In neurodegeneration, such as Alzheimer's disease (AD), apoptosis results in the loss of valuable neurons. A key mechanism in apoptosis is the activation of caspase-3. Caspase-3 activity first becomes detectable early in apoptosis, continues to increase as cells undergo apoptosis, and rapidly declines in late stages of apoptosis. Its activity is an early marker of cells undergoing apoptosis. Caspase-3 catalyzes the formation of beta-amyloid peptide, a hallmark of AD. The purpose of the study was to determine whether dietary aged garlic extract (AGE), with known antioxidant properties and neuroprotection against Alzheimer's beta-amyloid cytotoxicity, inhibits the caspase-3 activity in vitro. Caspase-3 activity was assayed according to the prescribed protocol and incubated overnight at ambient temperature. We report that AGE inhibits caspase-3 in dose dependent manner. Caspase-8 was not inhibited by AGE. As a caspase-3 inhibitor, AGE may be effective in reducing apoptotic death of neurons since caspase inhibitors have been shown to inhibit neuronal cell death. We propose a scheme for the ameliorative effect of AGE on deleterious effects of beta-amyloid and possibly uncontrolled caspase-3 activity.
Background
Senecio serratuloides
DC is used in folk medicine for treating hypertension, skin disorders, internal and external sores, rashes, burns and wounds. This study aimed at investigating the antihypertensive effects of the hydroethanol extract of
S. serratuloides
(HESS) in N-Nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats.
Methods: Acute toxicity of HESS was first determined to provide guidance on doses to be used in this study. Lorke’s method was used to determine safety of the extract in mice. Female Wistar rats were treated orally once daily with L-NAME (40 mg/kg) for 4 weeks and then concomitantly with L-NAME (20 mg/kg) and plant extract (150 and 300 mg/kg), captopril (20 mg/kg) or saline as per assigned group for 2 weeks followed by a 2-week period of assigned treatments only. Blood pressure was monitored weekly. Lipid profile, nitric oxide, renin and angiotensin II concentrations were determined in serum while mineralocorticoid receptor concentration was quantified in the kidney homogenate. Nitric oxide (NO) concentration was determined in serum and cardiac histology performed.
Results
HESS was found to be non-toxic, having a LD
50
greater than 5000 mg/kg. Blood pressure increased progressively in all animals from the second week of L-NAME treatment. HESS treatment significantly and dose-dependently lowered systolic blood pressure (
p
< 0.001), diastolic blood pressure (
p
< 0.01), low density lipoprotein cholesterol (
p
< 0.01) and triglycerides (
p
< 0.01). It significantly prevented L-NAME induced decrease in serum angiotensin II (
p
< 0.01), high density lipoprotein cholesterol (
p
< 0.001) and serum nitric oxide concentrations (
p
< 0.001). HESS also significantly (
p
< 0.01) prevented collagen deposition in cardiac tissue.
Conclusion
The hydro-ethanol extract of
Senecio serratuloides
showed antihypertensive, antihyperlipidemic and cardioprotective effects in rats thus confirming its usefulness in traditional antihypertensive therapy and potential for antihypertensive drug development.
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