Asian Journal of Pharmacodynamics and Pharmacokinetics

Xu HY et al. Asian Journal of Pharmacodynamics and Pharmacokinetics 2009; 9(1):11-25
percentage of LC in TP and the L/C ratio was
significantly lower in all the test drug treated groups
than those in the model group, respectively (P < 0.01),
especially prominent in the group treated with giant
knotweed rhizome. Although lowering of the two
indexes presented in all of the groups treated by
notoginseng saponins, Coptis chinensis and giant
knotweed rhizome, significant difference still
presented between giant knotweed rhizome treated
group vs notoginseng saponins and Coptis chinensis
treated group (P < 0.05). As for the expressions of
GM-CSF and TNF-α, in comparing with the
untreated model group, significant decreasing of the
TNF-α showed only in the rhubarb treated group,
while that of GM-CSF could be found in all the test
drug treated groups (P < 0.05). All the four drugs
tested in the recommended dosage can stabilize the
vulnerable plaques in ApoE knockout mice by
improving the constitution of plaque, among them,
giant knotweed rhizome and rhubarb, the drugs
possess both the actions of activating blood
circulation and detoxicating, show more significant
effect, and their mechanisms may be related to their
actions in regulating lipid metabolism and inhibiting
inflammatory reaction. [38]
We known that vascular smooth muscle cell
(SMC) proliferation plays an important role in the
pathogenesis of atherosclerosis and post-angioplasty
restenosis. Berberine is a well-known component of
Coptis chinensis, and is capable of inhibiting SMC
contraction and proliferation, yet the exact
mechanism is unknown. Therefore, Liang KW et al
investigated the effect of berberine on SMC growth
after mechanic injury in vitro. DNA synthesis and
cell proliferation assay were performed to show that
berberine inhibited serum-stimulated rat aortic SMC
growth in a concentration-dependent manner.
Mechanical injury with sterile pipette tip stimulated
the regrowth of SMCs. Treatment with berberine
prevented the regrowth and migration of SMCs into
the denuded trauma zone. Western blot analysis
showed that activation of the MEK 1/2
(mitogen-activated protein kinase 1/2 ), extracellular
signal-regulated kinase (ERK), and up-regulation of
early growth response gene (Egr-1), c-Fos and Cyclin
D1 were observed sequentially after mechanic injury
in vitro. Semi-quantitative reverse-transcription PCR
assay further confirmed the increase of Egr-1, c-Fos,
platelet-derived growth factor (PDGF) and Cyclin D1
expression in a transcriptional level. However,
berberine significantly attenuated MEK/ERK
activation and downstream target (Egr-1, c-Fos,
Cyclin D1 and PDGF-A) expression after mechanic
injury in vitro. Their study showed that berberine
blocked injury-induced SMC regrowth by
inactivation of ERK/Egr-1 signaling pathway thereby
preventing early signaling induced by injury in vitro.
The anti-proliferative properties of berberine may be
useful in treating disorders due to inappropriate SMC
growth. [39]
Berberine was considered to be useful in
treating some diseases of the cardiovascular system,
such as hypertension and chronic heart failure (CHF).
Hong Y et al investigated the inhibitory effect of
berberine on experimental cardiac hypertrophy,
which is regarded as a risk factor of CHF and other
heart diseases. Forty-two male SD rats were divided
into four groups: age-matched control, aortic banding
model, berberine-treated group and captopril-treated
group. Cardiac hypertrophy was induced by
suprarenal abdominal aorta constriction. These drugs
were orally administered for 8 weeks starting from 4
weeks after surgery at dosage of berberine 10 mg·kg -1
and captopril 50 mg·kg -1 . Blood pressure (BP) was
measured four times during the period of the
experiment, and hemodynamic parameters, cardiac
index, cell size of left ventricular myocardium and
total protein of left ventricular tissue were detected 8
weeks after treatment with these drugs. The data from
the present study showed that: The BP of the aorta
banded rats was increased compared with those of the
normal (P < 0.001) and the age-matched control rats
(P< 0.001), and berberine showed no significant
effect on it; after 8 weeks of treatment with berberine,
the elevated left ventricular end diastolic pressure
(LVEDP) was slightly decreased compared with the
aortic banded rats. Meanwhile, the maximum rates of
contraction and relaxation (± dp/dtmax) was
increased (P < 0.05) and the time to reach the point
of maximum rate from beginning of contraction
(t-dp/dt) was shortened (P < 0.01), indicating that the
functions of heart, both contraction and relaxation,
were improved; cardiac growth was inhibited by
treatment with berberine. Both whole heart and left
ventricular weight were notably decreased compared
with the banded rats (P < 0.05 and P < 0.01); and the
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