Amelioration by Catalpol of Atherosclerotic Lesions in Hypercholesterolemic Rabbits

Abstract

The aim of the present study was to evaluate the effects of catalpol administration on atherosclerosis. Atherogenesis was induced by a high-cholesterol chow in male New Zealand White rabbits that were randomly assigned to receive atorvastatin (5 mg/kg/day), catalpol (5 mg/kg/day), or vehicle by oral gavage for 12 weeks. The rabbits were sacrificed after 12 weeks, and the thoracic aorta and serum were collected for further pathological and molecular biological analysis. Catalpol administration resulted in significantly attenuated atherosclerotic lesions. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol were remarkably reduced, and high-density lipid cholesterol was elevated in the catalpol-treated group. Catalpol reduced the levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1 in the serum, as well as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-α protein, inducible nitric oxide synthase, matrix metalloproteinases-9, and nuclear factor-κB protein65 in the aortic arch. In addition, catalpol treatment reduced the lipid peroxidation levels, while elevating antioxidant capacity. Catolpol pretreatment inhibited the nuclear translocation and DNA binding activity of nuclear factor-κB protein in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. Furthermore, catolpol pretreatment activated nuclear factor erythroid 2-related factor 2 and upregulated the expression of its downstream antioxidant enzyme heme oxygenase. In summary, catalpol attenuated atherosclerotic lesions by the inhibition of inflammatory cytokines and oxidative stress status in a rabbit atherosclerotic model and enhanced the antioxidant capacity in oxygenized low-density lipoprotein-stimulated EA.hy926 cells. These results suggest that catalpol may be used to prevent and attenuate atherosclerosis.

Multiple Biological Effects of an Iridoid Glucoside, Catalpol, and Its Underlying Molecular Mechanisms

“…Catalpol significantly reduced TNF-α, soluble VCAM-1, ICAM-1, IL-6, and MCP-1 in the serum and reduced the levels of VCAM-1, MCP-1, MMP-9, TNF-α, NF-κB, and iNOS protein in aortic arch tissue. Additionally, catalpol reduced lipid peroxidation levels, and elevated antioxidant activity [71]. Catalpol may have a beneficial effect in stroke in view of its ability to protect against middle cerebral artery occlusion in rats; in this model catalpol showed a significant vasoprotective and angiogenic effect through stimulation of the JAK-STAT pathway [72].…”

“…Catalpol (5 mg/kg daily p.o. for 12 weeks) reduced atherosclerotic lesions in rabbits fed a high cholesterol diet, this effect was accompanied by a marked reduction in circulating total cholesterol, triglycerides, and low-density lipoprotein cholesterol and an elevation in high-density lipid cholesterol [71]. Catalpol significantly reduced TNF-α, soluble VCAM-1, ICAM-1, IL-6, and MCP-1 in the serum and reduced the levels of VCAM-1, MCP-1, MMP-9, TNF-α, NF-κB, and iNOS protein in aortic arch tissue.…”

The Effects of Natural Iridoids and Anthocyanins on Selected Parameters of Liver and Cardiovascular System Functions

“…As in the examples quoted earlier, catalpol lowers the levels of total cholesterol, triglycerides, and low-density lipoproteins in blood serum and boosts the level of high-density lipoproteins. Furthermore, the reduction of TNF-α, Il-6, MCP-1, soluble VCAM-1, and soluble ICAM-1 levels in the serum was observed in a rabbit study [51]. Meanwhile, the depletion of VCAM-1, MCP-1, TNF-α, iNOS, matrix metalloproteinase-9, and NF-κB expression levels in the aortic arch was noticed.…”

Loganic acid and anthocyanins from cornelian cherry (Cornus mas L.) fruits modulate diet-induced atherosclerosis and redox status in rabbits

“…The positive effects on lipids and atherosclerosis were also proven for other iridoids isolated from various plants. [24][25][26] Nevertheless, knowledge about the effects of loganic acid we found in cornelian cherry on living systems, especially on atherogenesis, is poor.…”