Ginkgolide B caused the activation of the Akt/eNOS pathway through the antioxidant effect of SOD1 in the diabetic aorta

Taguchi, Kumiko; Okudaira, Kanami; Matsumoto, Takayuki; Kobayashi, Tsuneo

doi:10.1007/s00424-023-02790-3

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…We found that in human ECs, Nur77 markedly upregulated SOD1 expression through directly binding to the SOD1 promoter. SOD1 has been shown to be either downregulated or upregulated in aorta under high glucose conditions [ 51 , 52 ]. In this study, we show that HG barely affected the expression of SOD1 in aortic ECs isolated from wild-type mice, but markedly inhibits SOD1 expression in Nur77-deficient ECs, suggesting that Nur77 is required for maintaining SOD1 expression under HG conditions.…”

Section: Discussionmentioning

confidence: 99%

Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways

Lu,

Jang,

Zhu

et al. 2024

Redox Biology

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Section: Discussionmentioning

confidence: 99%

Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways

Lu,

Jang,

Zhu

et al. 2024

Redox Biology

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“…This function is related to the TRPV4-coupled Ca2+/PKA/eNOS signaling pathway, which achieves vasodilation by increasing Ca2+ influx [ 86 ]. In addition, flavonoids from other traditional Chinese medicines (TCM), such as ginkgolide B, have been found to stimulate SOD activity and increase SOD1 expression in diabetic aortas, thereby activating the Akt/eNOS signaling pathway and causing endothelium-dependent relaxation [ 150 ]. Since the application of herbs in TCM is often in the form of compounded soups and often in certain ratios, future pharmacological studies on flavonoid compounds in Chinese herbs may try to combine them in anticipation of obtaining higher efficacy and developing a wider range of drug targets.…”

Section: Protective Effects Of Flavonoids On Endothelial Cellsmentioning

confidence: 99%

Research Progress of Flavonoids Regulating Endothelial Function

Li,

Zhang

2023

Pharmaceuticals

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The endothelium, as the guardian of vascular homeostasis, is closely related to the occurrence and development of cardiovascular diseases (CVDs). As an early marker of the development of a series of vascular diseases, endothelial dysfunction is often accompanied by oxidative stress and inflammatory response. Natural flavonoids in fruits, vegetables, and Chinese herbal medicines have been shown to induce and regulate endothelial cells and exert anti-inflammatory, anti-oxidative stress, and anti-aging effects in a large number of in vitro models and in vivo experiments so as to achieve the prevention and improvement of cardiovascular disease. Focusing on endothelial mediation, this paper introduces the signaling pathways involved in the improvement of endothelial dysfunction by common dietary and flavonoids in traditional Chinese medicine and describes them based on their metabolism in the human body and their relationship with the intestinal flora. The aim of this paper is to demonstrate the broad pharmacological activity and target development potential of flavonoids as food supplements and drug components in regulating endothelial function and thus in the prevention and treatment of cardiovascular diseases. This paper also introduces the application of some new nanoparticle carriers in order to improve their bioavailability in the human body and play a broader role in vascular protection.

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“…Oxidative stress and mitochondrial dysfunction are common hallmarks of atherosclerotic plaques, particularly in the hypoxic regions close to the necrotic core [ 108 – 110 ] . This may happen, as mentioned above, by ROS overproduction or by depletion of antioxidant defenses, such as superoxide dismutase 1, in the aorta of diabetic mice [ 111 ] . High ROS generation leads to membrane damage and mitochondrial DNA (mtDNA) release into the cytosol, which is closely related to nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome activation in macrophages [ 110 , 112 – 114 ] .…”

Section: Macrophage Metabolism In Atherosclerosismentioning

confidence: 99%

Macrophage immunometabolism in diabetes-associated atherosclerosis

Gindri dos Santos,

Goedeke

2023

Immunometabolism

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Macrophages play fundamental roles in atherosclerotic plaque formation, growth, and regression. These cells are extremely plastic and perform different immune functions depending on the stimuli they receive. Initial in vitro studies have identified specific metabolic pathways that are crucial for the proper function of pro-inflammatory and pro-resolving macrophages. However, the plaque microenvironment, especially in the context of insulin resistance and type 2 diabetes, constantly challenges macrophages with several simultaneous inflammatory and metabolic stimuli, which may explain why atherosclerosis is accelerated in diabetic patients. In this mini review, we discuss how macrophage mitochondrial function and metabolism of carbohydrates, lipids, and amino acids may be affected by this complex plaque microenvironment and how risk factors associated with type 2 diabetes alter the metabolic rewiring of macrophages and disease progression. We also briefly discuss current challenges in assessing macrophage metabolism and identify future tools and possible strategies to alter macrophage metabolism to improve treatment options for diabetes-associated atherosclerosis.

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Ginkgolide B caused the activation of the Akt/eNOS pathway through the antioxidant effect of SOD1 in the diabetic aorta

Cited by 5 publications

References 44 publications

Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways

Nur77 mitigates endothelial dysfunction through activation of both nitric oxide production and anti-oxidant pathways

Research Progress of Flavonoids Regulating Endothelial Function

Macrophage immunometabolism in diabetes-associated atherosclerosis

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