Phytochemical investigation of Egyptian riverhemp: a potential source of antileukemic metabolites

Authors: ABDELGAWAD, SHIMAA - University Of Mississippi; HETT, MONA - University Of Mississippi; IBRAHIMA, MOHAMED - University Of Mississippi; BALACHANDRAN, PREMALATHA - University Of Mississippi; ZHANG, JIN - University Of Mississippi; Wang, Mei; FAWZY, GHADA - Cairo University; EL-ASKARY, HESHAM - Cairo University; ROSS, SAMIR - University Of Mississippi

Submitted to: Journal of Natural Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/24/2022
Publication Date: 8/29/2022
Citation: Abdelgawad, S.M., Hett, M.H., Ibrahima, M.A., Balachandran, P., Zhang, J., Wang, M., Fawzy, G.A., El-Askary, H.I., Ross, S.A. 2022. Phytochemical investigation of Egyptian riverhemp: a potential source of antileukemic metabolites. Journal of Natural Medicine. https://doi.org/10.1155/2022/8766625.
DOI: https://doi.org/10.1155/2022/8766625

Interpretive Summary: Leukemia is the most overwhelming malignancy in kids around the world, except in Africa, where non-Hodgkin lymphoma is the most widely recognized. To discover antileukemic natural compounds from plants, the leaf of S. sesban (Egyptian riverhemp), a perennial legume tree belonging to family Fabaceae, was investigated. One new and 34 known compounds were isolated encompassing 19 triterpenoids, 3 steroids, 11 flavonoid glycosides, 1 fatty alcohol and 1 phenolic compound. Thirty of them are reported for the first time from this species. The antileukemic activity of the isolated compounds was evaluated against leukemia K562 cell line in vitro and 11 triterpenoids exhibited a remarkable antileukemic activity against this cell line. Oleanolic acid 3-O-ß-D-glucuronopyranoside and jacoumaric acid exhibited the strongest activity. A mechanistic study was also carried out on a molecular genetics level against several transcription factors signaling pathways that are incorporated in the incidence of cancer.

Technical Abstract: In an effort to find alternative treatments for cancer, the aqueous ethanol extracts of fifty-six plants collected from Egypt were screened in vitro for their antileukemic activity against leukemia K562 cell line. Sesbania sesban L. Merr. (SS; Egyptian riverhemp) was one of the active plants that were selected for further chemical and biological investigations. Bio-guided fractionation of SS leaves hydroethanolic extract resulted in isolation of one undescribed compound (33) (Hederatriol 3-O-ß-D-glucuronic acid methyl ester) as well as thirty-four known compounds. Seven compounds (34, 22, 20, 24, 21, 19, 35) showed high anti-proliferative effect (IC50 = 22.3, 30.8, 31.3, 33.7, 36.6, 37.5, 41.5 µM, respectively), while four compounds (32, 5, 29, 1) showed milder activity with (IC50 = 56.4, 67.6, 83.3, 112.3 µM, respectively). A mechanistic study was further carried out on a molecular genetics level against several transcription factors signaling pathways that are incorporated in the incidence of cancer. The results showed that compounds (22, 21) demonstrated specific inhibition of Wnt pathway (IC50 = 3.8, 4.6 µM, respectively), while compound (22) showed specific inhibition of Smad pathway (IC50 = 3.8 µM). Compound (34) was shown to strongly altered the signaling pathways of Smad and E2F (IC50 = 5 µM). The bioactive metabolites were furtherly investigated in silico by docking against several targets related to K562 cell line. The results showed that compounds 22 and 34 exhibited a strong binding affinity towards topoisomerase (docking score = -7.8056 and -9.2972 Kcal/Mole, respectively). Compounds 22 and 34 demonstrated strong binding affinity towards EGFR-Tyrosine kinase (docking score = -7.1200, and -7.350 Kcal/Mole, respectively). Moreover, compound 34 showed a strong binding affinity towards Abl kinase (docking score = -7.0463 Kcal/Mole).