Catalpol Exerts an Anti-Epilepticus Effect, Possibly by Regulating the Nrf2-Keap1-ARE Signaling Pathway

Abstract

BackgroundStatus epilepticus (SE) is a refractory neurological disease with high mortality and morbidity rates. SE can be induced by numerous factors, including oxidative stress. Catalpol has several biological activities, including regulating the oxidative stress response. However, the role of catapol in SE has not been fully elucidated.Material/MethodsThirty Wistar rats were randomly and equally divided into 3 groups: a control group, an SE group established by LiCl-pilocarpine intraperitoneal injection, and an SE+catalpol group established administering catalpol to SE rats. Epileptic seizure level and after-discharge duration (ADD) were analyzed. Cognitive function was assessed by Morris water maze. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were tested. Keap1 and ARE mRNA expressions were detected by real-time PCR. Nrf2 protein expression was determined by Western blot.ResultsCatalpol significantly decreased epileptic seizure level, extended ADD, and improved cognitive function compared with the SE group (P<0.05). MPO was increased, SOD was reduced, Keap1 mRNA was upregulated, and Nrf2 protein and ARE mRNA were reduced in the SE group compared with the control group (P<0.05). Catalpol markedly decreased MPO, enhanced SOD activity, decreased Keap1 mRNA level, and elevated Nrf2 protein and ARE mRNA expressions compared with the SE group (P<0.05).ConclusionsCatalpol plays an anti-epileptic role and improves cognitive function by regulating the Nrf2-Keap1-ARE signaling pathway to inhibit oxidative stress response.

Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

“…CAT simultaneously, as a major component of RG, has been reported to display neuroprotective and antiapoptotic effects (Liang et al, 2009;Cai et al, 2011;Liu et al, 2014). In addition, CAT has been found to have anti-inflammatory and neuroprotective roles in inflammation-mediated Parkinson's disease, which can reduce neuronal degeneration caused by inflammation-triggered oxidative stress and ER stress (Liu et al, 2014;Xiong et al, 2017;Gao et al, 2018). CAT was also reported to protect podocytes in diabetic nephropathy via inhibiting apoptosis.…”

Catalpol and Mannitol, Two Components of Rehmannia glutinosa, Exhibit Anticonvulsant Effects Probably via GABAA Receptor Regulation

“…Based on these all results, it can be suggested that the anticonvulsant properties of catalpol and mannitol might be mediated by other pathways as well as GABAA receptor activities. For example, Gao et al (2018) reported that catalpol decreased LiCl/pilocarpine-induced seizure responses and altered Nrf2-Keap1-ARE expression.…”

“…Several RG components, including aucubin, acteoside, catalpol, and mannitol, were screened to determine whether they have anticonvulsant effects, and catalpol, mannitol, and their combination were chosen for further assessment. Recently, using LiCl/pilocarpine, electroencephalography (EEG), or extracellular field recording in brain slice, some studies have reported that catalpol or mannitol might have anticonvulsant effects (Haglund and Hochman, 2005;Serafini, 2017;Gao et al, 2018), however, their roles remain unclear. In this study, their protective effects as well as that of their combination against electroshock-or chemically (PTZ or strychnine)-induced seizures, were evaluated in mice.…”

Natural Products as Modulators of Nrf2 Signaling Pathway in Neuroprotection

“…Models of stress-induced depression showed that Nfr2 and HO-1 are downregulated, but catalpol (10 mg/kg) was shown to restore their levels and may target depression via the PI3K/Akt/Nrf2/HO-1 signaling pathway [ 100 ]. Studies on hyperglycemia-induced depression showed that catalpol (5, 10, and 20 mg/kg) reversed pathological phosphorylation of PI3K and Akt and restored Nrf2 and HO-1 levels, attributed to the upregulation of the PI3K/Akt/Nrf2/HO-1 signaling pathway [ 101 ].…”