Gastrodin Inhibits Non-alcoholic Fatty Liver Disease via Mediating SREBP1c Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of gastrodin on the steroid regulatory element-binding protein 1c （SREBP1c） signaling pathway in high-fat high-cholesterol diet （HFHC）-induced mice and explore the mechanism of gastrodin in the treatment of non-alcoholic fatty liver disease （NAFLD）. MethodEight-week-old male C57BL/6J mice were used in vivo and divided into the following four groups， with six mice in each group： normal group， gastrodin group （50 mg·kg-1）， model group， and model + gastrodin group （50 mg·kg-1）. NAFLD model was established by feeding mice with HFHC for four weeks， and the mice were euthanized and the liver tissues were collected after four weeks. In vitro experiments were performed using Huh7 cells which were divided into five groups， and induced with free fatty acids （FFA， 200 μmol·L-1， oleic acid-palmitic acid 2∶1） to establish an NAFLD cell model. After 24 h， different concentrations of gastrodin （0， 5， 10， 20， and 40 μmol·L-1） were added to each group and cultured for another 24 h. Oil red O staining was used to detect lipid accumulation in mouse liver and Huh7 cells. Hematoxylin-eosin （HE） staining was used to observe pathological changes in liver tissue. Levels of serum total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and triglycerides （TG） were measured using an automatic biochemical analyzer. Relevant assay kits were used to detect liver TC， TG， and FFA levels. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of lipid synthesis-related proteins fatty acid synthase （FASN）， acetyl-CoA carboxylase 1 （ACC1）， and stearoyl-CoA desaturase 1 （SCD1）. ResultCompared with the normal group， the model group showed significantly increased serum TC， LDL-C， and TG levels （P<0.01）， liver TC， TG， and FFA levels （P<0.01）， increased lipid accumulation in Huh7 cells （P<0.01）， and significantly increased expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells （P<0.01）. Compared with the model group， after gastrodin treatment， the serum TC， LDL-C， and TG levels in mice significantly decreased （P<0.05， P<0.01）， the severity of fatty liver disease improved significantly， liver TC， TG， and FFA levels decreased significantly （P<0.05， P<0.01）， lipid accumulation in Huh7 cells decreased significantly （P<0.05， P<0.01）， the expression levels of lipid synthesis-related genes SREBP1c， FASN， ACC1， and SCD1 in mice and Huh7 cells decreased significantly （P<0.05， P<0.01）. ConclusionGastrodin can reduce hepatic lipid accumulation and blood lipid levels， improve HFHC-induced NAFLD， and its mechanism of action may be related to the regulation of the SREBP1c lipid synthesis-related signaling pathway.

The effects of gastrodin on TLR4 expression in microglia induced by ischemia and hypoxia / 神经解剖学杂志

Objective:To determine the effect of gastrodin(GAS)on toll-like receptor 4(TLR4)expression in mi-croglia after hypoxic-ischemic brain damage.Methods:Hypoxia-ischemic brain damage(HIBD)model was established in neonatal rat in vivo.Thirty 3 d SD rats of were randomly divided into there groups:Sham group,HIBD model group,HIBD model+gastrodin intervention group(HIBD+G).Oxygen glucose deprivation(OGD)model was established in BV2 cells in vitro,Control group(Control),oxygen glucose deprivation group(OGD),OGD+gastrodin intervention group(OGD+G)were randomly set in vitro.Both Western Blot and immunofluorescence staining techniques were used to detect the expression of TLR4 in cells of each group in vitro and in the left corpus callosum region in vivo.Results:The expression of TLR4 was significantly increased in OGD-induced microglia.After gastrodin intervention,TLR4 expression was decreased significantly(P＜0.05).Conclusion:GAS can inhibit the expression of TLR4 in activated microglia and thus play a neuroprotective role in HIBD.

Gastrodin intervention attenuates inflammatory injury in ischemic stroke rats / 中国组织工程研究

BACKGROUND:Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke,and its mechanism of action is still unclear. OBJECTIVE:To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats. METHODS:Fifty Sprague-Dawley rats were divided into sham-operated group,model group,positive control group,high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method,with 10 rats in each group.Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group.Administration in each group started on the 3rd day after surgery,and the rats in the positive control group were intraperitoneally injected with edaravone injection(6 mg/kg),the rats in the high-and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively,and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline.After 14 days of continuous treatment in each group,the pathological changes in rat brain tissue were observed,and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected. RESULTS AND CONCLUSION:Compared with the sham-operated group,the volume of cerebral infarction became larger in the model group;the structure of brain tissue was loose,irregular cavities could be observed,and the number of neurons was reduced and irregularly arranged;the positive expression of NLRP3 inflammasome increased(P<0.01);and the protein and mRNA expression levels of Toll-like receptor 4,myeloid differentiation factor 88,apoptosis-associated speck-like protein containing a caspase-recruitment domain,Caspase-1,and interleukin-1β increased(P<0.01).Compared with the model group,the volume of cerebral infarction became smaller in the high-and low-dose gastrodin groups;the neurons were regularly arranged,increased in number,and uniformly distributed;the positive expression of NLRP3 inflammasome was decreased(P<0.05);the protein and mRNA expression levels of Toll-like receptor 4,myeloid differentiation factor 88,apoptosis-associated speck-like protein containing a caspase-recruitment domain,Caspase-1,and interleukin-1β were decreased in the high-dose gastrodin group(P<0.01);Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group,and the protein and mRNA expression of the other inflammatory response-associated factors decreased(P<0.05,P<0.01).To conclude,gastrodin attenuates inflammatory injury in ischemic stroke rats,and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression.

Gastrodin inhibits microglia-mediated inflammatory response in isch-emic hypoxic neonatal mice via CCR5/JAK1/STAT1 signaling pathway / 中国病理生理杂志

AIM:To investigate the effect of gastrodin(GAS)on microglia-mediated inflammatory response after hypoxic-ischemic brain damage(HIBD)neonatal mice by regulating the expression of JAK1/STAT1 pathway through C-C chemokine recepeor 5(CCR5).METHODS:Forty-eight C57BL/6J mice at about 10 days after birth were randomly divided into sham group,HIBD model group and HIBD+GAS group.BV-2 microglia were divided into control(Con)group,oxygen glucose deprivation(OGD)group,oxygen glucose deprivation with gastrodin intervention(OGD+GAS)group,GAS group,Maraviroc(MVC)group,OGD+MVC group,and OGD+MVC+GAS group.The mRNA expression of CCL4 and CCR5 were detected by RT-qPCR.The protein expression of CCR5,p-JAK1,p-STAT1,tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by Western blot.The expression of CCR5,p-JAK1 and p-STAT1 in cells were observed by immunofluorescence staining.RESULTS:(1)Compared with sham group,the expression levels of CCL4 and CCR5 mRNA,and CCR5,p-JAK1 and p-STAT1 proteins were significantly higher in the ischemic side of the corpus callosum in HIBD group(P＜0.05).(2)Compared with Con group,the protein levels of CCR5,p-JAK1 and p-STAT1 significantly increased in BV-2 cells of OGD group(P＜0.05).The protein levels of CCR5,p-JAK1 and p-STAT1 in BV-2 cells of OGD+GAS group were significantly lower than those of OGD group(P＜0.05).(3)Maraviroc did not cause significant BV-2 cell death in the 0～80 μmol/L range.The p-JAK1 and p-STAT1 protein levels in MVC+OGD group were significantly lowered compared with OGD group(P＜0.05),but no significant difference was found between MVC+ OGD and OGD+MVC+GAS groups.CONCLUSION:Gastrodin can exert neuroprotective effects via CCR5/JAK1/STAT1 signaling pathway.

Effects of gastrodin on the expression of BDNF and IL-6 in the striatum of rats with cerebral ischemia / 中国临床药理学与治疗学

AIM: To investigate the effect of gastrodin on the expression of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the striatum of cerebral ischemia rats, and to explore the potential mechanism of gastrodin in treating cerebral ischemia. METHODS: The rats were randomly divided into four groups: normal, sham, model, and gastrodin groups, each consisting of 10 rats. After successful modeling using middle cerebral artery occlusion (MCAO), the gastrodin group received intraperitoneal injection of gastrodin injection at a dose of 10 mg/kg once a day for 14 consecutive days. Pathological changes in striatal neurons were observed using Nissl staining. Immunohistochemistry was utilized to detect positive expression of BDNF and IL-6 proteins in the striatum. Additionally, immunoblot analysis was performed to determine the expression levels of BDNF and IL-6 proteins in the striatum. RESULTS: Nissl staining revealed clear and intact structures of striatal neurons in the normal and sham groups, with tightly arranged cells. In the model group, the number of cells was significantly reduced compared to the sham group (P0.05). Compared to the sham group, the model group showed a decrease in the protein expression level of BDNF in the striatum on the ischemic side (P<0.01) and an increase in the protein expression level of IL-6 (P<0.05, P<0.01). In contrast, the gastrodin group showed an increase in the protein expression level of BDNF in the striatum on the ischemic side (P<0.05, P<0.01) and a decrease in the protein expression level of IL-6 (P< 0.05, P<0.01) compared to the model group. CONCLUSION: Gastrodin has a significant protective effect on striatal injury caused by cerebral ischemia, and its mechanism may be related to the up-regulation of the anti-inflammatory factor BDNF and the down-regulation of the pro-inflammatory factor IL-6.

Protective effect of gastrodin on A β 25-35-induced HT22 cell injury by improving glycolytic function through activating PI3K/Akt/BACH1 signaling axis / 中国药理学与毒理学杂志

OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.

Gastrodin Improves BV-2 Microglia Pyroptosis by Inhibiting AKT/NLRP3 Pathway / 世界科学技术-中医药现代化

Objective To investigate the effects of Gastrodin on AKT/NLRP3 pathway in BV-2 microglial pyroptosis model.Methods BV-2 microglia were divided into normal control group and model group(1 μg·mL-1 LPS+10 μmol·L-1 Nigericin),Gastrodin group(10,100 μg·mL-1 Gastrodin),inhibitor control group(10 μmol·L-1 LY294002),inhibitor group(100 μg·mL-1 Gastrodin+10 μmol·L-1 LY294002),using 1 μg·mL-1 LPS combination 10 μmol·L-1 Nigericin co intervened to induce pyroptosis of BV-2 microglia.CCK-8 observed the effect of Gastrodin on cell activity,and western blot detected p-AKT,NLRP3,ASC,caspase-1,IL-1β expression,immunofluorescence detection of NLRP3,p-AKT protein expression,Real-time PCR observation of IL-1β mRNA content.Molecular docking was used to determine the binding sites of Gastrodin to p-AKT1/2/3 and NLRP3 proteins.Results Compared with the control group(0 μg·mL-1 Gastrodin),0.1-1000 μg·mL-1 Gastrodin had no significant effect on BV-2 cell activity(P>0.05).In the western blot experiment,compared with the normal group,the expression p-AKT,NLRP3,ASC,caspase-1,IL-1β in model group was significantly increased(P<0.01);Compared with the model group,the expression of p-AKT,NLRP3,ASC,caspase-1,IL-1β in Gastrodin group decreased(P<0.05 or P<0.01).In immunofluorescence,the expression of NLRP3 in model group was significantly higher than that in normal group(P<0.01);Compared with the model group,the expression of p-AKT and NLRP3 in Gastrodin group decreased significantly(P<0.01);Compared with Gastrodin group,the expression of p-AKT and NLRP3 in the inhibitor group decreased(P<0.01).In the Real-time PCR experiment,compared with the normal group,IL-1β mRNA content in model group cells increased significantly(P<0.01);Compared with the model group,IL-1β mRNA content in Gastrodin group cells decreased(P<0.01).In the LDH content test,compared with the normal group,the LDH activity in the model group cells increased significantly(P<0.01);Compared with the model group,the intervention of 100 μg·mL-1 Gastrodin can reduce the LDH activity in the pyroptosis cells(P<0.01).In molecular docking,Gastrodin had the binding ability with AKT1/2/3 and NLRP3,with the binding energy range of(-6.6)-(-6.8),and the binding mode included hydrogen bond,van der Waals force,etc.Conclusion Gastrodin can improve the pyroptosis of BV-2 microglia by inhibiting AKT/NLRP3 pathway.

Gastrodin injection alleviates lung injury caused by focal cerebral ischemia in rats through NGF/TrkA pathway-mediated activation of the anti-inflammatory pathway / 南方医科大学学报

OBJECTIVE@#To investigate the therapeutic mechanism of gastrodin injection for alleviating lung injury caused by focal cerebral ischemia in rats and the role of the NGF-TrkA pathway in mediating this effect.@*METHODS@#Forty SD rats were equally randomized into normal group, sham-operated group, model group and gastrodin group, and in the latter two groups, rat models of focal cerebral ischemia were established by embolization of the right middle cerebral artery. After successful modeling, the rats were treated with intraperitoneal injection of gastrodin injection at the daily dose of 10 mg/kg for 14 days. After the treatment, the wet/dry weight ratio of the lung tissue was determined, the pathological changes in the lung tissue were observed using HE staining, and the levels of IL-10 and TNF-α in the arterial blood were detected with ELISA. The expressions of NF-κB p65 and TNF-α in the lung tissue were detected with Western blotting, and the expressions of NGF and TrkA were detected using immunohistochemical staining and Western blotting.@*RESULTS@#Compared with the normal control and sham-operated groups, the rats in the model group showed obvious inflammatory lung injury, significantly increased wet/ dry weight ratio of the lungs (P < 0.01), increased TNF-α level in arterial blood (P < 0.01), and significantly up-regulated protein expressions of NF-κB p65 (P < 0.01), TNF-α (P < 0.01), NGF (P < 0.05) and TrkA(P < 0.05) in the lung tissue. Treatment with gastrodin injection obviously alleviated lung inflammation, decreased the wet/dry weight ratio of the lungs (P < 0.05), and significantly lowered TNF-α level (P < 0.01) and increased IL-10 level in the arterial blood in the rat models (P < 0.01); gastrodin injection also significantly decreased the protein expressions of NF-κB p65 and TNF-α (P < 0.05) and up-regulated the expressions of NGF and TrkA in the lung tissue of the rats (P < 0.05).@*CONCLUSION@#The NGF/TrkA pathway may participate in cerebral ischemia-induced inflammatory lung injury, which can be obviously alleviated by gastrodin through the activation of the anti-inflammatory pathway mediated by the NGF/TrkA pathway.

Cardiovascular protective properties of gastrodin

@# Cardiovascular diseases cause significant morbidity and mortality worldwide, incurring a major public health burden. Gastrodia elata Blume is a traditional Chinese herbal medicine that has been widely used to treat central nervous system and cardiovascular diseases. Gastrodin, as the major active component in Gastrodia elata Blume, can confer protection against cardiovascular diseases. In this review, we summarize the anti-inflammatory actions, anti-cardiac hypertrophy, anti-hypertension, anti-atherosclerosis, and angiogenic effects of gastrodin, as well as its protective effects on vascular cells and against myocardial ischemia-reperfusion injury. The medical potential of gastrodin in diabetes-related cardiovascular diseases is also discussed.

Gastrodin combined with dexamethasone protects H9C2 cell from injury induced by oxygen-glucose deprivation / 中国临床药理学与治疗学

AIM: To investigate the role and possible mechanism of gastrodin combined with dexamethasone in myocardial cell injury induced by oxygen-glucose deprivation. METHODS: Oxygen-glucose deprivation (OGD) model was established. The cells were divided into 5 groups: normal control group, OGD group, DEX group, GAS group and DEX+GAS group. The activity of myocardial cells was detected by CCK-8 test in each group. The activity of LDH was detected by colorimetry in each group. The apoptosis of myocardial cells was detected by TUNEL method in each group. The ELISA assay was used to detect the inflammatory factors in culture medium of myocardial cells in each group. Western blot was used to detect the expression of Notch1, Bax, Bcl-2 and Beclin1 in myocardial cells in each group.RESULTS: The results showed that GAS combined with DEX could significantly increase the activity of myocardial cells and decrease the apoptosis, reduce production of TNF-α, IL-6, IL-1β and promote production of IL-10, decrease the release of LDH significantly of myocardial cells induced by OGD. The results of Western blot showed that GAS combined with DEX increased the expression of Notch1, Bcl-2 and autophagy-related gene Beclin1, but decreased the expression of Bax of myocardial cells induced by OGD. CONCLUSION: The combination of GAS and DEX may promote autophagy and increase cell activity, inhibit apoptosis and inflammatory reaction by activating Notch signaling pathway, thereby reducing OGD-induced myocardial cells damage.

Gastrodin inhibits H / 中国临床药理学与治疗学

AIM: To investigate the protective mechanism of gastrodin against hydrogen peroxide (H

Systematic review and Meta-analysis of efficacy and safety of gastrodin in treatment of tension-type headache / 中国中药杂志

The efficacy of gastrodin as a Chinese herbal medicine extract in the treatment of tension-type headache has been confirmed. This paper systematically reviewed the efficacy and safety of gastrodin in the treatment of tension-type headache, aiming to provide a new choice for the treatment of this disease. In this study, four Chinese databases, four English databases and two trial registries were searched from the date of establishment to September 2020. The related randomized controlled trials(RCTs) were screened out according to the predetermined criteria. The bias risk assessment tool developed by Cochrane collaboration was used to evaluate the quality of the reports. RevMan 5.4.1 was used for Meta-analysis, and GRADE system for the evidence-based evaluation on the quality of outcome indicators. A total of 177 articles were retrieved and 8 articles were finally included for analysis, with a total sample size of 1 091 cases, which included 565 cases in the treatment group and 526 cases in the control group. The overall quality of included stu-dies was not high. The results of Meta-analysis are as follows:(1)In terms of headache frequency, gastrodin group was better than wes-tern medicine group(MD=-2.90, 95%CI[-3.76,-2.03], P<0.000 01).(2)In terms of number of abnormal blood vessels in TCD, gastrodin group was better than western medicine group(MD=-88.96, 95%CI[-102.36,-75.55], P<0.000 01).(3)In terms of effective rate, gastrodin group was better than western medicine group(RR=1.47, 95%CI[1.29, 1.68], P<0.000 01). The results of subgroup analysis are as follows:(1)Effective rate based on age, for the patients upper age limit 40-46 years old, gastro-din group was better than western medicine group(RR=1.69, 95%CI[1.50, 1.90], P<0.000 01); for the patients upper age limit 55-60 years old, gastrodin group was better than western medicine group(RR=1.27, 95%CI[1.16, 1.38], P<0.000 01).(2)Effective rate based on dosage form, both the gastrodin capsules and injection groups were better than western medicine group(RR_(capsules)=1.42, 95%CI[1.08, 1.88], P=0.01; RR_(injection)=1.50, 95%CI[1.26, 1.77], P<0.000 01). GRADE evaluation showed that the above outcomes had low quality of evidence. Only one article detailed the occurrence of adverse reactions and thus the present study cannot make a positive conclusion on the safety of gastrodin in the treatment of tension-type headache. The small number and low quality of the included reports affected the reliability of the results. In the future, more high-quality randomized controlled trails are needed to improve the evaluation on the efficacy and safety of gastrodin in the treatment of tension-type headache.

Antioxidant mechanism of gastrodin combined with isorhynchophylline in inhibiting MPP~+-induced apoptosis of PC12 cells / 中国中药杂志

Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis is the most frequently used herbal pair in the treatment of Parkinson's disease(PD). Gastrodin and isorhynchophylline are important components of Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis herb pair with anti-Parkinson mechanism. This study aimed to investigate the effect of gastrodin combined with isorhynchophylline on 1-methyl-4-phenylpyridinium(MPP~+)-induced apoptosis of PC12 cells and their antioxidant mechanism. The leakage of lactate dehydrogenase(LDH) from cells to media was analyzed by spectrophotometry. Apoptotic cells were labeled with Annexin V-fluorescein isothiocyanate(FITC) and propidium iodide(PI) and analyzed by flow cytometry. The cell cycle was analyzed using propidium iodide(PI) staining. Lipid peroxidation(LPO) level was analyzed by spectrophotometry. The mRNA expression of caspase-3 was examined by Real-time RT-PCR. The protein expressions of heme oxygenase 1(HO-1) and NADPH: quinoneoxidore-ductase 1(NQO-1) were determined by Western blot. Gastrodin combined with isorhynchophylline reduced the percentage of Annexin V-positive cells and cell cycle arrest in MPP~+-induced PC12 cells. Gastrodin combined with isorhynchophylline down-regulated the mRNA expression of caspase-3, up-regulated the protein expressions of HO-1 and NQO-1, and reduced LPO content in MPP~+-induced PC12 cells. PD98059, LY294002 or LiCl could partially reverse these changes pretreated with gastrodin combined with isorhynchophylline, suggesting that gastrodin combined with isorhynchophylline inhibited MPP~+-induced apoptosis of PC12 cells and oxidative stress through ERK1/2 and PI3 K/GSK-3β signal pathways. Our experiments showed that gastrodin combined with isorhynchophylline could down-re-gulate the mRNA expression of caspase-3 and up-regulate the protein expressions of HO-1 and NQO-1, so as to reduce oxidative stress and inhibit apoptosis.

Study on Absorption Characteristics of Gastrodia elata Powder with Different Particle Sizes Based on Rat Everted Intestinal Sac Model in vitro / 中国药房

OBJECTIVE：To compar e the absorpt ion characteristics of gastrodin ，parishin A ，parishin B and parishin C of Gastrodia elata powder，and to explore the effect of particle size on intestinal absorption of above components. METHODS ：Based on everted intestinal sac model ，using accumulative absorption amount （Q）and absorption rate constant （Ka）as indexes ，UPLC-MS/MS method was used to determine the absorption of gastrodin ，parishin A ，parishin B and parishin C from different doses （2.5，5，10 g/L） of G. elata powder with different particle sizes （fine powder 146 μm，superfine powder 52 μm，ultrafine powder 37 μm）in different segments（duodenum，jejunum，ileum and colon ）. RESULTS ：Q and Ka of gastrodin and parishin B （intestinal segment ），Q（colon） and Ka（ileum and colon ）of parishin C in 2.5 g/L G. elata superfine powder ；Q and Ka of gastrodin （intestinal segment ），Q and Ka of parishin B （duodenum，jejunum，ileum）and Ka of parishin C （colon）in 2.5 g/L G. elata ultrafine powder ；Q of gastrodin （duodenum），Q of parishin A and parishin B （intestinal segment ）and Q of parishin C （duodenum，jejunum）in 5 g/L G. elata superfine powder ；Q（duodenum jejunum ，colon）and Ka（intestinal segment ）of gastrodin ，Q of parishin B （duodenum，ileum and colon）and Q of parishin C （duodenum，ileum）in 5 g/L G. elata ultrafine powder ；Q and Ka of parishin B （jejunum，ileum），Q of parishin C （jejunum，ileum）in 10 g/L G. elata superfine powder as well as Q（colon）and Ka（duodenum）of gastrodin ，Q （duodenum，ileum，colon）and Ka（duodenum，colon）of parishin B ，Q（duodenum，ileum）and Ka（duodenum）of parishin C in 10 g/L G. elata ultrafine powder were all increased significantly ，compared with the same dose of G. elata fine powder （P＜0.05 or P＜0.01）. Ka of parishin A （jejunum）and Q of parishin C （duodenum）in 2.5 g/L G. elata superfine powder ；Ka of parishin A （jejunum，ileum）， Q and Ka of parishin C （duodenum，jejunum）in 2.5 g/L G. elata ultrafine powder ；Ka of gastrodin （jejunum，ileum and colon ），Ka of parishin A （colon），Ka of parishin B （ileum）and Ka of parishin C （jejunum，ileum）in 5 g/L G. elata superfine powder ；Ka of gastrodin and parishin C （jejunum，ileum and colon ），Q（jejunum，colon）and Ka（colon）of parishin A ，Ka of parishin B （jejunum，ileum）in 5 g/L G. elata ultrafine powder ；Q and Ka of parishin A （ileum）in 10 g/L G. elata superfine powder ；Q（duodenum）and Ka（jejunum） of parishin A ，Ka of parishin C （jejunum）in 10 g/L G. elata ultrafine powder were decreased significantly ，compared with the same dose of G. elata fine powder （P＜0.05 or P＜0.01）. Q of gastrodin （colon），Q（colon）and Ka（ileum，colon）of parishin A ，Q and Ka of parishin B （jejunum，colon），Q and Ka of parishin C （ileum，colon）in 2.5 g/L G. elata fine powder ；Q and Ka of gastrodin （colon），Q（ileum，colon）and Ka（jejunum，ileum，colon）of parishin A ，Ka of parishin C （colon）in 2.5 g/L G. elata superfine powder；Q（colon）and Ka（jejunum，ileum，colon）of parishin A and C ，Q and Ka（ileum，colon）of parishin B in 2.5 g/L G. elata ultrafine powder ；Q and Ka of gastrodin ，parishin A and C （colon），Ka of parishin B （colon）in 5 g/L G. elata fine powder ；Q and Ka of gastrodin and parishin A （colon），Q and Ka of parishin C （jejunum，ileum，colon）in 5 g/L G. elata superfine powder ；Q and Ka of gastrodin（ileum，colon），Q of parishin A （jejunum，ileum，colon），Q and Ka of parishin B （jejunum，colon），Q（jejunum，colon） and Ka（jejunum，ileum，colon）of parishin C in 5 g/L G. elata ultrafine powder ；Q of gastrodin （colon），Q and Ka of parishin A ，B and C （jejunum，ileum，colon）in 10 g/L G. el ata fine powder ；Q of gastrodin （colon），Q and Ka of parishin A and C （jejunum， ileum，colon），Q and Ka of parishin B （colon）in 10 g/L G. elata superfine powder ；Q（colon）and Ka（jejunum，ileum，colon）of gastrodin，Q and Ka of parishin A and C （jejunum，ileum，colon），Q（jejunum，ileum，colon）and Ka（ileum，colon）of parishin B in 10 g/L G. elata ultrafine powder were decreased significantly ，compared with duodeum of the same group （P＜0.05）. Q and Ka of gastrodin（jejunum）in 2.5 g/L G. elata superfine pow

Research progress on biosynthesis of gastrodin / 中草药

Gastrodin is a major active ingredient in Gastrodia elata, which is one of the traditional rare medicinal herbs in China. It has lots of pharmacological activities, such as reducing blood pressure, anti-epileptic, anti-tumor, and protecting nerve, etc. With the increasing demand for gastrodin in the market and the inherent problems of traditional methods on obtaining gastrodin, new methods are urgently needed to solve various difficulties in the actual production of gastrodin. Biosynthesis is a new method instead of the traditional acquisition method, and has made great progress and achievements in gastrodin acquisition. Therefore, it is necessary to systematically review the biosynthesis of gastrodin from three aspects of biosynthetic pathway, plant transformation and microbial transformation in this paper, hoping to provide valuable reference for further improvement and perfection of gastrodin production method in the future to meet public increasing demand for gastrodin.

Research progress on antidepressant substances and their mechanisms in Gastrodia elata / 中草药

Gastrodia elata is a valuable traditional Chinese medicine with many pharmacological activities such as calming, anti-depression, anti-anxiety, anti-oxidation, anti-virus, and anti-tumor. In this paper, the research progress of the pharmacodynamic basis and antidepressant mechanism of anti-depression effect of G. elata is summarized. And combined with the current clinical application of G. elata anti-depression, a reference is provided for the further research and development of G. elata.

Fresh Gastrodia elata ameliorates learning and memory impairments in sleep interruption induced mice / 中草药

Objective: To study the learning and memory enhancement effect of fresh Gastrodia elata (FG) on deficits induced by sleep interruption (SI) in mice. Methods: The contents of gastrodin and p-hydroxybenzyl alcohol in FG were determined by HPLC, and the content of polysaccharide were determined by phenol-sulfuric acid method. Then the learning and memory enhancement effects of FG on sleep deficits induced mice were studied. A total of 60 ICR male mice were randomly divided into the control group, the SI model group, the modafinil group, and the FG groups (3 and 9 g/kg). The mice were sleep interrupted continuously for 14 d, behavioral tests were performed by using open field test, novel object recognition (NOR) experiment, Morris water maze (MWM) task, and passive avoidance method. The levels of SOD and MDA in the serum and the hippocampus, Ach, Glu and NE in the hippocampus were measured. Results: There were no significant changes in locomotor activities among all groups. Compared with the control group, the discrimination index (DI) of SI model group in NOR was decreased significantly, the longer escape latency in MWM was observed in SI mice group, in passive avoidance test the errors times increased and the latent period decreased. In addition, the levels of MDA in the serum and the hippocampus were increased, while the contents of SOD, Ach, Glu and NE in the serum and the hippocampus were decreased significantly. In comparison with the SI group, FG (3 and 9 g/kg) treatment markedly enhanced the discriminative ability by elevating DI in NOR, improved the acquisition and retention of spatial memory by decreasing escape latency, decreased the errors times, and prolonged the latency time in passive avoidance test. Administration of FG significantly reduced the elevated MDA level in the serum and the hippocampus and raised the reduced SOD, Ach, Glu and NE levels in the hippocampus. Conclusion: The results reveal that FG treatment can improve SI-induced learning and memory impairments, and ameliorate oxidative stress damage and raise neurotransmitter content. FG is a potential traditional Chinese medicine for improving learning and memory impairments.

The protective effects of gastrodin on methamphetamine-induced neurotoxicity / 中国药理学通报

Aim To compare the protective effects of gastrodin and melatonin on methamphetamine ( MA )-induced neurotoxicity of cortical neurons. Methods Cortical neuron cells were treated with different concentrations of methamphetamine for 24 h, then the cell viability was detected by CCK-8 kit to choose the optimal concentration of MA. The cells were treated with different concentrations of gastrodin or melatonin 2 h before the treatment of cells with optimal concentration of MA for 24 h. The optimal concentrations of gastrodin and melatonin were determined by CCK-8 kit as well. Cortical neuron cells were randomly divided into con trol group, MA group, gastrodin plus MA group, and melatonin plus MA group. Then the apoptotic rate of cells was detected by TUNEL method . The expression of Caspase-3 in cells was assessed by immunofluorescence. Results The optimal concentration of MA was 0. 5 mmol • L"1. After treating with MA, the numbers of cortical neurons decreased, the length of synapses became shorter, and the cell vacuolation, the number of dead cells increased. The optimal concentration of gastrodin was 25 mg • L'1, and the optimal concentration of melatonin was 10 jimol • L"1. Gastrodin treatment could reduce the apoptosis of cortical neurons induced by MA, and the expression of Caspase-3 decreased as well, and there was no significant difference compared with the intervention effect of gastrodin with melatonin. Conclusions MA has neurotoxic damage to cortical neurons. Gastrodin could attenuate MA-in-duced neurotoxicity via alleviating the apoptosis induced by MA.

Study on the Mechanism of Improvement Effects of Gastrodin Injection on Methamphetamine Induced Neurotoxic Damage in Rats via nNOS Pathway / 中国药房

OBJECTIVE：To stu dy the mechanism of improvement effects of Gastrodin injection on methamphetamine induced neurotoxic damage in rats via nNOS pathway. METHODS ：SD rats were randomly divided into control group ，methamphetamine group，regular-dose of gastrodin group ，double-dose of gastrodin group ，negative control （NC）adenovirus group ，NC adenovirus+ methamphetamine group ，NC adenovirus+gastrodin group and nNOS adenovirus+gastrodin group ，with 10 rats in each group. Control group was given normal saline intraperitoneally ，twice a day. Methamphetamine group was given methamphetamine intraperitoneally（7.5 mg/kg），twice a day. Regular-dose and double-dose of gastrodin groups were respectively given different doses of Gastrodin injection （10，20 mg/kg）intraperitoneally 30 min earlier ，once a day ，and then given methamphetamine intraperitoneally by the same way as methamphetamine group. NC adenovirus group was given NC adenovirus （4.8×107 PFU）3 μL once in the striatum and normal saline intraperitoneally ，twice a day. NC adenovirus+methamphetamine group was given NC adenovirus by the same way and methamphetamine （7.5 mg/kg）intraperitoneally，twice a day. NC adenovirus+gastrodin group was given NC adenovirus+methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. nNOS adenovirus+gastrodin group was given nNOS adenovirus and methamphetamine by the same way ，meanwhile given Gastrodin injection intraperitoneally （20 mg/kg）30 min before methamphetamine ，once a day. Each group was given relevant medicine intraperitoneally 1 mL/100 g，for consecutive 3 days. The stereotyped behavior of rats were observed and scored ；the apoptotic rate ，the protein expression of apoptotic factors （Bcl-2，Bax，Cleaved caspase- 3），the levels of oxidative stress factors （MDA，SOD，GPx） and NO ，the protein expression of nNOS were detected. RESULTS ： Compared with control group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase-3 and nNOS ，the levels of MDA and NO were increased significantly in methamphetamine group ；while the protein expression of Bcl- 2 and the levels of SOD and GPx were decreased significantly （P＜0.05 or P＜0.01）. Compared with methamphetamine group ，stereotyped behavior score ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in regular-dose and double-dose of gastrodin groups ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly ，and most above indexes in double-dose of gastradin group were better than regular-dose of gastrodin group （P＜0.05 or P＜0.01）. Compared with NC adenovirus group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were increased significantly in NC adenovirus+methamphetamine group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. Compared with NC adenovirus+methamphetamine group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS ，the levels of MDA and NO were decreased significantly in NC adenovirus+ gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were increased significantly （P＜0.01）. Compared with NC adenovirus+gastrodin group ，cell apoptosis rate of striatum ，protein expression of Bax ，Cleaved caspase- 3 and nNOS，the levels of MDA and NO were increased significantly in nNOS adenovirus+gastrodin group ；while the protein expression of Bcl- 2，the levels of SOD and GPx were decreased significantly （P＜0.01）. CONCLUSIONS ：Gastrodin injection can protect rats against neurotoxic damage induced by methamphetamine ，and the effect is related to the inhibition of nNOS-mediated apoptosis and oxidative stress.

Research progress on mechanism of gastrodin and p-hydroxybenzyl alcohol on central nervous system / 中国中药杂志

Gastrodin(GAS) and p-hydroxybenzyl alcohol(HBA) are extracts of dried tubers of Gastrodia elata, which is the material basis for its efficacy and belongs to phenolic compounds. Modern pharmacology studies have shown that they have significant effects on central nervous system diseases, such as insomnia, convulsions, depression, ischemic stroke, anxiety, and cognitive impairment, and these diseases are closely related to neurotransmitters and cytokines. This paper described various mechanisms of GAS and HBA monomer components on the central nervous system. They alleviate hippocampal neuronal toxicity mainly by regulating a variety of neurotransmitters, such as acetylcholine, glutamic acid(GLU), γ-aminobutyric acid(GABA), serotonin(5-HT), dopamine(DA), norepinephrine(NE), 5-indoleacetic acid(5-HIAA), high vanillic acid(HVA) and dihydroxyphenylacetic acid(DOPAC), pro-inflammatory cell growth factors, such as IL-1β, IL-6 and TNF-α and relevant receptor functions, and exert neuropharmacological effects by effectively increasing mRNA expressions of brain neurotrophic factors, such as BDNF and GDNF, and further inhibiting the apoptosis of damaged neurons. This paper summarized various mechanisms on the central nervous system, which provides a scientific basis for the further research of the neuropharmacological mechanism of GAS and HBA and the development of new drugs and functional food.