Gastrodin Inhibits Glutamate-Induced Apoptosis of PC12 Cells via Inhibition of CaMKII/ASK-1/p38 MAPK/p53 Signaling Cascade

Abstract

Previous research demonstrated that glutamate induces neuronal injury partially by increasing intracellular Ca(2+) concentrations ([Ca(2+)]i), and inducing oxidative stress, leading to a neurodegenerative disorder. However, the mechanism of glutamate-induced injury remains elusive. Gastrodin, a major active component of the traditional herbal agent Gastrodia elata (GE) Blume, has been recognized as a potential neuroprotective drug. In the current study, a classical injury model based on glutamate-induced cell death of rat pheochromocytoma (PC12) cells was used to investigate the neuroprotective effect of gastrodin, and its potential mechanisms involved. In this paper, the presence of gastrodin inhibits glutamate-induced oxidative stress as measured by the formation of reactive oxygen species (ROS), the level of malondialdehyde (MDA), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD); gastrodin also prevents glutamate-induced [Ca(2+)]i influx, blocks the activation of the calmodulin-dependent kinase II (CaMKII) and the apoptosis signaling-regulating kinase-1 (ASK-1), inhibits phosphorylation of p38 mitogen-activated kinase (MAPK). Additionally, gastrodin blocked the expression of p53 phosphorylation, caspase-3 and cytochrome C, reduced bax/bcl-2 ratio induced by glutamate in PC12 cells. All these findings indicate that gastrodin protects PC12 cells from the apoptosis induced by glutamate through a new mechanism of the CaMKII/ASK-1/p38 MAPK/p53-signaling pathway.

Gastrodin: An ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species

“…Recently, the anti-oxidative property of gastrodin has been investigated [22,27]. In this study, we could partially reverse H 2 O 2 -induced production of reactive oxygen species by treatment with gastrodin.…”

“…Gastrodia elata, a traditional herbal agent, is officially listed in the Chinese Pharmacopoeia [22]. Gastrodin (whose structure is exhibited in Fig.…”

“…1, PubChem CID: 115067) is the chief pharmacologically active component found in G. elata [23]. Previous studies show that gastrodin is involved in some pharmacological activities, such as relaxation on smooth muscle [24], anti-cell death [25], anti-apoptosis [26] and anti-oxidative [22,27] activities. It is a potent antioxidant and free radical scavenger that can reduce the levels of lipid peroxidation [28], inhibit uncoupled oxidative phosphorylation [29], and elevate expression of genes encoding antioxidant proteins [30].…”

“…It is a potent antioxidant and free radical scavenger that can reduce the levels of lipid peroxidation [28], inhibit uncoupled oxidative phosphorylation [29], and elevate expression of genes encoding antioxidant proteins [30]. Gastrodin supplementation partially inhibits glutamate-induced oxidative damage as detected by the production of reactive oxygen species, the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) [22].…”

Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK/Nrf2 Pathway

“…Cellular AMPK could be activated by upstream kinases like liver kinase B1 (LKB1) and Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII), as well as inhibition of mitochondrial function (Yin et al, ). It was reported that GSTD could block the activation of CaMKII in neurons (Jiang et al, ). Here, our results clearly demonstrate that GSTD activated LKB1 in liver cells.…”