Bioactive Cardenolides from the Stems and Twigs of Nerium oleander

Abstract

Four new cardenolide monoglycosides, cardenolides N-1 (1), N-2 (2), N-3 (3), and N-4 (4), were isolated from Nerium oleander, together with two known cardenolides, 5 and 12, and seven cardenolide monoglycosides, 6-11 and 13. The structures of compounds 1-4 were established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 1, 5, 6, and 11-13 were active at an IC50 value of less than 1 microM. The cytotoxicity of compounds 1-13 was evaluated against three human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 1, 4, 6, and 11-13 were active toward V-13 cells, and compounds 1, 11, and 12 were active toward HepG2 cells at IC50 values of less than 1 microM. Compounds 4, 5, 10, and 12 showed selective cell growth inhibitory activity toward V-13 tumor cells compared with that of parental normal WI-38 cells. The MDR-reversal activity of compounds 1-13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 4, 9, and 10 showed significant effects on calcein accumulation, compound 4 showing stronger activity than that of verapamil.

Chemical biology of inflammatory cytokine signaling

“…Among these compounds, odoroside A (Figure 7a) was found to inhibit ICAM-1 expression induced by TNF-a or IL-1 at IC 50 values o1 mM. [119][120][121][122][123] Odoroside A has been shown to directly inhibit the ATP-hydrolyzing activity of Na + /K + -ATPase as potently as ouabain. 124 However, in contrast to previous studies, we have found that odoroside A and ouabain affect neither TNF-a-induced early NF-kB signaling pathway nor mRNA expression, but rather prevent NF-kB-inducible protein expression by blocking Na + -dependent amino acid transport.…”

Exploring a natural MDR reversal agent: potential of medicinal food supplement Nerium oleander leaf distillate

“…So cell membrane is the very important target of MDR modulators. Zhao et al reported that new cardenolide compounds obtained from Nerium oleander by infusion method reversed MDR resistance in 2780AD ovary cancer cell lines [9] . However N. oleander distillate did not exert any MDR modulator activity on drug resistant cells in our study.…”

“…Total extract of the plant exhibited antinosiseptive, antiinflammatory, antibacterial and anticancer effects [7,8] . Zhao et al declared that the cardenolide compounds extracted from N. oleander exhibited MDR modulator effect on doxorubicin resistant ovarian carcinoma cell line 2780AD [9] . Bas et al reported that N. oleander distillate may be used as dietary supplement to treat high blood cholesterol level in diabetic rats [10] .…”

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“…A growing number of reports document the ability of some CS to circumvent cancer cell chemoresistance [50][51][52][53][54], making them an interesting starting point for the development of new anti-chemoresistance treatment strategies.…”