Studies On Hematopoietic-Regulating Mechanism Of Active Monomer, SS8, Extracted From Spatholobus Suberectus Dunn

Hematopoiesis is an active process of cell proliferation, differentiation and release. It is the process during which hematopoietic stem cells (HSCs) proliferate and differentiate to mature blood cells under the effect of hemetopoietic growth factors (HGFs) in certain hematopoietic microenvironment. Both HSC and hematopoietic progenitor cell (HPC) are the key points of hematopoiesis regulation.We have extracted nine monomers (i.e. SS5, SS7, SS8, SS9, SS12, SS16, SS17, SS25 and SS28) from Spatholobus Suberectus Dunn(SSD), a traditional Chinese herb often used to nourish blood in clinic, and their structures have been elucidated by means of various modern spectroscopic techniques and chemical methods. SS5, SS7, SS8, SS25, SS28, SS16 are flavanone compounds. SS9 is pyromucic acid and SS12, SS17 are phenylic acids. Among them, SS5, SS8, SS9, SS12 and SS16 were obtained from Spatholobus genus for the first time and the content of SS8 was the maximum.Influence of the nine monomers on proliferation of HPC in bone marrow depressed mice was observed by serum pharmacology experiment. All of them showed various degrees in stimulating HPC to proliferate, among which SS8 was the best stimulator.It is reported that not all the hematopoietic cells in normal bonemarrow are proliferating. The formation of colony-unit of HPC relies on the existence of HGF in culture system. The number and the type of colony-unit formed are related with the category, content and activity of HGF. In our experiment, effect of SS8 on bone marrow cell cycle and the variation of CSA in SPCM of mice induced by SS8 were investigated, and further, the expression of IL-6mRNA and GM-CSFmRNA induced by SS8 was detected by RT-PCR technique in order to clarify the mechanism of SS8 deeply. Results showed that SS8 could accelerate bone marrow cells of normal and bone marrow-depressed mice into cell cycle. After being induced by SS8, the level of CSA in SPCM rose significantly and IL-6mRNA and GM-CSFmRNA were highly expressed.In a word, SS8 is an active component contributing to hematopoiesis. It can promote the expression of IL-6mRNA and GM-CSFmRNA in spleen cells of mice, increase the level of CSA in SPCM, and moreover, has a synergistic effect on HGF. Thus, it can help the bone marrow cells of marrow-depressed mice to get out of "Gi-phase-block" and enter into cell cycle, accelerate the proliferation and differentiation of HSC and HPC, increase the numbers of colony-unit of HPC and radically remedy the qualitative and quantitative defects of HSC/HPC caused by radiation. This may be the mechanism of hematopoietic-supportive effect of SS8.The structure of SS8 was determined as (2R, 3R)-ent-catechin.