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Article

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

by
Sang-Hyun Ihm
1,2,†,
Sin-Hee Park
1,3,†,
Jung-Ok Lee
4,
Ok-Ran Kim
1,3,
Eun-Hye Park
1,3,
Kyoung-Rak Kim
4,
Jong-Hoon Kim
5,
Byung-Hee Hwang
1,3,
Ho-Joong Youn
1,3,
Min-Ho Oak
6,* and
Kiyuk Chang
1,3,*
1
College of Medicine, Cardiovascular Research Institute for Intractable Disease, The Catholic University of Korea, Seoul 06591, Korea
2
Division of Cardiology, Department of Internal Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
3
Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
4
Research and Development Center, Han Wha Pharma, Co., Ltd., Chuncheon 24468, Korea
5
Research Center, YangJi Chemicals, Suwon 16229, Korea
6
College of Pharmacy, Mokpo National University, Muan-gun 58554, Korea
*
Authors to whom correspondence should be addressed.
†
Equal contributors.
Plants 2021, 10(11), 2493; https://doi.org/10.3390/plants10112493
Submission received: 21 October 2021 / Revised: 11 November 2021 / Accepted: 11 November 2021 / Published: 18 November 2021
(This article belongs to the Special Issue Plant Therapeutics)
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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.
Keywords: Lindera obtusiloba; apolipoprotein E-deficient mice; atherosclerosis; endothelium Lindera obtusiloba; apolipoprotein E-deficient mice; atherosclerosis; endothelium
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MDPI and ACS Style

Ihm, S.-H.; Park, S.-H.; Lee, J.-O.; Kim, O.-R.; Park, E.-H.; Kim, K.-R.; Kim, J.-H.; Hwang, B.-H.; Youn, H.-J.; Oak, M.-H.; et al. A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice. Plants 2021, 10, 2493. https://doi.org/10.3390/plants10112493

AMA Style

Ihm S-H, Park S-H, Lee J-O, Kim O-R, Park E-H, Kim K-R, Kim J-H, Hwang B-H, Youn H-J, Oak M-H, et al. A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice. Plants. 2021; 10(11):2493. https://doi.org/10.3390/plants10112493

Chicago/Turabian Style

Ihm, Sang-Hyun, Sin-Hee Park, Jung-Ok Lee, Ok-Ran Kim, Eun-Hye Park, Kyoung-Rak Kim, Jong-Hoon Kim, Byung-Hee Hwang, Ho-Joong Youn, Min-Ho Oak, and et al. 2021. "A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice" Plants 10, no. 11: 2493. https://doi.org/10.3390/plants10112493

APA Style

Ihm, S.-H., Park, S.-H., Lee, J.-O., Kim, O.-R., Park, E.-H., Kim, K.-R., Kim, J.-H., Hwang, B.-H., Youn, H.-J., Oak, M.-H., & Chang, K. (2021). A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice. Plants, 10(11), 2493. https://doi.org/10.3390/plants10112493

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