Bufadienolide glycosides and bufadienolides from the whole plants of Helleborus lividus, and their cytotoxic activity. (August 2020)

• Record Type: Journal Article
• Authors: Iguchi, Tomoki; Yokosuka, Akihito; Tamura, Naoya; Takano, Shingo; Mimaki, Yoshihiro
• Is Part Of: Phytochemistry. Volume 176(2020)
• Publication Date: 2020-08
• Subjects: Helleborus lividus -- Ranunculaceae -- Bufadienolides -- Bufadienolide glycosides -- Cytotoxicity -- Apoptosis -- HL-60 cells -- A549 cells -- Na+/K+ ATPase; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2020.112415
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: Cytotoxicity-guided fractionation of the MeOH extract of Helleborus lividus Aiton ex Curtis (Ranunculaceae) resulted in the isolation of five undescribed bufadienolide glycosides and two undescribed bufadienolides, along with three known compounds. Their structures were determined by detailed spectroscopic analysis and hydrolysis studies. The isolated compounds showed cytotoxicity against HL-60 human leukemia cells and A549 human lung adenocarcinoma cells, with IC50 values ranging from 2.20 ± 0.01 nM to 0.77 ± 0.01 μM. The undescribed compound 3β-[( O -β-d -glucopyranosyl-(1 → 4)-α-l -rhamnopyranosyl)oxy]-14β, 16β-dihydroxy-5β-bufa-20, 22-dienolide induced apoptosis in HL-60 cells via a mitochondria-dependent apoptotic pathway. The average IC50 values of bufadienolide monorhamnosides for HL-60 and A549 cells were 10–20 times lower than those for Na + /K + ATPase, implying that they induce tumor cell death via a mechanism of action other than Na + /K + ATPase inhibition. Graphical abstract: Cytotoxicity-guided fractionation of the MeOH extract of Helleborus lividus (Ranunculaceae) resulted in the isolation of five undescribed bufadienolide glycosides and two undescribed bufadienolides, along with three known compounds. The isolated compounds showed cytotoxicity against HL-60 human leukemia cells and A549 human lung adenocarcinoma cells with IC50 values ranging from 2.20 ± 0.01 nM to 0.77 ± 0.01 μM. Image 1 Highlights: Seven undescribed bufadienolide derivatives were isolated from Helleborus lividus. Their structures were determined by spectroscopic analysis and hydrolysis studies. Isolated compounds showed cytotoxicic to both HL-60 and A549 cells. An undescribed bufadienolide diglycoside induced apoptosis in HL-60 cells.