Potential antidiabetic and antioxidant activities of a heliangolide sesquiterpene lactone isolated from Helianthus annuus L. leaves

Samuel O. Onoja 1 , Charles O. Nnadi 2 , Samuel C. Udem 3  and Aruh O. Anaga 3
  • 1 Department of Veterinary Physiology and Pharmacology, Umuahia, Nigeria
  • 2 Department of Pharmaceutical and Medicinal Chemistry, Nsukka, Nigeria
  • 3 Department of Veterinary Physiology and Pharmacology, Faculty of Veterinary Medicine, Nsukka, Nigeria


Heliangolide is a naturally occurring sesquiterpene lactone and its derivatives are biologically active compounds present in most medicinal plants. This study evaluated the antioxidant and antidiabetic properties of a heliangolide sesquiterpene lactone isolated from Helianthus annuus L. leaves. The heliangolide sesquiterpene lactone was isolated through a combination of solvent-solvent partitioning, column chromatography, thin layer chromatography and high-performance liquid chromatography techniques. The antioxidant activity of the compound was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assays while the antidiabetic effects were investigated in alloxan-induced diabetic rats. The heliangolide derivative at the concentration of 954.2 µmol L−1 showed 23.7 % DPPH and 26 % nitric oxide radical inhibitions compared with 96.6 and 50.9 %, resp., displayed by the controls (2,271.2 µmol L−1). It also reduced the fasting blood glucose (FBG) levels in a time-dependent manner. The highest activity was recorded within 6 h post-treatment at 0.2 mmol kg−1 bm. The heliangolide derivative exhibited significant (p < 0.05) antioxidant and antidiabetic properties and provides a basis for further development of constituents of Helianthus annuus leaves for the management of such diseases.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. A. Chawla, R. Chawla and S. Jaggi, Microvasular and macrovascular complications in diabetes mellitus: distinct or continuum?, Indian J. Endocr. Metab. 20 (2016) 546–551; https://doi.org/10.4103/2230-8210.183480

  • 2. American Diabetes Association, Classification and diagnosis of diabetes: standards of medical care in diabetes – 2018, Diabetes Care 41 (Suppl. 1) (2018) S13–S27; https://doi.org/10.2337/dc18-S002

  • 3. S. Asgary, M. Rafieian-Kopaei, F. Shamsi, S. Najafi and A. Sahebkar, Biochemical and histopathological study of the anti-hyperglycemic and anti-hyperlipidemic effects of cornelian cherry (Cornus mas L.) in alloxan-induced diabetic rats, J. Complement. Integr. Med. 11 (2014) 63–69; https://doi.org/10.1515/jcim-2013-0022

  • 4. G. L. Khatik, A. K. Datusalia, W. Ahsan, P. Kaur, M. Vyas, A. Mittal and S. K. Nayak, A retrospect study on thiazole derivatives as the potential antidiabetic agents in drug discovery and developments, Curr. Drug Discov. Technol. 15 (2018) 163–177; https://doi.org/10.2174/1570163814666170915134018

  • 5. S. Gothai, P. Ganesan, S. Y. Park, S. Fakurazi, D. K. Choi and P. Arulselvan, Natural phyto-bioactive compounds for the treatment of type 2 diabetes: inflammation as a target, Nutrients 8 (2016) Article ID 461 (28 pages); https://doi.org/10.3390/nu8080461

  • 6. A. Roy and R. Manikkam, Cytotoxic impact of costunolide isolated from Costus speciosus on breast cancer via differential regulation of cell cycle - an in-vitro and in-silico approach, Phytother. Res. 29 (2015) 1532–1539; https://doi.org/10.1002/ptr.5408

  • 7. Q. Zhang, D. Caim and J. Liu, Matrix solid-phase dispersion extraction coupled with HPLC-diode array detection method for the analysis of sesquiterpene lactones in root of Saussurea lappa C. B. Clarke, J. Chromatogr. B 879 (2011) 2809–2814; https://doi.org/10.1016/j.jchromb.2011.08.008

  • 8. H. W. Park, J. H. Lee, S.-U. Choi, N.-I. Baek, S.-H. Kim, J. H. Yang and D. K. Kim, Cytotoxic germacranolide sesquiterpenes from the bark of Magnolia kobus, Arch. Pharm. Res. 33 (2010) 71–74; https://doi.org/10.1007/s12272-010-2227-5

  • 9. A. Rasul, B. Yu, L. Yang, M. Arshad, M. Khan, T. Ma and H. Yang, Costunolide, a sesquiterpene lactone induces G2/M phase arrest and mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells, J. Med. Plants Res. 6 (2012) 1191–1200; https://doi.org/10.5897/JMPR11.922

  • 10. A. Robinson, T. V. Kumar, E. Sreedhar, V. G. M. Naidu, S. R. Krishna, K. S. Babu, P. V. Srinivas and J. M. Rao, A new sesquiterpene lactone from the roots of Saussurea lappa: structure–anticancer activity study, Bioorg. Med. Chem. Lett. 18 (2008) 4015–4017; https://doi.org/10.1016/j.bmcl.2008.06.008

  • 11. P. R. Vadaparthi, C. P. Kumar, K. Kumar, A. Venkanna, V. L. Nayak, S. Ramakrishna and K. S. Babu, Synthesis of costunolide derivatives by Pd-catalyzed Heck arylation and evaluation of their cytotoxic activities, Med. Chem. Res. 24 (2015) 2871–2878; https://doi.org/10.1007/s00044-015-1337-5

  • 12. J. R. Woods, H. Mo, A. A. Bieberich, T. Alavanja and D. A. Colby, Amino-derivatives of the sesquiterpene lactone class of natural products as prodrugs, Med. Chem. Commun. 4 (2013) 27–33; https://doi.org/10.1039/C2MD20172K

  • 13. A. H. El-Far, H. M. Shaheen, A. W. Alsenosy, Y. S. El-Sayed, S. K. Al Jaouni and S. A. Mousa, Costus speciosus: Traditional uses, phytochemistry, and therapeutic potentials. Pharmacogn. Rev. 12 (2018) 120–127; https://doi.org/10.4103/phrev.phrev_29_17

  • 14. J. Eliza, P. Daisy and S. Ignacimuthu, Antioxidant activity of costunolide and eremanthin isolated from Costus speciosus (Koen ex. Retz) Sm., Chem. Biol. Interact. 188 (2010) 467–472; https://doi.org/10.1016/j.cbi.2010.08.002

  • 15. M. F. Mahomoodally, Quantitative ethnobotanical study of common herbal remedies used against 13 human ailments catergories in Mauritius, Afr. J. Tradit. Complement. Altern. Med. 11 (2014) 1–32; https://doi.org/10.4314/ajtcam.v11i6.1

  • 16. R. K. Upadhyay and S. Ahmad, Ethno-medicinal plants and their pharmaceutical potential, J. Pharm. Res. 5 (2012) 2162–2173.

  • 17. S. O. Onoja and A. O. Anaga, Evaluation of the antidiabetic and antioxidant potentials of methanolic leaf extract of Helianthus annuus L. on alloxan-induced hyperglycemic rats, Comp. Clin. Pathol. 23 (2014) 1565–1573; https://doi.org/10.1007/s00580-013-1824-3

  • 18. Y. Bibi, S. Nisa, F. M. Chaudhary and M. Zia, Antibacterial activity of some selected medicinal plants of Pakistan, BMC Complement. Altern. Med. 11 (2011) Article ID 52; https://doi.org/10.1186/1472-6882-11-52

  • 19. S. O. Onoja, M. I. Ezeja, Y. N. Omeh and B. C. Onwukwe, Antioxidant, anti-inflammatory and antinociceptive activities of methanolic extract of Justicia secunda Vahl leaf, Alexandria J. Med. 53 (2017) 207–213; https://doi.org/10.1016/j.ajme.2016.06.001

  • 20. L. Marcocci, J. J. Maguire, M. T. Droylefaix and L. Packer, The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761, Biochem. Biophys. Res. Commun. 201 (1994) 748–755; https://doi.org/10.1006/bbrc.1994.1764

  • 21. H. Sebai, S. Selmi, K. Rtibi, N. Gharbi and M. Sakly, Protective effect of Lavandula stoechas and Rosmarinus officinalis essential oils against reproductive damage and oxidative stress in alloxan-induced diabetic rats, J. Med. Food 18 (2015) 241–249; https://doi.org/10.1089/jmf.2014.0040

  • 22. F. Bohlmann, G. Schmeda-Hirschmann and J. Jakupovic, Heliangolides and germacrolides from Disynaphia multicrenulata, Phytochemistry 23 (1984) 1435–1437; https://doi.org/10.1016/S0031-9422(00)80481-1

  • 23. T. Konishi, Y. Shimada, T. Nagao, H. Okabe and T. Konoshima, Antiproliferative sesquiterpene lactones from the roots of Inula helenium, Biol. Pharm. Bull. 25 (2002) 1370–1372; https://doi.org/10.1248/bpb.25.1370

  • 24. J. Eliza, P. Daisy, S. Ignacimuthu and V. Duraipandiyan, Normo-glycemic and hypolipidemic effect of costunolide isolated from Costus speciosus (Koen ex. Retz.) Sm. in streptozotocin-induced diabetic rats, Chem. Biol. Interact. 179 (2009) 329–334; https://doi.org/10.1016/j.cbi.2008.10.017

  • 25. K. Fukuda, S. Akao, Y. Ohno, K. Yamashita and H. Fujiwara, Inhibition by costunolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1, Cancer Lett. 1 (2001) 7–13; https://doi.org/10.1016/S0304-3835(00)00704-7

  • 26. M. Taniguchi, T. Kataoka, H. Suzuki, M. Uramoto, M. Ando, K. Arao, J. Magae, T. Nishimura, N. Ōtake and K. Naga, Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes, Biosci. Biotechnol. Biochem. 59 (1995) 2064–2067; https://doi.org/10.1271/bbb.59.2064


Journal + Issues