| Natural
Nutrient Mixture of Ascorbic Acid with Amino Acids Lysine, Arginine,
Cysteine and Proline, and Green Tea Polyphenols Effectively Reduces
Collagen Matrix Contraction Driven by Human Uterine Smooth Muscle
Cells
V.Ivanov, S. Ivanova, M. W. Roomi, A. Niedzwiecki,
M. Rath
Matthias Rath BV, Research Institute, Santa Clara, CA, USA
Presented at: 12th International Congress of
Endocrinology, Lisbon, Portugal, August 31-September 4, 2004.
Published in: Conference proceedings, Abstract
#1166, pg 360.
Abstract
Background:
Abnormal uterine myometrial contractility causes preterm delivery
contributing to perinatal morbidity and mortality. Disturbances
in the hormonal regulation and inflammation-related processes
have been attributed a role in pathophysiological mechanisms of
alternated uterine contractility.
Objective:
To study the effects of natural nutrients on uterine tissue contractility.
Methods:
We used an in vitro model of collagen I gel contraction driven
by embedded cultured human uterine smooth muscle cells (UtSMC).
Effects of tested compounds were evaluated by their capacity to
affect gel contraction (measured by reduction in gel area during
24-hour incubation in serum free medium). Cellular expression
of matrix metalloproteinases (MMPs) was followed by gel zymography.
Results:
Collagen gel contraction driven by UtSMC was significantly stimulated
by potassium chloride, pituitary hormone oxytocin and by inflammatory
cytokine tumor necrosis factor alpha. Accelerated gel contraction
was accompanied by elevated secretion of MMP-2 and MMP-9 into
cell culture media. Among a variety of purified bioflavonoids
and polyphenol-enriched plant extracts tested for their ability
to counteract UtSMC-dependent collagen gel contraction, the strongest
effects were demonstrated by epigallocatechin gallate and green
tea leaf extract, respectively. Addition of ascorbic acid and
amino acids lysine, arginine, cysteine and proline to green tea
extract further increased its effectiveness. A reduction in gel
contraction correlated with decreased MMP expression.
Conclusion:
Pathophysiological mechanisms of abnormal uterine myometrial contractility
can involve extracellular matrix remodeling and can be effectively
counteracted by a combination of naturally occurring nutrients.
Comments
Disturbances in hormone regulation and inflammation-related
processes have been shown to play roles in abnormal uterine
contractility, which causes preterm delivery and can lead
to perinatal morbidity and mortality. We used an in vitro
model of collagen I gel contraction driven by embedded cultured
human uterine smooth muscle cells to study the effect of various
nutrients on uterine contraction. Among the bioflavonoids
and plant extracts tested, we found that green tea leaf extract
and epigallocatechin gallate showed the strongest ability
to counteract uterine smooth muscle cell contraction. Furthermore,
addition of ascorbic acid and amino acids lysine, arginine,
cysteine and proline to green tea extract further increased
its effectiveness. A reduction in gel contraction correlated
with decreased MMP. The results of this study are significant
since they demonstrate the great potential of nutrients in
preventing preterm delivery and its sequelae. |
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