In vitro and in silico cytotoxic activities of triterpenoids from the leaves of Aralia dasyphylla Miq. and the assessment of their ADMET properties

• Published in: Journal of biomolecular structure & dynamics 2023-08, Vol.41 (12), p.5863-5871
• Main Authors: Nguyen Thi Thu, Hien, Nguyen Huu Huong, Duyen, Nguyen Thi Dieu, Thuan, Tran Thi Ngoc, Hanh, Pham Van, Huyen, Hoang Thi Ngoc, Anh, Nguyen Xuan, Ha, Pham, Ngoc Khanh, Nguyen Manh, Cuong, Nguyen Huu Toan, Phan
• Format: Article
• Language: English
• Subjects: Aralia - chemistry; Aralia dasyphylla; Araliaceae; HepG2; hGLUT1; Humans; LU-1; Miq; Molecular Docking Simulation; Molecular Structure; Oleanolic Acid - pharmacology; Plant Leaves - chemistry; Triterpenes - chemistry; Ursolic Acid
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2022.2098822

From the methanol extract of the leaves of Aralia dasyphylla Miq. (Araliaceae), ten triterpenoids including five ursane-type triterpenoids, ursolic acid (1), 3-O-α-l-arabinopyranosyl ursolic acid (2), ursolic acid 28-O-β-D-glucopyranosyl ester (3), 3-O-[β-D-glucopyranosyl (l→3)]-α-L-arabinopyranosyl ursolic acid (4), and matesaponin 1 (5), and five oleanane-type triterpenoids, elatoside E (6), elatoside F (7), 3-O-[β-D-glucopyranosyl (l→3)]-α-L-arabinopyranosyl oleanolic acid (8), 3-O-α-L-arabinopyranosyl oleanolic acid (9) and oleanolic acid 28-O-β-D-glucopyranosyl ester (10) were isolated. Their structures were elucidated based on 1D-, 2D-NMR and ESI-MS spectra as well as by comparison with those reported in the literature. All isolated compounds were evaluated in vitro for their cytotoxic activities against three human cancer cell lines (HepG2, LU-1 and RD) and in silico by molecular docking studies on human glucose transporter 1 (hGLUT1) protein. The triterpenoids 2, 4, 6, 8 and 9 exhibited good growth inhibition of HepG2 and LU-1 cancer cell lines with IC 50 values in the range 1.76 − 7.21 (μM). The oleanane type triterpenoid 8 was the highest cytotoxic compound to inhibit all the tested cancer cell lines with IC 50 values of 2.73 ± 0.12, 1.76 ± 0.11, 2.63 ± 0.10 μM, respectively. The in silico molecular docking study results showed that compounds 4 and 6 had the highest binding affinity. Compounds 1-10 were evaluated for their in silico ADMET of absorption, distribution, metabolism, excretion and oral toxicity parameters. Compounds 6, 8, 9 and 10 from A. dasyphylla are potential hGLUT1 inhibitors and worth of further investigation for the prevention or treatment of diabetes and cancer. Communicated by Ramaswamy H. Sarma