A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.

Eun-Hye Park,Sang-Hyun Ihm,Ho-Joong Youn,Ok-Ran Kim,Kiyuk Chang,Kyoung-Rak Kim,Jung-Ok Lee,Min-Ho Oak,Jong-Hoon Kim,Byung-Hee Hwang,Sin-Hee Park

doi:10.3390/plants10112493

Abstract

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE−/−) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE−/− mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE−/− mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

Highlights

Atherosclerosis is a narrowing of the arteries caused by the buildup of plaque
Compared with aortic rings isolated from chow diet-fed C57BL/6 mice, those obtained from western diet (WD)-fed apoE−/− mice showed decreased relaxation to acetylcholine (Ach), suggesting impaired endothelium-dependent vascular relaxation (Figure 1)
Both Lindera obtusiloba extract (LOE) and losartan treatment significantly improved the endotheliumdependent vascular relaxation of aorta rings derived from WD-fed apoE−/− mice (Figure 1)

Summary

Introduction

Atherosclerosis is a narrowing of the arteries caused by the buildup of plaque. It is characterized by endothelial dysfunction, oxidative stress and chronic low-grade inflammation [1,2,3]. Endothelial dysfunction is the initial event leading to atherogenesis and is associated with increased generation of NADPH oxidase-derived reactive oxygen species (ROS) in vessel walls [4,5]. Increased vascular ROS generation, including hydrogen peroxide and superoxide anions, contributes to the formation of atherosclerotic plaque by inducing oxidative stress, reducing nitric oxide (NO) bioavailability, and promoting proinflammatory responses [3,6,7]. Upregulation of adhesion molecules, cytokines, and chemokines expressed in endothelial cells and their complex interaction promotes leukocyte infiltration into the vascular wall, followed by transendothelial migration, which triggers atherogenesis [14,15]

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