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Sophorae Radix, the dried roots of Sophora flavescens AITON (Leguminosae), has been used in Oriental traditional medicine for treatment of skin and mucosal ulcers, sores, gastrointestinal hemorrhage, diarrhea, inflammation and arrhythmia. In the present study, we examine the effect of the aqueous extract of Sophorae Radix (AESR) on cell proliferation and cell cycle regulation in human oral mucosal fibroblasts (HOMFs). To study the molecular mechanisms of cell cycle regulation by AESR, we also measured the intracellular levels of cell cycle regulatory proteins such as cyclin D, cyclin-dependent kinases (CDK)-4, CDK-6, cyclin E, CDK-2, p53, p21^WAF1/CIP1 and p16^INK4. Cell proliferation was increased in the presence of 10~500 μg/ml of AESR. Maximal growth stimulation was observed in those cells exposed to 100 μg/ml of AESR. Exposure of HOMFs to 100 μg/ml of AESR resulted in an increase of cell cycle progression. The levels of cyclin E and CDK-2 were increased in HOMFs after 100 μg/ml of AESR treatment, but the levels of cyclin D, CDK-4, and CDK-6 were unchanged. After exposure to 100 μg/ml of AESR, the protein levels of p16^INK4A and p53 were decreased as compared to that of the control group, but the level of p21^WAF1/CIP1 was similar in the cells treated with 100 μg/ml of AESR and untreated cells. The results suggest that AESR may increase cell proliferation and cell cycle progression in HOMFs, which is linked to increased cellular levels of cyclin E and CDK-2 and decreased cellular levels of p53 and p16^INK4A. Further studies are necessary to clarify the active constituents of AESR responsible for such biomolecular activities.

The underlying biochemical mechanisms that drive the cell division cycle involve the interactions and feedback controls between the cytoplasmic proteins cdc2 and cyclin, and the activities of the cdc2-cyclin complex MPF. Alternation between interphase and mitosis is associated with oscillatory MPF and cyclin levels. This paper describes an ordinary differential equations (ODE) model and a functional differential equations (FDE) model of the cell cycle based on experimental work with the newly fertilized frog egg. One major difference of these models from previous ones is the use of nonspecific reaction terms in describing the interactions between cdc2, cyclin and MPF. This qualitative approach makes possible the evaluation of the roles of the various reactions and feedback mechanisms in the control of the cell cycle.

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