Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats

Germoush, Mousa O.; Othman, Sarah I.; Al-Qaraawi, Maha A.; Al-Harbi, Hanan M.; Hussein, Omnia E.; Al-Basher, Gadh; Alotaibi, Mashael Alhumaidi; Elgebaly, Hassan A.; Sandhu, Mansur A.; Allam, Ahmed A.; Mahmoud, Ayman M.

doi:10.1016/j.biopha.2018.03.104

Cited by 52 publications

(36 citation statements)

References 63 publications

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“…Previous work from our lab has demonstrated the antioxidant and anti-inflammatory activities of UMB in different animal models [30,34,44]. UMB administration mitigated Oxidative Medicine and Cellular Longevity cyclophosphamide-induced oxidative damage and inflammatory response through marked elevation of Nrf2, HO-1, and PPARγ expression.…”

Section: Urolithin Amentioning

confidence: 83%

“…In addition, UMB suppressed NF-κB p65 and TGF-β1/Smad3 and upregulated hepatic PPARγ [34]. Moreover, UMB attenuated lipid peroxidation, NO release, and cerebral inflammation and downregulated nNOS and soluble guanylate cyclase expression in the cerebrum of hyperammonemic rats [30].…”

Section: Urolithin Amentioning

confidence: 86%

“…The Umbelliferae family is inclusive of economically important herbs, such as celery, cumin, fennel, parsley alexanders, angelica, asafoetida, and giant hogweed [9,170]. UMB possesses a variety of bioactivities, and several investigators have previously reported its in vivo antioxidant and anti-inflammatory effects and studied the underlying mechanisms of action in several animal models [30,[171][172][173][174][175]. The anticancer activity of UMB in hepatocellular [176], colon [177], and oral [178] carcinomas has been well-acknowledged.…”

Section: Urolithin Amentioning

confidence: 99%

“…Inhibition of matrix metalloproteinases (MMPs) and cancer cell growth, migration, and invasion and induction of apoptosis have been demonstrated as the effects underlying the anticancer activity of coumarins [28,29]. Coumarins have also shown antihyperglycemic, antifibrotic, antiadipogenic, and cytochrome P450 inhibitory activities [30][31][32][33][34]. In a mouse model of cerebral ischemia/reperfusion (I/R) injury, the coumarin esculetin showed a potent neuroprotective effect when administered intracerebroventricularly [35].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, oxidative stress is implicated in the pathogenesis of a wide range of metabolic disorders and chronic diseases [41][42][43]. Given their ability to suppress excessive ROS generation and enhance antioxidants [30,34,44], the pharmacologic effects of coumarins could be mediated through their antioxidant efficacy. The present review presents an overview of the modulatory role of a number of plant-derived coumarins ( Figure 1) on nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor which protects against oxidative injury and inflammation [45].…”

Section: Introductionmentioning

confidence: 99%

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Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

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156

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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Section: Urolithin Amentioning

confidence: 83%

Section: Urolithin Amentioning

confidence: 86%

Section: Urolithin Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

Self Cite

156

106

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Nephroprotective effect of umbelliferone against cisplatin‐induced kidney damage is mediated by regulation of NRF2, cytoglobin, SIRT1/FOXO‐3, and NF‐kB‐p65 signaling pathways

Ali

Hassanein

El-Bahrawy

et al. 2021

J Biochem & Molecular Tox

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Cisplatin (Cis) is one of the most potent and effective broad‐spectrum antitumor drugs, but its use is limited due to nephrotoxicity. The current study investigated the renoprotective effect of umbelliferone (UMB) on Cis‐induced nephrotoxicity in rats. Renal injury was induced by a single injection of Cis (7 mg/kg, ip). Our results exhibited that the injection of Cis significantly disrupted renal function biomarkers as well as KIM‐1 expression. The expressions of TNF‐α, IL‐1β, NF‐kB‐p65, and IKKβ were elevated along with downregulation of IkBα expression. Also, Cis disrupted cellular oxidant/antioxidant balance through the reduction of glutathione (GSH), glutathione‐S‐transferase (GST), and superoxide dismutase (SOD) levels and elevation of malondialdehyde (MDA) content. On the contrary, the levels of renal function biomarkers, cytokines, NF‐kB‐p65, IkBα, IKKβ, and oxidant/antioxidant status have been improved after UMB treatment. Mechanistically, rats administered Cis only exhibited a significant decrease in NRF2 and cytoglobin expressions as well as the CREB, SIRT1, FOXO‐3, and PPAR‐γ genes. Treatment with UMB significantly upregulated NRF2 and cytoglobin proteins, as well as effectively increased the expression of CREB, SIRT1, FOXO‐3, PPAR‐γ, and NRF2 genes. Histopathological findings strongly supported our biochemical results, as evidenced by attenuation of renal hemorrhage, cast diffusion, and inflammatory cell infiltration. Interestingly, UMB significantly enhanced Cis cytotoxicity in both HL‐60 and HeLa cells in a dose‐dependent manner. Together, our results demonstrated that UMB can protect against Cis‐induced nephrotoxicity in normal rats along with the enhancement of its in vitro antitumor activity. These findings suggested that UMB could be used as a potential adjuvant therapy in Cis chemotherapeutic protocols.

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Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation

Hindam

Sayed

Skalicka‐Woźniak

et al. 2020

Phytotherapy Research

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The aim of the present study was to assess the neuroprotective effects of xanthotoxin and umbelliferone in streptozotocin (STZ)‐induced cognitive dysfunction in rats. Animals were injected intracerebroventricularly (ICV) with STZ (3 mg/kg) once to induce a sporadic Alzheimer's disease (SAD)‐like condition. Xanthotoxin or umbelliferone (15 mg/kg, i.p.) were administered 5 hr after ICV‐STZ and daily for 20 consecutive days. Xanthotoxin or umbelliferone prevented cognitive deficits in the Morris water maze and object recognition tests. In parallel, xanthotoxin or umbelliferone reduced hippocampal acetylcholinestrase activity and malondialdehyde level. Moreover, xanthotoxin or umbelliferone increased glutathione content. These coumarins also modulated neuronal cell death by reducing the level of proinflammatory cytokines (tumour necrosis factor‐alpha and interleukin‐6), inhibiting the overexpression of inflammatory markers (nuclear factor κB [NF‐κB] and cyclooxygenase II), and upregulating the expression of NF‐κB inhibitor (IκB‐α). Interestingly, xanthotoxin diminished phosphorylated JAK2 and phosphorylated STAT3 protein expression, while umbelliferone markedly replenished nuclear factor erythroid‐derived 2‐like 2 (Nrf2) and haem oxygenase‐1 (HO‐1) levels. The current study provides evidence for the protective effect of xanthotoxin and umbelliferone in STZ‐induced cognitive dysfunction in rats. This effect may be attributed, at least in part, to inhibiting acetylcholinestrase and attenuating oxidative stress, neuroinflammation and neuronal loss.

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Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats

Cited by 52 publications

References 63 publications

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Nephroprotective effect of umbelliferone against cisplatin‐induced kidney damage is mediated by regulation of NRF2, cytoglobin, SIRT1/FOXO‐3, and NF‐kB‐p65 signaling pathways

Xanthotoxin and umbelliferone attenuate cognitive dysfunction in a streptozotocin‐induced rat model of sporadic Alzheimer's disease: The role of JAK2/STAT3 and Nrf2/HO‐1 signalling pathway modulation

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