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Hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium benth leaf in type 2 diabetic rats via fetuin-A and tumor necrosis factor-alpha

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Abstract

Background

This study assessed the hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium Benth on diabetes-induced type 2 rats via Fetuin-A and tumor necrosis factor-alpha (TnF-α).

Methods

In a standard procedure, the flavonoid-rich extract was prepared. For experimental rats, streptozotocin was injected intraperitoneally (45 mg/kg body weight) to induce diabetes mellitus. Following this, rats were given 5% of glucose water for 24 h. Hence, the animals were randomly divided into five groups of ten rats each, consisting of non-diabetic rats, diabetic controls, diabetic rats treated with low and high doses of flavonoid rich-extracts from Gongronema latifolium leaf (FREGL) (13 and 26 mg/kg, respectively), and diabetic rats treated with 200 mg/kg of metformin glibenclamide orally for 3 weeks. Afterwards, the animals were sacrificed, blood and liver were harvested to evaluate different biochemical parameters, hepatic gene expressions and histological examinations.

Results

The results revealed that FREGL (especially at the low dose) significantly (p < 0.05) reduced alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphate (ALP) activities, lipid peroxidation level, as well as relative gene expressions of fetuin-A and TNF-α in diabetic rats. Furthermore, diabetic rats given various doses of FREGL showed an increase in antioxidant enzymes and hexokinase activity, as well as glucose transporters (GLUT 2 and GLUT 4), and glycogen levels. In addition, histoarchitecture of the liver of diabetic rats administered FREGL (especially at the low dose) was also ameliorated.

Conclusion

Hence, FREGL (particularly at a low dose) may play a substantial role in mitigating the hepatopathy complication associated with diabetes mellitus.

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References

  1. Arumugam G, Manjula P, Paari N (2013) Antidiabetic medical plants used in diabetes mellitus. J Acute Dis 2:196–200

    Article  Google Scholar 

  2. Yanhong X, Long C, Yanfang F, Peng Y, Suting L, Xiaohui Z (2019) The effect of boletus polysaccharides on diabetic hepatopathy in rats. Chem Biol Interact 308:61–69

    Article  Google Scholar 

  3. Nadia SM, Azza MM, Fatma SE (2012) Chemical constituents of the Egyptian Plant Anabasis articulata (Forssk) Moq and its antidiabetic effects on rats with streptozotocin-induced diabetic hepatopathy. J Appl Pharmac Sci 02(04):54–65

    Google Scholar 

  4. International Diabetes Federation (IDF) (2021). Diabetes Atlas. 10th Edition

  5. Omotayo FO, Borokini TI (2012) Comparative phytochemical and ethnomedical survey of selected medicinal plants in Nigeria. Sci Res Essays 7(9):989–999

    Google Scholar 

  6. Yazdi HB, Hojati V, Shiravi A, Hosseinian S, Vaezi G, Hadjzadeh MAR (2019) Liver dysfunction and oxidative stress in streptozotocin-induced diabetic rats: protective role of artemisia turanica. J Pharmacopuncture 22(2):109–114

    Article  Google Scholar 

  7. Celebi G, Genc H, Gurel H, Sertoglu E, Kara M, Tapan S, Acikel C, Karslioglu Y, Ercin CN, Dogru T (2015) The relationship of circulating fetuin-a with liver histology and biomarkers of systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease. Saudi J Gastroenterol 21(3):139–145. https://doi.org/10.4103/1319-3767.157556

    Article  PubMed  PubMed Central  Google Scholar 

  8. Morebise O (2015) A review on Gongronema latifolium, an extremely useful plant with great prospects. Eur J Med Plants, 1–9.

  9. George P (2011) Concerns regarding the safety and toxicity of medicinal plants: an overview. J Appl Pharmac Sci 1(6):40–44

    Google Scholar 

  10. Palanichamy P, Krishnamoorthy G, Kannan S, Marudhamuthu M (2018) Bioactive potential of secondary metabolites derived from medicinal plant endophytes. Egypt J Basic Appl Sci 5(4):303–312

    Google Scholar 

  11. Obafemi TO, Akinmoladun AC, Olaleye MT, Agboade SO, Onasanya AO (2017) Antidiabetic potential of methanolic and flavonoid-rich leaf extracts of synsepalum dulcificum in type 2 diabetic rats. J Ayurveda Integrat Med 8(4):238–246

    Article  CAS  Google Scholar 

  12. Ajiboye BO, Ojo OA, Akuboh OS, Abiola OM, Idowu O, Amuzat AO (2018) Anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cumini Linn leaves in alloxan-induced diabetic rats. J Evidence-Based Entegrat Med. https://doi.org/10.1177/2515690X18770630

    Article  Google Scholar 

  13. Oyinloye BO, Ajiboye BO, Johnson O, Owolabi OV, Ejeje JN, Brai BIC, Omotuyi OI (2022) Ameliorative effect of flavonoid-rich extracts from Gongronema latifolium against diabetic cardiomyopathy via serpin A3 and socs3-a in streptozocin treated rats. Biomarkers 27(2):169–177. https://doi.org/10.1080/1354750X.2021.2023220

    Article  CAS  PubMed  Google Scholar 

  14. Varshney R, Kale RK (1990) Effects of calmodulin antagonists on radiation induced lipid peroxidation in microsomes. Int J Rad Biol 58:733743

    Article  Google Scholar 

  15. Del-Maestro RF, McDonald W, Anderson R (1983) Superoxide dismutase, catalase, and glutathione peroxidase. in experimental and human brain tumours: oxy radicals and their scavenger systems. In: Greenwald R, Cohen G (eds). (Vol. 2). Elsevier Publisher: New York, pp 16–34

  16. Sinha KA (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  Google Scholar 

  17. Moron MS, Depierre JW, Mannervik B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et biophysica acta 582(1):67–78. https://doi.org/10.1016/0304-4165(79)90289-7

  18. Hafemann SF, Chilman CS (1974) Implications of vasectomy for social work practice. Social Casework 55(6):343–351

    Article  Google Scholar 

  19. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139

    Article  CAS  Google Scholar 

  20. Lo S, Russell JC, Taylor AW (1970) Determination of glycogen in small tissue samples. J Appl Physiol 28(2):234–236. https://doi.org/10.1152/jappl.1970.28.2.234

    Article  CAS  PubMed  Google Scholar 

  21. Akinyosoye F, Fawole M, Akinyanju J (1987) Studies on some enzymes of carbohydrate metabolism in Geotrichum candidum. Niger J Microbiol 7(1987):154–161

    Google Scholar 

  22. Ajiboye BO, Oyinloye BE, Agboinghale PE, Onikanni SA, Asogwa E, Kappo AP (2019) Antihyperglycaemia and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Pharmaceutical Biology 57(1):604–611. https://doi.org/10.1080/13880209.2019.1657907

  23. Omotuyi OI, Nash O, Inyang OK, Ogidigo J, Enejoh O, Okpalefe O, Hamada T (2018) Flavonoid-rich extract of Chromolaena odorata modulate circulating GLP-1 in Wistar rats. 3 Biotech 8:124. https://doi.org/10.1007/s13205-018-1138-x

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chang TI, Horal M, Jain S, Wang F, Patel R, Loeken MR (2003) Oxidant regulation of gene expression and neural tube development: insights gained from diabetic pregnancy on molecular causes of neural tube defects. Diabetologia 46:538–545

    Article  CAS  Google Scholar 

  25. Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9

    Article  CAS  Google Scholar 

  26. Dunlop M (2000) Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl 77:S3–S12

    Article  CAS  Google Scholar 

  27. King GL, Kunisaki M, Nishio Y, Inoguchi T, Shiba T, Xia P (1996) Biochemical and molecular mechanisms in the development of diabetic vascular complications. Diabetes 45(3):S105–S108

    Article  CAS  Google Scholar 

  28. Xia P, Aiello LP, Ishii H, Jiang ZY, Park DJ, Robinson GS, Takagi H, Newsome WP, Jirousek MR, King GL (1996) Characterization of vascular endothelial growth factor’s effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. J Clin Invest 98:2018–2026

    Article  CAS  Google Scholar 

  29. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H (2000) High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49:1939–1945

    Article  CAS  Google Scholar 

  30. Nishikawa T, Edelstein D, Du XL, Yamagishi SI, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790

    Article  CAS  Google Scholar 

  31. Banjarnahor SDS, Artanti N (2014) Antioxidant properties of flavonoids. Med J Indones 23(4):23–244

    Google Scholar 

  32. Ajiboye TO, Ahmad FM, Daisi AO, Yahaya AA, Ibitoye OB, Muritala HF, Sunmonu TO (2017) Hepatoprotective potential of Phyllanthus muellarianus leaf extract: studies on hepatic, oxidative stress and inflammatory biomarkers. Pharm Biol 55(1):1662–1670. https://doi.org/10.1080/13880209.2017.1317819

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ajiboye BO, Shonibare T, Oyinyole BE (2020) Antidiabetic activity of watermelon (Citrullus lanatus) in alloxan-induced diabetic rats. J Diabetes Metab Disord 19(1):343–352

    Article  CAS  Google Scholar 

  34. Moller DE (2000) Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11(6):212–217. https://doi.org/10.1016/s1043-2760(00)00272-1

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Basiru Olaitan Ajiboye.

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This study was in accordance with ABUAD Animal Ethical Committee with Approval Number 20/ABUADSCI/013.

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Ajiboye, B.O., Oyinloye, B.E., Udebor, E.A. et al. Hepatoprotective potential of flavonoid-rich extracts from Gongronema latifolium benth leaf in type 2 diabetic rats via fetuin-A and tumor necrosis factor-alpha. Mol Biol Rep 49, 8391–8400 (2022). https://doi.org/10.1007/s11033-022-07657-x

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