dc.description.abstract |
Guava leaf is a folklore remedy for hypertension, however, limited scientific basis support this
usage. Hence, this study investigated the molecular mechanism underlying the antihypertensive
effect of the leaves of three guava varieties (white, red and pink) in normotensive and
hypertensive rats with /or without captopril administration. The aqueous extract of guava leaves
were prepared, and the in vitro antioxidant (DPPH*, Fe2+ chelation, ferric reducing antioxidant
properties, and lipid peroxidation) and enzymes [arginase, cholinesterase (AChE and BChE),
angiotensin I-converting enzyme (ACE)] inhibitory assays were carried out. Thereafter,
toxicological evaluation at 50, 500, and 5000 mg/kg, 250 and 500 mg/kg of the extracts on
normotensive and hypertensive rats with/without captopril on haemodynamic indices and
biochemical [lipid profile, arginase, AChE, BChE, purinergic enzymes (e-NTPDase,
5’nucleotidase and adenosine deaminase (ADA)] parameters and endogenous antioxidant
status as well as liver and kidney function test were carried out. The ACE mRNA gene
expression in the rat’s kidney was also determined. The result revealed that all the extracts
exhibited strong antioxidant properties and inhibited key enzymes relevant to hypertension in
vitro. The extracts elicited neither systemic or organ toxicity at the concentrations tested, as the
LD50 of the extracts were greater than 5000 mg/kg. The extracts modulate systolic (SBP) and
diastolic (DBP) blood pressure, enzymes activities, and significantly boosted the antioxidant
status in normotensive rats. However, the extracts significantly (p <0.05) lower systolic (SBP)
and diastolic (DBP) blood pressure, reduced elevated plasma liver and kidney function markers
and ACE, arginase and cholinesterases activities, modulated e-NTPDase, 5’nucleotidase and
ADA activities lipid profile in hypertensive rats. Furthermore, the extracts significantly (p <
0.05) downregulated ACE mRNA expression in both normotensive and hypertensive rats. Coadministration
of the extracts with captopril elicited an additive effect on the antihypertensive
properties without any observable biochemical/physiological alterations. The HPLC analysis of the extracts revealed rutin (123.90±0.26, 126.45±0.77, 123.93±0.20 mg/100 g) and
chlorogenic acid (149.79±0.45, 157.17±0.41, 150.52±0.61 mg/100 g) as the dominant
polyphenols in white, red and pink of guava leaves respectively. This study suggest that
antihypertensive property of the leaves may be due to their rich polyphenolic content with
potent antioxidant properties, and ability to modulate lipid profile, purinergic signalling, key
enzymes relevant to blood pressure, as well as downregulate ACE mRNA expression, which
culminated in SBP and DBP. |
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