|Neurochem Int. 2014 Sep;75:79-88. |
|Gastrodin protects against MPP(+)-induced oxidative stress by up regulates heme oxygenase-1 expression through p38 MAPK/Nrf2 pathway in human dopaminergic cells.[Pubmed: 24932697]|
|Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside Gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity.|
METHODS AND RESULTS:
The present study aimed to investigate the protective effects of Gastrodin on 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with Gastrodin for 1h significantly reduced the MPP(+)-induced viability loss, apoptotic rate and attenuated MPP(+)-mediated ROS production. In addition, Gastrodin inhibited MPP(+)-induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the Gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed Gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed Gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of Gastrodin against MPP(+)-induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of Gastrodin against MPP(+)-induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on Gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of Gastrodin against MPP(+)-induced cell death.
Taken together, these findings suggest that Gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP(+)-induced oxidative cell death. Thus our study indicates that Gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases.
|Biochem Pharmacol. 2013 Apr 15;85(8):1124-33. |
|Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-κB and MAPKs activation via the phosphatidylinositol 3-kinase signaling.[Pubmed: 23376120 ]|
|The phenolic glucoside Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties. However, the role and precise molecular mechanisms explaining how Gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown. |
METHODS AND RESULTS:
To study this, rat H9c2 cardiomyocytes were treated with Gastrodin and/or lipopolysaccharide (LPS). Our results showed that Gastrodin treatment strongly suppressed nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes. Simultaneously, Gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner. However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of Gastrodin on LPS-stimulated H9c2 cardiomyocytes. Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of Gastrodin on the phosphorylation of inhibitor κB-α (IκB-α), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-κB.
Here we report activation of the PI3-K/Akt signaling by Gastrodin and that inhibition of this pathway reverses the inhibitory effects of Gastrodin on NF-κB and MAPKs activation in H9c2 cardiomyocytes.
|Neurosci Lett. 2015 May 6;594:40-5. |
|Ameliorative effect of gastrodin on 3,3'-iminodipropionitrile-induced memory impairment in rats.[Pubmed: 25817367]|
|3,3'-Iminodipropionitrile (IDPN), one of the nitrile derivatives inducing neurotoxicity, causes the dyskinetic syndrome and cognitive impairment. Gastrodin is widely used to treat neurological disorders and showed to improve cognitive functions. |
METHODS AND RESULTS:
The present study aimed to determine whether treatment with Gastrodin can attenuate IDPN-induced impairment of memory consolidation in the passive avoidance (PA) task, and to explore the possible neural mechanisms. Our results showed that intragastric administration of Gastrodin (200mg/kg) reversed the IDPN-induced impairment of memory consolidation as indicated by the prolonged retention latency in the PA task. Furthermore, Gastrodin reverted IDPN-induced reduction of serotonin (5-HT) and elevation of serotonin turnover ratio. Gastrodin treatment prevented the increase of serotonin transporter (SERT) and the decrease of serotonin 1A (5-HT1A) receptor expression in the hippocampus of IDPN-treated rats.
These results suggest that long-term Gastrodin treatment could represent a novel pharmacological strategy for IDPN-induced memory impairment, as well that its protective effect is mediated through normalization of the serotoninergic system.
|PLoS One. 2012;7(6):e39647. |
|Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons.[Pubmed: 22761855 ]|
|Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, Gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. |
METHODS AND RESULTS:
By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of Gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of Gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of Gastrodin, we examined the effects of Gastrodin on transient sodium currents (I(NaT)) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I(NaT) and a decrease of potassium currents, especially slowly inactivating potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(NaT) and total potassium current as well as I(AS) currents induced by STZ were normalized by GAS.
This study provides a clear cellular basis for the peripheral analgesic action of Gastrodin for the treatment of chronic pain, including PDN.