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.
Benzyl Alcohols/pharmacology* ; Central Nervous System/drug effects* ; Gastrodia/chemistry* ; Glucosides/pharmacology* ; Humans ; Plant Extracts/pharmacology*

The conversion of exogenous p-hydroxybenzaldehyde to p-hydroxy-methyl-phenol-beta-D-glucoside (gastrodin) was studied by using cell suspension culture of Datura tatula L. The chemical structure of this synthesized gastrodin was identified based on the spectral analysis and chemical evidence. The conversion procedure of p-hydroxybenzaldehyde into gastrodin by D. tatula L. cell suspension cultures was established. The synthesized gastrodin (II) was isolated from the ferment liquor and identified by spectral analysis. At the same time, the p-hydroxybenzyl alcohol (I) converted through biotransformation of p-hydroxybenzaldehyde by cell suspension cultures of D. tatula L. was also isolated and identified. The efficiency of glucosylation of p-hydroxybenzaldehyde was remarkably enhanced by adding salicylic acid (0.1 mg/L) and keeping the lower pressure (0.001MPa) in 25L airlift loop bioreactor. The biotransformation of exogenous p-hydroxybenzaldehyde to gastrodin by cell suspension culture of D. tatula L. is a promising approach.
Benzaldehydes ; metabolism ; Benzyl Alcohols ; chemistry ; Bioreactors ; Biotransformation ; Datura ; metabolism ; Glucosides ; biosynthesis ; chemistry ; Salicylic Acid ; pharmacology ; Suspensions

Basidiomycete PM2, a lignin-degrading white rot fungus, produces lgnin peroxidase (Lip) and manganese peroxidase (Mnp) in nutrient nitrogen limited liquid cultures. This fungus was selected for its ability to decolorize azo group of dyes. In order to improve production of the peroxidases and rapid dye decolorizing activity by basidiomycete PM2, the addition of veratryl alcohol or Tween 80 to nutrient nitrogen limited liquid cultures were tested. It was found to have a large stimulatory effect on Mnp activities and decolorization rate of azo dyes. A maximum Mnp activities of 254.2 u/L with veratryl alcohol and 192.2 u/L with Tween 80 were achieved respectively. These values were about 3.4-fold and 2.5-fold higher than that obtained in the control cultures (without alcohol or Tween 80), whereas the levels of Lip activity detected were very low (about 12 u/L)in all the cultures. In further experiments using three kinds of azo dyes of congo red, orange G and orange IV, enzyme activities and dye decolorization were investigated in the above-mentioned cultures. The results showed that Mnp activities and decolorization were notably higher than those obtained in the control cultures in the presence of azo dyes. Cultures supplemented with Tween 80 were more adequate for dye decolorization. The rates of the decolorization with Tween 80 of congo red (95.4%), orange G (98.5%) and orange IV (54.4%) after 24 hours of dye incubation were higher than that supplemented with veratryl alcohol. According to the results, Mnp activities secreted by basidiomycete PM2 play an essential role in the process of dye decolorization. Tween 80 was the main factor affecting the decolorization. The analysis of structure of the three kinds of azo dyes indicats that the extent of decolorization is affected by the dye molecular structure. The types and quantity of the substituted groups on the aromatic ring of azo dyes have effect on the percentage of biological decolorization.
Azo Compounds ; metabolism ; Basidiomycota ; enzymology ; metabolism ; Benzyl Alcohols ; pharmacology ; Coloring Agents ; metabolism ; Oxygenases ; biosynthesis ; Peroxidases ; biosynthesis ; Polysorbates ; pharmacology

OBJECTIVETo study the effect of gastrodin on isolated thoracic aorta rings of rats and to investigate the potential mechanism.

METHODSA perfusion model of isolated thoracic aorta rings of rats was applied. The effect of cumulative gastrodin (5, 50, 100,150, 200, and 250 μmol/L) on endothelium-intact aorta rings was investigated. The same procedure was applied to observe the effect of gastrodin on endothelium-intact/denuded aorta rings pre-contracted with 10(-6) mol/L phenylephrine hydrochloride (PE). The aorta rings incubated by 200 mmol/L gastrodin in the Ca(2+)-free (K-H) solution was contracted by using PE. The effect of 200 mmol/L gastrodin on endothelium-denuded aorta rings pre-contracted with 60 mmol/L KCl was also observed.

RESULTSCompared with the denuded gastrodin group, the intact gastrodin group could significantly relax the PE-contracted aorta rings (P<0.01). In Ca(2+)-free (K-H) solution KHS, the PE-induced contraction rate of aorta rings pre-incubated by gastrodin was 6.5%±0.7%, which was significantly less than the control group (11.8%±0.9%,P<0.01). However, after 3 mmol/L CaCl2 was added, the Ca(2+)-induced contraction in the gastrodin group (51.7%±2.4%) was similar to that in the control group (49.8%±2.8%). The contractile rate of rings in the KCl-contracted gastrodin group (96.3%±0.6%) was not significantly different from that in the control group (96.8%±1.2%).

CONCLUSIONSGastrodin has the effect of vasorelaxation on isolated thoracic aorta rings of rats. The mechanism of the vasorelaxation of gastrodin may mainly work through the inhibition of inositol 1, 4, 5-trisphosphosphate receptor on the sarcoplasmic reticulum of the arterial smooth muscle, which leads to the reduction of the Ca(2+) released from the sarcoplasmic reticulum.

Animals ; Aorta, Thoracic ; drug effects ; physiology ; Benzyl Alcohols ; pharmacology ; Calcium ; metabolism ; Endothelium, Vascular ; physiology ; Female ; Glucosides ; pharmacology ; In Vitro Techniques ; Male ; Phenylephrine ; pharmacology ; Rats ; Rats, Wistar ; Vasodilation ; drug effects

OBJECTIVETo investigate the effect of gastrodin in relaxing isolated thoracic aorta rings in rats and discuss its possible mechanism.

METHODIsotonic tension of isolated thoracic aortic rings in rats with norepineprine (NE) and KCl was recorded to observe the vasodilatory effect of gastrodin and the influence of various drugs on it.

RESULTGastrodin had the effect in relaxing thoracic aortas with or without endothelium, and there was no significant difference. NG-nitro-L-argininemethylester (L-NAME, 1 x 10(-4) mol x L(-1)), methylene blue (MB, 1 x 10(-5) mol x L(-1)), indomethacin (INDO, 1 x 10(-5) mol x L(-1)) had no effect on the vasodilation action of gastrodin on thoracic aortas precontracted by NE. 4-aminopyrimide (4-AP, 1 x 10(-4) mol x L(-1)), tetrathylamonium (TEA, 1 x 10(-3) mol x L(-1)), BaCl2 (1 x 10(-4) mol x L(-1)) and glibenclamide (Gli, 1 x 10(-5) mol x L(-1)) could inhibit gastrodin's effect in relaxing thoracic aorta rings. In the absence of Ca2+, pre-incubated gastrodin showed a notable inhibitory effect in relaxing NE contraction.

CONCLUSIONGastrodin shows a dose-dependent and endothelium-independent effect in relaxing rat isolated thoracic aorta rings. The mechanism is related to K+ channel, inhibition of release of Ca+ stored in endoplasmic reticulum of vascular smooth muscle cells and inflow of external calcium Ca2+.

Animals ; Aorta, Thoracic ; drug effects ; physiology ; Benzyl Alcohols ; pharmacology ; Calcium ; metabolism ; Endothelium, Vascular ; physiology ; Glucosides ; pharmacology ; In Vitro Techniques ; Male ; Norepinephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects

BACKGROUNDGastrodin, as one of the major components extracted from the Chinese herb Gastrodia elata Bl., has many biologic effects, one of which is anti-apoptosis. Apoptosis is considered to be one of the pathogenetic mechanisms in steroid-induced osteonecrosis of the femoral head (ONFH). Therefore, we performed this study to investigate whether gastrodin has the potential to prevent steroid-induced ONFH.

METHODSAll 18 male adult Wistar rats were divided equally into three groups: the steroid group, the gastrodin+steroid group, and the control group. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone. Histomorphometric method was used to determine the incidence of osteonecrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to detect apoptotic index of osteocytes and osteoblasts. Real-time PCR and Western blotting were performed to detect mRNA and protein expression of Bax, Bcl-2, and Caspase-3. Fisher's exact probability test and one-way analysis of variance (ANOVA) with Turkey's post hoc test were used to examine significant differences between groups.

RESULTSThe incidence of osteonecrosis in the gastrodin+steroid group (16.7%) was significantly lower than that in the steroid group (83.3%). According to TUNEL assay, the apoptotic indices in the steroid group, the gastrodin+steroid group, and the control group were 91.1%, 27.1%, and 5.4%, respectively, and the differences were significant between groups. Compared with the control group and the gastrodin+steroid group, the mRNA and protein expression levels of Bax and Caspase-3 were significantly higher in the steroid group, but the Bcl-2 mRNA and protein expression levels were significantly lower.

CONCLUSIONGastrodin could prevent steroid-induced ONFH by anti-apoptosis.

Animals ; Apoptosis ; drug effects ; Benzyl Alcohols ; therapeutic use ; Femur Head Necrosis ; drug therapy ; prevention & control ; Glucosides ; therapeutic use ; Lipopolysaccharides ; pharmacology ; Male ; Rats ; Rats, Wistar ; Steroids ; pharmacology

This study is to screen the Chinese herbal compounds which could inhibit the production of Abeta and investigate the underlying mechanism. Ten types of compounds which have potential value in the treatment of AD were selected as initial screening trial. The cell models which used could overexpress Abeta and beta-secretases or Abeta and gamma-secretases. Extracellular Abeta was determined by ELISA after the cell models treated with different concentrations of compounds (0.5-100 micromol x L(-1)), separately. Then the compounds were selected which could inhibit extracellular Abeta and their best concentration ranges were decided, too. Furthermore, the cell viability and apoptosis rate, the level of intracellular Abeta, beta and gamma-secretases were determined after the cell models treated with different concentrations of selected compounds. The results showed that 4 of the 10 compounds could reduce the level of extracellular Abeta; they were cryptotanshinone, astragalosides, gastrodin and paeoniflorin, and their best concentration ranges were 0.5-5.0, 0.5-5.0, 5.0-50, 1.0-25 micromol x L(-1), respectively. Further study indicated that the 4 selected compounds were nontoxic to the cellular models and lowering intracellular Abeta were more effective compared with extracellular; of which astragalosides and gastrodin showed dose-dependent inhibition to the activities of beta and gamma-secretases, with the maximum inhibiting rates of 78.2% and 80.3%, respectively. In conclusion, cryptotanshinone, astragalosides, gastrodin and paeoniflorin could inhibit the expression and secretion of Abeta, and the underlying inhibiting mechanism of astragalosides and gastrodin were related with the reduction of the beta and gamma-secretase activities, respectively.
Amyloid Precursor Protein Secretases ; metabolism ; Amyloid beta-Peptides ; antagonists & inhibitors ; Apoptosis ; Benzyl Alcohols ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Glucosides ; pharmacology ; Humans ; Monoterpenes ; pharmacology ; Phenanthrenes ; pharmacology ; Saponins ; pharmacology

The paper aims to study the pharmacokinetic parameters of gastrodin in rats effected by compound compatibilitiy and different doses of Tiangou Jiangya capsule. The extracts from Gastrodiae Rhizoma( equivalent to gastrodin 16.82 mg x kg(-1) and Tiangou jiangya capsule (equivalent to gastrodin 8.410, 16.82, 33.64 mg x kg(-1)) were oral administrated to rats respectively. The plasma were taken at various time points and treated with acetonitrile to measure the contents of gastrodin by HPLC method. The mean plasma concentration-time data were analyzed by 3P97 pharmacokinetic software and the pharmacokinetic parameters between groups were treated by SPSS 16.0. The results showed that gastrodin in rat was fitted to one-compartment model, Cmax and AUC of Tiangou Jiangya capsule were in direct proportion to oral administration, and t1/2Ka had nothing to do with doses, which indicated that gastrodin was fitted first-order rate transfter process in vivo. Morever, comparison with the Gastrodiae Rhizoma extract, isodose gastrodin in Tiangou Jiangya capsule showed a significant decrease for Cmax, Ke and increase for t1/2Ke, V/Fc, this indicated that compound compatibility can delay the absorbtion of gastrodin, prolong the resident time and promote the distribution in vivo, but its bioavailability is not significantly effected.
Administration, Oral ; Animals ; Benzyl Alcohols ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Blood Pressure ; drug effects ; Female ; Flavonoids ; chemistry ; pharmacology ; Furans ; chemistry ; pharmacology ; Gastrodia ; chemistry ; Glucosides ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Lignans ; chemistry ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Software

OBJECTIVETo investigate the effect of gastrodine on the expression of NR1 mRNA of NMDA receptor in cultured rat cerebral cortical neurons injury induced by hypoxia.

METHODThe injury models of cultured rat cerebral cortical neurons was made by hypoxia and hypoglucose. The concentration of 13, 26, 52 mg x L(-1) of gastrodine was respectively added to the injured cells. The R-PCR technique was used to study the expression of NR1 mRNA of NMDA receptor.

RESULTThe expression of NR1 mRNA increased markedly in hypoxia and hypoglucose injured cells, the increased expression can be weakened by gastrodine, more significant effect was found in the concentration of 26 mg x L(-1) 52 mg x L(-1).

CONCLUSIONGastrodine may act as a neuro - protector by weakening the expression of NR1 mRNA in cultured rat cerebral cortical neurons injury induced by hypoxia and hypoglucose.

Animals ; Benzyl Alcohols ; pharmacology ; Cells, Cultured ; Cerebral Cortex ; cytology ; Female ; Gene Expression Regulation ; drug effects ; Glucosides ; pharmacology ; Hypoxia ; genetics ; Neurons ; cytology ; metabolism ; Pregnancy ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVEInflammatory factors have been known to induce nerve cells apoptosis and decrease learning capacity of diabetics. The aim of this study is to evaluate the inhibitory effect of Gastrodine on the expression of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) in culturing for gitter cells (BV-2 cells) induced by high concentration of glucose.

METHODThe BV-2 cells incubated in vitro with different concentrations of glucose and gastrodine were divided into five groups: control group (glucose: 25 mmol x L(-1)), high concetration of glucose (glucose: 45 mmol x L(-1) HCG) group and Gastrodine groups (glucose 45 mmol x L(-1) with gastrodine 25 mg x L(-1) (LG), 50 mg x L(-1) (MG), 100 mg x L(-1) (HG). After culturing for 24 h, morphological changes of cells were observed by inverted phase contrast microscope. The supernatant protein of IL-1 beta and IL-6 was detected by ELISA. The mRNA expression of IL-1 beta and IL-6 was assessed by Reverse transcription polymerase chain reaction (RT-PCR).

RESULTThe cells were proned to aggregate, some of them with hypertrophy, distinct nucleoli and branch-shaped hyperplasy in HCG group, while less change in Gastrodine groups. The supernatant protein of IL-1 beta is higher in HCG group than control group (119.53 +/- 15.91) ng x L(-1) vs (25.74 +/- 15.72) ng x L(-1) (P < 0.01), but lower in the gastrodine groups than HCG LG (99.32 +/- 19.66) ng x L(-1), MG (76.94 +/- 17.16) ng x L(-1), HG (88.35 +/- 18.72) ng x L(-1) vs (119.53 +/-15.91) ng x L(-1) (P < 0.05). The supernatant protein of IL-6 protein also higher in HCG than control group (393.7 +/- 17.51) ng x L(-1) vs (125.85 +/- 36.62) ng x L(-1) (P < 0.01), and lower in the gastrodine groups than HCG (LG 327.06 +/- 23.53) ng x L(-1), MG (217.36 +/- 28.81) ng x L(-1), HG (263.17 +/- 22.32) ng x L(-1) vs (393.7 +/- 17.51) ng x L(-1), P < 0.05). The mRNA expression of IL-1 beta was increased significantly higher in HCG than control group (2.77 +/- 0.29) vs (1.13 +/- 0.27) (P < 0.05), but decreased significantly in gastrodine groups than HCG LGA (2.66 +/- 0.31), MGA (2.1 +/- 0.41), HGA (2.4 +/- 0.28) vs (2.77 +/- 0.29) (P < 0.05). The mRNA Expression of IL-6 was higher in HCG than control group (3.97 +/- 0.33) vs (1.05 +/- 0.13) (P < 0.05, but lower in gastrodine groups than HCG LG (3.28 +/- 0.3), MG (2.65 +/- 0.33), HG (3.04 +/- 0.26), vs (3.97 +/- 0.33) (P < 0.05).

CONCLUSIONGastrodine can inhibit the expression of IL-1 beta, IL-6 in cultured BV-2 cells induced by high concentration of glucose.

Animals ; Benzyl Alcohols ; pharmacology ; Cells, Cultured ; Down-Regulation ; Gene Expression ; drug effects ; Glucose ; metabolism ; Glucosides ; pharmacology ; Interleukin-1beta ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Mice ; Microglia ; drug effects ; metabolism