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The effects of different initial processing methods on the amount of gastrodin and gastrodigenin isolated from Gastrodia elata Blume were investigated and the best initial processing technology was optimized. The contents of gastrodin and gastrodigenin were analyzed by high performance liquid chromatography (HPLC). It is established that G. elata boiling in water followed by ethanol extraction is the best initial processing technology, which can provide the basis and reference for the standardized processing of G. elata herbs.

According to the basic theories of traditional Chinese medicine, Gastrodia elata (GE) is clinically utilized for the treatment of cephalalgia and migraine. The gastrodigenin (p–hydroxybenzyl alcohol, HBA), one of the effective components of GE, may pass through the blood–brain barrier (BBB) to exert its pharmacological effects. This study aimed to investigate BBB permeability of HBA via in vitro hCMEC/D3 BBB model and in vivo microdialysis in rats. For the establishment of in vitro BBB model, hCMEC/D3 cells were used to construct the monolayer. The integrity of the monolayer was evaluated by TEER measurements, expression analysis of tight junction proteins (claudin-5, zo-1 and occludin) and apparent permeability coefficients (Papp) of fluorescein disodium. During the 6-day incubation of hCMEC/D3 cells, the values of TEER gradually increased and maintained above 100 Ω·cm2. Besides, the expression levels of claudin-5 and zo-1 in hCMEC/D3 cells increased over time, and tended to be stable, suggesting that integrity of the monolayer has been completely established. Moreover, the Papp of fluorescein disodium was 3.94 × 10−7 cm·s−1 after administration for 180 min, indicating that the monolayer retains the characteristics of BBB and can restrict the diffusion of hydrophilic small-molecule compounds. A sensitive HPLC method was established for HBA detection, and the transport rate of HBA was assessed by a transwell system. HBA crossed the hCMEC/D3 BBB model rapidly, but a plateau was observed when HBA concentrations were relatively similar between the two sides of transwell. Permeability assay revealed that 32.91% of HBA could penetrate the in vitro BBB model after 240 min of administration. In vivo BBB permeability was evaluated by determining the concentrations of HBA in blood and brain simultaneously. Following HBA administration, the samples of microdialysis were collected at 20, 40 and 60 min, and then every 30 min until the procedure ended. Pharmacokinetic parameters of HBA showed that HBA could pass through BBB and reach its maximum concentration at 40 min in blood and brain tissue. Furthermore, AUC0–t and AUC0–inf for the brain–to–blood distribution ratio of HBA were 0.1925 and 0.2083, respectively, indicating that approximately 20% of HBA in blood could pass through the BBB and subsequently transported into the brain. Both in vitro and in vivo experiments confirmed that HBA could penetrate the BBB. In summary, the findings of this study highlight that a promising amount of HBA in blood can pass through the BBB and exerts its pharmacological effects on central nervous system (CNS) diseases.

Gastrodigenin rhamnopyranoside (GR) is a hepatoprotective compound that exists in Moringa oleifera seeds. However, the UPLC-MS/MS method for the determination of GR (in-vitro/in-vivo) is lacking clarification. Herein, this study established the UPLC-MS/MS technique, which was effective and sensitive for the investigation of the pharmacokinetics and biodistribution of GR in rats and mice. The separation was achieved with a Shim-pack XR-ODS III C18 column (2.0 × 75 mm, 1.6 μm) at 40 °C, while the mobile phase (Acetonitrile/0.1% Formic acid =12:82, v/v) was at an eluting rate of 0.2 mL/min. The Multiple Reaction Monitoring (MRM) was selected for quantification, i.e., m/z [M + HCOO]− 314.9 → 269 for GR and m/z [M + HCOO] - 182.85 → 137 for Tyrosol as the internal standard. The calibration curves were linearly ranged from 10 to 2500 ng/mL (r ≥ 0.999) with a lower-limit-of-quantification (LLOQ) of 10 ng/mL in the various biological samples (plasma, liver, heart, lung, spleen, brain, kidney). The intra- and inter-day precision was within 5%, while accuracy ranged from −11.4% - 8.33%. Recovery and matrix effect were with 80.32 to 101.31% and 90.36 to 103.76%, respectively, in a reasonable range. After oral and intravenous administration, GR was detected within 3 h but decreased rapidly in plasma, indicating fast elimination. Also, GR was quickly distributed in the various tissues, particularly in the kidney and spleen. The results demonstrated that the established UPLC-MS/MS method was highly linear, precise and accurate with the potential to be used for the quantitative analysis of GR in-vivo.

Tianma pills, a traditional formula made from Ligusticum chuanxiong and Gastrodia elata, are efficacious for the treatment of primary headache. Tetramethylpyrazine (TMP) and Ferulic acid (FA) are the bioactive ingredients of Ligusticum chuanxiong, while Gastrodin and Gastrodigenin are the bioactive ingredients of Gastrodia elata. Pharmacokinetic assessment of TMP, FA, gastrodin or gastrodigenin in blood or brain interstitial fluid (BIF) has been reported in healthy animals. However, the pharmacokinetic properties of TMP and FA have not been studied when they are co-administered in a blood-stasis migraine model. The present research investigated the pharmacokinetic behavior of TMP and FA after oral administration in the presence of different concentrations of gastrodin and gastrodigenin in a blood-stasis migraine model. Pharmacokinetic parameters were determined using blood-brain microdialysis in combination with the UHPLC-MS method. Compared to the control group, in which TMP and FA were administrated without gastrodin or gastrodigenin, the T1/2, MRT, Cmax and AUC0-∞ of TMP and FA were increased. These results indicate that varying concentrations of gastrodin and gastrodigenin play an important role in affecting the pharmacokinetics of TMP and FA. Low concentrations of gastrodin and gastrodigenin (similar to those found in Tianma pills) were more efficacious, validating the utility of the ancient formulation.

Objective: Gastrodin, a glucoside of gastrodigenin, inhibits cerebral oxidant stress and apoptosis in multiple central nervous system injury, but its effect in intracerebral hemorrhage (ICH) remains unclear. This study investigated the effect of gastrodin on neuronal apoptosis and neurological deficits in rat ICH model. Methods: In vitro experiments were performed using hematoma lysate-induced cell damage model in primary cortical neurons. Rat ICH model was produced by a caudatum injection of collagenase. Gastrodin was intraperitoneal injected after 2 hours following ICH. Cell viability, brain water content, neurological score, western blot, and immunofluorescence experiments were performed. Results: Gastrodin significantly decreased hematoma lysate-induced reduction of cell viability and cell apoptosis in primary cortical neurons. Gastrodin significantly improved brain edema and neurological deficits post-ICH. Moreover, gastrodin administration significantly reduced levels of ROS, 8-OHDG, 3-Nitrotyrosine and MDA, while increased GSH-Px and SOD activity, and stimulated the upregulation of Keap1, Nrf2, and HO-1 signaling at 72 hours post-ICH. Furthermore, gastrodin significantly increased Bcl-2 expression, while reduced level of Bax, active caspase-3 and active caspase-9, also reduced the number of active caspase-3 or TUNEL positive neurons at 72 hours post-ICH. Conclusion: These results suggest that gastrodin is neuroprotective after ICH and the mechanism may be associated with the inhibition of oxidative stress and neuronal apoptosis.

The purpose of this article was to investigate the effects of different processing methods on the content of gastrodin and gastrodigenin in Gastrodia elata Blume, so as to obtain the best processing method of G. elata. The contents of gastrodin and gastrodigenin in the samples were determined by HPLC method in turn. The results showed that the content of gastrodin and gastrodigenin were the highest in the sample obtained by extraction with 50% ethanol after boiling. Therefore, according to the two indexes of gastrodin and gastrodigenin, alcohol extraction after boiling was the best processing method, which could provide the reference for production.

Gastrodigenin (HBA) and gastrodin (GAS) are phenolic ingredients found in Gastrodia elata Blume (GEB), a traditional Chinese herbal medicine. These compounds have been previously used to treat cognitive dysfunction, convulsion, and dizziness. However, at present, there is no available information regarding their potential ionic effects in electrically excitable cells. In the current study, the possible effects of HBA and GAS on different ionic currents in pituitary GH3 cells and hippocampal mHippoE-14 neurons were investigated using the patch-clamp technique. The addition of HBA or GAS resulted in the differential inhibition of the M-type K+ current (IK(M)) density in a concentration-dependent manner in GH3 cells. HBA resulted in a slowing of the activation time course of IK(M), while GAS elevated it. HBA also mildly suppressed the density of erg-mediated or the delayed-rectifier K+ current in GH3 cells. Neither GAS nor HBA (10 &micro, M) modified the voltage-gated Na+ current density, although they suppressed the L-type Ca2+ current density at the same concentration. In hippocampal mHippoE-14 neurons, HBA was effective at inhibiting IK(M) density as well as slowing the activation time course. Taken together, the present study provided the first evidence that HBA or GAS could act on cellular mechanisms, and could therefore potentially have a functional influence in various neurologic disorders.

Gastrodia elata tuber (GET) is a popular traditional Chinese medicines (TCMs). In this study, response surface methodology (RSM) with a Box&ndash, Behnken design (BBD) was performed to optimize the extraction parameters of gastrodin-type components (gastrodin, gastrodigenin, parishin A, parishin B, parishin C and parishin E). Different from the conventional studies that merely focused on the contents of phytochemical, we gave consideration to both quantitative analysis of the above six components by HPLC and representative bioactivities of GET, including antioxidation and protection of human umbilical vein endothelial cells (HUVEC). Four independent variables (ethanol concentration, liquid-material ratio, soaking time and extraction time) were investigated with the integrated evaluation index of phytochemical contents. With the validation experiments, the optimal extraction parameters were as follows: ethanol concentration of 41%, liquid&ndash, solid ratio of 28.58 mL/g, soaking time of 23.91 h and extraction time of 46.60 min. Under the optimum conditions, the actual standardized comprehensive score was 1.8134 &plusmn, 0.0110, which was in accordance with the predicted score of 1.8100. This firstly established method was proved to be feasible and reliable to optimize the extraction parameters of the bioactive components from GET. Furthermore, it provides some reference for the quality control and extraction optimization of TCMs.

Gastrodia elata Blume (G. elata), a traditional Chinese medicine, is widely used for treatment of various neuro dysfunctions. However, its quality control is still limited to the determination of gastrodin. In the present study, two novel strategies based on quantitative evaluation of total gastrodin and gastrodigenin with base hydrolysis and total gastrodigenin with base-enzymatic hydrolysis followed by HPLC-FLD were put forward and successfully applied to evaluate the quality of 47 batches of G. elata from eight localities. Meanwhile, a systematic comparison of the novel strategy with the multiple markers and the Pharmacopeia method was performed. The results showed that the parishins category could be completely hydrolyzed to gastrodin by sodium hydroxide solution, and gastrodin could further utterly hydrolyze to gastrodigenin with β-d-glucosidase buffer solution. The contents of total gastrodin and gastrodigenin ranged from 1.311% to 2.034%, and total gastrodigenin from 0.748% to 1.120% at the eight localities. From the comparison, we can conclude that the two novel strategies can comprehensively reveal the characteristics of overall active ingredients in G. elata for quality control. The present study provides a feasible and credible strategy for the quality control of G. elata, suggesting a revision of the latest Chinese Pharmacopoeia or European Pharmacopoeia methods for the modernization of G. elata use.

Both borneol and gastrodin are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of gastrodin to the brain in mice via oral administration was investigated. Gastrodin concentrations in plasma and gastrodigenin (active metabolite of gastrodin) concentrations in the brain of mice were determined by reversed-phase high-performance liquid chromatography, after intragastric administration of gastrodin (200 mg kg(-1)) alone or combined with different doses (200, 400 and 600 mg kg(-1)) of borneol simultaneously or the same dose (400 mg kg(-1)) of borneol given 20 and 40 min beforehand, respectively. Compared with the administration of gastrodin alone, gastrodin coadministrated with borneol could have been rapidly absorbed from the gastrointestinal tract; the peak time of gastrodin in the plasma became shorter (5-15 vs. 30 min); the bioavailability of gastrodigenin in the brain was increased by 33.6-108.8%; and obvious brain-targeting effect was observed. The enhancing effect was attenuated when the dose of borneol was too high (600 mg kg(-1)), or the time interval between the administration of borneol and gastrodin was longer than 40 min. The results indicate that borneol can accelerate the absorption of gastrodin in the gastrointestinal tract and promote its distribution to the brain. Therefore, borneol is a promising promoter for oral brain-targeting drug delivery.

Tianma, the steamed and dried rhizome of Blume, is one of the most popular traditional Chinese medicines and a famous foodstuff in China. Main chemical constituents in the rhizomes include phenolic glycoside, organic acid, volatile oil, sterol, polysaccharides, etc. Phenolic glycosides such as gastrodin and its aglycone gastrodigenin are considered as main bioactive compounds in the fresh or steamed and dried rhizome as well as the commercial products from the medicinal market. The pharmacological actions are shown to be anticonvulsant, sedative, analgesic, neuroprotective, antioxidative and immunomodulatory activities as well as anti-aging, anti-hypertension, expanding the coronary blood vessels, improving peripheral circulation and learning memory, etc. Although Tianma is a relatively safe herbal medicine, it is still strongly recommended to use it under proper conditions.

Fresh Rhizoma Gastrodiae (Tianma) was processed in a microwave oven at 2450 MHz in order to study the effect on the main chemical component changes taking place during microwave treatment. It was found that microwave affected the chemical composition of Tianma. Seven compounds, including gastrodin, gastrodigenin (p-hydroxybenzylalcohol), p-hydroxybenzaldehyde, vanillyl alcohol, vanillin, adenine, and 5-hydroxymethylfurfural, were identified in this study. As major active compounds, the contents of gastrodin and gastrodigenin in MWT Tianma were both twice as much as those in raw Tianma. Besides, the MS data show that there are still some unidentified compositions in Tianma, and there are also many converted compounds in MWT Tianma, which is worthy of further work. The results have indicated that microwave treated fresh Tianma might be helpful in designing the processing of traditional Chinese medicine and the application of microwave technology in traditional Chinese medicine needs to be researched further in the future.

Pharmacokinetic characters of rhynchophylline (RIN), gastrodin (GAS), and gastrodigenin (p-hydroxybenzyl alcohol, HBA) were investigated after oral administration of different prescriptions ofYizhi:Yizhitablets or effective parts oftianma(total saponins from Gastrodiae, EPT) andgouteng(rhynchophylla alkaloids, EPG). At different predetermined time points after administration, the concentrations of GAS, HBA, and RIN in rat plasma were determined by an HPLC-ESI/MS method, and the main pharmacokinetic parameters were investigated. The results showed that the pharmacokinetic parametersCmaxandCmax⁡andAUC0–∞(P<0.05) were dramatically different after oral administration of different prescriptions ofYizhi. The data indicated that the pharmacokinetic processes of GAS, HBA, and RIN in rats would interact with each other or be affected by other components inYizhi. The rationality of the compatibility ofUncariaandGastrodia elataas a classic “herb pair” has been verified from the pharmacokinetic viewpoint.

To study the chemical constituents in Bletilla ochracea Schltr., repeated column chromatographies and preparative TLC were used for the isolation of compounds, and spectroscopic techniques (NMR, IR, UV and MS) were used for their structural identification. Seven compounds, 2,7-bis (allyloxy)-5-methoxy-3-methyl-9,10-dihydrophenanthrene ( 1 ), gastrodin ( 2 ), gastrodigenin ( 3 ), β-sitosterol ( 4 ), stigmasterol ( 5 ), 4-hydroxybenzaldehyde ( 6 ), and daucosterol ( 7 ) were obtained from the roots of B. ochracea Schltr. Compound 1 is structurally illustrated as a novel compound, and the others are isolated from the title plant for the first time.

To compare three traditional extraction methods (extraction with cold water, ultrasonic extraction and circumfluence extraction with hot water) of gastrodin and gastrodigenin, the best one is circumfluence extraction with hot water. And the optimum extraction process was carried out through orthogonal experiment. The best extraction temperature was 60°C, and extracted 3 times by 70% alcohol. The time for each extraction was 1 hour, and the quantity of alcohol used 10 times more than the quantity of sample. The contents of samples in different harvest festivals (from August to January) were determined. The best time is in September.

OBJECTIVE To investigate the intestinal absorption characteristics of gastrodigenin. METHOD In vitro everted gut sac model and in situ rat single-pass intestinal perfusion model were used to evaluate the absorption characteristics of gastrodigenin in the different intestinal segments. The concentrations of gastrodigenin in the samples were determined by Ultra Performance Liquid Chromatography (UPLC) method, and the relevant absorption parameters were calculated. RESULT In the everted gut sac tests, no significant difference of absorption among the four segments was observed. A positive correlation was found between drug concentration and the accumulated absorption amount (Q). At the concentration of 400 mg x L(-1), the Q of gastrodigenin in the duodenum, jejunum, ileum and colon were 224.33, 225.81, 233.18 and 189.25 microg, respectively. The in situ rat single-pass intestinal perfusion tests showed that there was also no significant difference of absorption among the four segments. The absorption rates (A) of gastrodigenin in the duodenum, jejunum, ileum and colon were 45.8%, 48.39%, 47.00%, 54.35%, respectively. CONCLUSION Gastrodigenin can be well absorbed via passive diffusion in the intestine. The absorption rates of gastrodigenin in the different intestinal segments show no regioselectivity.

A new citryl glycoside, trimethylcitryl-beta-D-galactopyranoside (1) along with a known phenolic compound, gastrodigenin (2) have been isolated from the active fraction of the rhizomes of Gastrodia elata (Orchidaceae). Their structures were elucidated on the basis of spectroscopic data and chemical reaction. 1 inhibited GABA transaminase activity by 56.8% at the final concentration of 10 microg/ml.

A rapid and specific HPLC method for the simultaneous determination of gastrodin and its metabolite gastrodigenin (p-hydroxybenzyl alcohol) in rat plasma, bile, liver, urine and faeces is described. The separation was achieved by using a reversed phase column (YWG-C18) eluted with methanol-water (2.5:97.5 v/v). Phloroglucinolum was used as internal standard and the peaks were detected at UV 221 nm. The protein precipitation with ethanol was a very simple and rapid method for sample preparation. The gastrodin and gastrodigenin were quantitated by measuring the peak-height ratios. There was a linear concentration range of 10-320 micrograms/mL in the assay for both compounds. The coefficients of variation (within-day) for samples spiked with gastrodin and gastrodigenin were 2.94% and 3.08%, respectively. The method demonstrated a high specificity and was suitable for use in pharmacokinetic studies.