Authentication of tejocote (Crataegus mexicana) dietary supplements based on DNA barcoding and chemical profiling.

Tejocote (Crataegus mexicana, Mexican hawthorn), known as a weight-loss supplement, has been marketed online and is easily available for overseas direct purchase. Alipotec (brand name) is known as one of the most popular products containing tejocote in Mexico and other countries. However, adverse effects have been reported by users of these supplements. Therefore it is necessary to find the reason for the side effect. Dietary supplement samples labelled as containing tejocote were analysed using mass spectrometry and DNA barcoding analysis. Our results demonstrate that Alipotec samples contained ingredients from different species, yellow oleander instead of tejocote. The rpoB barcode region was able to differentiate between tejocote and yellow oleander species. Moreover, it was also observed that three compounds, including thevetin B, neriifolin, and digitoxigenin, clearly distinguish between tejocote and yellow oleander samples. This is the first and preliminary investigation to use an integrated approach of both chemical and genomic profiling for the authentication of dietary supplement containing tejocote.

Negligible Oleandrin Content of Hot Dogs Cooked on Nerium oleander Skewers.

INTRODUCTION: The Nerium oleander plant contains cardenolides that may cause human poisoning when ingested. A long-standing belief holds that it is possible to be poisoned by eating hot dogs or other foods cooked on Nerium oleander branch skewers. Oleandrin levels in frankfurters cooked on fresh and dry Nerium oleander skewers were measured. METHODS: Hot dogs were cooked separately on either dried or fresh oleander branch skewers using a disposable charcoal grill. The hot dogs were then frozen and transported to an analytical laboratory where oleandrin content was measured via liquid chromatography/mass spectroscopy (LC/MS). RESULTS: The oleandrin content of hot dogs cooked on dried and fresh skewers did not exceed 343 ng and 701 ng, respectively. CONCLUSION: Hot dogs cooked on Nerium oleander skewers contain a negligible amount of oleandrin with respect to that sufficient to cause human poisoning. Reports of poisonings occurring in this manner are most likely the result of an urban myth.

First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf-κΒ and p70s6k, in patients with advanced solid tumors.

BACKGROUND: PBI-05204, a Nerium oleander extract (NOE) containing the cardiac glycoside oleandrin, inhibits the α-3 subunit of Na-K ATPase, as well as FGF-2 export, Akt and p70S6K, hence attenuating mTOR activity. This first-in-human study determined the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in patients with advanced cancer. Methods Forty-six patients received PBI-05204 by mouth for 21 of 28 days (3 + 3 trial design). Dose was escalated 100% using an accelerated titration design until grade 2 toxicity was observed. Plasma PK and mTOR effector (p70S6K and pS6) protein expressions were evaluated. Results Dose-limiting toxicities (grade 3 proteinuria, fatigue) were observed at dose level 8 (0.3383 mg/kg/day). Common possible drug-related adverse were fatigue (26 patients, 56.5%), nausea (19 patients, 41.3%) and diarrhea (15 patients, 32.6 %). Electrocardiogram monitoring revealed grade 1 atrioventricular block (N = 10 patients) and grade 2 supraventricular tachycardia (N = 1). The MTD was DL7 (0.2255 mg/kg) where no toxicity of grade ≥ 3 was observed in seven patients treated. Seven patients (15%) had stable disease > 4 months. Mean peak oleandrin concentrations up to 2 ng/mL were achieved, with area under the curves 6.6 to 25.5 µg/L*hr and a half-life range of 5-13 h. There was an average 10% and 35% reduction in the phosphorylation of Akt and pS6 in PBMC samples in 36 and 32 patients, respectively, tested between predose and 21 days of treatment. Conclusions PBI-05204 was well tolerated in heavily pretreated patients with advanced solid tumors. The recommended Phase II dose is 0.2255 mg/kg/day.

Unexpectedly dangerous escargot stew: oleandrin poisoning through the alimentary chain.

A female, aged 43 and a male, aged 66, experienced gastrointestinal and cardiovascular symptoms after a meal including snail stew. Twelve hours after the ingestion, they presented with nausea, vomiting, diarrhea, and cardiovascular symptoms typical of acute toxic digoxin ingestion and were hospitalized. The man's electrocardiogram was altered, and the woman's was normal. Serum digoxin levels, measured on a Roche COBAS Integra 800 with the Roche On-Line Digoxin reagent, were 1.14 and 1.00 nmol/L, respectively. Potassium levels were normal in both patients. The serum digoxin concentration decreased on the second day, and symptoms resolved on the third day with patients fully recovered (i.e., reversion to a normal sinus rhythm). Cardiac-glycoside-like intoxication symptoms follow the ingestion of leaves or flowers of Nerium oleander. The consumed snails were suspected to be responsible for the intoxication. In the homogenized snail tissue, the concentration expressed in digoxin equivalents was 0.282 nmol/g. The presence of oleandrin and oleandrigenin in the snails was confirmed by liquid chromatography-tandem mass spectrometry analysis, which was performed on a ionic-trap Finnigan LXQ instrument using an electrospray ionization interface. High-pressure liquid chromatographic separation was performed on a C18 column with a gradient of methanol/water. An extract of oleander leaves was used as reference.

Oleander toxicity: an examination of human and animal toxic exposures.

The oleander is an attractive and hardy shrub that thrives in tropical and subtropical regions. The common pink oleander, Nerium oleander, and the yellow oleander, Thevetia peruviana, are the principle oleander representatives of the family Apocynaceae. Oleanders contain within their tissues cardenolides that are capable of exerting positive inotropic effects on the hearts of animals and humans. The cardiotonic properties of oleanders have been exploited therapeutically and as an instrument of suicide since antiquity. The basis for the physiological action of the oleander cardenolides is similar to that of the classic digitalis glycosides, i.e. inhibition of plasmalemma Na+,K+ ATPase. Differences in toxicity and extracardiac effects exist between the oleander and digitalis cardenolides, however. Toxic exposures of humans and wildlife to oleander cardenolides occur with regularity throughout geographic regions where these plants grow. The human mortality associated with oleander ingestion is generally very low, even in cases of intentional consumption (suicide attempts). Experimental animal models have been successfully utilized to evaluate various treatment protocols designed to manage toxic oleander exposures. The data reviewed here indicate that small children and domestic livestock are at increased risk of oleander poisoning. Both experimental and established therapeutic measures involved in detoxification are discussed.