Biological Activity And Mechanism Of Diosgenin Of Mpd

Furostanol biglycoside steroid in diosgenin with many bioactivitives and medical values was main pivotal intermediate used to synthetize teroid hormone.But the ingredient in diosgenin was multiplicity,it was necessary to study its simple substance in bioactivity and mechanism.Methyl protodioscin(MPD),a natural furostanol biglycoside steroid from diosgenin was studied in our research.In vitro,We investigated the effects of MPD on the proliferation MCF-7,K562 and Hela which were estrogenic hormone dependent cancer cell lines.It showed that MPD had inhibition against the cell lines K562 with IC50=71.49ug/ml.MCF-7 and HeLa showed inversely growth after incubation with MPD,and growth rate showed dose dependent dose dependent.The single-cell gel electrophoresis was used to evaluate the detection of DNA damage in the K562 by MPD and showed that MPD induced K562 DNA damage by competitive binding hormone receptor to advance apoptosis in K562.MPD also promoted proliferation in cultured fibroblast and increased protein synthesis in cardiomyocytes from neonatal rats.For the growth of fibroblast and cardiomyocytes in vitro depended on estrogenic hormone,MPD could bind to target cell hormone receptor and has hormonelike bioactivity.After 8 days peritoneal injection with MPD to mouse, the content of CYP450 in liver increased and was no infuence on the aminopyrine-N-demethylase of CYP2C19,CYP2C8,CYP2C18.In vivo,Furostanol biglycoside steroid could metabolism to steroid,like testosterone,which was transformed to estrone and estradiol by P450 aromatizing enzyme that existed in heart,breast,liver et al.The results showed that the biological transformation path of MPD was by P450 aromatizing enzyme,the self of MPD or its metabolins had hormonelike bioactivity.With isolated heart irrigation technique,MPD could slow down the frequency of the toad heart. The frequency and strength of cultured cardiomyocytes were degraded by MPD in 5min,but incubation 24h with MPD enhanced the frequency and strength of cardiomyocytes.In anoxia/reoxygenation injury of cardiomyocytes,the leakage of LDH was decreased by MPD and the activitives of Na⁺-K⁺-ATPase,Ca²⁺-Mg²⁺-ATPase were maintained.These showed that MPD could affect the heart function by sodium pump and calcium pump.In the experiment of myocardial cell intracellular Ca²⁺by Fura-2/AM,MPD could block the volt dependent form calcium channel in cellular membrane,the expression of mRNA in sodium-calcium exchanger was down-regulated and no influence on mRNA of SERCA2a in endocytoplasmic reticulum.These results showed that MPD remained low calcium in the internal environment in cardiomyocytes by blockage of Ca²⁺inflow and function maintain of sodium pump and calcium pump.In result,MPD had hormonelike and calcium-antagonislike bioactivity.One of its activities was gene path by binding hormone receptor directly or indirectly,to activate intracellular signal protein then to affect cell protein synthesis and proliferation,thought the effection was slow but the last time was long.Another was non-gene path or called membrane path,in promptly to block Ca²⁺inflow and to maintain activity of sodium pump and calcium pump,so that MPD could prevent intracellular calcium overload or decrease the frequency of cardiomyocytes or heart.