They key toxic component of oleander is oleandrin. It only accounts for 0.08 % of total cardenolides and have a bioavailability of 30 %. The yellow flowered oleander contains Peruvoside. The primary mode of action of these cardenolides is inhibition of Na+/K+-ATPase pump on cardiomyocytes, which results in intracellular Na+ build up. Upon Na+/K+-ATPase, intracellular K+ is elevated, leading to cytosolic Ca2+ buildup through Na+/Ca2+ exchanger on plasma membrane. Increasing of intracellular Ca2+ induces more Ca2+ release form the sarcoplasmic reticulum. The cytosolic Ca2+ binds to troponin-C (actin binding protein) and induces inotropy, resulting in cardiac muscle contraction and vasoconstriction.
On the hand, Peruvoside can be used for the research of heart failure. On the one hand, Peruvoside can be used for cancer research.
Peruvoside is a potent inhibitor of Src, PI3K, JNK, STAT, and EGFR. First, Peruvoside induces apoptosis and autophagy and possesses a broad spectrum of anticancer activity in breast, lung, liver cancers and leukemia. Peruvoside (50-1000 nM, 24 h) inhibits the viability and proliferation in PC9, PC9/gef, H3255, and H1975 cell lines. Second, Peruvoside (0.005-0.5 μM, 72 h) sensitizes A549, PC9/gef and H1975 to Gefitinib when in combination with Gefitinib (0.01~0.5 μM). Third, Peruvoside (0-100 μM, 24 h) induces cell cycle arrest and apoptosis in MCF-7, HpG2, and A549 cells. Meanwhile, Peruvoside (0.1 mg/kg for i.p.; once daily for 28 days) suppresses the tumour growth in lung cancer mice model. Peruvoside (0.59 mg/kg for i.p.; once daily for 7 days) reduces mortality in EV-A71-infected mice model.
Furthermore, Peruvoside is a broad-spectrum and potent antiviral activity against positive-sense RNA viruses.
Reference:
[1] Dey P. Biomed Pharmacother. 2020 Sep;129:110422.
[2] Lai Y, et al. Am J Cancer Res. 2022 Jun 15;12(6):2576-2593.
[3] Reddy D, et al. Life Sci. 2020 Jan 15;241:117147.