications: a mechanism-based approach. Phytochemistry Reviews18(5), 1277-1298.

    Lakmal, K., Yasawardene, P., Jayarajah, U. & Seneviratne, S.L. (2021). Nutritional and medicinal properties of Star fruit (Averrhoa carambola): A review. Food Science & Nutrition9(3), 1810-1823.

    Lee, W. C., Wang, C. J., Chen, Y. H., Hsu, J. D., Cheng, S. Y., Chen, H. C., & Lee, H. J. (2009). Polyphenol extracts from Hibiscus sabdariffa Linnaeus attenuate nephropathy in experimental type 1 diabetes. Journal of Agriculture and Food Chemistry, 57, 2206– 2210.

    Lorke, D. A. (1983). A New Approach to Practical Acute Toxicity Test. Archives of Toxicology, 54, 275-286.

    Lozano-Grande, M. A., Gorinstein, S., Espitia-Rangel, E., Dávila-Ortiz, G., & Martínez-Ayala, A.L. (2018). Plant sources, extraction methods, and uses of squalene. International Journal of Agronomy2018(1), 1829160.

    Luan, F., Peng, L., Lei, Z., Jia, X., Zou, J., Yang, Y., He, X. & Zeng, N. (2021). Traditional uses, phytochemical constituents and pharmacological properties of Averrhoa carambola L.: a review. Frontiers in Pharmacology12, 699899.

    Manda, H., Vyas, K., Pandya, A. & Singhal, G. (2012). A complete review on: Averrhoa carambola. World Journal of Pharmacy and Pharmaceutical Sciences1(1), 17-33.

    Mbaebie, B. O., Edeoga, H. O., & Afolayan, A. J. (2012). Phytochemical analysis and antioxidants activities of aqueous stem bark extract of Schotia latifolia Jacq. Asian Pacific Journal of Tropical Biomedicine2(2), 118-124.

    Morais, F. S., Canuto, K. M., Ribeiro, P. R., & Silva, A. B., Pessoa, O. D., Freitas, C. D., Alencar, N. M., Oliveira, A. C., & Ramos, M. V. (2020). Chemical profiling of secondary metabolites from Himatanthus drasticus (Mart.) Plumel latex with inhibitory action against the enzymes α-amylase and α-glucosidase: In vitro and in silico assays. Journal of Ethnopharmacology, 253, 112644.

    Muscolo, A., Mariateresa, O., Giulio, T., & Mariateresa, R. (2024). Oxidative stress: the role of antioxidant phytochemicals in the prevention and treatment of diseases. International Journal of Molecular Sciences25(6), 3264.

    Mutha, R. E., Tatiya, A. U., & Surana, S. J. (2021). Flavonoids as natural phenolic compounds and their role in therapeutics: An overview. Future Journal of Pharmaceutical Sciences, 7, 1-3.

    Muthu, N., Lee, S. Y., Phua, K. K. & Bhore, S. J. (2016). Nutritional, medicinal and toxicological attributes of star-fruits (Averrhoa carambola L.): a review. Bioinformation12(12), 420.

    Neha, K., Haider, M. R., Pathak, A. & Yar, M. S. (2019). Medicinal prospects of antioxidants: A review. European Journal of Medicinal Chemistry178, 687-704.

    Nwozo, O. S., Effiong, E. M., Aja, P. M., & Awuchi, C. G. (2023). Antioxidant, phytochemical, and therapeutic properties of medicinal plants: A review. International Journal of Food Properties26(1), 359-388.

    Ouandaogo, H. S., Diallo, S., Odari, E., & Kinyua, J. (2023). Phytochemical screening and GC-MS analysis of methanolic and aqueous extracts of Ocimum kilimandscharicum leaves. ACS omega8(50), 47560-47572.

    Pandey, K. B., & Rizvi, S. I. (2010). Protection of protein carbonyl formation by quercetin in erythrocytes subjected to oxidative stress. Medicinal Chemistry Research, 19, 186–192.

    Park, C. J., & Han, J. S. (2015). Hypoglycemic effect of jicama (Pachyrhizus erosus) extract on streptozotocin-induced diabetic mice. Preventive Nutrition and Food Science, 20(2), 88.

    Patil, A. G., Patil, D. A., Phatak, A. V. & Chandra, N. (2010). Physical and chemical characteristics of carambola (Averrhoa carambola L.) fruit at three stages of maturity. International Journal of Applied Biology and Pharmaceutical Technology1(2), 624-629.

    Paudel, M. R., Sharma, S., Joshi, P. R., Pant, B., Wagner, S. H., Gurung, P., Pant, K. K.  & Pant, B. (2025). Antioxidant and cytotoxic properties of protocorm-derived phenol-rich fractions of Dendrobium amoenum. BMC Complementary Medicine and Therapies25(1), 61.

    Perez Gutierrez, R. M. (2016). Antidiabetic and antioxidant properties, and α-amylase and α-glucosidase inhibition effects of triterpene saponins from Piper auritumFood Science and Biotechnology25(1), 229-239.

    Pisoschi, A. M., & Pop, A. (2015). The role of antioxidants in the chemistry of oxidative stress: A review. European Journal of Medicinal Chemistry97, 55-74.

    Proença, C., Freitas, M., Ribeiro, D., Oliveira, E. F., Sousa, J., & Tome, S. M, et al. (2017) α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 1216-1228. Https://doi.org/10.1080/14756366.2017.1368503.

    Rhaman, M. M., Shoeb, M., & Islam, M. N. (2022). Averrhoa carambola L. Dhaka University Journal of Pharmaceutical Sciences, 21(2), 147-151. DOI: https://doi.org/10.3329/dujps.v21i2.63115

    Saghir, S. A., Abdulghani, M. A., Alruhaimi, R. S., Ahmeda, A. F., Al-Gabri, N. A., Alomaisi, S. A., Sadikun, A., Murugaiyah, V. & Mahmoud, A.M. (2022). Acute and sub-chronic toxicological evaluation of Averrhoa carambola leaves in Sprague Dawley rats. Environmental Science and Pollution Research29(60), 90058-90069.

    Salehi, B., Ata, A. V., Anil Kumar, N., Sharopov, F., Ramírez-Alarcón, K., Ruiz-Ortega, A., Abdulmajid Ayatollahi, S., Valere Tsouh Fokou, P., Kobarfard, F., Amiruddin Zakaria, Z., & Iriti, M. (2019). Antidiabetic potential of medicinal plants and their active components. Biomolecules9(10), 551.

    Shehadeh, M. B., Suaifan, G. A., & Abu-Odeh, A. M (2021). Plants secondary metabolites as blood glucose-lowering molecules. Molecules, 26(14), 4333. https://doi.org/10.3390/molecules26144333.

    Shekhar, T. C., & Anju, G. (2014). Antioxidant activity by DPPH radical scavenging method of Ageratum conyzoides Linn. leaves. American Journal of Ethnomedicine, 1(4), 244-249.

    Silva, K. B., Pinheiro, C. T., Soares, C. R., Souza, M. A., Matos-Rocha, T. J., Fonseca, S. A., Pavão, J. M., Costa, J. G., Pires, L. L., Santos, A. F. (2020). Caracterização fitoquímica, potencial antioxidante e atividade antimicrobiana de Averrhoa carambola L. (Oxalidaceae) frente a patógenos multirresistentes. Brazilian Journal of Biology, 81, 509-15.

    Singh, S., Bansal, A., Singh, V., Chopra, T., & Poddar, J. (2022). Flavonoids, alkaloids and terpenoids: a new hope for the treatment of diabetes mellitus. Journal of Diabetes & Metabolic Disorders21(1), 941-950.

    Subhashini, R., Rao, U. M., Sumathi, P., & Gunalan, G. (2010). A comparative phytochemical analysis of cocoa and green tea. Indian Journal of Science and Technology, 3(2), 188-192.

    Thilagam, E., Parimaladevi, B., Kumarappan, C., & Mandal, S C. (2013). α-Glucosidase and α-amylase inhibitory activity of Senna surattensis. Journal of Acupuncture and Meridian Studies, 6(1), 24-30.

    Ubulom, P. M., Ettebong, E. O., Akpabio, E. I., & Etokakpan, K. E. (2017). Evaluation of antiplasmodial activity of ethanol extract and fractions of Maesobotrya barteri root. Journal of Pharmacy and Bioresources, 14(1), 68-74.

    Unuofin, J. O., & Lebelo, S. L. (2020). Antioxidant effects and mechanisms of medicinal plants and their bioactive compounds for the prevention and treatment of type 2 diabetes: an updated review. Oxidative Medicine and Cellular Longevity, 1, 1356893.

    Vargas-Madriz, Á. F., Kuri-García, A., Vargas-Madriz, H., Chávez-Servín, J. L. & Ayala-Tirado, R. A. (2021). Phenolic profile and antioxidant capacity of fruit Averrhoa carambola L.: a review. Food Science and Technology42, p.e69920.

    Wang, Q., Wu, X., Shi, F., & Liu, Y. (2019). Comparison of antidiabetic effects of saponins and polysaccharides from Momordica charantia L. in STZ-induced type 2 diabetic mice. Biomedicine & Pharmacotherapy109, 744-750.

    Wanjala Wafula, K., Kiambi Mworia, J., & Piero Ngugi, M. (2023). Phytochemical Screening and In Vitro Evaluation of the Antioxidant Potential of Dichloromethane Extracts of Strychnos henningsii Gilg. and Ficus sycomorus L. The Scientific World Journal, 1(1), 8494176.

    Wojcik, M., Burzynska-Pedziwiatr, I., & Wozniak, L.A. (2010). A review of natural and synthetic antioxidants important for health and longevity. Current Medicinal Chemistry17(28), 3262-3288.

    World Health Organization. (2011). Glucose analyser. Core medical equipment information. www.who.int/medical_devices/en/index.html. Accessed 5 June, 2019.

    Yang, C. Y., Yen, Y. Y., Hung, K. C., Hsu, S. W., Lan, S. J., & Lin H. C. (2019). Inhibitory effects of pu-erh tea on alpha glucosidase and alpha amylase: a systemic review. Nutrition & Diabetes, 1, 23. https://doi.org/10.1038/s41387-019-0092-y.

    Yang, J., Luo, J., Tian, X., Zhao, Y., Li, Y., & Wu, X. (2024). Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases. Antioxidants13(4), 394.

    Yang, Y., Jia, X., Xie, H. & Wei, X. (2020). Dihydrochalcone C-glycosides from Averrhoa carambola leaves. Phytochemistry174, 112364.

    Zainudin, M. A. M., Hamid, A. A., Anwar, F., Osman, A. & Saari, N. (2014). Variation of bioactive compounds and antioxidant activity of carambola (Averrhoa carambola L.) fruit at different ripening stages. Scientia Horticulturae172, 325-331.

    Zujko, M. E., & Witkowska, A. M. (2023). Dietary antioxidants and chronic diseases. Antioxidants12(2), 362.