Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway

Abstract

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aβ). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/β-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

Rhizoma Gastrodiae Water Extract Modulates the Gut Microbiota and Pathological Changes of P-TauThr231 to Protect Against Cognitive Impairment in Mice

“…Substantially, WERG-H significantly alleviated D-gal/AlCl 3 -stimulated cognitive impairment, p-Tau Thr231 protein formation, and pathological changes. Consistent with the present study, gastrodin significantly inhibited lead-induced p-Tau accumulation in the mouse brain (Liu et al, 2020). Similarly, another study confirmed that gastrodin suppressed the deposition of p-Tau in the brain of the unilateral intracerebroventricular injection of the Aβ 1-42 mouse model (Luo et al, 2022).…”

Study on the Efficacy and Mechanism of Lycium barbarum Polysaccharide against Lead-Induced Renal Injury in Mice

“…However, this is not always the case. The experiments of Liu et al [ 67 ] and Liu et al [ 68 ] showed that lead inhibited the expression of Nrf2 signaling-related proteins and then induced oxidative stress, inflammation, and apoptosis. Interestingly, our experimental results are not entirely consistent with previous studies.…”

Gastrodin and Vascular Dementia: Advances and Current Perspectives

“…Through this way, GAS can significantly reduce nerve edema after ischemia and improve neuronal apoptosis [ 68 – 70 ]. Gastrodin can also activate Wnt/ β -catenin signaling pathway through NRF2-mediated antioxidant signals and reduce cycx-2 (COX-2) activation, showing neuroprotective properties [ 71 ] ( Figure 3 ).…”

“…Common toxic substances, such as A β , glutamate, and NO, increase, and neurotrophic substances decrease in VaD patients [ 74 ]. Gastrodin can reverse the above pathological changes and play a role in increasing neuronal survival, improving synaptic function and promoting neural differentiation [ 71 ]. Studies have shown that GAS can reduce the expression of A β 1-40/42, APP, and β -site APP Exceller enzyme 1.…”