Ameliorative Potential of the Polyphenolic Compounds in Cucumis sativus (Linn.) Fruit Pulp Extract on Streptozotocin-induced Diabetes in Male Wistar Rats
Year 2025,
Volume: 6 Issue: 2, 42 - 71, 02.04.2025
Olasunkanmi Awote
,
Adesegun Adeyemo
,
Olabisi Ogunrinola
,
Blessing Ogunyinka
,
Ibrahim Adenekan
,
Babajide Kayode
Abstract
Diabetes mellitus continues to be a major global public health concern, underscoring the urgent need for continuous exploration of locally available medicinal plants and functional foods that are affordable, accessible, and capable of supporting effective management and improved health outcomes. This study investigated the effect of Cucumis sativus pulp extract (CSPE) on selected oxidative stress and diabetes-related biochemical indices. A total of 24 male Wistar rats were divided into 4 groups (n=6), including control, diabetic-untreated, and diabetic-treated groups (with CSPE or glibenclamide). Oxidative stress (hydrogen peroxide [H2O2], nitric oxide [NO], malondialdehyde [MDA], glutathione [GSH]); lipid profile (total cholesterol [TC], triglyceride [TRIG], high-density [HDL-Chol, low-density [LDL-Chol], and very-low-density [VLDL-Chol] lipoprotein cholesterol; liver antioxidant (superoxide dismutase [SOD], catalase [CAT]); and liver function (alanine [ALT], and aspartate [AST] aminotransferase) enzymes were evaluated using standard biochemical kits and procedures. PyRx and Biovia Discovery Studio were used for molecular docking studies while swissADME and ProTox were used to predict the ADME/T properties. Results showed that treatment with CSPE had a significant (p<0.05) increase in liver antioxidant enzymes, HDL-Chol, and GSH levels and decrease in liver function, TC, TRIG, LDL-Chol, VLDL-Chol, H2O2, MDA, and NO compared to the diabetic-untreated group. β-sitosterol bound well with α-amylase (-8.9 kcal/ mol) and aldose reductase (-8.8 kcal/mol) while hesperidin bound to α-glucosidase (-8.8 kcal/mol) and sorbitol dehydrogenase (-10.6 kcal/mol) with favorable ADME and non-toxicity profiles. In conclusion, CSPE can serve as a therapeutic agent in addition to its known nutritional properties in managing diabetes and its related complications.
Ethical Statement
Current national and international criteria were followed in the care and usage of the Wistar rats during the study. With the ethical approval number LASU/23/REC/055, the Lagos State University Research Ethics Committee authorized the study procedure.
Thanks
The authors want to deeply appreciate the favor, wisdom, and mercies of God for the success of this research.
References
- Adamu, A. U., Abdulmumin, Y., & Mustapha, R. K. (2021). Green Synthesis, Characterization and Phytochemicals Analysis of Silver Nano-Particles Using Aqueous Peel Extract of Cucumis sativus. J. Mater. Environ. Sci, 12(12), 1627-1636.
- Andrés, C. M. C., Lastra, J. M. P. D. L., Juan, C. A., Plou, F. J., & Pérez-Lebeña, E. (2023). Chemical insights into oxidative and nitrative modifications of DNA. International Journal of Molecular Sciences, 24(20), 15240.
- Andrés, C. M. C., Pérez de la Lastra, J. M., Juan, C. A., Plou, F. J., & Pérez-Lebeña, E. (2024). Antioxidant Metabolism Pathways in Vitamins, Polyphenols, and Selenium: Parallels and Divergences. International Journal of Molecular Sciences, 25(5), 2600.
- Afzal, S., Abdul Manap, A. S., Attiq, A., Albokhadaim, I., Kandeel, M., & Alhojaily, S. M. (2023). From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration. Frontiers in Pharmacology, 14, 1269581.
- Awote OK, Amisu KO, Anagun OS, Dohou FP, Olokunola ER and Elum NO. (2024). In vitro and Molecular Docking Evaluation of the Antibacterial, Antioxidant, and Antidiabetic Effects of Silver Nanoparticles from Cymbopogon citratus Leaf. Tropical Journal of Natural Product Research (TJNPR), 8(9): 8400–8411.
- Awote, O.K., Kazeem, M.I., Ojekale, A.B., Ayanleye, O.B., & Ramoni, H.T. (2023). Prospects of silver nanoparticles (AgNPs) synthesized by Justicia secunda aqueous extracts on diabetes and its related complications. Proc Nig Acad Sci., 16(1): 87-105.
- Awote, O.K., Apete, S.K., Igbalaye, J.O., Adeyemo, A.G., Dele-osedele, P.I., Thomas-Akinwale, K., Boniwey, T.S., Ogunbamowo, A.A., Ebube, S.C., Folami, S.O. (2022). Phytochemical Screening, Antioxidant, and α-Αmylase Inhibitory Activities of Acacia nilotica Seed Methanol Extract. Adv J Curr Res., 7(8): 1-27.
- Awote, O. K., Igbalaye, J. O., & Gideon, A. (2021). Effect of Phragmanthera incana Leaves Extracts on Lipid Profile in Wistar Rats Fed High-Fat Diet. International Journal of Formal Sciences: Current and Future Research Trends, 12(1), 23-32.
- Banu, S., & Bhowmick, A. (2017). Therapeutic targets of type 2 diabetes: An overview. MOJ Drug Des. Dev. Ther, 1(11).
- Bhosale, H. J., Mamdapure, S. V., Panchal, R. B., & Dhuldhaj, U. P. (2024). α-Amylase, α-glucosidase, and aldose reductase inhibitory and molecular docking studies on Tinospora cordifolia (Guduchi) leaf extract. Future Journal of Pharmaceutical Sciences, 10(1), 107.
- Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., Calina, D., & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198.
- Chmiel, T., Mieszkowska, A., Kempińska-Kupczyk, D., Kot-Wasik, A., Namieśnik, J., & Mazerska, Z. (2019). The impact of lipophilicity on environmental processes, drug delivery and bioavailability of food components. Microchemical Journal, 146, 393-406.
- Daliri, E. B. M., Oh, D. H., & Lee, B. H. (2017). Bioactive peptides. Foods, 6(5), 32.
- Drabińska, N. (2024). Current Perspective About the Effect of a Ketogenic Diet on Oxidative Stress–a Review. Polish Journal of Food and Nutrition Sciences, 74(1), 92-105.
- Dubey, K., Dubey, R., Gupta, R., & Gupta, A. K. (2020). α-Amylase, α-Glucosidase and Aldose reductase Inhibitory Potential of Betanin for the Management of Diabetes and its complications. Journal of Advanced Scientific Research, 11(03), 92-95.
- Dulsat, J., López-Nieto, B., Estrada-Tejedor, R., & Borrell, J. I. (2023). Evaluation of free online ADMET tools for academic or small biotech environments. Molecules, 28(2), 776.
- Farid, M. M., Aboul Naser, A. F., Salem, M. M., Ahmed, Y. R., Emam, M., & Hamed, M. A. (2022). Chemical compositions of Commiphora opobalsamum stem bark to alleviate liver complications in streptozotocin-induced diabetes in rats: Role of oxidative stress and DNA damage. Biomarkers, 27(7), 671-683.
- Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Analytical biochemistry, 126(1), 131-138.
- Haghani, F., Arabnezhad, M. R., Mohammadi, S., & Ghaffarian-Bahraman, A. (2022). Aloe vera and streptozotocin-induced diabetes mellitus. Revista Brasileira de Farmacognosia, 32(2), 174-187.
- Heidari, H., Kamalinejad, M., & Eskandari, M. R. (2012). Hepatoprotective activity of Cucumis sativus against cumene hydroperoxide induced-oxidative stress. Research in Pharmaceutical Sciences, 7(5), 936.
- Hossain, M. J., Al‐Mamun, M., & Islam, M. R. (2024). Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Health Science Reports, 7(3), e2004.
- Ivanović, V., Rančić, M., Arsić, B., & Pavlović, A. (2020). Lipinski’s rule of five, famous extensions and famous exceptions. Popular Scientific Article, 3(1), 171-177.
- Jollow, D. J., Mitchell, J. R., Zampaglione, N. A., & Gillette, J. R. (1974). Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11(3): 151-169.
- Khan, A., Mishra, A., Hasan, S. M., Usmani, A., Ubaid, M., Khan, N., & Saidurrahman, M. (2022). Biological and medicinal application of Cucumis sativus Linn.–review of current status with future possibilities. Journal of Complementary and Integrative Medicine, 19(4), 843-854.
- Kulkarni, A., Thool, A. R., & Daigavane, S. (2024). Understanding the Clinical Relationship Between Diabetic Retinopathy, Nephropathy, and Neuropathy: A Comprehensive Review. Cureus, 16(3):e56674.
- Latha, P. S., Sangeetha, S., Vijayakarthikeyan, M., & Shankar, R. (2024). Prevalence and influencing factors of metabolic syndrome among rural adult population in a district of South India. Journal of Family Medicine and Primary Care, 13(8), 3122-3128.
- Lipinski, CA. (2004). Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4): 337-41.
- Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193: 265–275
- Magliano, D. J., & Boyko, E. J. (2022). IDF diabetes atlas.
- Małkiewicz, M. A., Szarmach, A., Sabisz, A., Cubała, W. J., Szurowska, E., & Winklewski, P. J. (2019). Blood-brain barrier permeability and physical exercise. Journal of neuroinflammation, 16, 1-16.
Mannino, G., Iovino, P., Lauria, A., Genova, T., Asteggiano, A., Notarbartolo, M., Porcu, A., Serio, G., Chinigò, G.,
- Occhipinti, A. and Capuzzo, A., Medana, C., Munaron, L., & Gentile, C. (2021). Bioactive triterpenes of Protium heptaphyllum gum resin extract display cholesterol-lowering potential. International Journal of Molecular Sciences, 22(5), 2664.
- Mbatha, B., Khathi, A., Sibiya, N., Booysen, I., & Ngubane, P. (2022). A Dioxidovanadium Complex cis‐[VO2 (obz) py] Attenuates Hyperglycemia in Streptozotocin (STZ)‐Induced Diabetic Male Sprague‐Dawley Rats via Increased GLUT4 and Glycogen Synthase Expression in the Skeletal Muscle. Evidence‐Based Complementary and Alternative Medicine, 2022(1), 5372103.
- Molly, J., Edison, S., Vijajaraghavan, R., & Ajith, T. A. (2017). Effect of curry leaves and cucumber fruit on lipid profile in menopausal women with hyperlipidemia: a randomized controlled pilot study. Int J Clin Trials, 4(1), 7-13.
- Mukai, E., Fujimoto, S., & Inagaki, N. (2022). Role of reactive oxygen species in glucose metabolism disorder in diabetic pancreatic β-cells. Biomolecules, 12(9), 1228.
- Ntie-Kang, F., Nyongbela, K. D., Ayimele, G. A., & Shekfeh, S. (2019). “Drug-likeness” properties of natural compounds. Physical Sciences Reviews, 4(11), 20180169.
- Ogunyinka, B.I., Oyinloye, B.E., Osunsanmi, F.O., Opoku, A.R., & Kappo, A.P. (2017). Protective effects of Parkia biglobosa protein isolate on streptozotocin-induced hepatic damage and oxidative stress in diabetic male rats. Molecules, 22(10): 1654.
- Oladimeji, S.O., Soares, A.S., Igbalaye, J.O., Awote, O.K., Adigun, A.K., & Awoyemi, Z.O. (2022). Ethanolic Root Extract of Urtica dioica Exhibits Pro-fertility and Antioxidant Activities in Female Albino Rats. International Journal of Biochemistry Research & Review. 31(8):29-38.
- Oladimeji, S.O., Igbalaye, J.O., Awote, O.K., Shodimu, B.O., Oladeinde, D.T., Omorowa, V.T., Oluwole, S.M., Akinyemi, Y.A., Shobowale, A.Y., Jimoh, D., & Balogun, S.T. (2023). Cissampelos pareira ethanolic extract modulates hormonal indices, lipid profile, and oxidative parameters in transient infertility-induced female albino rats. Bio-Research, 21(2), pp.1961-1972.
- Oloruntola, O. D., & Ayodele, S. O. (2022). Phytochemical, proximate, and mineral composition, antioxidant and antidiabetic properties evaluation and comparison of mistletoe leaves from moringa and kolanut trees. Turkish journal of agriculture-food science and technology, 10(8), 1524-1531.
- Padhi, S., Nayak, A. K., & Behera, A. (2020). Type II diabetes mellitus: a review on recent drug-based therapeutics. Biomedicine & Pharmacotherapy, 131, 110708.
- Popoviciu, M. S., Paduraru, L., Nutas, R. M., Ujoc, A. M., Yahya, G., Metwally, K., & Cavalu, S. (2023). Diabetes mellitus secondary to endocrine diseases: an update of diagnostic and treatment particularities. International Journal of Molecular Sciences, 24(16), 12676.
- Prince, P.S.M., & Menon, V.P., (2003). Hypoglycaemic and hypolipidaemic action of alcohol extract of Tinospora cordifolia root in chemical-induced diabetes in rats. Phytotherapy Research 17: 410–413.
- Quranayati, Q., Iqhrammullah, M., Saidi, N., Nurliana, N., Idroes, R., & Nasution, R. (2023). Extracts from Phyllanthus emblica L stem barks ameliorate blood glucose level and pancreatic and hepatic injuries in streptozotocin-induced diabetic rats. Arabian Journal of Chemistry, 16(9), 105082.
- Sahu, M. K., Nayak, A. K., Hailemeskel, B., & Eyupoglu, O. E. (2024). Exploring recent updates on molecular docking: Types, method, application, limitation & future prospects. International Journal of Pharmaceutical Research and Allied Sciences, 13(2-2024), 24-40.
- Saidu, A. N., Oibiokpa, F. I., & Olukotun, I. O. (2014). Phytochemical screening and hypoglycemic effect of methanolic fruit pulp extract of Cucumis sativus in alloxan-induced diabetic rats. Journal of Medicinal Plants Research, 8(39), 1173-1178.
- Sari, T. A., Chandra, B., & Rivai, H. (2021). Overview of traditional use, phytochemical, and pharmacological activities of cucumber (Cucumis sativus L.). International Journal of Pharmaceutical Sciences and Medicine, 6(3), 39-49.
- Singh, R., Gholipourmalekabadi, M., & Shafikhani, S. H. (2024). Animal models for type 1 and type 2 diabetes: advantages and limitations. Frontiers in Endocrinology, 15, 1359685.
- Sood, A., Kaur, P., & Gupta, R. (2012). Phytochemical screening and antimicrobial assay of various seeds extract of Cucurbitaceae family.
- Stratton, C. F., Newman, D. J., & Tan, D. S. (2015). Cheminformatic comparison of approved drugs from natural product versus synthetic origins. Bioorganic & medicinal chemistry letters, 25(21), 4802-4807.
- Thabti, I., Elfalleh, W., Hannachi, H., Ferchichi, A., & Campos, M. D. G. (2012). Identification and quantification of phenolic acids and flavonol glycosides in Tunisian Morus species by HPLC-DAD and HPLC–MS. Journal of Functional Foods, 4(1), 367-374.
- Varshney, R., & Kale, R. K. (1990). Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes. International journal of radiation biology, 58(5), 733-743.
- Wolff, S.P. (1994). Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods in Enzymology, 233: 182–189.
- World Health Organization. (2019). Global action plan on physical Activity 2018-2030: More Active People for a healthier world. World Health Organization.
- Yedjou, C. G., Grigsby, J., Mbemi, A., Nelson, D., Mildort, B., Latinwo, L., & Tchounwou, P. B. (2023). The management of diabetes mellitus using medicinal plants and vitamins. International Journal of Molecular Sciences, 24(10), 9085.