Mulkijanyan Karen
Tbilisi State Medical University, Georgia
Title: Steroidal compounds of vegetable origin in treatment of circulatory disorders
Biography
Biography: Mulkijanyan Karen
Abstract
Abstract
vasoactive anti-inflammatory drugs free of unwanted side effects that characterize the majority of currently available corticosteroids and NSAIDs.
The presented study aimed to determine specific pharmacologic properties of spiro- and furostanol type steroidal glycosides obtained from the Butcher’s broom (Ruscus ponticus L.) and estimate their possible mechanism of action.
Assessment of the specific anti-inflammatory activity of RE on "granuloma pouch" model revealed that it caused statistically significant (Ñ€ <0.001) difference both in exudate volume and mass of dried granuloma. Further investigation on the formalin-induced rat paw edema confirmed the anti-exudative activity of RE. As the observed effect can be conditioned by several reasons including the change in the diameter of blood vessels, stimulation of a-adrenoreceptors or blocking the release of histamine and bradykinin, more detailed study of the mechanism of action of RE, a series of experiments were conducted, using vital dyes Evans blue (EB) and sodium fluorescein (SF). In intact animals SF after intravenous administration rapidly permeates into all organ tissues in contrast with EB, which does not leave the blood vessels.
Subcutaneous administration of SF and EB on the background of adrenalin or histamine altered the shape of SF pharmacokinetic curve reflecting the vasotropic effects of the agents, whereas for EB it remains unchanged. RE does not change the Tmax of SF, but the concentration of the dye increases. No alterations are observed for EB.
In in situ experiments it was found RE causes the constriction of the mice mesenteric vessels along with increased blood flow. Moreover, RE neutralizes effects of histamine, probably due to stimulation of α1-adrenoceptors.
Finally, it was found, that both prazosin (a1-blocker) and diltiazem (Ca2+ channel blocker) decrease the contractility of isolated femoral vein rings caused by RE, suggesting that observed vasotropic effects of RE are mediated by stimulation of vascular adrenoreceptors along with the simultaneous increase of Ca2+ in vascular endothelium.
Assessment of safety of RE in chronic 90-day experiment revealed the absence of any toxic effects on major systems.
Summarizing the obtained data, it may be concluded that the studied RE can be considered as prospective candidate for the development of anti-inflammatory vasoactive remedy free of toxic/side effects.