Molecular docking and ex vivo pharmacological evaluation of constituents of the leaves of Cleistanthus collinus (Roxb.) (Euphorbiaceae).

OBJECTIVE

To investigate the involvement of alpha adrenergic receptors in hypotension induced by cleistanthin A and cleistanthin B.

METHODS

Cleistanthins A and B were isolated from the leaves of Cleistanthus collinus using a column chromatographic method and purified. Structures were confirmed by spectroscopic analysis. The compounds were prepared for molecular docking studies using Ligprep 2.3 module and Induced Fit Docking was carried out against α-1 adrenergic receptors using Glide. The ex vivo experiments were carried out on male Wistar rats. Under anaesthesia, the femoral vein and carotid artery were cannulated for drug administration and for monitoring the blood pressure, respectively. The effect of epinephrine, norepinephrine, acetylcholine, histamine and dopamine were recorded before and after the administration of cleistanthin A or cleistanthin B. The molecular docking studies showed favorable molecular interactions, glide score, energy and emodel.

RESULTS

Cleistanthins A and B per se reduced the mean blood pressure and the effect was dose dependent. Both the compounds reduced the effect of epinephrine, norepinephrine and α-1 receptor activity of dopamine. Cleistanthin B significantly increased the duration of action of acetylcholine on mean blood pressure.

CONCLUSIONS

The molecular docking and ex vivo studies conclude that cleistanthin A and cleistanthin B have significant α-1 adrenergic receptor antagonist effect on the peripheral vascular system.