Medicinal Chemistry Research https://doi.org/10.1007/s00044-018-2157-1 MEDICINAL CHEMISTR Y RESEARCH ORIGINAL RESEARCH Insulin releasing effect of some pure compounds from Moringa oleifera on mice islets 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 Received: 5 October 2017 / Accepted: 12 February 2018 © Springer Science+Business Media, LLC, part of Springer Nature 2018 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 1 H NMR. The compounds 1, 3–5 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, 3–5 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 1–3 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, 3–5 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, 3–5 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 Introduction Research records of the folkloric use of various plant-based fractions for the management of many diseases are well documented worldwide (Cragg and Newman 2013). Increased prevalence of diabetes and several challenges facing its management have motivated several research groups to search for novel agents with antidiabetic effects. Ever since ancient times, in search for cure of disease, local people looked for drugs in nature, since then several plants have been known to serve as herbal candidates by ancestral medicine practitioners for the treatment of several diseases including diabetes (Rios et al. 2015). Moringa oleifera (M. oleifera) is considered as the “miracle tree” due to its uniquely diverse array of nutri- tional, medicinal, and purifying properties with incredible * Rahman M. Hafizur hafizpcmd@yahoo.com hafizur.rahman@iccs.edu 1 Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan 2 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi 75270, Pakistan 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi 74600, Pakistan Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00044-018-2157-1) contains supplementary material, which is available to authorized users. 1234567890();,: