Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway

Abstract

Imperatorin, an active ingredient extracted from Angelica and Qianghuo, has anti-inflammatory, anti-oxidative stress damage, blocking calcium channels, and other properties. Our preliminary findings revealed the protective role of imperatorin in the treatment of vascular dementia, we further explored the underlying mechanisms concerning the neuroprotection function of imperatorin in vascular dementia. The cobalt chloride (COCl2)-induced chemical hypoxia and hypoglycemia of hippocampal neuronal cells was applied as in vitro vascular dementia model. Primary neuronal cells was isolated from the hippocampal tissue of SD suckling rats within 24 h of birth. Hippocampal neurons were identified by immunofluorescence staining of microtubule-associated protein 2. Silencing or overexpression of Nrf2 was conducted by transfection of corresponding plasmids in hippocampal neuronal cells. Cell viability was detected by MTT assay to determine the optimal modeling concentration of CoCl2. Mitochondrial membrane potential, intracellular reactive oxygen species and apoptosis rate was measured by flow cytometry. The expression of anti-oxidative proteins was detected by quantitative real-time PCR and western blot, including Nrf2, NQO-1 and HO-1. Nrf2 nuclear translocation was detected using laser confocal microscopy. The modeling concentration of CoCl2 was 150umol/l, and the best interventional concentration of imperatorin was 7.5umol/l. Significantly, imperatorin facilitated the nuclear localization of Nrf2, promoted the expressions of Nrf2, NQO-1, and HO-1 relative to the model-control group. Moreover, imperatorin reduced the mitochondrial membrane potential and ameliorated CoCl2-induced hypoxic apoptosis in hippocampal neurons. On the contrary, silencing Nrf2 completely abrogated the protective effects of imperatorin. Imperatorin might be an effective drug for preventing and treating vascular dementia.

Phenolic Acids Rescue Iron-Induced Damage in Murine Pancreatic Cells and Tissues

“…Supplementation with phenolic acid, tannic acid, decreased liver iron, MDA and ROS levels [ 41 ]. Natural compounds including phenolic acids exhibit not only a direct antioxidant mechanism by removing ROS but may also impact an endogenous protective mechanism such as the Nrf2 defense signaling pathway [ 42 ]. Nrf2 is the central regulator involved in maintaining cellular redox homeostasis and modulating the expression of phase II enzymes such as NQO1, GCLC, GPX4 and HO-1, which in turn protect cells from oxidative damage, inflammation, and apoptosis [ 43 ].…”

Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport

“…We wish to point out that published work has demonstrated that imperatorin exhibits low general toxicity [29]. For instance, imperatorin demonstrated minimal toxicity, with over 80% cell viability observed at concentrations up to 100 μM in normal hippocampal neuronal cells [32] and up to 50 μM in mouse bone-marrow-derived mast cells [51]. In our present investigation, we assessed the cytotoxicity of imperatorin in human embryonic kidney (HEK293) cells, a widely employed mammalian expression system.…”

“…Imperatorin, a natural coumarin compound [24], can be isolated from various sources such as Notopterygium incisum (also referred to as Hansenia weberbaueriana) [25], Rhodiola bupleuroides [26], Foeniculum vulgare Mill [27], and Angelica dahurica [28]. Extensive research has detailed the pharmacological effects of imperatorin [29], encompassing its antibacterial [30], antiviral [31], antioxidant [32], antihypertensive [33,34], anti-inflammatory [35,36], hepatoprotective [37], and neuroprotective [38,39] properties. In addition, imperatorin has exhibited inhibitory effects on cell proliferation in a range of cancer types [40][41][42][43][44][45][46][47][48][49][50].…”

The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis

“…This condition promotes free radical formation, causing mitochondrial dysfunction, inducing white matter abnormalities, and increasing blood brain barrier permeability [ 8 , 9 ]. Emerging evidence suggests that oxidative stress also plays an important role in the pathogenesis of VaD [ 10 , 11 ]. Activated microglia in VaD can generate excessive reactive oxygen species (ROS), which can initiate oxidative stress and lead to neuronal damage and apoptosis, thus resulting in neuropathological changes and brain tissue injury and, ultimately, cognitive decline and behavioural dysfunction [ 12 , 13 ].…”