SPECIAL ISSUE ORIGINAL ARTICLE
Vernonia amygdalina stimulates muscle glucose uptake and modulates redox activities and functional chemistry in oxidative hepatic injury
Ochuko L. Erukainure,
Md. Shahidul Islam,
Ochuko L. Erukainure
Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
Contribution: Writing - original draft
Search for more papers by this authorCorresponding Author
Md. Shahidul Islam
Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
Correspondence
Md. Shahidul Islam, Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
Email: [email protected]
Contribution: Writing - review & editing
Search for more papers by this authorOchuko L. Erukainure,
Md. Shahidul Islam,
Ochuko L. Erukainure
Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
Department of Pharmacology, School of Clinical Medicine, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
Contribution: Writing - original draft
Search for more papers by this authorCorresponding Author
Md. Shahidul Islam
Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
Correspondence
Md. Shahidul Islam, Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa.
Email: [email protected]
Contribution: Writing - review & editing
Search for more papers by this authorAbstract
The ethyl acetate, ethanol, and aqueous extracts sequentially obtained from the leaves of Vernonia amygdalina were investigated for their antidiabetic and antioxidant protective effect in oxidative hepatic injury. The extracts showed significant (p < .05) free radical scavenging and reducing power activities. They significantly (p < .05) elevated reduced glutathione level, superoxide dismutase, and catalase activities, with concomitant depletion of malondialdehyde level. The ethanol and aqueous extracts caused a removal of oxidative-included chemical functional group at 1,500–1,200 (amide II)/cm region, with the inclusion of a functional group at 3,000–2,800 (carboxylic acid)/cm region. The extracts significantly (p < .05) inhibited the activities of α-glucosidase and α-amylase and stimulated glucose uptake in rat muscles. Gas chromatography-mass spectrometric (GC-MS) analysis revealed phytol as the predominant compound, with ethanol having the highest concentration. Based on the IC50 values, the ethanol extract exhibited the best activities, followed by the ethyl acetate extract, while the aqueous extract was the least. These results suggest the antioxidative and antidiabetic properties of V. amygdalina as evident by their modulation of antioxidant biomarkers and oxidative-induced chemistry changes and stimulate muscle glucose uptake.
Practical applications
Vernonia amygdalina (bitter leaf) is amongst the common leafy vegetables in West Africa reported for its various medicinal and nutritional properties. It is utilized as a food ingredient as well as supplement for the treatment and management of type 2 diabetes. The ability of its extracts to stimulate glucose uptake and protect against diabetic-induced changes in the chemical functional groups of the liver gives more credence to its reported antidiabetic properties. Being a common leafy vegetable, V. amygdalina can be a cheap source of nutraceutical for the treatment and management of type 2 diabetes and its complications.
CONFLICT OF INTEREST
The authors report no conflict of interest.
Supporting Information
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REFERENCES
- Adaramoye, O. A., Akintayo, O., Achem, J., & Fafunso, M. A. (2008). Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in rats fed on high cholesterol diet. Vascular Health and Risk Management, 4(1), 235. https://doi.org/10.2147/vhrm.2008.04.01.235
- Adesanoye, O. A., & Farombi, E. O. (2010). Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride. Experimental and Toxicologic Pathology, 62(2), 197–206. https://doi.org/10.1016/j.etp.2009.05.008
- Aebi, H. (1984). Catalase in vitro. In Methods in enzymology (Vol. 105, pp. 121–126). Elsevier.
- Afolabi, I. S., Osikoya, I. O., Fajimi, O. D., Usoro, P. I., Ogunleye, D. O., Bisi-Adeniyi, T., Adeyemi, A. O., & Adekeye, B. T. (2012). Solenostemon monostachyus,Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: Methanolic extracts of novel plants for the management of sickle cell anemia disease. BMC Complementary and Alternative Medicine, 12(1), 262. https://doi.org/10.1186/1472-6882-12-262
- Ajibola, C. F., Eleyinmi, A. F., & Aluko, R. E. (2011). Kinetics of the inhibition of renin and angiotensin I converting enzyme by polar and non-polar polyphenolic extracts of Vernonia amygdalina and Gongronema latifolium leaves. Plant Foods for Human Nutrition, 66(4), 320–327. https://doi.org/10.1007/s11130-011-0257-x
- Andrews, N. C. (1999). Disorders of iron metabolism. New England Journal of Medicine, 341(26), 1986–1995.
- Arhoghro, E. M., Ekpo, K., Anosike, E., & Ibeh, G. (2009). Effect of aqueous extract of bitter leaf (Vernonia amygdalina Del) on carbon tetrachloride (CCl4) induced liver damage in albino Wistar rats. European Journal of Scientific Research, 26(1), 122–130.
- Aslan, M., ThornleY-Brown, D., & Freeman, B. A. (2000). Reactive species in sickle cell disease. Annals of the New York Academy of Sciences, 899(1), 375–391.
- Atangwho, I., Ebong, P., Egbung, G., Eteng, M., & Eyong, E. (2007). Effect of Vernonia amygdalina Del. on liver function in alloxan-induced hyperglycaemic rats. Journal of Pharmacy & Bioresources, 4(1), 25–30.
- Atangwho, I., Ebong, P., Eyong, E., Williams, I., Eten, M., & Egbung, G. (2009). Comparative chemical composition of leaves of some antidiabetic medicinal plants: Azadirachta indica,Vernonia amygdalina and Gongronema latifolium. African Journal of Biotechnology, 8(18), 4685–4689.
- Atangwho, I. J., Yin, K. B., Umar, M. I., Ahmad, M., & Asmawi, M. Z. (2014). Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats. BMC Complementary and Alternative Medicine, 14(1), 426.
- Benzie, I. F., & Strain, J. J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Analytical Biochemistry, 239(1), 70–76.
- Berlett, B. S., & Stadtman, E. R. (1997). Protein oxidation in aging, disease, and oxidative stress. Journal of Biological Chemistry, 272(33), 20313–20316.
- Braca, A., Sortino, C., Politi, M., Morelli, I., & Mendez, J. (2002). Antioxidant activity of flavonoids from Licania licaniaeflora. Journal of Ethnopharmacology, 79(3), 379–381. https://doi.org/10.1016/S0378-8741(01)00413-5
- Chan, C. Y., Khan, A. A., Choi, J. H., Ng, C. M., Cadeiras, M., Deng, M., & Ping, P. (2013). Technology platform development for targeted plasma metabolites in human heart failure. Clinical Proteomics, 10(1), 7. https://doi.org/10.1186/1559-0275-10-7
- Chikezie, P. (2006). Studies on the anti-sickling effects of Azadirachta indica and Vernonia amygdalina on HbSS erythrocytes. International Journal of Natural and Applied Sciences, 2(1), 24–28.
10.4314/ijonas.v2i1.36041 Google Scholar
- Chowdhury, P., & Soulsby, M. (2002). Lipid peroxidation in rat brain is increased by simulated weightlessness and decreased by a soy-protein diet. Annals of Clinical & Laboratory Science, 32(2), 188–192.
- Chukwuma, C. I., & Islam, M. S. (2015). Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: A multi-mode study. Food & Function, 6(3), 955–962.
- Coskun, O., Kanter, M., Korkmaz, A., & Oter, S. (2005). Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacological Research, 51(2), 117–123.
- Dalle-Donne, I., Rossi, R., Giustarini, D., Milzani, A., & Colombo, R. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Clinica Chimica Acta, 329(1), 23–38.
- Dinis, T. C., Madeira, V. M., & Almeida, L. M. (1994). Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Archives of Biochemistry and Biophysics, 315(1), 161–169. https://doi.org/10.1006/abbi.1994.1485
- Dreosti, I. E. (2000). Antioxidant polyphenols in tea, cocoa, and wine. Nutrition, 16(7), 692–694.
- Dudonné, S., Vitrac, X., Coutiere, P., Woillez, M., & Mérillon, J.-M. (2009). Comparative study of antioxidant properties and total phenolic content of 30 plant extracts of industrial interest using DPPH, ABTS, FRAP, SOD, and ORAC assays. Journal of Agricultural and Food Chemistry, 57(5), 1768–1774. https://doi.org/10.1021/jf803011r
- Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77.
- Erasto, P., Van de Venter, M., Roux, S., Grierson, D., & Afolayan, A. (2009). Effect of leaf extracts of Vernonia amygdalina on glucose utilization in chang-liver, C2C12 muscle and 3T3-L1 cells. Pharmaceutical Biology, 47(2), 175–181.
- Erukainure, O. L., Ebuehi, O. A., Adeboyejo, F. O., Okafor, E. N., Muhammad, A., & Elemo, G. N. (2013). Fiber-enriched biscuit enhances insulin secretion, modulates β-cell function, improves insulin sensitivity, and attenuates hyperlipidemia in diabetic rats. PharmaNutrition, 1(2), 58–64. https://doi.org/10.1016/j.phanu.2013.02.001
- Erukainure, O. L., Mopuri, R., Oyebode, O. A., Koorbanally, N. A., & Islam, M. S. (2017). Dacryodes edulis enhances antioxidant activities, suppresses DNA fragmentation in oxidative pancreatic and hepatic injuries; and inhibits carbohydrate digestive enzymes linked to type 2 diabetes. Biomedicine & Pharmacotherapy, 96, 37–47.
- Erukainure, O. L., Oyebode, O. A., Sokhela, M. K., Koorbanally, N. A., & Islam, M. S. (2017). Caffeine–rich infusion from Cola nitida (kola nut) inhibits major carbohydrate catabolic enzymes; abates redox imbalance; and modulates oxidative dysregulated metabolic pathways and metabolites in Fe 2+-induced hepatic toxicity. Biomedicine & Pharmacotherapy, 96, 1065–1074.
- Ezuruike, U. F., & Prieto, J. M. (2014). The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations. Journal of Ethnopharmacology, 155(2), 857–924.
- Farombi, E. O., & Owoeye, O. (2011). Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid. International Journal of Environmental Research and Public Health, 8(6), 2533–2555. https://doi.org/10.3390/ijerph8062533
- Gee, P., & Davison, A. J. (1989). Intermediates in the aerobic autoxidation of 6-hydroxydopamine: Relative importance under different reaction conditions. Free Radical Biology and Medicine, 6(3), 271–284. https://doi.org/10.1016/0891-5849(89)90054-3
- Gutteridge, J. (1995). Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clinical Chemistry, 41(12), 1819–1828.
- I.D.F. (2016). IDF Diabetes Atlas (7th ed.). Author.
- Ijeh, I. I., & Ejike, C. E. (2011). Current perspectives on the medicinal potentials of Vernonia amygdalina Del. Journal of Medicinal Plants Research, 5(7), 1051–1061.
- Iwalokun, B., Efedede, B., Alabi-Sofunde, J., Oduala, T., Magbagbeola, O., & Akinwande, A. (2006). Hepatoprotective and antioxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice. Journal of Medicinal Food, 9(4), 524–530.
- Janero, D. R. (1990). Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radical Biology and Medicine, 9(6), 515–540.
- Jiang, R., Manson, J. E., Meigs, J. B., Ma, J., Rifai, N., & Hu, F. B. (2004). Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA, 291(6), 711–717. https://doi.org/10.1001/jama.291.6.711
- Kamal-Eldin, A., & Appelqvist, L. Å. (1996). The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids, 31(7), 671–701. https://doi.org/10.1007/BF02522884
- Liu, Q., & Yao, H. (2007). Antioxidant activities of barley seeds extracts. Food Chemistry, 102(3), 732–737. https://doi.org/10.1016/j.foodchem.2006.06.051
- Michael, U. A., David, B. U., Theophine, C. O., Philip, F. U., Ogochukwu, A. M., & Benson, V. A. (2010). Antidiabetic effect of combined aqueous leaf extract of Vernonia amygdalina and metformin in rats. Journal of Basic and Clinical Pharmacy, 1(3), 197.
- Oboh, G., & Ademosun, A. O. (2011). Shaddock peels (Citrus maxima) phenolic extracts inhibit α-amylase, α-glucosidase and angiotensin I-converting enzyme activities: A nutraceutical approach to diabetes management. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 5(3), 148–152. https://doi.org/10.1016/j.dsx.2012.02.008
- Okolie, U. V., Okeke, C. E., Oli, J. M., & Ehiemere, I. O. (2008). Hypoglycemic indices of Vernonia amygdalina on postprandial blood glucose concentration of healthy humans. African Journal of Biotechnology, 7(24), 4581–4585.
- Ong, K. W., Hsu, A., Song, L., Huang, D., & Tan, B. K. H. (2011). Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology, 133(2), 598–607. https://doi.org/10.1016/j.jep.2010.10.046
- Papuc, C., Goran, G. V., Predescu, C. N., Nicorescu, V., & Stefan, G. (2017). Plant polyphenols as antioxidant and antibacterial agents for shelf-life extension of meat and meat products: Classification, structures, sources, and action mechanisms. Comprehensive Reviews in Food Science and Food Safety, 16(6), 1243–1268. https://doi.org/10.1111/1541-4337.12298
- Pereira, R. M., Moura, L. P., Muñoz, V. R., Silva, A. S. R., Gaspar, R. S., Ropelle, E. R., & Pauli, J. R. (2017). Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise. Motriz: Revista de Educação Física, 23(SPE). https://doi.org/10.1590/s1980-6574201700si0004
- Rahimi, R., Nikfar, S., Larijani, B., & Abdollahi, M. (2005). A review on the role of antioxidants in the management of diabetes and its complications. Biomedicine & Pharmacotherapy, 59(7), 365–373. https://doi.org/10.1016/j.biopha.2005.07.002
- Rajpathak, S. N., Crandall, J. P., Wylie-Rosett, J., Kabat, G. C., Rohan, T. E., & Hu, F. B. (2009). The role of iron in type 2 diabetes in humans. Biochimica et Biophysica Acta (BBA)-General Subjects, 1790(7), 671–681. https://doi.org/10.1016/j.bbagen.2008.04.005
- Richard, D., Kefi, K., Barbe, U., Bausero, P., & Visioli, F. (2008). Polyunsaturated fatty acids as antioxidants. Pharmacological Research, 57(6), 451–455. https://doi.org/10.1016/j.phrs.2008.05.002
- Robertson, R. P., Harmon, J., Tran, P. O. T., & Poitout, V. (2004). β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes, 53(suppl 1), S119–S124. https://doi.org/10.2337/diabetes.53.2007.S119
- Saeed, N., Khan, M. R., & Shabbir, M. (2012). Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complementary and Alternative Medicine, 12(1), 221. https://doi.org/10.1186/1472-6882-12-221
- Saliu, J., Ademiluyi, A., Akinyemi, A., & Oboh, G. (2012). In vitro antidiabetes and antihypertension properties of phenolic extracts from bitter leaf (Vernonia amygdalina Del.). Journal of Food Biochemistry, 36(5), 569–576.
- Saltiel, A. R., & Kahn, C. R. (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 414(6865), 799.
- Santos, C. C. d. M. P., Salvadori, M. S., Mota, V. G., Costa, L. M., de Almeida, A. A. C., de Oliveira, G. A. L., Costa, J. P., de Sousa, D. P., de Freitas, R. M., & de Almeida, R. N. (2013). Antinociceptive and antioxidant activities of phytol in vivo and in vitro models. Neuroscience Journal, 2013, 949452.
- Satoh, T. (2014). Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes. International Journal of Molecular Sciences, 15(10), 18677–18692.
- Scheen, A. J. (1997). Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s. Drugs, 54(3), 355–368.
- Tiwari, B. K., Pandey, K. B., Abidi, A., & Rizvi, S. I. (2013). Markers of oxidative stress during diabetes mellitus. Journal of Biomarkers, 2013, 378790. https://doi.org/10.1155/2013/378790
- Toyokuni, S. (1999). Reactive oxygen species-induced molecular damage and its application in pathology. Pathology International, 49(2), 91–102.
- Volek, J. S., Phinney, S. D., Forsythe, C. E., Quann, E. E., Wood, R. J., Puglisi, M. J., & Feinman, R. D. (2009). Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids, 44(4), 297–309.
- Wellen, K. E., & Hotamisligil, G. S. (2005). Inflammation, stress, and diabetes. Journal of Clinical Investigation, 115(5), 1111–1119.
- Yeap, S. K., Ho, W. Y., Beh, B. K., San Liang, W., Ky, H., Yousr, A. H. N., & Alitheen, N. B. (2010). Vernonia amygdalina, an ethnoveterinary and ethnomedical used green vegetable with multiple bio-activities. Journal of Medicinal Plants Research, 4(25), 2787–2812.
- Yee, H. S., & Fong, N. T. (1996). A review of the safety and efficacy of acarbose in diabetes mellitus. Pharmacotherapy: Journal of Human Pharmacology and Drug Therapy, 16(5), 792–805.
