We compared analgesic activities of individual alkaloids extracted from Baikal aconite (Aconitum baikalensis): napelline, hypaconitine, songorine, mesaconitine, 12-epinapelline N-oxide. The detected analgesic activity was comparable to that of sodium metamizole. The mechanisms of analgesia were different in diterpene alkaloids of different structure. The antinociceptive effect of atisine alkaloids (12-epinapelline N-oxide, songorine) was naloxonedependent and realized via opioid receptor modulation.
We evaluated the possibility of hemopoiesis stimulation with hyaluronidase. The response of the blood system depended on the dose of this enzyme. Functional activity of hemopoietic precursor cells increased under the influence of hyaluronidase in a dose of 20 arb. units, which was accompanied by an increase in the secretion of hemopoietins by adherent myelokaryocytes and elevation of hemopoietic activity in blood plasma. The number of erythrokaryocytes and mature neutrophilic granulocytes in the bone marrow, as well as the count of reticulocytes and neutrophils in the peripheral blood increased under these conditions. Administration of hyaluronidase in a high dose (100 arb. units) led to uncoupling of proliferation and differentiation of hemopoietic precursors and produced no considerably changes in the blood.
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.
Signal pathways of realization of growth potential of mesenchymal progenitor cells related to transcription factor NF-κB were studied in vitro. NF-κB was found to participate in the proliferation and differentiation of progenitor elements that can be blocked by its specific inhibitor oridonin. NF-κB inhibitor aurothiomalate had no effect on the functions of fibroblastic CFU.
We compared anti-inflammatory activity of individual diterpene alkaloids isolated from Aconitum baikalense (napelline, songorine, hypaconitine, mesaconitine, 12-epinapelline N-oxide) under conditions of acute inflammation of different genesis. The tested substances showed high antiexudative activity comparable with that of sodium diclofenac. Unlike nonsteroidal anti-inflammatory drugs, diterpene alkaloids exerted no ulcerogenic effect.
Specific JNK and p53 inhibitors stimulated the formation of fibroblast colonies (CFU-F) and clusters (ClFU-F) and increased proliferative activity of mesenchymal progenitor cells. No effects of inhibitors of JNK and p53 on differentiation of progenitor elements were revealed.
We studied the reactions of granulocytic hemopoietic stem after acute hypoxia and during the development of posthypoxic encephalopathy. Damage to brain structures was associated with intensification of the bone marrow hemopoiesis due to activation of hemopoiesis-inducing microenvironment and more intense formation of hemopoietic islets, despite reduced proliferative capacity of granulocytic precursors.
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