Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy

Yerra, Veera Ganesh; Kalvala, Anil Kumar; Kumar, Ashutosh

doi:10.1016/j.jnutbio.2017.05.001

Cited by 95 publications

(49 citation statements)

References 70 publications

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“…The study also infers that neuroprotection afforded by morin hydrate was mediated through induction of cellular antioxidant defenses as well as mitochondrial‐specific antioxidants and by attenuation of ROS induced damage in experimental DN. The results corroborate the previous findings of therapeutic benefit accord by polyphenols and flavonoids in attenuating various deficits reported in DN .…”

Section: Discussionsupporting

confidence: 92%

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

et al. 2017

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Morin, a bioflavonoid with diverse pharmacological effects against various diseases; in most cases morin protective effects were attributed to its detoxifying effect against reactive oxygen species (ROS). Diabetic neuropathy (DN) is a chronic, debilitating neuronal pain associated with intense generation of free radicals and proinflammatory cytokine accumulation in peripheral neurons. We investigated the pharmacological effect of morin against metabolic excess mediated mitochondrial ROS generation and corresponding effect on Nrf2, NF-κB pathways in Streptozotocin (STZ)-induced diabetic rats and in high glucose insulted Mouse neuroblastoma cell line, Neuro 2A (N2A). Animals were evaluated for nerve function parameters, motor and sensory nerve conduction velocities (MNCV and SNCV) and nerve blood flow (NBF) followed by TUNEL and immunoblot analysis. Mitochondrial function was evaluated by performing JC-1 and MitoSOX assays in high glucose (30 mM) incubated N2A cells. Diabetic animals showed significant impairment in MNCV, SNCV, and NBF as well as increased pain hypersensitivity. However, oral administration of morin at 50 and 100 mg/kg improved SNCV, MNCV, and NBF and reduced sensorimotor alterations (hyperalgesia and allodynia) in diabetic animals. Studies in N2A cells have revealed that morin ameliorated the high glucose-induced mitochondrial superoxide production, membrane depolarization, and total ROS generation. Morin effectively counteracted NF-κB-mediated neuroinflammation by reducing ROS mediated IKK activation and increased Nrf2-mediated antioxidant defenses in high glucose-induced N2A cells. The results of our study suggest that morin has exquisite role in offering neuroprotection in experimental DN and further clinical investigation may reward in finding better alternative for the management of DN. © 2017 BioFactors, 44(2):109-122, 2018.

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Section: Discussionsupporting

confidence: 92%

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

et al. 2017

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“…It is gratifying to see that Fx can successfully reverse the decrease expression of FoxO3α and the increase of phosphorylated FoxO3α induced by HG. Rsv and MK2206, activators of Sirt1 and inhibitors of Akt, respectively, were used as positive control, which also successfully increased the expression of FoxO3α and decreased the phosphorylation of FoxO3α in GMCs stimulated by HG (Figure 3b,d) The acetylation modification of FoxO3α, similar to phosphorylation modification, is not conducive to its transcriptional activity [27]. In this experiment, we found that the expression of acetylated FoxO3α in GMCs stimulated by HG increased significantly; however, Fx and Rsv decreased the acetylated FoxO3α induced by HG, respectively ( Figure 3c).…”

Section: Fx Reverses the Expression Of Foxo3α Inhibited By Hg In Gmcsmentioning

confidence: 99%

“…It has been reported that both Akt and Sirt1 can regulate FoxO3α [27]. To further determine whether Fx regulates FoxO3α through Akt and Sirt1 signaling, we treated GMCs with EX527, an inhibitor of Sirt1, and SC79, an activator of Akt, followed by Fx, respectively.…”

Section: Fx Regulates the Expression Of Foxo3α Through The Akt And Simentioning

confidence: 99%

Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs

et al. 2019

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As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN.

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“…Therefore SirT1 inactivation may be one of the reasons for the pathogenesis of insulin resistance and T2DM associated vascular complications. Recently Yerra et al in 2017 have investigated the role of SirT1 activation by Isoliquiritigenin (ILQ) on AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling in peripheral nerves of diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells (Yerra et al, 2017[77]). ILQ, the known antioxidant, and the SirT1 activator are recently studied for its antidiabetic activity (Watanabe et al, 2016[72]).…”

Section: The Regulation Of Autophagy In Diabetes and Its Complicationsmentioning

confidence: 99%

“…Diabetic rats and N2A cells, exposed to high glucose showed low expression of SIRT1 with a reduction in mitochondrial biogenesis and autophagy. Upon administration of ILQ in diabetic rats and as well as high glucose-exposed N2A cells showed significant SIRT1 activation with a concurrent increase in mitochondrial biogenesis and autophagy (Yerra et al, 2017[77]).…”

Section: The Regulation Of Autophagy In Diabetes and Its Complicationsmentioning

confidence: 99%

Is autophagy associated with diabetes mellitus and its complications? A review

Bhattacharya

Mukhopadhyay²,

Bhattacharyya

et al. 2018

EXCLI Journal; 17:Doc709; ISSN 1611-2156

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Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy

Cited by 95 publications

References 70 publications

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

Morin exerts neuroprotection via attenuation of ROS induced oxidative damage and neuroinflammation in experimental diabetic neuropathy

Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs

Is autophagy associated with diabetes mellitus and its complications? A review

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