Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy

Chen, Jing; Ou, Zilin; Gao, Tiantian; Yang, Yuwei; Shu, Anmei; Xu, Hao; Chen, Yuping; Lv, Zhiyang

doi:10.1016/j.biopha.2022.113953

Cited by 66 publications

(29 citation statements)

References 40 publications

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“…Recent studies have revealed an association between SNPs of antioxidant enzymes and improper defence against ROS, leading to intracellular accumulation of free radicals and subsequent oxidative stress 24 . Many studies have suggested that oxidative stress is implicated in the development of T2D complications 25–27 . Increasing free radicals and improper defence by antioxidants, can cause oxidative damage to lipids, proteins and nucleic acids 28 .…”

Section: Discussionmentioning

confidence: 99%

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

Sultan,

Alharbi,

Alrayes

et al. 2023

Endocrino Diabet & Metabol

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IntroductionOne of the complications of diabetes mellitus (DM) is diabetic nephropathy (DN), which plays a significant role in the progression of end‐stage renal disease. Oxidative stress is implicated in DN pathogenesis, and genetic variations in antioxidant enzymes such as superoxide dismutase 2 (SOD2) and catalase (CAT) may contribute to the susceptibility. This study aimed to investigate the potential association between single nucleotide polymorphisms (SNPs) in antioxidant enzymes, specifically SOD2 rs4880 and CAT rs769217, and the risk of T2D and susceptibility to DN within the Saudi population.MethodsThis case–control study included 150 participants, comprising 50 patients with T2D without DN (group 1), 50 patients with T2D with DN (group 2), and 50 healthy participants (group 3). The samples were genotyped using real‐time PCR for SOD2 rs4880 and CAT rs769217 SNPs. Sanger sequencing was used for validation. Statistical analyses were performed to explore associations between these SNPs and T2D with or without DN.ResultsNo significant difference was observed in CAT rs769217 expression between the groups. However, a significant difference was observed in SOD2 rs4880 expression between the healthy controls and patients with T2D with DN (p = .028). Furthermore, SOD2 rs4880 was associated with approximately threefold increased risk of DN in patients with T2D compared to that in healthy participants (odds ratio [OR] = 2.99 [1.31–6.83]). Validation through Sanger sequencing further confirmed these findings.ConclusionsThe findings of this study provide evidence that SOD2 rs4880 SNP may contribute to inadequate defence by the antioxidant enzyme, SOD2, against DM‐induced oxidative stress and thus cause DN in Saudi patients with T2D. Therefore, SOD2 rs4880 may serve as a predictive marker to prevent the development and progression of DN in patients with T2D.

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Section: Discussionmentioning

confidence: 99%

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

Sultan,

Alharbi,

Alrayes

et al. 2023

Endocrino Diabet & Metabol

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show abstract

“…Inhibition of cysteine synthesis and GSH levels can directly affect the activity of GPX4, leading to increased ROS production and accumulation of lipid peroxidation induced ferroptosis [56] . Some studies have shown that inhibiting GPX4 ubiquitination can reduce oxidative stress and ferroptosis, thereby improving DN [57] . Zhang S, et al proved that the renal protection function of Vitexin in HK-2 cells stimulated by HG and in DN induced by HFD/STZ was achieved by reducing GPX4 mediated ferroptosis, and expounded the important role of GSH/GPX4 axis in preventing lipid oxidation induced DN [58] .…”

Section: Disscusionmentioning

confidence: 99%

Natural product Swietenine improve the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Akt/GSK-3β/Nrf2 signaling pathway

Lu,

Duan,

Liu

et al. 2024

Preprint

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Background Ferroptosis is a newly defined form of iron dependent regulatory cell death distinct from apoptosis, autophagy, and necrosis, characterized by an abnormal increase in intracellular lipid reactive oxygen species. Diabetes nephropathy (DN) is one of the most common complications of diabetes and the most common cause of end-stage renal disease. Recent studies have shown that ferroptosis plays an important role in the occurrence and development of diabetic nephropathy. Swietenine belongs to the limonin class of compounds, which are extracted from the the Swietenia macrophylla King, a plant of the genus Swietenia, family Meliaceae King and have not been artificially synthesized to date. It is a natural product with a variety of pharmacological activities such as anti diabetes, improving inflammation, anti-oxidation, anti-bacterial, anti-tumor, etc. However, it is unclear whether Swietenine can improve diabetes nephropathy by inhibiting the occurrence of ferroptosis in glomerular podocytes (MPC-5) and its potential mechanism. Objective This study investigated the natural product Swi through Akt/GSK-3β/Nrf2 signaling pathway inhibits MPC-5 ferroptosis and improves diabetes nephropathy in the process of diabetes. Method In vivo, 8-week-old SD rats were induced with STZ/HFD to investigate the effect of Swi on improving DN and resisting ferroptosis. In vitro, the inhibitory effects of Swi on MPC-5 death. By giving verify the activation effect of Akt/GSK-3β/Nrf2 signaling pathway related inhibitors on downstream anti ferroptosis related proteins. Results In this study, Swi treatment improved renal injury in DN rats, which was proved by renal function related indexes, histopathological parameters and podocyte damage protein. In addition, Swi inhibited ferroptosis in vivo. Swi improved HG-induced MPC-5 cell viability, inhibited ferroptosis in MPC-5 cells. Swi inhibits ferroptosis by activating the Akt/GSK-3β/Nrf2 signaling pathway, which promotes the expression of downstream anti-ferroptosis related proteins. Conclusion Our research findings suggest for the first time that it may be through a new Akt/GSK-3β/Nrf2 dependent ferroptosis regulates the signaling pathway, thereby reducing the level of high glucose induced ferroptosis and improving diabetes nephropathy, which is expected to become a promising candidate drug for the treatment of diabetes

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“…99 Recent therapeutic interventions, such as mangiferin monosodium salt, Ginkgolide B, and germacrone, target ferroptosis suppression and are effective in managing diabetic nephropathy through minimizing oxidative stress. 98,100,101 There is currently a paucity of evidence linking ferroptosis directly to podocytes in LN patients; however, recent magnetic resonance analyses referencing three single-nucleotide polymorphisms (rs855791, rs1800562, and rs1799945, which were identified in an expansive genome-wide association study) have associated serum iron levels with susceptibility to SLE. 97 Podocyte ferroptosis might have significant implications for LN patients, whether directly or indirectly.…”

Section: Ferroptosismentioning

confidence: 99%

“…Compounds that inhibit ferroptosis, such as ferrostatin‐1, exhibit therapeutic potential by mitigating the expression of GPX4 in podocytes, resulting in a marked reduction of proteinuria and a decrease in podocyte mortality in focal segmental glomerulosclerosis patients 99 . Recent therapeutic interventions, such as mangiferin monosodium salt, Ginkgolide B, and germacrone, target ferroptosis suppression and are effective in managing diabetic nephropathy through minimizing oxidative stress 98,100,101 …”

Section: Pathophysiology Of Podocyte Injury and Death In Lnmentioning

confidence: 99%

Podocyte injury and death: New insights into lupus nephritis pathogenesis and therapy

Shi,

Wang,

Tang

et al. 2023

Rheumatology & Autoimmunity

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Lupus nephritis (LN), an immune complex‐mediated glomerulonephritis, is one of the most severe complications of systemic lupus erythematosus. Current therapeutic regimens for LN mainly involve nonspecific immunosuppressants and biologics targeting immune cells, but these treatments are not always effective and some patients are nonresponsive and susceptible to recurrence. Podocytes are essential for maintaining the glomerular filtration barrier. Injury to and loss of podocytes lead to proteinuria, a hallmark of renal involvement and LN. Podocytes are, therefore, emerging as prospective therapeutic targets for LN. There are numerous mechanisms underlying podocyte malfunction in LN, with autophagy, mitochondrial dysregulation, and programmed cell death being the main processes behind podocyte loss. This review summarizes recent advances in understanding podocyte dysfunction in LN pathogenesis and discusses potential therapeutic interventions targeting podocytes in LN.

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Ginkgolide B alleviates oxidative stress and ferroptosis by inhibiting GPX4 ubiquitination to improve diabetic nephropathy

Cited by 66 publications

References 40 publications

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

Association of a single nucleotide polymorphism in SOD2 with susceptibility for the development of diabetic nephropathy in patients with type 2 diabetes: A Saudi population study

Natural product Swietenine improve the progression of diabetic nephropathy by inhibiting ferroptosis through activation of the Akt/GSK-3β/Nrf2 signaling pathway

Podocyte injury and death: New insights into lupus nephritis pathogenesis and therapy

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