STUDIES ON ANTIHYPERTENSIVE AND ANTICANCER PROPERTIES OF PERISTROPHE BICALYCULATA (RETZ) NEES EXTRACTS AND THE MOLECULAR BASIS OF THE ACTIVITIES
STUDIES ON ANTIHYPERTENSIVE AND ANTICANCER PROPERTIES OF PERISTROPHE BICALYCULATA (RETZ) NEES EXTRACTS AND THE MOLECULAR BASIS OF THE ACTIVITIES
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Date
2013-01
Authors
MANSURAH, ABDULAZEEZ
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Abstract
In the present study, the antihypertensive, anticancer and melanogenesis inhibitory
effects of leaf extracts of Peristrophe bicalyculata (Retz) Nees, a plant used in South
West Nigeria for the treatment of several cardiovascular diseases, including
hypertension were investigated. The antioxidant activities of the extract were also
investigated. Results of the radical scavenging, tyrosinase inhibition and metal ion
chelating activities of extracts of P. bicalyculata demonstrated its antioxidant activity.
Induction of hypertension in rats with L-NAME significantly (P < 0.05) increased
systolic blood pressure (from 113 ± 3.71 mm Hg to 212 ± 2.08 mm Hg by the fourth
week), which significantly (P < 0.05) reduced when rats were given 5 mg/kg captopril
(74.00 ± 4.36 mm Hg), the partially-purified extract of P. bicalyculata at 2.5 mg/kg
(103.33 ± 8.11 mm Hg) and at 25 mg/kg (94 ± 1.73 mm Hg). Hypertension increased
the activity of angiotensin converting enzyme (ACE) and decreased that of endothelial
nitric oxide synthase significantly (P < 0.05) in the serum, kidney and aorta of rats.
Treatment with 5 mg/kg captopril, the extract at 2.5 mg/kg and at 25 mg/kg significantly
(P < 0.05) decreased the activity of angiotensin converting enzyme and increased that of
endothelial nitric oxide synthase (eNOS) in the kidney, serum and aorta. At the level of
gene expression, ACE mRNA levels increased significantly (P < 0.05) in kidneys and
aorta of hypertensive rats. This significantly (P < 0.05) decreased in the kidneys of rats
given 5 mg/kg captopril and 25 mg/kg of the extract, but not in the aorta of these rats.
The expression of eNOS, which decreased significantly (P < 0.05) in the kidneys and
aorta of hypertensive rats, increased significantly in aorta of hypertensive rats given
captopril and the extract at both doses. However, treatment did not increase eNOS
mRNA levels in the kidneys. In rat aortic endothelial cells, captopril (0.52 ± 0.03)
significantly (P < 0.05) decreased ACE expression compared to cells treated with 2
mmol/L L-NAME (0.79 ± 0.05 fold). There was no significant difference in ACE
mRNA expression between control cells (0.55 ± 0.03), cells treated with captopril and
the partially purified extract (0.64 ± 0.08 fold). The eNOS expression in RAOECs
treated with L-NAME (0.48 ± 0.03 fold) was significantly (P<0.05) lower than control
cells (1.71 ± 0.15 fold). This increased significantly (P < 0.05) when cells were treated
with captopril (1.01 ± 0.10 fold), 10 μg/ml (1.05 ± 0.09 fold) and 100 μg/ml (0.95 ±
0.03 fold) of the purified extract. The levels of thiobarbituric acid-reactive substances
present in the serum, kidney and aorta also increased significantly (P < 0.05) in
hypertensive rats compared to rats in the control group. This reduced significantly (P <
0.05) when rats were given captopril, the extract at 2.5 mg/kg and 25mg/kg. The
induction of apoptosis by the partially purified anticancer fraction on human mouth
epidermal carcinoma (KB) cells was significantly (P < 0.05) higher than control cells
after 24 and 48 hours. The percentage necrotic cells increased significantly (P < 0.05)
after 48 hours when compared to 24 hours, showing a dose-dependent effect. Results of
the melanogenesis inhibitory effect of the extract showed that the methanolic butanol
fraction of methanol extract was capable of inhibiting melanin formation. The GC-MS
analysis of the partially-purified antihypertensive extract indicated an abundance of
P,P,P-triphenyl-Imino(triphenyl)phosphorane while the partially purified anticancer
extract of Peristrophe bicalyculata contained andrographolide in abundance. In
conclusion, this study has provided scientific evidence that Peristrophe bicalyculata
reduces blood pressure possibly via the renin angiotensin system by decreasing the
expression of ACE mRNA and increasing eNOS expression. It has also demonstrated
that the partially-purified anticancer fraction of Peristrophe bicalyculata is a potential
source of valuable anticancer therapy. This finding has also established the potential use
of Peristrophe bicalyculata for the treatment of melanoma.
Description
A DISSERTATION SUBMITTED TO THE POSTGRADUATE
SCHOOL, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA IN
PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE
AWARD OF THE DEGREE OF DOCTOR OF PHILOSOPHY IN
BIOCHEMISTRY
Keywords
ANTIHYPERTENSIVE, ANTICANCER, PROPERTIES, PERISTROPHE, BICALYCULATA, (RETZ), NEES, EXTRACTS, MOLECULAR, ACTIVITIES