Advertisement

Flowers of Clerodendrum volubile modulates redox homeostasis and suppresses DNA fragmentation in Fe2+ − induced oxidative hepatic and pancreatic injuries; and inhibits carbohydrate catabolic enzymes linked to type 2 diabetes

  • Ochuko L. Erukainure
  • Olajumoke A. Oyebode
  • Veronica F. Salau
  • Neil A. Koorbanally
  • Md. Shahidul IslamEmail author
Research article
  • 6 Downloads

Abstract

Introduction

Medicinal plants have long been recognized for their roles in the treatment and management of diabetes and its complications. The antioxidative and antidiabetic properties of Clerodendrum volubile flowers were investigated in vitro and ex vivo.

Methods

The flowers were sequentially extracted with solvents of increasing polarity (n-hexane, ethyl acetate, ethanol and water). The concentrated extracts were subjected to in vitro antioxidant assays using the 2,2′-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing antioxidant power (FRAP) protocols. Their inhibitory activities were investigated on α-glucosidase, pancreatic lipases, pancreatic ATPase and glucose-6-phosphatase activities. Their anti-oxidative and anti-apoptotic effects on Fe2+-induced oxidative injuries were also investigated in pancreatic and hepatic tissues ex vivo.

Results

The extracts showed potent free radical scavenging activity and significantly (p < 0.05) inhibited all studied enzymes. The GSH level was significantly (p < 0.05) elevated in both tissues with concomitant increase in superoxide dismutase (SOD) and catalase activities as well as reduced levels of malondialdehyde (MDA). The extracts significantly (p < 0.05) suppressed DNA fragmentation in hepatic tissue. These activities were dose-dependent. The ethanol extract showed the best activity and can be attributed to the synergetic effect of its chemical constituents identified via gas chromatography-mass spectroscopy (GC-MS).

Conclusion

These results suggest the antioxidative, antidiabetic and anti-obesogenic potentials of C. volubile flowers.

Keywords

Anti-hyperglycemia C. volubile Oxidative stress Type 2 diabetes 

Notes

Acknowledgments

This study was funded by a competitive research grant from the Research Office, University of KwaZulu-Natal (UKZN), Durban, South Africa. It was supported by an incentive grant for rated researchers and grant  support for women and young researchers from the National Research Foundation (NRF), Pretoria, South Africa.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    I.D.F. (International Diabetes Federation), IDF Diabetes Atlas. 7th ed: International Diabetes Federation; 2016.Google Scholar
  2. 2.
    Tiwari BK, Pandey KB, Abidi A, Rizvi SI. Markers of oxidative stress during diabetes mellitus. J Biomark. 2013;2013:378790.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Burkill HM. The useful plants of west tropical Africa. Edition 2. Kew: Royal Botanic Gardens; 1985.Google Scholar
  4. 4.
    Erukainure OL, Ebuehi OA, Choudhary IM, Adhikari A, Hafizur RM, Perveen S, et al. Iridoid glycoside from the leaves of Clerodendrum volubile beauv. Shows potent antioxidant activity against oxidative stress in rat brain and hepatic tissues. J Diet Suppl. 2014;11(1):19–29.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Erukainure OL, Zaruwa MZ, Choudhary MI, Naqvi SA, Ashraf N, Hafizur RM, et al. Dietary fatty acids from leaves of clerodendrum volubile induce cell cycle arrest, downregulate matrix metalloproteinase-9 expression, and modulate redox status in human breast cancer. Nutr Cancer. 2016;68(4):634–45.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Erukainure OL, Hafizur RM, Choudhary MI, Adhikari A, Mesaik AM, Atolani O, et al. Anti-diabetic effect of the ethyl acetate fraction of Clerodendrum volubile: protocatechuic acid suppresses phagocytic oxidative burst and modulates inflammatory cytokines. Biomed Pharmacother. 2017;86:307–15.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Erukainure OL, Mesaik AM, Muhammad A, Chukwuma CI, Manhas N, Singh P, et al. Flowers of Clerodendrum volubile exacerbate immunomodulation by suppressing phagocytic oxidative burst and modulation of COX-2 activity. Biomed Pharmacother. 2016;83:1478–84.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Liu Q, Yao H. Antioxidant activities of barley seeds extracts. Food Chem. 2007;102(3):732–7.CrossRefGoogle Scholar
  9. 9.
    Braca A, Sortino C, Politi M, Morelli I, Mendez J. Antioxidant activity of flavonoids from Licania licaniaeflora. J Ethnopharmacol. 2002;79(3):379–81.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239(1):70–6.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70–7.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Chance B, Maehly AC. Assay of catalase and peroxidase. Methods Enzymol. 1955;2:765–75.Google Scholar
  13. 13.
    Kakkar P, Das B, Viswanathan P. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21:130–2.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Chowdhury P, Soulsby M. Lipid peroxidation in rat brain is increased by simulated weightlessness and decreased by a soy-protein diet. Ann Clin Lab Sci. 2002;32(2):188–92.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75.Google Scholar
  16. 16.
    Oboh G, Ademosun AO. Shaddock peels (Citrus maxima) phenolic extracts inhibit α-amylase, α-glucosidase and angiotensin I-converting enzyme activities: a nutraceutical approach to diabetes management. Diabetes Metab Syndr: Clin Res Rev. 2011;5(3):148–52.CrossRefGoogle Scholar
  17. 17.
    Kim YS, Lee YM, Kim H, Kim J, Jang DS, Kim JH, et al. Anti-obesity effect of Morus bombycis root extract: anti-lipase activity and lipolytic effect. J Ethnopharmacol. 2010;130(3):621–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Adewoye O, Bolarinwa A, Olorunsogo O. Ca++, Mg++-ATPase activity in insulin-dependent and non-insulin dependent diabetic Nigerians. Afr J Med Med Sci. 2000;29(3–4):195–9.PubMedGoogle Scholar
  19. 19.
    Mahato AK, Bhattacharya S, Shanthi N. Design, synthesis and glucose-6-phosphatase inhibitory activity of diaminoguanidine analogues of 3-Guanidinopropionic acid and amino substituted (Pyridin-2-Yl) thiourea derivatives. J Pharmaceut Sci Res. 2011;3:896–902.Google Scholar
  20. 20.
    Zhang Y, Wang Z, Zhao Y, Zhao M, Wang S, Hua Z, et al. The plasma 5′-AMP acts as a potential upstream regulator of hyperglycemia in type 2 diabetic mice. Am J Physiol Endocrinol Metab. 2011;302(3):E325–E33.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Sellins KS, Cohen JJ. Gene induction by gamma-irradiation leads to DNA fragmentation in lymphocytes. J Immunol. 1987;139(10):3199–206.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Aliyu M, Odunola OA, Farooq AD, Rasheed H, Mesaik AM, Choudhary MI, et al. Molecular mechanism of antiproliferation potential of Acacia honey on NCI-H460 cell line. Nutr Cancer. 2013;65(2):296–304.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Drwal MN, Banerjee P, Dunkel M, Wettig MR, Preissner R. ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res. 2014;42(W1):W53–W8.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Alternat Med. 2012;12(1):221.CrossRefGoogle Scholar
  25. 25.
    Mohiuddin M, Amran MS, Hossain MA. The in vivo effects of caffeine on the hypoglycemic activity of gliclazide and metformin in healthy rats. Dhaka Univ J Pharmaceut Sci. 2009;8(1):47–51.CrossRefGoogle Scholar
  26. 26.
    Anahita A, Asmah R, Fauziah O. Evaluation of total phenolic content, total antioxidant activity, and antioxidant vitamin composition of pomegranate seed and juice. Int Food Res J. 2015;22:1212–7.Google Scholar
  27. 27.
    Freeman BL, Eggett DL, Parker TL. Synergistic and antagonistic interactions of phenolic compounds found in navel oranges. J Food Sci. 2010;75(6):C570–C6.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Davari S, Talaei S, Alaei H. Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome–gut–brain axis. Neurosci. 2013;240:287–96.CrossRefGoogle Scholar
  29. 29.
    Aslan M, ThornleY-Brown D, Freeman BA. Reactive species in sickle cell disease. Ann N Y Acad Sci. 2000;899(1):375–91.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kanias T, Acker JP. Biopreservation of red blood cells–the struggle with hemoglobin oxidation. FEBS J. 2010;277(2):343–56.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Arora R, Vig A, Arora S. Lipid peroxidation: a possible marker for diabetes. J Diabetes Metab. 2013;11:1–6.Google Scholar
  32. 32.
    Bischoff H. The mechanism of alpha-glucosidase inhibition in the management of diabetes. Clin Investig Med Med Clin Exp. 1995;18(4):303–11.Google Scholar
  33. 33.
    Bischoff H. Pharmacology of α-glucosidase inhibition. Eur J Clin Investig. 1994;24(S3):3–10.Google Scholar
  34. 34.
    Lunagariya NA, Patel NK, Jagtap SC, Bhutani KK. Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI J. 2014;13:897.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Owada S, Larsson O, Arkhammar P, Katz AI, Chibalin AV, Berggren P-O, et al. Glucose decreases Na+, K+-ATPase activity in pancreatic β-cells an effect mediated via ca2+−independent phospholipase a2 and protein kinase cdependent phosphorylation of the α-subunit. J Biol Chem. 1999;274(4):2000–8.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Van Schaftingen E, Gerin I. The glucose-6-phosphatase system. Biochem J. 2002;362(3):513–32.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Ghosh A, Shieh J-J, Pan C-J, Chou JY. Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-β forming a phosphohistidine enzyme intermediate during catalysis. J Biol Chem. 2004;279(13):12479–83.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Donath MY, Gross DJ, Cerasi E, Kaiser N. Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes. 1999;48(4):738–44.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Allameh A, Amini-Harandi A, Osati-Ashtiani F, O'Brien P. Iron overload induced apoptotic cell death in isolated rat hepatocytes mediated by reactive oxygen species. Iranian J Pharmaceut Res. 2010;7:115–21.Google Scholar
  40. 40.
    Santos CCMP, Salvadori MS, Mota VG, Costa LM, de Almeida AAC, de Oliveira GAL, et al. Antinociceptive and antioxidant activities of phytol in vivo and in vitro models. Neurosci J. 2013;2013:949452.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    El-Kashef DF, Hamed AN, Khalil HE, Kamel MS. Triterpenes and sterols of family Apocynaceae (2013-1955), A review. J Pharmacog Phytochem. 2015;4(2):21–39.Google Scholar
  42. 42.
    Rao N, Mittal S, Menghani E. Antioxidant potential and validation of bioactive B-Sitosterol in Eulophia campestris wall. Adv Biores. 2013;4(1):136–42.Google Scholar
  43. 43.
    Karan SK, Mishra SK, Pal D, Mondal A. Isolation of-sitosterol and evaluation of antidiabetic activity of Aristolochia indica in alloxan-induced diabetic mice with a reference to in-vitro antioxidant activity. J Med Plants Res. 2012;6(7):1219–23.Google Scholar
  44. 44.
    Ezuruike UF, Prieto JM. The use of plants in the traditional management of diabetes in Nigeria: pharmacological and toxicological considerations. J Ethnopharmacol. 2014;155(2):857–924.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Yüce B, Gülberg V, Diebold J, Gerbes AL. Hepatitis induced by noni juice from Morinda citrifolia: a rare cause of hepatotoxicity or the tip of the iceberg? Digestion. 2006;73(2–3):167–70.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Biochemistry, School of Life SciencesUniversity of KwaZulu-Natal, (Westville Campus)DurbanSouth Africa
  2. 2.Nutrition and Toxicology DivisionFederal Institute of Industrial ResearchLagosNigeria
  3. 3.Department of Pharmacology, School of Clinical Medicine, Faculty of Health SciencesUniversity of the Free StateBloemfonteinSouth Africa
  4. 4.School of Chemistry and PhysicsUniversity of KwaZulu-Natal, (Westville Campus)DurbanSouth Africa

Personalised recommendations