Strophanthus Seeds

Introduction:

Strophanthus is a genus of flowering plant native to the tropical parts of Africa, extending down as far as South Africa. There are also some species found in Asia, in India, Southern China and the Philippines. There are approximately 40 known species of Strophanthus, of which there are seeds from Strophanthus Hispidus, Strophanthus Kombe and Strophanthus Glabra (S. Gratus) found in the Department of Pharmacology of Trinity College Dublin, based in St. James’s University Hospital.

The specimens in the lab were sourced from ‘Corbyn, Stacey and Co.’ a firm of manufacturing and retail chemists found on High Holborn Street in London. The company was founded in 1726 and operated until 1927 dating the samples between 98 and 299 years old.

The active ingredient of each is:

• S. Kombe - K-Strophanthin 

• S. Glabra - G-Strophanthin/Ouabain 

• S. Hispidus - H-Strophanthin 

All potent cardiac glycosides.

Cultural and Historical Use:

All three types of seeds were used historically in Africa as components in arrow poison. The potent cardiac glycosides were employed in the hunting of large prey due to their rapid cardiotoxic effects. During the 19th century, explorers documented the use of Strophanthus and sent specimens to Europe and the study of their pharmacological potential began. 

The plant's effect is similar to that of digitalis - foxglove. 

S. Kombe is found in the South East of Africa (Malawi, Mozambique and Tanzania).

S. Hispidus is found in West and Central Africa (Senegal. Sierra Leone, Nigeria)

S. Glabra is found primarily in West Africa (Cameroon, Ivory Coast, Liberia, Nigeria)

Mechanism of Action of Strophanthin:

Overall MOA: 

Strophanthin is a cardiac glycoside which inhibits sodium-potassium ATPase on cardiac myocytes causing an increase in intracellular Na+. This increased Na+ decreases the driving force for the Na+/Ca2+ exchanger leading to decreased efflux of calcium and thus an increase in intracellular calcium. The increased calcium is pumped via SERCA into the Sarcoplasmic Reticulum, increasing available calcium for subsequent contractions. Ultimately, this leads to increased myofibril contraction and therefore increased cardiac inotropy. 

Effect on Myocardium:

Excitability, the ability of surrounding cells to respond to a stimulus, and automaticity, the ability of cells to spontaneously depolarise, are also increased.

Effect on Conductivity:

Sodium-Potassium ATPase are also found in the plasma membrane of neuronal cells. This increases parasympathetic tone and decreases sympathetic tone and thus Cardiac Glycosides have a negative chronotropic effect which is facilitated by this increased parasympathetic activity, reducing Sinoatrial (SA) firing. They also slow conduction velocity through the Atrioventricular node (AV) and prolong AV nodal effective refractory period. 

Indication/Use:

Strophanthins, particularly Strophanthin-G or Ouabain from Strophanthus Glabra, are used in Western medicine for heart-related issues, particularly Congestive Heart Failure and Atrial Fibrillation. 

Ouabain Pharmacokinetics: It is primarily administered intravenously due to poor oral bioavailability (10-20%). There is minimal hepatic metabolism before being renally excreted.

Strophanthin K and H are seldom used due to the development of safer and more effective treatments such as digoxin, a digitalis derivative. 

Side Effects:

Strophanthins can cause Arrhythmias such as delayed afterdepolarizations (DADs), ventricular tachycardia, AV block and bradycardia due to calcium overload and the inhibition of sodium-potassium ATPase. Nausea, vomiting, diarrhoea and anorexia are also common, alongside dizziness, confusion and fatigue.

Drug-Drug Interactions and Contradictions:

• Potassium competes with Strophanthins by binding to the same site on the sodium-potassium ATPase. Hyperkalaemia, therefore, can result in inhibition of binding of Strophanthins to Na/K ATPase, reducing their efficacy. On the other hand, in hypokalemia an increase in Strophanthins can lead to toxicity, resulting in a cardiotoxic effect. This was the desired effect of the poison arrows historically used in Africa, to induce glycoside toxicity.

• Potassium depleting diuretics decrease plasma potassium levels thus increasing the risk of toxicity.

• High intracellular calcium also facilitates toxicity. 

• Beta-Adrenergic antagonists decrease AV nodal conduction leading to an increase of AV block

• Beta-Adrenergic antagonists and Calcium Channel Blockers can decrease Cardiac Contractility and attenuate the ionotropic effects of cardiac glycosides

Samples #40, #41 and #42

Sample 40: Strophanthus Kombe

Sample 41: Strophanthus Hispidus

Sample 42 Strophanthus Glabra