纺神星
内分泌学
内科学
血管紧张素Ⅱ受体1型
氯沙坦
化学
血管紧张素II
谷胱甘肽过氧化物酶
NADPH氧化酶
活性氧
氮氧化物4
受体
氧化应激
生物
医学
超氧化物歧化酶
肾
生物化学
作者
Bao Trong Nguyen,Eun‐Joo Shin,Ji Hoon Jeong,Naveen Sharma,Seung Yeol Nah,Sung Kwon Ko,Jae Kyung Byun,Yi Lee,Xin Gen Lei,Dae-Joong Kim,Toshitaka Nabeshima,Hyoung‐Chun Kim
标识
DOI:10.1016/j.freeradbiomed.2022.07.003
摘要
Ginseng is known to possess anti-aging potential. Klotho mutant mice exhibit phenotypes that resemble the phenotype of the human aging process. Similar to Klotho deficient mice, patients with chronic kidney disease (CKD) suffer vascular damage and cognitive impairment, which might upregulate the angiotensin II AT1 receptor. Since AT1 receptor expression was more pronounced than endothelin ET-1 expression in the hippocampus of aged Klotho deficient (±) mice, we focused on the AT1 receptor in this study. Ginsenoside Re (GRe), but not ginsenoside Rb1 (GRb1), significantly attenuated the increase in AT1 receptor expression in aged Klotho deficient mice. Both GRe and the AT1 receptor antagonist losartan failed to attenuate the decrease in phosphorylation of JAK2/STAT3 in aged Klotho deficient (±) mice but significantly activated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling. Both GRe and losartan attenuated the increased NADPH oxidase (NOX) activity and reactive oxygen species (ROS) in aged Klotho deficient mice. Furthermore, of all the antioxidant enzymes, GRe significantly increased glutathione peroxidase (GPx) activity. GRe significantly attenuated the reduced phosphorylation of ERK and CREB in GPx-1 knockout mice; however, genetic overexpression of GPx-1 did not significantly affect them in aged mice. Klotho-, Nrf2-, and GPx-1-immunoreactivities were co-localized in the same cells of the hippocampus in aged Klotho wild-type mice. Both the GPx inhibitor mercaptosuccinate and Nrf2 inhibitor brusatol counteracted the effects of GRe on all neurobehavioral impairments in aged Klotho deficient (±) mice. Our results suggest that GRe attenuates all alterations, such as AT1 receptor expression, NOX-, ROS-, and GPx-levels, and cognitive dysfunction in aged Klotho deficient (±) mice via upregulation of Nrf2/GPx-1/ERK/CREB signaling.
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