Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model

Mazumdar, Suchismita; Marar, Thankamani; Devarajan, Shine; Patki, Jyoti

doi:10.1016/j.bbrep.2020.100904

Cited by 8 publications

(6 citation statements)

References 35 publications

(24 reference statements)

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“…Nox5 has also been shown to be important in VSMC phenotypic switching relevant to vascular calcification and aneurysm formation (145,146). With the emerging evidence that Nox5 may be an attractive therapeutic target in human cardiovascular disease, interest in developing selective Nox5 inhibitors is growing and a number of promising agents have been identified including melittin, gedunin and ML090 (147)(148)(149) .…”

Section: Multiple Nox Isoforms Are Involved In Hypertensionmentioning

confidence: 99%

“…Considering the potential importance of oxidative stress in the pathophysiology of hypertension and the convincing experimental data, it is reasonable to imagine that reducing ROS bioavailability through antioxidants, ROS scavengers, and Nox inhibitors would have protective and blood pressure-lowering effects. Interest in developing therapies to target Nox/ROS is growing as highlighted in recent reviews (136,(147)(148)(149).…”

Section: Clinical Perspectivesmentioning

confidence: 99%

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Oxidative Stress and Hypertension

Griendling

Camargo

Ríos

et al. 2021

Circulation Research

255

158

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A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.

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Section: Multiple Nox Isoforms Are Involved In Hypertensionmentioning

confidence: 99%

Section: Clinical Perspectivesmentioning

confidence: 99%

Oxidative Stress and Hypertension

Griendling

Camargo

Ríos

et al. 2021

Circulation Research

255

158

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“…Many factors (internal and external), such as obesity, sedentary lifestyle, and oxidative stress, are directly involved in these cell alterations ( Etsassala et al, 2020 ). Normal cellular homeostasis is maintained by the balance between endogenous pro-oxidant enzymes (NADPH oxidase), oxidants and endogenous anti-oxidants ( Mazumdar, Marar, Devarajan, & Patki, 2021 ). Growing evidences suggested that hyperglycemia can disturb the anti-oxidant-prooxidant balance through activation of NADPH oxidase to increase the level of intracellular reactive oxygen species (ROS) ( Najafi, Kavoosi, Siahbalaei, & Kariminia, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection

Xu,

Guo,

Chen

et al. 2024

Chinese Herbal Medicines

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“…Gedunin was described as a robust and non-toxic Nrf2 activator acting against oxidative stress, since Nrf2 is a key transcriptional regulator of antioxidant defense and detoxification [22]. The ROS scavenging of gedunin and its ability to reduce oxidative stress to augment current type 2 diabetes therapies were described [23]. Gedunin was also the first identified antimalarial limonoid agent from the neem tree [24].…”

Section: Introductionmentioning

confidence: 99%

Azadiradione, a Component of Neem Oil, Behaves as a Superoxide Dismutase Mimic When Scavenging the Superoxide Radical, as Shown Using DFT and Hydrodynamic Voltammetry

Sakib,

Caruso,

Belli

et al. 2023

Biomedicines

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The neem tree, Azadirachta indica, belongs to the Meliaceae family, and its use in the treatment of medical disorders from ancient times to the present in the traditional medical practices of Asia, Africa and the Middle East is well-documented. Neem oil, extracted from the seeds of the fruit, is widely used, with promising medicinal benefits. Azadiradione, a principal antioxidant component of the seeds of A. indica, is known to reduce oxidative stress and has anti-inflammatory effects. To directly measure the antioxidant ability of neem oil, we used Rotating Ring Disk Electrode (RRDE) hydrodynamic voltammetry to quantify how it can scavenge superoxide radical anions. The results of these experiments show that neem oil is approximately 26 times stronger than other natural products, such as olive oil, propolis and black seed oil, which were previously measured using this method. Next, computational Density Functional Theory (DFT) methods were used to arrive at a mechanism for the scavenging of superoxide radical anions with azadiradione. Our work indicates that azadiradione is an effective antioxidant and, according to our DFT study, its scavenging of the superoxide radical anion occurs through a reaction mechanism in which azadiradione mimics the antioxidant action of superoxide dismutase (SOD). In this mechanism, analogous to the SOD enzymatic reaction, azadiradione is regenerated, along with the production of two products: hydrogen peroxide and molecular oxygen. This antioxidant process provides an explanation for azadiradione’s more general and protective biochemical effects.

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Functional relevance of Gedunin as a bona fide ligand of NADPH oxidase 5 and ROS scavenger: An in silico and in vitro assessment in a hyperglycemic RBC model

Cited by 8 publications

References 35 publications

Oxidative Stress and Hypertension

Oxidative Stress and Hypertension

Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection

Azadiradione, a Component of Neem Oil, Behaves as a Superoxide Dismutase Mimic When Scavenging the Superoxide Radical, as Shown Using DFT and Hydrodynamic Voltammetry

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