Cleistanthin A causes peripheral vasoconstriction and myocardial depression in isolated tissue preparations

Abstract

Background

Cleistanthus collinus is a poisonous shrub commonly used for deliberate self-harm in rural south India. Boiled decoction or a paste made from its leaves is used for suicide. Cleistanthoside A and Cleistanthin A are the major toxins identified from this plant. In this study, we disclose the mechanism of Cleistanthin A toxicity and concentrations of the two toxins in different extracts of Cleistanthus collinus.

Methods

The effect of Cleistanthin A was studied on isolated goat leg arteries using two different preparations namely transverse cylinder and longitudinal strip. The influence of Cleistanthin A on peripheral vascular resistance and myocardial contractility was evaluated by rat hind limb and isolated rat heart experiments, respectively. For the quantification of toxins, five different extracts of C. collinus leaves were prepared. The extracts were subjected to analytical HPLC to quantify Cleistanthoside A and Cleistanthin A.

Results and Conclusion

Cleistanthin A increased vascular tension in transverse cylinder preparation and increased peak, trough and mean aortic pressures in the rat hind limb preparations. In isolated rat heart experiments, there was an increase in diastolic and mean ventricular pressure with a significant decrease in ventricular pulse pressure. These observations suggest that the hypotension in C. collinus poisoning patients may be due to cardiotoxicity and not due to vasodilation as is currently believed. Quantification of different extracts showed that boiled extracts had higher quantities of Cleistanthoside A whereas crushed leaf extracts yielded significantly higher amounts of Cleistanthin A.

Keywords:

• Cleistanthus collinus
• cleistanthin A
• myocardial depression
• high-performance liquid chromatography
• suicidal poisoning

Acknowledgements

The authors are grateful to Dr. Subrata Ghosh for identifying Cleistanthin A and providing its crystal structure.

Authors’ contributions

SS, KP, RP, GS, SMZ, NP and SMA were involved in the study conception and design. KP, RP, GS, SMZ, NP and SMA performed the experiments and were involved in data collection. SS, KP, RP, GS, SMZ, UB, JC and SG were involved in data analysis and interpretation. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [SS], upon reasonable request.

Additional information

Funding

This work was supported by Institutional Fluid Research Grant, Christian Medical College, Vellore, India.