Azemi, Ahmad Khusairi
(2021)
The effects of methanolic extract of clinacanthus nutans L. (belalai gajah) on atherogenic risk markers in a type 2 diabetic rat model.
PhD thesis, Universiti Sains Malaysia.
Abstract
Diabetes mellitus is associated with endothelial dysfunction (ED); causing
progressive vascular damage. Clinacanthus nutans has been documented to have
antioxidant, hypoglycemic, hypolipidemic and anti-inflammatory properties;
properties with the potential to improve endothelial function and prevent
atherosclerosis development. Firstly, this study aims to evaluate endothelial function,
early vascular structural changes, vascular oxidative stress and inflammation in a
model of type 2 diabetes (T2DM) rat induced by high-fat diet (HFD) and low-dose
streptozotocin (STZ). Secondly, to determine the effects of C. nutans methanolic
leaves extract (CNME) on the above parameters on the same model. First part of
study: Male Sprague-Dawley rats were divided into non-diabetic and diabetic groups
(n=12 per group). Diabetic groups were fed 4 weeks of HFD before intraperitoneal
injection of STZ; and sacrificed at week 15. Fasting blood glucose (FBG) and lipid
profile were measured prior to sacrifice. Upon sacrifice, the aorta was isolated;
endothelial-dependent and -independent relaxations and contractions were
determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS)
expression was assessed via Western blotting. Aortic superoxide dismutase (SOD),
malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), histopathological
changes and aortic intima-media thickness (IMT) were also measured. Second part
of study: Male Sprague-Dawley rats were divided into non-diabetic and diabetic
groups. After seven week of diabetes induction, rats were divided into five groups
(n=12 per group): non-diabetic control (C), non-diabetic treated with 4 weeks of
CNME (500 mg/kg/daily)(C+CNME), untreated diabetic rats (DM), diabetic treated
with metformin (300 mg/kg/daily)(DM+Met) and diabetic treated with CNME (500
mg/kg/daily)(DM+CNME). Rats were sacrificed after 4 weeks of treatment and
experimental parameters similar to part 1 of study were performed. Results; First
part: Diabetic rats have higher FBG, total cholesterol (TC), triglycerides (TG), lowdensity
lipoprotein cholesterol (LDL-C) and atherogenic index (AI) compared to
non-diabetic rats. Endothelium-dependent relaxation was decreased while
endothelial-dependent and -independent contractions were increased in diabetic rats.
eNOS expression was lower in diabetic rats. IMT, MDA and TNF-a levels were
increased while SOD activity lower in diabetic rats. Second part: Both DM+CNME
and DM+Met groups reduced FBG levels compared to the DM group. Treatment
with CNME and metformin in diabetic rats showed lower TC, TG, LDL-C and AI
compared to untreated diabetic rats. Both diabetic-treated with CNME and
metformin groups significantly improved the impairment in endothelium-dependent
vasorelaxation; this was associated with increased expression of eNOS. Treatment
with CNME and metformin also reduced endothelium-dependent and -independent
contractions in diabetics. Aortic IMT, MDA and TNF-α levels were reduced while
SOD activity was higher in both CMNE and metformin treated diabetic rats. These
results demonstrated that the T2DM model induced by HFD and low-dose STZ has
ED associated with early vascular structural changes, and increased vascular
oxidative stress and inflammation. Treatment with C. nutans extract improved
endothelial-dependent vasodilatation, reduced endothelial-dependent and -
independent contractions, increased eNOS expression and SOD levels, lower AI,
MDA, TNF-a levels, and reduced IMT in aorta of T2DM rats; all these effects were
comparable with metformin-treated diabetic rats. Thus, the methanolic extract of C.
nutans leaves has the potential to be further explored as an adjunct in the treatment
of T2DM to prevent or reduce severity of diabetes induced atherosclerosis.
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