Vinpocetine mitigates proteinuria and podocytes injury in a rat model of diabetic nephropathy

Wadie, Walaa; El-Tanbouly, Dalia M.

doi:10.1016/j.ejphar.2017.08.027

Cited by 22 publications

(11 citation statements)

References 48 publications

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“…After behavioural testing, all animals were sacrificed by decapitation under thiopental sodium (5 mg/kg) anaesthesia [ 28 ]. Brains were rapidly dissected out and the striata were isolated and stored at -80°C.…”

Section: Methodsmentioning

confidence: 99%

Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease

et al. 2018

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Countless neurodegenerative diseases are associated with perverse multiple targets of cyclic nucleotide signalling, hastening neuronal death. Cilostazol, a phosphodiesterase-III inhibitor, exerts neuroprotective effects against sundry models of neurotoxicity, however, its role against Huntington’s disease (HD) has not yet been tackled. Hence, its modulatory effect on several signalling pathways using the 3-nitropropionic acid (3-NP) model was conducted. Animals were injected with 3-NP (10 mg/kg/day, i.p) for two successive weeks with or without the administration of cilostazol (100 mg/kg/day, p.o.). Contrary to the 3-NP effects, cilostazol largely preserved striatal dopaminergic neurons, improved motor coordination, and enhanced the immunohistochemical reaction of tyrosine hydroxylase enzyme. The anti-inflammatory effect of cilostazol was documented by the pronounced reduction of the toll like receptor-4 (TLR-4) protein expression and the inflammatory cytokine IL-6, but with a marked elevation in IL-10 striatal contents. As a consequence, cilostazol reduced IL-6 downstream signal, where it promoted the level of suppressor of cytokine signalling 3 (SOCS3), while abated the phosphorylation of Janus Kinase 2 (JAK-2) and Signal transducers and activators of transcription 3 (STAT-3). Phosphorylation of the protein kinase B/glycogen synthase kinase-3β/cAMP response element binding protein (Akt/GSK-3β/CREB) cue is another signalling pathway that was modulated by cilostazol to further signify its anti-inflammatory and antiapoptotic capacities. The latter was associated with a reduction in the caspase-3 expression assessed by immunohistochemical assay. In conclusion the present study provided a new insight into the possible mechanisms by which cilostazol possesses neuroprotective properties. These intersecting mechanisms involve the interference between TLR-4, IL-6-IL-10/JAK-2/STAT-3/SOCS-3, and Akt/GSK-3β/CREB signalling pathways.

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Section: Methodsmentioning

confidence: 99%

Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease

et al. 2018

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“…These cytokines are produced in an NF- κ B-dependent manner, which indicates that targeting this signaling pathway can reduce inflammation. Vinpocetine has been shown to target NF- κ B in different inflammatory disease models [20, 24, 25, 27, 33, 66, 67] and also in human cells [68]. This effect in human cells was observed by the reduced levels of phosphorylation and degradation of I κ B α in the vinpocetine-treated peripheral blood mononuclear cells (PBMC) from patients with acute ischemic stroke [68].…”

Section: Discussionmentioning

confidence: 99%

Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation

Lourenco-Gonzalez

Fattori

Domiciano

et al. 2019

Mediators of Inflammation

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Clinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs with the ability of reducing ROS-triggered responses are promising candidates for analgesic drugs. Vinpocetine is a clinically used nootropic drug with antioxidant, anti-inflammatory, and analgesic properties. However, the effects of vinpocetine have not been investigated in a model with a direct relationship between ROS, inflammation, and pain. Based on that, we aimed to investigate the effects of vinpocetine in a model of superoxide anion-induced pain and inflammation using potassium superoxide (KO2) as a superoxide anion donor to trigger inflammation and pain. In the KO2 model, vinpocetine dose-dependently reduced pain-like behaviors (spontaneous pain and hyperalgesia), paw edema, and neutrophil and mononuclear cell recruitment to the paw skin (assessed by H&E staining, fluorescence, and enzymatic assays) and to the peritoneal cavity. Vinpocetine also restored tissue endogenous antioxidant ability and Nrf2 and Ho-1 mRNA expression and reduced superoxide anion production and gp91phox mRNA expression. We also observed the inhibition of IκBα degradation by vinpocetine, which demonstrates a reduction in the activation of NF-κB explaining the diminished production of IL-33, IL-1β, and TNF-α. Collectively, our data show that vinpocetine alleviates pain and inflammation induced by KO2, which is a mouse model with a direct role of ROS in triggering pain and other inflammatory phenomena. Thus, the results suggest the repurposing of vinpocetine as an anti-inflammatory and analgesic drug.

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“…Eight-week TM administration successfully regulated the levels of interleukins in the kidneys of db/db mice, further confirming its renal protective effects. In diabetes, hyperglycemia activates protein kinase C (PKC), which increases the expression of NF- κ B and induces both cytokines and chemokines [ 61 ], which contribute to the accumulation of the extracellular matrix and injury of podocytes in diabetic animals [ 62 ]. The JAK/STAT system mediates abnormal kidney diseases, and suppression of JAK2 expression can relieve DN progression [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress, which is related to the overproduction of ROS, has been identified as a general pathogenic factor in DN [ 62 , 65 ]. In contrast, antioxidant enzymes including SOD, GSH-Px, and CAT scavenge free radicals and prevent oxidative injury [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

The Antidiabetic and Antinephritic Activities of Tuber melanosporum via Modulation of Nrf2‐Mediated Oxidative Stress in the db/db Mouse

Jiang

Teng

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

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Tuber melanosporum (TM), a valuable edible fungus, contains 19 types of fatty acid, 17 types of amino acid, 6 vitamins, and 7 minerals. The antidiabetic and antinephritic effects of TM and the underlying mechanisms related to oxidative stress were investigated in db/db mice. Eight-week oral administration of metformin (Met) at 0.1 g/kg and TM at doses of 0.2 and 0.4 g/kg decreased body weight, plasma glucose, serum levels of glycated hemoglobin, triglyceride, and total cholesterol and increased serum levels of high-density lipoprotein cholesterol in the mice, suggesting hypoglycemic and hypolipidemic effects. TM promoted glucose metabolism by increasing the levels of pyruvate kinase and hepatic glycogen. It also regulated the levels of inflammatory factors and oxidative enzymes in serum and/or the kidneys of the mice. Additionally, TM increased the expression of nuclear respiratory factor 2 (Nrf2), catalase, heme oxygenase 1, heme oxygenase 2, and manganese superoxide dismutase 2 and decreased the expression of protein kinase C alpha, phosphor-janus kinase 2, phosphor-signal transducer and activator of transcription 3, and phosphor-nuclear factor-κB in the kidneys. The results of this study reveal the antidiabetic and antidiabetic nephritic properties of TM via modulating oxidative stress and inflammation-related cytokines through improving the Nrf2 signaling pathway.

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Vinpocetine mitigates proteinuria and podocytes injury in a rat model of diabetic nephropathy

Cited by 22 publications

References 48 publications

Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease

Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease

Repurposing of the Nootropic Drug Vinpocetine as an Analgesic and Anti-Inflammatory Agent: Evidence in a Mouse Model of Superoxide Anion-Triggered Inflammation

The Antidiabetic and Antinephritic Activities of Tuber melanosporum via Modulation of Nrf2‐Mediated Oxidative Stress in the db/db Mouse

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