Abstract

Purpose: To investigate the effect of leaf extract of Dioscorea deltoidea (Dioscoreaceae) leaf (DDE) on atherosclerosis-induced aorta wall damage in a rat model, and the underlying mechanism of action.Methods: Rats were fed high-fat diet containing vitamin D2 for 16 weeks to induce atherosclerosis. Histopathological changes in the aorta were examined using hematoxylin and eosin (H & E) staining, while ELISA kits were used to measure cytokine levels.Results: Treatment with DDE significantly (p < 0.05) alleviated atherosclerosis-induced increase in mean lesion area in the rat aorta. The mean lesion area in atherosclerotic rats was decreased to 51.5, 21.2 and 2.3 mm2, on treatment with DDE at doses of 2.5, 5 and 10 mg/kg, respectively. Furthermore, DDE significantly suppressed atherosclerosis-induced elevation in IL-1β and IL-6 levels in the rat aorta (p < 0.05). The levels of MCP-1 and TNF-α decreased in the artherosclerotic rats on treatment with DDE. In DDE-treated rats, the atherosclerosis-induced increase in the levels of Ang II, AT1, AT2, p-STAT3, p-p65 and p-p38 were significantly decreased, relative to the model group (p < 0.05). However, DDE treatment did not alter the levels of total STAT3, p65 and p38 in the rat aorta tissues.Conclusion: These results indicate that DDE inhibits inflammatory response and atherosclerosisinduced damage to aorta wall. Moreover, RAAS expression, inflammatory cytokines and JAK/STAT signalling pathway were down-regulated in atherosclerotic rats on treatment with DDE. Thus, DDE may be a potential source of drug for the management of atherosclerosis.

Highlights

  • Atherosclerosis, a common pathological condition, is the leading cause of cerebrovascular and coronary diseases associated with very high morbidity and mortality globally [1]

  • Treatment with deltoidea (Dioscoreaceae) leaf (DDE) led to significant reduction in atherosclerosis-induced increase in average lesion area in the rat aortas (p < 0.05)

  • Results from RT-polymerase chain reaction (PCR) showed that atherosclerosis caused increases in mRNA expression levels of angiotensin II (AngII), AT1 and AT2 in the DDE alleviated atherosclerosis-induced inflammatory pathways

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Summary

INTRODUCTION

Atherosclerosis, a common pathological condition, is the leading cause of cerebrovascular and coronary diseases associated with very high morbidity and mortality globally [1]. Studies on cytokine-deficient animals have revealed the key role of interleukins and apolipoprotein E in the pathogenesis of atherosclerosis [9]. The effect of leaf extract of Dioscorea deltoidea (DDE) on atherosclerosisinduced aorta wall damage in vivo was investigated in a rat model. One portion was processed into histological slides and subsequently stained using oil red dye for demonstration of presence of lipids Another portion of aorta was fixed in 4 % paraformaldehyde, sliced into thin sections, stained using hematoxylin and eosin (H&E), and examined under a light microscope. Inflammatory cytokine levels in the rat aorta tissues were measured using ELISA. Total protein was extracted from aorta tissues via homogenization in RIPA lysis buffer (Beyotime, Haimen China). Differences were taken as statistically significant at p < 0.05

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