Thevetin A

Investigation of cardiac glycosides from oleander in a human induced pluripotent stem cells derived cardiomyocyte model.[Pubmed:34371141]

Toxicol Lett. 2021 Oct 10;350:261-266.

The ingestion of Nerium oleander and Thevetia peruviana are common causes for poisoning in Southeast Asia. All parts of the oleander shrub contain cardiac glycosides of the cardenolide type. These glycosides act via inhibition of a Na(+)/K(+)-ATPase which might cause severe arrhythmia and subsequent death in oleander-poisoned patients. The current study uses human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) in a microelectrode array (MEA) system to assess the cardiac effects of neriifolin, oleandrin, digitoxigenin, peruvoside and Thevetin A from the oleander plant. Digoxin was used as established reference compound. All tested compounds showed a corrected field potential duration (FPDc) shortening and was the lowest for 600 nM digitoxigenin with -36.9 +/- 1.2 %. Next to the dose-dependent pro-arrhythmic potential, a complete beat arrest of the spontaneously beating hiPSC-CM was observed at a concentration of 300 nM for neriifolin, 600 nM for oleandrin and 1000 nM for digitoxigenin and peruvoside. Thevetin A did not cause arrhythmia up to a final concentration of 1000 nM. Thus, it was possible to establish a cardiac effect rank order of the tested substances: neriifolin > oleandrin > digitoxigenin = peruvoside > digoxin > Thevetin A.

Antifertility activity of Thevetia peruviana (Pers.) K. Schum leaf in female Sprague-Dawley rat.[Pubmed:28066105]

Indian J Pharmacol. 2016 Nov-Dec;48(6):669-674.

OBJECTIVES: Thevetia peruviana (Pers.) K. Schum. (Apocynaceae) is known to possess cardioactive glycoside such as Thevetin A, thevetin B, neriifolin, peruvoside, thevetoxin, and ruvoside. Traditionally, T. peruviana leaves are used as abortifacient. The aim of the present study is to evaluate antifertility potential of T. peruviana leaves. SUBJECTS AND METHODS: Cardiac glycoside freed leaves of T. peruviana were extracted with methanol using maceration method. The dried cardiac glycoside-free methanolic extract of T. peruviana leaves (TPL-Me-G) was screened for phytoconstituents and evaluated for its effect on estrogen-primed female Sprague-Dawley rat uterus model. It was further studied for effects on the estrous cycle, implantation, and effect on estrogen and progesterone. STATISTICAL ANALYSIS USED: Statistical analysis was done by ANOVA followed by Dunnett's t-test. RESULTS: Alkaloids, flavonoids, essential oils, carbohydrates, and amino acids were found to be present in the glycoside-free extract. Thin-layer chromatography (TLC) in n-butanol: acetone: water (4:1:5) revealed the presence of quercetin and kaempferol. The presence of flavonoids (quercetin 0.0326% and kaempferol 0.138% on dry weight basis) was reconfirmed by high-performance TLC analysis. The extract was able to induce uterine contractions (EC(50), 0.170 mg/ml) in a dose-dependent manner. Further investigation showed significant (P < 0.001) extension of estrous cycle and anti-implantation activity of the extract by reduction of the progesterone level. CONCLUSIONS: Methanolic extract of T. peruviana leaves (TPL-Me-G) containing quercetin 0.0326% and kaempferol 0.138% possesses a significant (P < 0.001) antifertility potential by virtue of decreasing the progesterone level.

A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) poisoning.[Pubmed:20438743]

Toxicon. 2010 Sep 1;56(3):273-81.

Nerium oleander (common oleander) and Thevetia peruviana (yellow oleander) are potentially lethal plants after ingestion. Poisoning by these plants is a common toxicological emergency in tropical and subtropical parts of the world and intentional self-harm using T. peruviana is prevalent in South Asian countries, especially India and Sri Lanka. All parts of these plants are toxic, and contain a variety of cardiac glycosides including neriifolin, Thevetin A, thevetin B, and oleandrin. Ingestion of either oleander results in nausea, vomiting, abdominal pain, diarrhoea, dysrhythmias, and hyperkalemia. In most cases, clinical management of poisoning by either N. oleander or T. peruviana involves administration of activated charcoal and supportive care. Digoxin specific Fab fragments are an effective treatment of acute intoxication by either species. However, where limited economic resources restrict the use of such Fab fragments, treatment of severely poisoned patients is difficult. Data from case reports and clinical studies were reviewed to identify treatments supported by evidence for the management of poisoning by N. oleander and T. peruviana.