Rosmarinic acid exerts an antagonistic effect on vascular calcification by regulating the Nrf2 signalling pathway

Ji, Renpeng; Sun, Huijun; Peng, Jinyong; Ma, Xiaodong; Bao, Liuchi; Fu, Yufeng; Zhang, Xiaoxue; Luo, Chunxu; Gao, Cong; Jin, Yue; Sun, Shiren

doi:10.1080/10715762.2018.1558447

Cited by 24 publications

(21 citation statements)

References 37 publications

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“…However, the effects of RA in NAFLD have not been fully clarified. In our previous experiments, it was found that RA has a good antioxidant effect, and it can improve vascular calcification by regulating the Nrf2/ARE signaling pathway and reducing intracellular ROS content (Ji et al, 2019). In addition, RA inhibits high glucose‐induced cardiomyocyte apoptosis by improving mitochondrial function and activating STAT3 (Diao et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway

Luo

Sun

Peng

et al. 2020

Phytotherapy Research

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Rosmarinic acid (RA) is a water‐soluble phenolic compound extracted from Boraginaceae and Lamiaceae. This study was designed to investigate the role and mechanism of action of RA in improving nonalcoholic fatty liver disease (NAFLD). Male SD rats maintained on a high fat diet and L02 cells stimulated with oleic acid were treated with RA. Our results showed that RA significantly reduced total cholesterol, triglycerides, low‐density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels and increased high‐density lipoprotein cholesterol, superoxide dismutase and adenosine triphosphate levels both in vivo and in vitro. Hematoxylin and eosin staining and oil red O staining showed that RA had a good lipid‐lowering effect and substantial protective effects on liver injury. Transmission electron microscopy and JC‐1 fluorescence results showed that RA could improve mitochondrial damage in hepatocytes. Additionally, flow cytometry results indicated that RA inhibited ROS generation and apoptosis in L02 cells. The impaired hepatocytes were restored by using RA in NAFLD models characterized by down‐regulating YAP1 and TAZ, meanwhile up‐regulating PPARγ and PGC‐1α. When YAP1 was over‐expressed, RA reduced the expression of YAP1; however, the action of RA was significantly blocked by silencing YAP1. The experimental results indicated that RA markedly alleviated NAFLD by repairing mitochondrial damage and regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway

Luo

Sun

Peng

et al. 2020

Phytotherapy Research

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“…A detailed review on this topic has been published recently [ 183 ]. Some naturally occurring plant compounds, such as quercetin, puerarin, apocynin, and rosmarinic acid, have been reported to possess anti-calcification properties through ROS scavenging [ 94 , 184 , 185 , 186 , 187 ]. Multiple medicines, such as simvastatin, a drug used to lower LDL cholesterol, and metformin, the first-line medication for the treatment of type 2 diabetes, also exhibit antioxidant properties and are effective against vascular calcification in experimental settings [ 188 , 189 ].…”

Section: Controlling Ros Production As a Therapeutic Approach To Pmentioning

confidence: 99%

“…In the nucleus, Nrf2 binds to antioxidant response elements (ARE) and increases transcription of various antioxidant and anti-inflammatory genes [ 193 ]. Different agents, such as dimethyl fumarate, resveratrol, rosmarinic acid, or hydrogen sulfide, have been shown to inhibit vascular calcification through stimulation of Nrf2 activity [ 185 , 194 , 195 , 196 ]. Yao et al showed that overexpression of Nrf2 protects VSMCs from high Pi-induced calcification [ 197 ].…”

Section: Controlling Ros Production As a Therapeutic Approach To Pmentioning

confidence: 99%

Regulation of Vascular Calcification by Reactive Oxygen Species

2020

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Vascular calcification is the deposition of hydroxyapatite crystals in the medial or intimal layers of arteries that is usually associated with other pathological conditions including but not limited to chronic kidney disease, atherosclerosis and diabetes. Calcification is an active, cell-regulated process involving the phenotype transition of vascular smooth muscle cells (VSMCs) from contractile to osteoblast/chondrocyte-like cells. Diverse triggers and signal transduction pathways have been identified behind vascular calcification. In this review, we focus on the role of reactive oxygen species (ROS) in the osteochondrogenic phenotype switch of VSMCs and subsequent calcification. Vascular calcification is associated with elevated ROS production. Excessive ROS contribute to the activation of certain osteochondrogenic signal transduction pathways, thereby accelerating osteochondrogenic transdifferentiation of VSMCs. Inhibition of ROS production and ROS scavengers and activation of endogenous protective mechanisms are promising therapeutic approaches in the prevention of osteochondrogenic transdifferentiation of VSMCs and subsequent vascular calcification. The present review discusses the formation and actions of excess ROS in different experimental models of calcification, and the potential of ROS-lowering strategies in the prevention of this deleterious condition.

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“…We identified five types of potential antioxidants with therapeutic effects against VC based on the literature search, including linalool 61 , lipoic acid 22–24 , rosmarinic acid 63 , fermentation broth extracts from Actinobacteria 59 , and polysaccharide from Fuzi product 60 . Two (40%) of them have ROS scavenging ability, while the other three (60%) do not (Fig.…”

Section: Antioxidants From Natural Non-dietary Sourcesmentioning

confidence: 99%

“…Rosmarinic acid is a phenolic compound purified from medicinal plants belonging to the families Apiaceae , Boraginaceae , and Lamiaceae with anti-inflammatory and antioxidant properties 78 . Ji et al showed that rosmarinic acid reduced VSMC calcification by upregulating Nrf2, NADPH quinone dehydrogenase 1 (NQO1) expression, increasing antioxidant enzyme levels while inhibiting NF-κB and β-catenin signaling in vitro and in vivo 63 . Finally, extracts of bacterial and plant products are also found to counteract VC experimentally.…”

Section: Antioxidants From Natural Non-dietary Sourcesmentioning

confidence: 99%

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

et al. 2019

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Vascular calcification (VC) is highly prevalent in patients with advanced age, or those with chronic kidney disease and diabetes, accounting for substantial global cardiovascular burden. The pathophysiology of VC involves active mineral deposition by transdifferentiated vascular smooth muscle cells exhibiting osteoblast-like behavior, building upon cores with or without apoptotic bodies. Oxidative stress drives the progression of the cellular phenotypic switch and calcium deposition in the vascular wall. In this review, we discuss potential compounds that shield these cells from the detrimental influences of reactive oxygen species as promising treatment options for VC. A comprehensive summary of the current literature regarding antioxidants for VC is important, as no effective therapy is currently available for this disease. We systematically searched through the existing literature to identify original articles investigating traditional antioxidants and novel compounds with antioxidant properties with regard to their effectiveness against VC in experimental or clinical settings. We uncovered 36 compounds with antioxidant properties against VC pathology, involving mechanisms such as suppression of NADPH oxidase, BMP-2, and Wnt/β-catenin; anti-inflammation; and activation of Nrf2 pathways. Only two compounds have been tested clinically. These findings suggest that a considerable opportunity exists to harness these antioxidants for therapeutic use for VC. In order to achieve this goal, more translational studies are needed.

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Rosmarinic acid exerts an antagonistic effect on vascular calcification by regulating the Nrf2 signalling pathway

Cited by 24 publications

References 37 publications

Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway

Rosmarinic acid exerts an antagonistic effect on nonalcoholic fatty liver disease by regulating the YAP1/TAZ‐PPARγ/PGC‐1α signaling pathway

Regulation of Vascular Calcification by Reactive Oxygen Species

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

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