Effects of Oleandrin on Cardiovascular System

 

Dr. Shoaib Ahmad

University School of Pharmaceutical Sciences, Rayat-Bahra University, Mohali 140104 India

 

ABSTRACT:

Nerium oleander is a member of plant family Apocynaceae. Almost all of its parts contain cardioactive glycoside oleandrin with anticancer activity. Oleandrin has been subjected to numerous pharmacological studies. Pharmacological effects of oleandrin and other established cardiac glycosides (viz. g-strophanthin, digoxin and digitoxin) have been compared in several studies. Oleandrin primarily produces characteristic effects through Na+,K+-ATPase. Oleandrin is used to treat myocardial insufficiency. Oleander and oleandrin cause toxicity because of the action on cardiovascular tissues. Oleandrin can be used for anticancer therapy for cancerous cell-targeting. The present article is an attempt to outline the historical developments in the area of cardiovascular pharmacology of oleandrin.

 

 

INTRODUCTION:

Nerium oleander (Apocynaceae) is an important medicinal plant. It produces flowers in the varying shades/mixes of pink, red, white. Almost all plant parts contain cardio active glycoside oleandrin which also has anticancer activities^1,2,3,4,5. Several activities have been attributed to this unique molecule. The effects of the true oleander glycoside oleandrin have been documented ⁶.

 

Cardiovascular Pharmacology of Oleandrin:

Effect of oleandrin was determined on the embryo chick heart⁷. Cardiotonic actions of oleandrin and digitoxin were compared⁸. A comparison of the pharmacology of oleandrin and other established cardiac glycosides (viz. g-strophanthin, digoxin and digitoxin) ⁹. Effect of oleandrin on cardiac contractility of the normal dog was studied. Oleandrin (0.05 mg/kg) led to a significant increase in left ventricular contractility.

 

7Oleandrin elicited both qualitatively and quantitatively actions much similar to those of the better known cardiac glycosides¹⁰. Effect of oleandrin was also evaluated on cardiovascular hemodynamic of the dog¹¹. Oleandrin was shown to produce intracellular calcium level changes in isolated calcium-tolerant adult rat cardiomyocytes as well as cultured neonatal rat cardiomyocytes. This study was performed using a real-time fluorescence imaging techniques¹². Three effects were observed with the adult cardiomyocytes:

1.        Intracellular calcium levels registered increase in a concentration-dependent fashion.

2.        Transient calcium heights decreased and led to cessation of beating.

3.        Increased sparking led to beating and consequential calcium overload.

 

It was observed that the oleander extract was quite potent and caused high calcium concentrations in cardiomyocytes which were unable to release the accumulated calcium. It indicated a possibility that oleandrin might be involved in the following processes:

1.        Blockade of calcium release channels in ryanodine receptors.

2.        Calcium uptake through inhibition of Na+, K+-ATPase.

3.        The disrupted functioning of calcium release channels in sarcolemma.

 

Na (+), K(+) -ATPase alpha3 subunit was shown to be a receptor for cardiac glycosides. These included cardenolides as well as bufadienolides. A study evaluated intracellular distribution of Na (+), K (+) -ATPase alpha3 in cancer and normal cells. The cancer cells were taken from mucosa biopsy samples of lung and colorectal cancer patients. ATPase alpha3 isoform was located near the cytoplasmic membrane in normal cells from colon and lung epithelia. In contrast, it moved to peri-nuclear position in the cancerous cells. Oleandrin (10 to 20nM) resulted in autophagic cell death undifferentiated CaCO-2 (colorectal cancer) cells. These data indicated the location of cancerous cells and offered a potential target opportunity for cancer therapy¹³.

Oleandrin has been used in therapy of myocardial insufficiency^14-15. Oleander and oleandrin proved toxic because of the action on cardiovascular tissues. Dipotassium edentate was used as antidote in the poisoning from oleander as well as oleandrin¹⁶.

 

Mechanism of Action:

Oleandrin might be involved in the following processes:

1.        Blockade of calcium release channels in ryanodine receptors.

2.        Calcium uptake through inhibition of Na+, K+-ATPase.

3.        The disruption of calcium release channels in sarcolemma. Na (+), K (+)-ATPase alpha3 subunit is be a receptor for oleandrin as in case of other cardiac glycosides¹³.

 

Toxicity:

Oleandrin proves toxic because of the pronounced effects on cardiovascular tissues. Dipotassium edentate can be used as antidote¹⁶.

 

Uses:

Oleandrin is used in treatment of myocardial insufficiency^14-15.

 

Potential applications:

Oleandrin can be used to target the specific cancerous cells¹³.

 

CONCLUSIONS:

Oleandrin is a potent cardenolide obtained from N. oleander (Apocynceae). It acts on Na (+), K (+)-ATPase alpha3 subunit to produce its cardiovascular effects. Oleandrin toxicity can be countered by dipotassium edentate. Presently, oleandrin is used in myocardial insufficiency and may find applications in cell-selective anticancer therapy.

 

REFERENCES:

1.        Ahmad S. Studies on the normal and genetically transformed tissue cultures of Nerium oleander Linn. Hamdard National Fellowship Progress Report, Jamia Hamdard, New Delhi. 2003.

2.        Zafar R, Ahmad S. genetically transformed tissue cultures of a drug plant (Nerium oleander Linn.). AICTE-MODROBS Progress Report, Jamia Hamdard, New Delhi. 2004.

3.        Ahmad S. Studies on the Normal and Genetically Transformed Cultures of a Medicinal Plant for the Production of Bioactive Natural Products. Ph. D. thesis, Jamia Hamdard, New Delhi, 2005.

4.        Zafar R, Ahmad S. genetically transformed tissue cultures of a drug plant (Nerium oleander Linn.). AICTE-MODROBS Final Project Report, Jamia Hamdard, New Delhi. 2005.

5.        Ahmad S. Oleandrin – An Anticancer drug of Plant Origin. National Conference on “Emerging Trends in Pharmacological Research and Pharmacy Practice at Rayat-Bahra University, Mohali. Oct 16-17, 2015.

6.        Storz H. On the effect of the oleander glycoside Corrigen (Oleandrin). Clinical studies. Med Welt 1967 28, 1650-1655.

7.        Wolfred MM. The evaluation of the glycoside oleandrin, on the embryo chick heart. J Am Pharm Assoc Am Pharm Assoc 1949 38(11), 581-584.

8.        Li CT, et al. Comparison of cardiotonic actions between oleandrin and digitoxin. Yao Xue Xue Bao 1964 11, 540-544.

9.        Yeau KL, et al. The pharmacology of oleandrin compared with g-strophanthin, digoxin and digitoxin. Yao Xue Xue Bao 1965 12, 180-184.

10.     Deavers S, et al. The effects of oleandrin on cardiac contractility in the normal dog. Arch Int. Pharmacodyn Ther 1979 239(2), 283-295.

11.     Deavers SI, et al. Effects of oleandrin on cardiovascular hemodynamics in the dog. Am J Vet Res 1979 40(10), 1421-1425.

12.     Poindexter BJ, et al. Oleandrin produces changes in intracellular calcium levels in isolated cardiomyocytes, a real-time fluorescence imaging study comparing adult to neonatal cardiomyocytes. J Toxicol Environ Health A 2007 70(6), 568-574.

13.     Yang P, et al. Cellular location and expression of Na+, K+ -ATPase alpha subunits affect the anti-proliferative activity of oleandrin. Mol Carcinog 2014 53(4), 253-263.

14.     Martelli A Results of the use of oleandrin in therapy of myocardial insufficiency; review and personal experience. Minerva Med 1954 45(20), 690-694.

15.     Fazzini G. Oleandrin associated with a coronary dilator in the treatment of cardiac insufficiency. Riforma Med 1963 77, 876-880.

16.     Burton LE, et al. Dipotassium edetate as an antidote in poisoning from oleander and its chief glycoside, oleandrin. Arch Int. Pharmacodyn Ther 1965 158(1), 202-211.

 

 

 

 

 

Received on 08.03.2017          Modified on 14.04.2017

Accepted on 29.04.2017      ©A&V Publications All right reserved