Protective Effects Of Gastrodin Research Articles

The protective effects of gastrodin on neurological disorders: an update and future perspectives.

Neurological disorders are characterized by high mortality and disability rates. Furthermore, the burden associated with disability and mortality resulting from neurological disorders has been increasing at an alarming rate. Botanical drugs and their bioactive components have emerged as a prominent area of research, offering a promising avenue for developing novel alternatives for treating neurological diseases. Gastrodin is the principal active component derived from the traditional Chinese medicinal plant Gastrodia elata Blume (GEB). Existing literature reveals that gastrodin exerts various pharmacological protective actions against neurological disorders. This review aimed to collate novel literature on gastrodin for treating neurological disorders from Web of Science, PubMed, Embase and CNKI. The pharmacokinetics of gastrodin, its therapeutic role in neurological disorders, the main mechanisms of action and clinical application were addressed. Furthermore, a detailed overview of gastrodin drug delivery systems and physical enhancement methods was presented, offering invaluable insights into potential research and the extensive applications of gastrodin.

Gastrodin alleviates microglia-mediated inflammatory responses in neonatal mice with hypoxic-ischemic brain damage by regulating CCR5/AKT signaling

To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage (HIBD) in neonatal mice. Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group, HIBD (induced by ligation of the left common carotid artery followed by hypoxia for 40 min) group, and HIBD with gastrodin treatment groups (n=12). In gastrodin treatment group, 100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia. After the treatments, the expressions of CCR5, AKT, p-AKT, and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining. In a BV2 microglial cell model of oxygen-glucose deprivation (OGD), the effects of pretreatment with gastrodin and Maraviroc (an CCR5 antagonist) on protein expressions of CCR5, AKT, p-AKT, TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining. The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues, and GAS treatment obviously reversed these changes. HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice, which was obviously lowered by gastrodin treatment. In BV2 cells, OGD significantly increased the expressions of CCR5, TNF-α, and IL-1β and decreased the expression of p-AKT, and these changes were inhibited by treatment with gastrodin, Maraviroc or their combination; the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone. Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Protective Effects of Gastrodin Against Gentamicin-Induced Vestibular Damage by the Notch Signaling Pathway.

Gentamicin is a broad-spectrum antibiotic commonly used in clinical practice. However, the drug causes side effects of ototoxicity, leading to disruption in balance functionality. This study investigated the effect of gastrodin, a prominent compound present in Gastrodia, and the underlying mechanism on the development of gentamicin-induced vestibular dysfunction. Wild-type C57BL/6 mice were randomly assigned to three groups: control, gentamicin, and gentamicin + gastrodin groups. The extent of gentamicin-induced vestibular impairment was assessed through a series of tests including the swimming test, contact righting reflex test, and air-righting reflex. Alterations in vestibular hair cells were monitored through immunofluorescence assay, and cellular apoptosis was observed using TUNEL staining. The mRNA and protein expression of Notch1, Jagged1, and Hes1 was quantified through qRT-PCR, immunofluorescence, and western blot analyses. Gentamicin treatment led to pronounced deficits in vestibular function and otolith organ hair cells in mice. Nevertheless, pretreatment with gastrodin significantly alleviated these impairments. Additionally, the Notch signaling pathway was activated by gentamicin in the utricle, contributing to a notable increase in the expression levels of apoptosis-associated proteins. By contrast, gastrodin treatment effectively suppressed the Notch signaling pathway, thereby mitigating the occurrence of apoptosis. Collectively, these findings underscore the crucial role of gastrodin in safeguarding against gentamicin-induced vestibular dysfunction through the modulation of the Notch signaling pathway. This study suggests the potential of gastrodin as a promising therapeutic agent for preventing vestibular injuries.

Gastrodin suppresses pyroptosis and exerts neuroprotective effect in traumatic brain injury model by inhibiting NLRP3 inflammasome signaling pathway.

Traumatic brain injury (TBI), also known as head injury or brain injury, refers to the head injury caused by mechanical impact. It is necessary to develop effective new therapies for TBI injury. Gastrodin (GAS) is the main bioactive ingredient from the rhizome of Gastrodia elata and has significant therapeutic effect on nervous system diseases. However, the protective effects of GAS on brain tissue and related regulatory mechanism in traumatic brain injury remain elusive. Herein, we explored the role of GAS in traumatic brain injury and its related mechanism. We found Gastrodin reduced brain tissue injury and improved functional recovery of injury nerve in TBI rats, and alleviated inflammation. Gastrodin decreased the level of pyroptosis in brain tissue of TBI rats. Further, we found GAS suppressed NLRP3 inflammasome signaling pathway, and therefore suppressed pyroptosis and exerted neuroprotective effect. GAS could serve as a promising drug for TBI treatment.

The protective effect of gastrodin against the synergistic effect of HIV-Tat protein and METH on the blood-brain barrier via glucose transporter 1 and glucose transporter 3.

Many individuals infected with human immunodeficiency virus (HIV) are also afflicted with HIV-associated neurocognitive disorders (HANDs). Methamphetamine (METH) abuse puts HIV-1 patients at risk for HANDs because METH and HIV-1 proteins, such as trans-activator of transcription (Tat), can synergistically damage the blood-brain barrier (BBB). However, the underlying mechanism of METH- and HIV-Tat-induced BBB damage remains unclear. In this study, male adult tree shrews and human brain capillary endothelial cells were treated with HIV-Tat, METH, and gastrodin. We used western blotting to examine the expressions of glucose transporters (GLUT1 and GLUT3), tight junctions, and junctional adhesion molecule A (JAMA) and to evaluate the damage and detect Evans blue (EB) and fluorescein sodium in the brain to assess BBB permeability to study the effect of METH and the HIV-1 Tat protein on BBB function in vitro and in vivo. The results showed that the group treated with Tat and METH experienced a significant change at the ultrastructural level of the tree shrew cerebral cortex, decreased protein levels of occluding, claudin-5, Zonula occludens 1 (ZO1), and JAMA in vitro and in vivo, and increased levels of EB and fluorescein sodium in the tree shrew cerebral cortex. The protein levels of GLUT1 and GLUT3 was downregulated in patients with Tat- and METH-induced BBB damage. Pretreatment with gastrodin significantly increased the levels of EB and fluorescein sodium in the tree shrew cerebral cortex and increased the expressions of occluding, ZO1, JAMA, and GLUT1 and GLUT. These results indicate that gastrodin may offer a potential therapeutic option for patients with HANDs.

Protective effect of gastrodin against methamphetamine-induced autophagy in human dopaminergic neuroblastoma SH-SY5Y cells via the AKT/mTOR signaling pathway

Methamphetamine (METH) has been shown to induce neuropathological dysfunction and irreversible brain cell damage. Prior studies indicated the involvement of autophagy in METH-induced neurotoxicity. However, the underlying mechanism by which autophagy contributes to METH-induced neurotoxicity remains elusive. Gastrodin, a primary bioactive constituent of Gastrodia elata—an orchid used in traditional Chinese medicine—is used widely to treat stroke, dementia, and headache. This study investigates whether METH induces autophagy in the human dopaminergic neuroblastoma cell line SH-SY5Y, then examines the neuroprotective effects of gastrodin against autophagy in METH-treated SH-SY5Y cells. The effects of METH on the protein expressions of autophagy-related genes (LC3B and Beclin-1) were evaluated with and without gastrodin. The presence of autophagosomes in the METH-induced treatment with and without gastrodin is revealed through transmission electron microscopy. Pharmacological intervention was employed to study the role of the AKT/mTOR signaling pathway in the gastrodin-mediated neuroprotection against METH-induced autophagy. The present results indicate that METH exposure elevates the protein expression levels of LC3B and Beclin-1 in a dose- and time-dependent manner. Gastrodin is observed to block the METH-induced upregulation of LC3B and Beclin-1 protein expression significantly. Gastrodin is found to exhibit an anti-autophagic effect on the inhibition of the METH-induced Beclin-1 protein expression, partly via the AKT/mTOR These findings may aid the development of a gastrodin-based therapeutic strategy for treating METH-induced neurotoxicity.

Protective effect of gastrodin on myocardial ischemia-reperfusion injury and the expression of Bax and Bcl-2.

The protective effects of gastrodin on myocardial ischemia-reperfusion injury in rats and the underlying mechanism were investigated. Sprague Dawley (SD) rats were randomly divided into three groups, of which the gastrodin group was treated with gastrodin, and the other two groups were treated with normal saline. In the myocardial ischemia-reperfusion model group, myocardial ischemia was induced by ligation of the left anterior descending coronary artery, and myocardial reperfusion was performed by ligature removal. Only thread without ligation for the sham operation group was conducted. The rats were euthanized 8 days after surgery. Heart tissues were harvested and used for measurement of apoptotic rate and expression levels of apoptosis-related proteins. Serum levels of cytokines were measured also using blood samples. Compared with the myocardial ischemia-reperfusion model group, significant reduction of cardiomyocyte apoptosis was observed in the gastrodin group (P<0.05). In the gastrodin group, the protein and mRNA expression levels for Bax and activated caspase-3 decreased, while for Bcl-2 increased (P<0.05). Gastrodin can downregulate inflammatory cytokines (P<0.05) and upregulate anti-inflammatory cytokines such as IL-10 (P<0.05) in serum of SD rats. Therefore, gastrodin played a protective role in myocardial ischemia-reperfusion injury by regulating the expression levels of apoptosis-related signaling proteins and inflammatory cytokines.

Protective effect of gastrodin on peripheral neuropathy induced by anti-tumor treatment with vincristine in rat models

Cancer is a common disease threatening human health, chemotherapy is widely used in clinical treatment of cancer, but chemotherapy-induced peripheral neuropathy (CIPN) has a relevant impact on life quality of cancer patients. Administration of gastrodin can relieve chronic pain to cancer patients with CIPN and attenuated the inflammatory response by reducing the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). However, its exact molecular mechanisms remain unclear. In this study, we established an animal model of CIPN using Walker-256 breast cancer cell and vincristine. We found that the mechanical and thermal pain threshold of rats was decreased with treatment of vincristine. Using gastrodin could restore the mechanical and thermal threshold without interfering anti-tumor effect of vincristine. Gastrodin relieved CIPN by inhibiting activation of spinal microglia through Fractalkine (CX3CL1) and its receptor CX3CR1, then inhibited P38/mitogen-activated protein kinase (MAPK) signaling pathway and reduced the expression of inflammatory factor TNF-α and interleukin-1β (IL-1β). Taking together, our study demonstrated that gastrodin is a potential drug for the treatment of CIPN and likely to improve cancer patient’s life quality.

Mechanism of gastrodin in cell apoptosis in rat hippocampus tissue induced by desflurane.

This study investigated the protective effect ofgastrodin on cell apoptosis in rats hippocampus tissues induced by desflurane to explore its mechanism. A total of 36 rats were randomly divided into three groups: Blank control group (C group, n=12), desflurane anesthesia group (DF group, n=12) and gastrodin treatment group (GT group, n=12). Rats in DF group were treated with anesthesia using desflurane. Rats in GT group were treated with gavage using gastrodin and the same treatment as DF group. After the experiment, novel object recognition test and water maze test were performed. The hippocampus tissues were taken from the rat after the behavioral experiment; then the number of apoptotic cells was detected using the terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) kit, and the mRNA and protein expression levels of p38 and interleukin-1 (IL-1) were detected via semi-quantitative polymerase chain reaction (PCR) and western blot analysis. After the desflurane anesthesia, novel object recognition showed that compared with that in DF group, the exploration capacity of novel objects in GT group was increased (P<0.01). The water maze test showed that the escape latencies in DF group, T1 in GT group was significantly shortened, but T2 was significantly prolonged (P<0.01). TUNEL assay showed that the number of apoptotic cells in hippocampus tissues in GT group was significantly fewer than that in group DF (P<0.01). Semi-quantitative PCR and western blot analysis showed that the expression levels of p38 and IL-1β in GT group were lower than those in DF group (P<0.01). The results show that gastrodin has a protective effect on the apoptosis of hippocampus cells of rats induced by desflurane. Its protection mechanism may be realized through decreasing the increased p38 and IL-1β expression levels induced by desflurane, thus blocking the p38 mitogen-activated protein kinase (p38 MAPK) pathway.

Protective Effects of Gastrodin Against Autophagy-Mediated Astrocyte Death.

Gastrodin is an active ingredient derived from the rhizome of Gastrodia elata. This compound is usually used to treat convulsive illness, dizziness, vertigo, and headache. This study aimed to investigate the effect of gastrodin on the autophagy of glial cells exposed to lipopolysaccharides (LPS, 1 µg/mL). Autophagy is a form of programmed cell death, although it also promotes cell survival. In cultured astrocytes, LPS exposure induced excessive autophagy and apoptosis, which were significantly prevented by the pretreatment cells with gastrodin (10 μM). The protective effects of gastrodin via autophagy inhibition were verified by the decreased levels of LC3-II, P62, and Beclin-1, which are classical markers for autophagy. Furthermore, gastrodin protected astrocytes from apoptosis through Bcl-2 and Bax signaling pathway. The treatment of astrocytes with rapamycin (500 nM), wortmannin (100 nM), and LY294002 (10 μM), which are inhibitors of mTOR and PI3K, respectively, eliminated the known effects of gastrodin on the inhibited Beclin-1 expression. Furthermore, gastrodin blocked the down-regulation of glutamine synthetase induced by LPS exposure in astrocytes. Our results suggest that gastrodin can be used as a preventive agent for the excessive autophagy induced by LPS.

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease.

The protective effects of gastrodin on the brain injury and the integrity of myelin in striatum after cerebral ischemia-reperfusion in mice

Objective To investigate the effects of gastrodin on neural function and the expression of myelin basic protein(MBP) and neurofilament high molecular weight(NFH) in the striatum during cerebral ischemia-reperfusion in mice. Methods 36 Kunming mice were randomly divided into sham group, MCAO group and gastrodin (GAS) group. The middle cerebral artery occlusion(MCAO) was established by artery embolization.The mice in sham group were received fake surgery and saline, and the mice in MCAO and GAS group were exposed to MCAO, and received saline and GAS (100 mg/(kg·d)) injection, respectively, immediately after the operation for 7 days. On the 8th day of operation, the neurological severity scores of the mice were observed and the volume ratio of the cerebral infarction was estimated by triphenyl tetrazolium chloride (TTC) staining. Immunohistochemistry was used to detect the MBP and NF-H in the striatum. Results (1) The mice in MCAO group showed significant neurologic deficient in comparison with sham group, and the neurological severity scores of gastrodin group(3.13±0.64) were significantly higher than that(1.38±0.52) of MCAO group (P<0.05). (2) Results of TTC staining showed that the infarction volume was obviously larger in the injured cerebral tissue in MCAO group in comparison with sham group, and the volume ratio of the cerebral infarction significantly decreased after the intervention with GAS (P<0.05). (3) The integral optical density of MBP(272 968.14±1215.23) and NF-H(12 142.73±47.16) in MCAO group decreased as compared to that((43 855.23±2434.16), (275 321.00±926.15)) in sham group and GAS group((321 531.2±2376.14), (106 135.73±598.15))(P<0.05). Conclusion GAS can improve neural function of mice after middle cerebral artery occlusion, and it may play an important role in protecting myelin and nerve fibers of striatum. Key words: Gastrodin; Brain ischemic and reperfusion; Myelin basic protein; Neurofilament high molecular weight

Gastrodin suppresses the amyloid β-induced increase of spontaneous discharge in the entorhinal cortex of rats.

Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer's disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ 1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ 1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ 1−42 and that GAS can effectively reverse Aβ 1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ 1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ 1−42-induced hyperactivity in EC neurons of rats.

Protective Effects of Gastrodin on Lead-Induced Synaptic Plasticity Deficits in Rat Hippocampus

Lead is a well-known toxin in the environment that causes severe damage to the nervous system. Gastrodin is the main bioactive component of Tian ma ( GASTRODIA ELATA Bl.), which is a traditional herbal medicine widely used in eastern Asia. Increasing lines of evidence show that gastrodin has diverse effects, especially neuroprotective effects. In the present study, we investigated whether gastrodin supplementation can rescue impairments of synaptic plasticity produced by developmental lead exposure. We examined three electrophysiological parameters of synaptic plasticity: input/output (I/O) function, paired-pulse facilitation (PPF), and long-term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) in the hippocampal CA1 region of rats on postnatal day 22 (P22). Our results showed that lead exposure significantly impaired synaptic plasticity in the hippocampal CA1 region and that gastrodin can effectively rescue these lead-induced impairments. Therefore, gastrodin may have potential therapeutic value for lead-induced impairments during human developmental stages.

Protective Effects of Gastrodin on Hypoxia-Induced Toxicity in Primary Cultures of Rat Cortical Neurons

The phenolic glucoside gastrodin is the main component extracted from the rhizome of Gastrodia elata (Orchidaceae), a Chinese herbal medicine, which has long been used for treating dizziness, epilepsy, stroke and dementia. The present study aims to investigate the effect of gastrodin on hypoxia-induced neurotoxicity in cultured rat cortical neurons. Neuron survival and extracellular glutamate level were measured after an insult by hypoxia. Glutamate concentrations were determined by an HPLC-ECD system. The results demonstrated that neurons were significantly damaged by hypoxia for 24 h. When pretreated with gastrodin (100, 200 microg/mL) in hypoxia, neuron survival was significantly increased compared with no gastrodin treatment. Moreover, the enhancement of extracellular glutamate level stimulated by hypoxia was inhibited by pretreatment with gastrodin (100 microg/mL). Further studies demonstrated that gastrodin prevented glutamate- and NMDA-induced neurotoxicity. In addition, gastrodin also inhibited the extracellular glutamate level induced by NMDA insult. These findings suggest that gastrodin has a neuroprotective action against hypoxia in the cultured cortical neuron, and the mechanism may involve a decreasing of the extracellular glutamate level.