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

Abstract

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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“…The neuroprotective effects of xanthotoxin and umbelliferone on streptozotocin (STZ)-induced cognitive dysfunction in rats were evaluated [ 54 ]. Alzheimer’s disease was induced in these animals and both compounds were administrated, proving to prevent cognitive deficits in the Morris water maze and object recognition tests.…”

8-Methoxypsoralen has Anti-inflammatory and Antioxidant Roles in Osteoarthritis Through SIRT1/NF-κB Pathway

“…In addition, Protectin DX has been verified to inhibit the NF-κB pathway by promoting AMPK, and thus alleviating IL-1β-induced chondrocyte inflammation and inhibiting OA progression in rats ( Piao et al, 2020 ). Interestingly, 8-Methoxypsoralen (also known as Xanthotoxin) has been identified to repress NF-κB activation and inflammatory reactions ( Lee et al, 2017 ; Li et al, 2019 ; Hindam et al, 2020 ). In this study, we found that 8-MOP obviously promoted the expression of SIRT1 and inhibited the expression of NF-κB in the OA model.…”

Twice as Nice: The Duff Formylation of Umbelliferone Revised

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