20-Hydroxyecdysone from Dacrycarpus imbricatus bark inhibits the proliferation of acute myeloid leukemia cells

OBJECTIVE@#To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus (Blume) de Laub.@*METHODS@#Column chromatography was used for isolation of compounds from plant material. The structure of the isolated compound was identified by mass spectrometry and nuclear magnetic resonance techniques, including HSQC, HMBC, NOE-difference experiments. The isolated compound was tested for its anti-proliferative activity in acute myeloid leukemia (AML) and OCI-AML cells.@*RESULTS@#Compound 1 was isolated from the ethyl acetate fraction of Dacrycarpus imbricatus barks by column chromatography. Its chemical structure was identified as 20-hydroxyecdysone (20HE), a cholestane-type ecdysteroid, by a combination of mass spectrometry and nuclear magnetic resonance spectrometric analyses. Our goal was to test the anti-proliferative activity of 20HE using the OCI-AML cell line. 20HE significantly decreased OCI cell number at a concentration of 1 mg/mL, whereas lower concentrations were ineffective. Moreover, this decrease was due to partial blockage of the G/S phase of the cell cycle, with a reduction of cells in the GM phase, not due to increased apoptosis.@*CONCLUSIONS@#This indicates that 20HE significantly decreases the number of cells in the G/S phase of the cell cycle in human AML cells. This is the first time that the anti-proliferative activity of 20HE against a human tumor cell line has been reported.

20-Hydroxyecdysone from Dacrycarpus imbricatus bark inhibits the proliferation of acute myeloid leukemia cells

Objective To investigate the anti-proliferative effects of 20-hydroxyecdysone isolated from the bark of Dacrycarpus imbricatus (Blume) de Laub. Methods Column chromatography was used for isolation of compounds from plant material. The structure of the isolated compound was identified by mass spectrometry and nuclear magnetic resonance techniques, including HSQC, HMBC, NOE-difference experiments. The isolated compound was tested for its anti-proliferative activity in acute myeloid leukemia (AML) and OCI-AML cells. Results Compound 1 was isolated from the ethyl acetate fraction of Dacrycarpus imbricatus barks by column chromatography. Its chemical structure was identified as 20-hydroxyecdysone (20HE), a cholestane-type ecdysteroid, by a combination of mass spectrometry and nuclear magnetic resonance spectrometric analyses. Our goal was to test the anti-proliferative activity of 20HE using the OCI-AML cell line. 20HE significantly decreased OCI cell number at a concentration of 1 mg/mL, whereas lower concentrations were ineffective. Moreover, this decrease was due to partial blockage of the G

RHAPONTICUM UNIFLORUM (L.) AND SERRATULA CENTAUROIDES (L.) AS THE / Монголын эм зүй, эм судлал

Rhaponticum unifl orum (L.) and Serratula centauroides (L.) are prospective adaptogenic ecdysteroid-containing plants of Buryatia Republic. Underground organs of Rhaponticum unifl orum (L.) and the grass of Serratula centauroides (L.) may be suggested as a plant material containing ecdysteroids for creation of new adaptogenic remedies. Key words: ecdysteroid, Rhaponticum unifl orum (L.), Serratula centauroides (L.) Adaptogenes possess a specifi c combination of peculiar pharmacological properties: being non-toxic substances these preparations manifest anabolic properties which set condition for physiological stimulation of the protective system functions in the body, i.e. bring the body to the state of non-specifi c increased resistance. Adaptogenes have stimulating effect and promote the increase of the resistance to various unfavorable factors. It is worthy to note that adaptogenic properties are characteristic features of natural preparations or compounds being natural metabolites. Some polysaccharides, vaccines, as well as synthetic preparations – stimulators with “economizing” type of the effect have certain adaptogenic properties which are manifested in the regulation of immune system functions. Nevertheless, specifi c stimulating properties and preventive effect manifested in the preparation of the bodily systems to overloading are the most peculiar features of typical adaptogenes [1,2]. At present the use of ecdysteroid-containig plants for developing new adaptogenic medicinal preparations and tonics are of great interest. Plant ecdysteroids have practical signifi cance: they are contained almost in all plants but the difference in concentration levels reaches 8-9 orders. Only few species are characterized by high content of ecdysteroids. Rhaponticum unifl orum (L.) and Serratula centauroides (L.) are ecdysteroid-containing plants growing in the territory of Buryatia [3]. The aim of the present work is to study the chemical composition of ecdysteroid-containing plants - Rhaponticum unifl orum (L.) and Serratula centauroides (L.).

Pharmacophore based approach to design inhibitors in Crustaceans: An insight into the molt inhibition response to the receptor guanylyl cyclase.

The first set of competitive inhibitors of molt inhibiting hormone (MIH) has been developed using the effective approaches such as Hip-Hop, virtual screening and manual alterations. Moreover, the conserved residues at 71 and 72 positions in the molt inhibiting hormone is known to be significant for selective inhibition of ecdysteroidogenesis; thus, the information from mutation and solution structure were used to generate common pharmacophore features. The geometry of the final six-feature pharmacophore was also found to be consistent with the homology-modeled MIH structures from various other decapod crustaceans. The Hypo-1, comprising six features hypothesis was carefully selected as a best pharmacophore model for virtual screening created on the basis of rank score and cluster processes. The hypothesis was validated and the database was virtually screened using this 3D query and the compounds were then manually altered to enhance the fit value. The hits obtained were further filtered for drug-likeness, which is expressed as physicochemical properties that contribute to favorable ADME/Tox profiles to eliminate the molecules exhibit toxicity and poor pharmacokinetics. In conclusion, the higher fit values of CI-1 (4.6), CI-4 (4.9) and CI-7 (4.2) in conjunction with better pharmacokinetic profile made these molecules practically helpful tool to increase production by accelerating molt in crustaceans. The use of feeding sub-therapeutic dosages of these growth enhancers can be very effectively implemented and certainly turn out to be a vital part of emerging nutritional strategies for economically important crustacean livestock.