Death from cardiac glycoside "pong-pong" following use as weight-loss supplement purchased on Internet.

Cerbera odollam or "pong-pong" tree contains cardiac glycosides similar to digoxin, oleander and yellow oleander. Cerbera odollam is a common method of suicide in South East Asia and has also been used as a weight loss supplement. We present a case of a 33-year-old female presenting with lethargy, vomiting, bradycardia, severe hyperkalemia of 8.9 mEq/L, slow atrial fibrillation followed by cardiovascular collapse following the ingestion of "pong-pong", the kernel of Cerbera odollam, as a weight loss supplement. Despite the administration of a total of nine vials of digoxin-specific Fab the patient could not be resuscitated. Clinicians should be aware of natural cardiac glycosides being uses as weight-loss agents and consider acute cardiac glycoside poisoning in patients with hyperkalemia, abnormal cardiovascular signs, symptoms and abnormal ECG findings.

Study on Clinical Profile and Predictors of Mortality in Cerbera odollam Poisoning.

CONTEXT: Cerbera odollam is a tree native to South Asia. It belongs to the poisonous Apocynaceae family. Deliberate self-harm with fruit of this plant is a major clinical problem in the developing world. Ingestion of C. odollam kernels is the cause of deaths in more than half of Kerala's plant poisoning deaths. The data on clinical features and complications of C. odollam poisoning are sparse, apart from a few case reports and limited studies. AIMS: The present study was done to find the mode of presentation, complications, need for cardiac pacing, inhospital mortality, and the predictors of mortality in patients with C. odollam poisoning. SETTINGS AND DESIGN: This was a retrospective study conducted in the department of general medicine in a tertiary care center in Alappuzha district, Kerala. The study period was for 1 year from January 1, 2016, to December 31, 2016. SUBJECTS AND METHODS: All the patients admitted with a history of ingestion of odollam during the study period were included in the study. Data were collected from case records. The study was approved by the institutional ethics committee and research committee (IEC/TDMCA/EC3.dated29/11/201). STATISTICAL ANALYSIS USED: The data were analyzed using SPSS 16 for Windows (SPSS Inc., Chicago, IL, USA). RESULTS: In this study, 102 patients were identified with C. odollam poisoning, and the mortality rate was 16.7%. Electrocardiogram (ECG) changes were common in our patients, and we observed different types of heart block in the same ECG itself. Ingestion of more than two kernels of odollam, late presentation to hospital, vomiting, bradycardia, hypotension, hyperkalemia, and more severe ECG changes were associated with significantly higher mortality in this study. CONCLUSIONS: C. odollam poisoning is a common method of deliberate self-harm in Kerala. It carries a high mortality rate, and the predictors of mortality include vomiting, bradycardia, hypotension, hyperkalemia, and the presence of severe ECG changes.

Bintaro (Cerbera odollam and Cerbera manghas): an overview of its eco-friendly use, pharmacology, and toxicology.

Bintaro is a tropical mangrove plant often used as a shade tree found in Asia, Australia, Madagascar, and the Islands of the Western Pacific Ocean. The word Bintaro is also often pinned to its closest relative species, the Cerbera odollam. Flower color is one of the distinguishing features between these two species. Human poisoning with the cardiotoxic plant Bintaro is common in Southeast Asia because it bears a fruit that yields a powerful poison that has been used for suicide and homicide, hence it is also called the "Indian suicide tree". The seeds of Bintaro contain Cerberin, a cardiac glycoside toxin of the heart that blocks the calcium ion channels in heart muscles, resulting in disruption of the heartbeat most often fatally. The bio-active compound in the kernels of Bintaro varies due to which plant possesses other properties as well. The plant may also be used for medicinal purposes as it shows many pharmaceutical properties. The seeds of the plant have auspicious anticancer properties through apoptotic activity and the leaf extract of the plant was screened for its antioxidant activities. In addition, it is also used as an insecticide, pesticide, or antifungal agent. This review highlights the Pharmaceutical, toxicological, and environmentally friendly approaches of Bintaro.

Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition.

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI50 values < 90 nM), colony formation and migration. Significant G2/M cell cycle arrest preceded time- and dose-dependent apoptosis-induction in human cancer cell lines corroborated by dose-and time-dependent PARP cleavage and caspase 3/7 activation, in addition to reduced Bcl-2 and Mcl-1 expression. CR potently inhibited PI3K/AKT/mTOR signalling depleting polo-like kinase 1 (PLK-1), c-Myc and STAT-3 expression. Additionally, CR significantly increased the generation of reactive oxygen species (ROS) producing DNA double strand breaks. Preliminary in silico biopharmaceutical assessment of CR predicted >60% bioavailability and rapid absorption; doses of 1-10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside.

Cerbera odollam toxicity: A review.

Cerbera odollam is a plant species of the Apocynaceae family. It is often dubbed the 'suicide tree' due to its strong cardiotoxic effects, which make it a suitable means to attempt suicide. The plant grows in wet areas in South India, Madagascar, and Southeast Asia; and its common names include Pong-Pong and Othalanga. The poison rich part of the plant is the kernel which is present at the core of its fruit. The bioactive toxin in the plant is cerberin, which is a cardiac glycoside of the cardenolide class. Cerberin has a mechanism of action similar to digoxin; hence, Cerbera odollam toxicity manifests similar to acute digoxin poisoning. Ingestion of its kernel causes nausea, vomiting, hyperkalemia, thrombocytopenia, and ECG abnormalities. Exposure to high doses of Cerbera odollam carries the highest risk of mortality. Initial management includes supportive therapy and administration of atropine followed by temporary pacemaker insertion. Administration of digoxin immune Fab may be considered in severe cases, although efficacy is variable and data limited to isolated case reports.

Clinical Profile and Management of Poisoning with Suicide Tree: An Observational Study.

INTRODUCTION: The clinical features, management, and the associations of dosage in poisoning with the cardiotoxic plant Cerbera odollam (suicide tree), responsible for more than half of plant poisoning deaths in the South Indian State of Kerala alone, have not been evaluated. There are only few studies on its clinical features and none on the usage of cardiac pacing in its management, given its rarity in the Western world. We depend on data for similar toxins to form our management protocols. AIMS: Our aim was to describe the clinical features of C. odollam poisoning, dosage, and its relations to clinical features and pacemaker initiation therapy and to study the characteristics of temporary pacemaker therapy in its management. SUBJECTS AND METHODS: This study was conducted in fifty consecutive cases who presented with a history of C. odollam poisoning from whom clinical data were obtained. Cases initiated on temporary cardiac pacemaker therapy due to the toxin effects were also studied. Effect of dosage on various clinical manifestations and pacing was analyzed. RESULTS: All cases were due to suicidal ingestion. Vomiting (54%), thrombocytopenia (50%), and sinus bradycardia (32%) were the most common features. The need for cardiac pacing had a significant association with dosage in kernels ingested (P < 0.05) and with thrombocytopenia (P < 0.05). There was no association between hyperkalemia and death. Thirty-six percent of cases had to be paced, of which 16% died. In-hospital mortality of odollam poisoning was 12%. CONCLUSIONS: C. odollam poisoning cases merit monitoring and treatment in Intensive Care Unit with facilities for electrocardiographic monitoring and temporary cardiac pacing. The clinical features and the factors associated with mortality are different from other cardiac glycosides.

Cytotoxicity studies of semi-synthetic derivatives of theveside derived from the aqueous extract of leaves of 'suicide tree' Cerbera odollam.

We report the isolation of two known iridoid glucosides theviridoside (1) and theveside (2) from the aqueous extract of leaves of Cerbera odollam and semi-synthetic derivatisation of theveside prepared in a single step under protection group-free conditions. Derivatives 2a-j were evaluated for cytotoxicity towards five human cancer cell lines of different origins, namely SKBR3 (breast), HeLa (cervical), A375 (skin), HepG2 (liver) and HCT-116 (colon), and IC50 values were determined. Derivatives 2b and 2h exhibited moderate cytotoxicity against HCT-116 and A375 cell lines, respectively.