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Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1408–1418 | Cite as

Insulin releasing effect of some pure compounds from Moringa oleifera on mice islets

  • Rahman M. Hafizur
  • Kiran Maryam
  • Abdul Hameed
  • Lubna zaheer
  • Samina Bano
  • Saima Sumbul
  • Aisha Sana
  • Rubeena Saleem
  • Sehrish Naz
  • Rizwana S. Waraich
  • Zaheer Ul-Haq
  • Shaheen Faizi
Original Research
  • 124 Downloads

Abstract

The anti-diabetic activity of extracts, fractions and compounds of Moringa oleifera have been reported; however, several constituents from this well known medicinal plant are not yet screened for bio-perspecting role for diabetes. Current studies demonstrated the anti-diabetic properties of five chemical constituents of the plant viz, 4-hydroxyphenylacetonitrite (1), fluoropyrazine (3), methyl-4-hydroxybenzoate (4), vanillin (5), and 4-α-L-rhamnopyranosyloxybenzyl isothiocyanate (6) along with one related compound 3,4-dihydroxy benzonitrile (2) for the first time in vitro and in vivo. Furthermore, the mechanism of action of compounds was predicted by utilizing molecular docking with protein kinase A (PKA) and exchange protein activated by cAMP (Epac2A). The structure of compounds was elucidated by UV, IR, MS, and 1H NMR. The compounds 1, 35 induced significant insulin secretion at stimulatory (16.7 mM) glucose, but not at basal (3 mM) glucose concentration, and compound 3 seems to be the most active. Compounds 1, 35 showed dose-dependent insulin secretory activity with optimum response at 200 μM. In silico studies revealed that compound 3 has a noticeable electrostatic and hydrophobic interaction with protein kinase A (PKA). In vitro studies also showed that there was significant reduction of compounds 13 mediated insulin secretion in the presence of PKA inhibitor suggesting that there is a possible role of PKA signaling pathway on insulin secretion. Upon oral administration of 1, 35 to diabetic rats, compounds 1 and 3 significantly reduced blood glucose level in diabetic rats in a dose- and time-dependent manner. The oral glucose tolerance test in diabetic rats showed that compound 3 significantly enhanced plasma insulin and improved beta-cell function. In cytotoxicity assay, compounds 1, 35 did not show any toxic effect upto 200 μM. The insulin releasing characteristic of different constituents from M. oleifera conceivably correlate the lowering of blood glucose in in vivo diabetic rats by triggering glucose-induced insulin secretion from pancreatic islets possibly by PKA-mediated insulin secretory pathway.

Keywords

Moringa oleifera Insulin secretion Methyl-4-hydroxybenzoate Vanillin Fluoropyrazine Insulinogenic index 

Notes

Acknowledgements

This work was supported by NRPU Research Grant (20-4091/NRPU/R&D/HEC/14/375) to Md. Hafizur Rahman from Higher Education Commission (HEC), Pakistan.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2157_MOESM1_ESM.docx (3.7 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Rahman M. Hafizur
    • 1
  • Kiran Maryam
    • 1
  • Abdul Hameed
    • 1
  • Lubna zaheer
    • 2
  • Samina Bano
    • 2
  • Saima Sumbul
    • 2
  • Aisha Sana
    • 3
  • Rubeena Saleem
    • 3
  • Sehrish Naz
    • 1
  • Rizwana S. Waraich
    • 1
  • Zaheer Ul-Haq
    • 1
  • Shaheen Faizi
    • 2
  1. 1.Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS)University of KarachiKarachiPakistan
  2. 2.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS)University of KarachiKarachiPakistan
  3. 3.Department of Pharmaceutical Chemistry, Faculty of PharmacyHamdard UniversityKarachiPakistan

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