Role of Receptors to Fibroblast Growth Factor (FGF) on Mesenchymal Precursor Cells in the Realization of Regenerative Effects of Alkaloid Songorine

Abstract

We studied the mechanisms of regenerative (wound healing) effects of songorine associated with functional activation of mesenchymal progenitor cells. The key role of FGF receptors on these progenitor cells in the stimulation of realization of their growth potential under the effect of the alkaloid was demonstrated. Under in vitro conditions, the antibodies to FGF receptor abolished the songorine-induced increase in the number of fibroblast colony-forming units in bone marrow cell culture. The intensity of differentiation of mesenchymal precursors remained unchanged.

Cerebroprotective and Regenerative Effects of Alkaloid Z77 under Conditions of Brain Ischemia

“…A sharp increase in the yield of neurospheres (CFU-N) after addition of this alkaloid to the culture medium (up to 278.9% from the level of intact cells; Fig. 2) was recorded in vitro indicating signifi cant increase in the degree of realization of the growth potential of neural SC, probably associated with the activation of FGFR [1,4].…”

“…In this, regenerative activity of the compound determined by its effect on neural SC [1,4,15] apparently had an important role in the process of restoration of the structure and functions of the CNS. However, the relatively rapid emergence of therapeutic effects indicated the anti-ischemic effect of substance, which could be due to a change in the functioning of elements of the microenvironment of nervous tissue, glial cells with membrane expression of FGFR, which is a pleiotropic and multifunctional factor [1,7,10].…”

“…Alkaloids were identifi ed possessing a stimulating effect on the function of progenitor cells of different classes [10][11][12]. The mechanisms of action of these substances are underlain by the direct effect on the receptor apparatus of progenitor cells and their effect on tissue microenvironment elements [3,4,[10][11][12]. In addition, we have identifi ed atisine-type diterpene alkaloid Z77 and revealed its marked activity against mesenchymal progenitor elements associated with exposure to fi broblast growth factor receptors (FGFR).…”

“…In addition, we have identifi ed atisine-type diterpene alkaloid Z77 and revealed its marked activity against mesenchymal progenitor elements associated with exposure to fi broblast growth factor receptors (FGFR). The above pleiotropic immediate-early growth factor is known to be essential in determining the proliferative and differentiation status also of neural SC [3,4]. Thus, the study of the therapeutic properties of alkaloid Z77 in diseases of the nervous system is of undoubted interest.…”

Mechanisms of Psychopharmacological Effects of Alkaloid Z77 Under Conditions of Brain Ischemia

“…In this connection, the development of original cerebroprotective drugs with radically new mechanisms of action is an urgent problem. In the course of developing "Pharmacological Strategies of Regenerative Medicine" at E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine [1,[8][9][10][11][12][13][14] on the model of cerebral subtotal ischemia, pronounced cerebroprotective effect of alkaloid Z77, which is capable to stimulate the functions of endogenous brain neural stem cells (SC) were revealed [2]. At the same time, the detected psychoneurological events including the normalization of orientation and exploratory behavior of the experimental animals do not allow us to talk unambiguously about cerebroprotective effects of above pharmacological agent.…”