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.
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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
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