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Gastrodin (Gas) represents the major active component of Gastrodia elata, a Chinese herb. Clinically, Gas is widely used for its sedative, anticonvulsive and neuroprotective properties. This work aimed to assess Gas for its efficacy in Tourette Syndrome (TS) treatment. Twenty-four rats were randomized to the blank control (n = 6) and experimental (n = 18) groups. The experimental group was administered continuous injection of 3, 3′-iminodipropionitrile (IDPN) intraperitoneally for 7 days, and subdivided into the IDPN + NS, IDPN + Hal, and IDPN + Gas groups (n = 6). The control and IDPN + NS groups received saline intragastrically, while the IDPN + Hal and IDPN + Gas groups were administered Gas and Haloperidol, respectively, for 8 weeks. Then, micro-positron emission tomography (PET) was performed for measuring the density and brain distribution of dopamine D2 receptors (D2Rs), dopamine transporters (DATs), 5-HT2A receptors (5-HT2ARs) and 5-HT transporters (SERTs). According to stereotypical behavior experiments, IDPN significantly induced abnormal stereotypical behaviors in rats in comparison with control animals. In addition, micro-PET revealed that by reducing the amounts of D2Rs and increasing those of DATs, Gas could significantly reduce stereotypical TS-like behaviors in this rat model system. Furthermore, Gas treatment reduced the density of SERTs, which could indirectly decrease DA release. The current study demonstrated that Gas could be effective in treating TS.

The tubers of Dioscorea persimilis have been widely consumed as a food and for the treatment of sonasthenia, intestinal disease, diarrhea, long-term dysentery, spermatorrhea, metritis, kidney failure, back pain, dizziness, and night sweats. The present study describes the isolation of 11 secondary metabolites, including three new phenanthrenes namely diospersimilosides A (1) and B (2) and diosbiphenanthrene (3), and eight known phenolic compounds: 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (4), aerosin (5), gastrodin (6), 2-phenylethyl-β- d -glucopyranoside (7), afzelechin (8), catechin (9), eucomic acid (10), and vanillic acid-4-O-β- d -glucopyranoside (11) from the tubers of D. persimilis. Their chemical structures were elucidated based on comprehensive analyses of the NMR and mass spectra. Evaluation of their cytotoxicity against three human cancer cell lines, including liver (HepG2), breast (MCF7), and melanoma (SK-Mel-2) revealed that the phenanthrene metabolites (3-5) possess cytotoxicity toward all the cell lines, with IC50 values ranging from 8.2–68.4 μM. Our results revealed that the free of the hydroxy groups plays an important role in cytotoxicity of the phenanthrenes and suggests that pohydroxylated dihydrophenanthrene and biphenanthrene metabolites could be considered as promising cytotoxic agents against human cancer cells.

Two new phenolic glycosides, eulophiosides A and B (3, 4), were isolated from Eulophia andamanensis in addition to six known compounds. The known compounds were identified as gastrodin (1), vitexnegheteroin A (2), grammatophylloside A (5), grammatophylloside B (6), pleionoside E (7), and pleionoside F (8). Their structures were determined based on the physical data and the spectroscopic evidence including 1D and 2D NMR experiments.

Microglia contribute to the regulation of neuroinflammation and play an important role in the pathogenesis of brain disorders. Thus, regulation of neuroinflammation triggered by activation of microglia has become a promising therapeutic strategy. Here, we investigated the beneficial effects of Gastrodin in activated microglia and analyzed the underlying molecular mechanisms. Microglia activation was regulated by Gastrodin not only in terms of microglia population size but also production of inflammatory mediators. Gastrodin inhibited the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclin-D1 and Ki67 in lipopolysaccharide (LPS)-stimulated BV-2 or primary microglia. Gastrodin also suppressed the expression of iNOS and Ki67 in activated microglia in three-day-old LPS-injected postnatal rats. In addition, the present results have shown that Gastrodin inhibited LPS-induced phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser 9 and β-catenin activity. We further extended our investigation to determine whether Wnt/β-catenin signaling pathway was involved in the anti-inflammatory and anti-proliferation function of Gastrodin. β-Catenin antagonist (XAV939) was used to block LPS-mediated upregulation of iNOS, TNF-α, cyclin-D1, nitric oxide (NO) and the number of cells in the G2/M+S phase of cell cycle. Moreover, treatment with LiCl, a special Wnt/β-catenin pathway agonist significantly blocked Gastrodin-mediated down-regulation of iNOS, TNF-α, cyclin-D1, NO and the number of cells in the G2/M+S phase of cell cycle in LPS-stimulated BV-2 microglia. Taken together, the present results suggested that Gastrodin mediated anti-inflammatory and anti-proliferation effects in activated microglia by modulating the Wnt/β-catenin signaling pathway.

The ubiquitous environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to trigger neurotoxicity. In this study, we investigated the protective effects of gastrodin on TCDD-induced neurotoxicity and the underlying molecular mechanisms. The results show that gastrodin decreased cell viability, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release, and inducible nitrix oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) expression in TCDD-treated C6 cells. TCDD stimulated NF-κB signalling activation, demonstrated by increased p-NF-κB expression and translocation of nuclear Factor kappa B (NF-κB) to the nucleus. TCDD did not affect TRAF6 protein expression but enhanced the attenuated the Src-suppressed-C Kinase Substrate (SSeCKS)–tumor necrosis factor receptor-associated factor 6 (TRAF6) interaction, thereby triggering NF-κB signalling activation. Gastrodin inhibited TCDD-induced NF-κB signalling activation by lessening the SSeCKS–TRAF6 interaction in vitro. Gastrodin attenuated SSeCKS–TRAF6 interaction in vivo and protected mice from NF-κB signalling activation following TCDD exposure. Finally, gastrodin blocked the apoptosis of PC12 neuronal cells induced by medium conditioned with TCDD-treated astrocytes. In summary, gastrodin inhibited TCDD-induced NF-κB signalling activation by lessening the SSeCKS–TRAF6 interaction, resulting in attenuated astrocyte activation and subsequent neuronal apoptosis. These findings will contribute to an improved understanding of TCDD-induced neurotoxicity and strategies to antagonise it using gastrodin.

The bioassay-guided fractionation of the hydroalcoholic extract from aerial parts of Bacopa procumbens (Mill.) Greenm., allowed to isolate the known phenolic compound arbutin (1) as well as three new gastrodin derivatives which were denominated procumgastrodin A, procumgastrodin B and procumgastrodin C. These bioactive compounds were characterized using spectroscopic (1H-NMR, 13C-NMR, 1H-1H COSY, HSQC, HMBC) and spectrometric analysis (HRFAB-MS) as gastrodin 5-(4′”-hydroxybenzoyl)-shikimate (2), gastrodin 5-(cis-p-coumaroyl)-shikimate (3) and gastrodin 5-(trans-p-coumaroyl)-shikimate (4). The extracts and fractions showed antimicrobial activity with minimum inhibitory concentration (MIC) between 75 and 400 μg/mL and isolated compounds (1-4) showed activities of 12.5 to 100 μg/mL. All analyzed compounds displayed activity against any of the bacteria and yeast evaluated. A mixture of 3 and 4 exhibited particularly potent activity against the yeast Candida albicans.

Puerariae Radix (PR) and Gastrodiae Rhizome (GR) is frequently used in traditional herbal formulas to treat cardio-cerebral vascular diseases due to their synergistic effects. In this study, to elucidate the action mechanism of PR-GR in vivo, a simple and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of nine bioactive ingredients from PR-GR in plasma was developed and applied to a comparative pharmacokinetic study following oral administration of PR, GR, and PR-GR aqueous extracts in rats. The effect of GR on the absorption of components of PR was also investigated by single-pass intestinal perfusion study. Results showed that comparing to the single herbs, PR-GR extract significantly increased the systemic exposure of puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, 6″-O-xylosylpuerarin, daidzin, genistein, and gastrodin. Moreover, the intestinal absorption of puerarin and daidzin could be improved by GR extract and inhibitors of P-glycoprotein and multidrug resistanceassociated protein 2, respectively. These results indicate that the combination of PR and GR increases the levels of their bioactive ingredients exposed in the blood, and GR increases the absorption of ingredients of PR may by inhibition of the efflux mediated by P-glycoprotein and multidrug resistanceassociated protein 2. This is the first report for the pharmacokinetics and intestinal absorption of PR-GR, which may explain their synergetic effects in the treatment of circulatory systematic diseases and provide a meaningful insight for their clinical applications.

Microglia activation and its mediated production of proinflammatory mediators play important roles in different neurodegenerative diseases; hence, modulation of microglia activation has been considered a potential therapeutic strategy to ameliorate neurodegeneration. This study was aimed to determine whether Gastrodin, a common herbal agent known to possess neuroprotective property, can attenuate production of proinflammatory mediators in activated microglia through the renin-angiotensin system (RAS) and Sirtuin3 (SIRT3). Expression of various members of the RAS including ACE, AT1, AT2, and SIRT3 in activated microglia was assessed by immunofluorescence and Western blot in hypoxic-ischemia brain damage (HIBD) in postnatal rats, and in BV-2 microglia in vitro challenged with lipopolysaccharide (LPS) with or without Gastrodin treatment. Expression of NOX-2, a subunit of NADPH oxidase, and proinflammatory mediators including iNOS and TNF-α, was also evaluated. The present results showed that expression of ACE, AT1, NOX-2, iNOS and TNF-α was markedly increased in activated microglia in the corpus callosum of HIBD rats, and in LPS stimulated BV-2 microglia. Remarkably, the expression was markedly attenuated following Gastrodin treatment. Conversely, Gastrodin enhanced AT2 and SIRT3 protein expression. In BV-2 microglia treated with Azilsartan, a specific inhibitor of AT1 (AT1I group), NOX-2 expression was decreased whereas that of SIRT3 in LPS + AT1I and LPS + Gastrodin group was increased when compared with the controls. In LPS + AT1I + Gastrodin group, SIRT3 expression was further augmented. More importantly, Gastrodin effectively reduced caspase 3 protein expression level in the HIBD rats coupled with a significant decrease in caspase 3 positive cells. We conclude that Gastrodin can exert its protective effects against the hypoxic-ischemia brain damage in the present experimental HIBD model. It is suggested that this is mainly through suppression of expression of RAS (except for AT2 and SIRT3) and proinflammatory mediators e.g. TNF-α in activated microglia.

Scaffolds are used in tissue engineering to provide a temporary structural template for cell colonization and matrix formation. Here, an emerging polyurethane (PU) porous scaffold incorporated with renewable gastrodin was developed, and its mechanical properties and cell behavior were evaluated. The results showed that the scaffold had an interconnected porous structure, the chemical modification of PU by 8.99 wt% gastrodin synergistically enhanced initial modulus by 222% and porosity by 63%; the stem cells seeded on such scaffold exhibited higher cytocompatibility, the proper pore size was favorable for cell attachment and proliferation compared to the scaffold without gastrodin. This study for the first time demonstrates that gastrodin can chemically-polymerized onto the polyurethane matrix, improving mechanical properties and cell activity. The findings in this study highlight that this scaffold holds great promise in regenerative medicine.

Gastrodin (GAS), a monomeric component exacted from the herb Gastrodia elata Bl, may have cardioprotective effects during injury caused by myocardial ischemia/reperfusion (I/R). For the significant role of autophagy in I/R process, we targeted to explore whether autophagy was contributing to the GAS-induced protective effects during I/R procedure. Male C57BL/6 mice were subjected to reversible left coronary artery ligation and cultured neonatal rat cardiomyocytes (NRCs) exposed to hypoxia were preconditioned with GAS prior to ischemia or hypoxia, following reperfusion for 2 h or re-oxygennation for 3 h respectively. Our results demonstrated that GAS pretreatment increased autophagy and reduced apoptosis during I/R, this effect was weakened by co-treatment with the autophagic flux inhibitor chloroquine (Cq). Compared to mice subjected solely to I/R, GAS-pretreated mice had a notably smaller heart infarct size and an elevation in cardiac function. In GAS-pretreated NRCs, WB data showed that autophagy was promoted (expression of p62 was inhibited and LC3II was increased). In addition, tandem fluorescent mRFP-GFP-LC3 assays illustrated that autophagosomes were degraded duo to an increase in autophagic flux. Co-administration of Cq blocked the autophagic flux. Furthermore, GAS pretreatment increased the mitochondrial membrane potential of NRCs with subjected to H/R and increased the cardiomyocyte survival rate. These protective effects were reversed with Cq. Besides, GAS-induced the enhaucement of autophagy may correlated with activating AMP-activated protein kinase (AMPK) phosphorylation and reduced Mammalian target of rapamycin (mTOR) phosphorylation, which was abrogated by Compound C (Com C, AMPK-specific inhibitor). Our results establish that GAS pretreatment attenuates myocardial I/R injury by increasing autophagic flux aimed at eliminating dysfunctional mitochondria, therefore protecting neighbouring mitochondria and cardiomyocytes.

Vibrio harveyi hemolysin (VHH) is an important virulence determinant of V. harveyi. It is an extracellular protein with phospholipase activity and plays a key role in the process of pathogen infection of the host. The key role of VHH in the virulence of V. harveyi makes it an ideal target for the design of new antiviral drugs. We found that gastrodin is a natural flavonoid with no antibacterial activity and an effective antagonist of VHH-mediated hemolysis. The compound can effectively inhibit the damage caused by V. harveyi in cell culture and animal infection models. Gastrodin can down-regulate the transcription of the vhh gene, and molecular modeling and mutation analysis show that it directly blocks the amino acid residues in the active center of the protein, thereby inhibiting its cytotoxicity. Our research results indicate that gastrodin is an effective antitoxin agent for VHH, which can be further developed into a new drug for the treatment of Vibrio infection.

The blood-cerebrospinal fluid barrier (BCSFB) is another gatekeeper between systemic circulation and the central nervous system (CNS), mainly present at the boundary between choroid plexuses and the ventricular system. This study demonstrates BCSFB opening in rats by single pulse of low-energy focused shockwave (FSW, energy flux density 0.03 mJ/mm2, 2 × 106 microbubbles/kg) treatment at lateral ventricle, resulting in significantly elevated cerebrospinal fluid (CSF) concentrations of systemically-administered gastrodin (GTD) (4 times vs. control within 3 hrs) that remained detectable for 24 hrs. The FSW-GTD group had significantly lower Racine’s scale (

Gastrodia elata Blume (GE) is an orchid herbal material widely used in China for thousands of years. Recently, the Chinese government has noted that GE can be legally used as functional food, which brings a huge food market for GE. The processing of herbal materials is considered to be the most critical technology to ensure quality and efficacy. Proper processing can transform raw materials into food or drugs with appropriate ingredients and functions. However, due to the unprocessed or the fresh GE can be easily bought in the market, the ingredient and efficiency difference between fresh and processed GE need to further investigate. Based on the understanding of the mechanism of processing in the GE and its possible application in the dietary treatment for anxious people, this paper studied the ingredient changes of the main active constituents of the GE before and after processing. Meanwhile, blood concentrations of three active ingredient including gastrodin (GAS), p-hydroxylbenzyl alcohol (HBA) and Parishin were investigated. Moreover, the different efficacy of the GE in various animal models and the potential mechanisms were studied. Finally, water steamed GE showed distinct better bioactivity than the fresh GE. Further mechanism based on the metabolomics was investigated. The difference of tryptophan related metabolites was observed and discussed to be the possible cause of the increasing bioactive efficiency in GE with steaming process.

Atherosclsis is a critical actuator causing cardiac-cerebral vascular disease with a complicated pathogeneon, refered to the disorders of intestinal flora and persistent inflammation. Gastrodin (4-(hydroxymethyl) phenyl-β-D- Glucopyranoside) is the most abundant glucoside extracted from the Gastrodiaelata, which is a traditional Chinese herbal medicine for cardiac-cerebral vascular disease, yet its mechanisms remain little known. In the present study, the gastrodia extract and gastrodin attenuate the lipid deposition and foam cells on the inner membrane of the inner membrane of the thoracic aorta in the early atherosclerosis mice. Blood lipid detection tips that TC and LDL-C were reduced in peripheral blood after treatment with the gastrodia extract and gastrodin. Furthermore, unordered gut microbes are remodeled in terms of bacterial diversity and abundance at family and genus level. Also, the intestinal mucosa damage and permeability were reversed, accompaniedwith the reducing of inflammatory cytokines. Our findings revealed that the functions of gastrodia extract and gastrodin in cardiac-cerebral vascular disease involved to rescued gut microbes and anti-inflammation may be the mechanismof remission lipid accumulation.

Ethnopharmacological relevance Temporal lobe epilepsy remains one of the most drug-resistant focal epilepsy, leading to enormous healthcare burden. Among traditional herb medicine, some ingredients have the potential to treat seizure and alleviate the neuronal excitoxicity. The dried rhizome of Gastrodia elata Blume has been used to treat convulsive disorder, dizziness, dementia and migraine in eastern Asia. Aim of the study To determine whether gastrodin, an active ingredient of Gastrodia elata Blume, can reduce lithium-pilocarpine induced seizure severity and neuronal excitotoxicity and explore the underlying mechanism. Materials and methods We divided the Sprague-Dawley rats into an experimental group (gastrodin group) and a control group (Dimethyl sulfoxide, vehicle group) and performed the behavioral analysis and electroencephalography to determine the effect of gastrodin on the seizure severity induced by lithium-pilocarpine injection. Nissl-stained histopathology elucidated the degree of rat hippocampal neuronal damage as markers of acute and subacute neuronal excitotoxicity. Besides, the Western blotting of dissected hippocampus was carried out to demonstrate the protein expression involving GABAergic transmission and metabolic pathway. Results Gastrodin reduced the acute seizure severity in lithium-pilocarpine-induced seizure model. In electroencephalography recording, gastrodin exerted inhibitory action on epileptiform discharge. Compared with control group, gastrodin exhibited neuroprotective effect against seizure related hippocampal neuronal damage at acute and subacute stages. The Western blotting showed that gastrodin reversed the degradation of GABAA receptor after pilocarpine-induced seizures. Conclusions In the experimental seizure model, gastrodin showed anti-seizure and neuroprotective abilities. Enhancing the expression of GABAA receptor plays an important role in its antiepileptic mechanism. The results offer a new insight of developing new antiepileptic drugs from traditional Chinese medicine.

In order to comprehensively elucidate the chemical biosynthesis process of the beige-scape Gastrodia elata Blume (Wutianma) as a traditional herbal medicines, the untargeted analysis-based UHPLC-PDA-ESI-Q-TOF-MS reveals the metabolites ranging from the skeletons to novel dimers of citric acids in fresh and dried immature/mature stem tubers. Interestingly, two novel types of dimers for citric acids with the anhydride groups at sn-1 and/or sn-5 were discovered in fresh samples. Moreover, the classical mono- versus novel di-mers, and the aglycons versus the glycosides could be easily discriminated by signature fragmentation patterns and some novel adduct ions. The heat map of contents demonstrated more p-hydroxybenzyl metabolites than gastroxyl ones were determined in fresh Wutianma revealing a significant specificity with the lack of the sufficient gastrodin and gastroxyl products in biosynthetic pathway.

Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip® PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients.

Bone is a rigid yet dynamic organ, and this dynamism is mediated by the delicate balance between osteoclastic bone resorption and osteoblastic bone formation. However, excessive activation of osteoclasts is responsible for many bone diseases such as osteoporosis, Paget disease, and tumor bone metastasis. Agents that could inhibit osteoclast formation or function are regarded as promising alternatives to treat osteoclast-related diseases. Recently, traditional Chinese medicine has attracted attention because of its multiple activities in bone metabolism. Among them, gastrodin has been reported as an anti-osteoporosis agent that reduces reactive oxygen species. However, the direct action of gastrodin on osteoclast differentiation and bone resorption, and its underlying molecular mechanism, remain unknown. In this study, we investigated the effects of gastrodin on receptor activator NF-κB ligand (RANKL)-activated osteoclasts formation and bone resorption. Our results showed that gastrodin retarded RANKL-induced osteoclast differentiation efficiently by downregulating transcriptional and translational expression of nuclear factor of activated T cells cl (NFATc1), a major factor in RANKL-mediated osteoclastogenesis. Meanwhile, gastrodin prevented osteoclast maturation and migration by inhibiting the gene expression of dendrocyte expressed seven transmembrane protein (DC-STAMP), an osteoclastic-specific gene that controls cells fusion and movement. And gastrodin prevented RANKL-induced osteoclastic bone erosion in vitro. In addition, gastrodin also stimulated bone mesenchymal stem cell (BMSC) spreading and osseointegration in titanium plate. In summary, gastrodin could prevent osteoclasts formation and bone resorption via blockage of NFATc1 activity, and stimulate osseointegration in vitro. Gastrodin could be developed as a potent phytochemical candidate to treat osteolytic diseases.

Objective Cerebrovascular disease is one of the major diseases that seriously harm human health currently. The purpose of this study is to find an effective treatment and clarify its mechanism of action to provide a new idea and drug target for the clinical treatment of ischemic cerebrovascular disease. Methods The microglia cell line (BV2 cell line) was cultured in vitro. Prepare a hypoxia ischemia cell model by OGD and simulate the pathophysiological process of ischemic cerebrovascular disease in vivo. According to the techniques of LDH Cytotoxicity Assay Kit, flow cytometry of Annexin V-FITC Apoptosis Detection Kit, Laser Confocal Fluorescence Immunostaining (Double staining method), enzyme-linked immunosorbent assay (ELISA), and Western blotting, BV2 cells are observed through morphology and function changes induced by OGD. Moreover, these techniques were used to analyze changes in key proteins expression of signal transduction pathway in ischemic cerebrovascular disease, to explore the mechanism of gastrodin on ischemic cerebrovascular disease, and to elucidate the available ways for cell protection following ischemia and hypoxia. Results Gastrodin has no obvious toxic effect on BV-2 cells under physiological conditions. The death rate of BV-2 cells increases as the time of hypoxia increase. In the absence of oxygen, Gastrodin has a protective effect on the survival of BV-2 cells. This protective effect is related to the reduction of apoptosis rate. It can also improve the hypoxic tolerance of BV-2 cells, and there is no obvious Gastrodin dose-dependence. Moreover, Gastrodin has dual effects on BV-2 cells. The dual role of Gastrodin is closely related to the expression of several proteins which can affect the MAPK signal transduction pathway. Conclusion Gastrodin has a dual effect on microglia with OGD. On the one hand, Gastrodin can inhibit the inflammatory cytokines secreted by microglia and aggravate the inflammatory response; on the other hand, Gastrodin can promote the secretion of protective cytokines from microglia to reduce the inflammatory response.

Gastrodia elata and Ligusticum chuanxiong are used to treat primary headaches for many years. Gastrodin (GAS) and tetramethylpyrazine (TMP)/ferulic acid (FA) are the main active ingredients of Gastrodia elata and Ligusticum chuanxiong, respectively. Previous studies demonstrated the pharmacokinetics of GAS, TMP, and FA in the blood and brain interstitial fluids (BIF) in healthy animals but not in animal model with liver-yang hyperactivity migraine. Hence, this study examined the pharmacokinetics of GAS after its oral administration in the presence of different concentrations of TMP and FA in animals with liver-yang migraine hyperactivity. In the control group, GAS was administrated without TMP and FA. Pharmacokinetic parameters were determined using the blood-brain microdialysis in combination with the high-performance liquid chromatography method. Results revealed that the maximum drug concentrations (Cmax) in the serum, area under curve (AUC), and mean residence time (MRT) of GAS decreased in normal animals, whereas Cmax increased significantly in model animals. These findings indicate that varying concentrations of TMP and FA play an important role in the pharmacokinetics of GAS in both normal and migraine model animals, validating the utility of the ancient formulation.

Gastrodia elata Blume – an important medicinal crop widely cultivated and used in Asian countries especially China, when favorably dried can give high recovery/yield of its bioactive compounds. Traditionally, gastrodia tubers are processed (cured) before drying to increase their bioactive phytochemical constituents, most importantly gastrodin. Since, the conventional method is tedious and time-consuming, the current work investigates a rapid single step post-harvest curing-drying method based on microwave to achieve high yields of gastrodin from gastrodia. HPLC analysis depict that microwave drying (MWD) increased the total phenolic content by 3.4 times compared with conventional techniques. Drying kinetics depicted that MWD dehydrated gastrodia in 2 h compared with 48−59 h by conventional processes. Minimum change in surface color (ΔE: 5.8 ± 0.02) and highly porous internal structure was observed in MWD samples compared with conventionally dried samples. Low power microwave energy (100 W) yielded more phytochemical content than higher powers. UPLC/Q-TOF MS analysis of MWD gastrodia identified gastrodin and 14 other compounds. According to Spin-spin relaxation times (T2) by LF-NMR, only bound water was present in fully dried samples, whereas all 3 water states were found in fresh and half-dried samples. Scanning electron micrographs (SEM) showed honey-comb internal microstructure of MWD samples with distinct vascular tissues. 3-dimensional volume datasets (3D X-ray) depicted porosity and pore space arrangements inside samples before and after MWD. MWD also affected the intrinsic starch and enzymes in gastrodia causing variations to phytochemicals. FTIR spectra of starches from dried gastrodia tubers indicated changes in ordered crystallinity indicating partial gelatinization during drying. Moreover, MWD also inactivated enzymes (β-D-glucosidase) that hydrolyze gastrodin to p-hydroxybenzyl alcohol, thus preventing its hydrolysis. Therefore, it was observed that MWD is a simple, rapid, economical and benign alternative technique to dry gastrodia than other conventional methods.

Da Chuan Xiong Decoction Compound preparation (DCXDCP) is a classic TCM formula of an aqueous extract made from Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., umbelliferae) and Tianma Rhizoma (Gastrodia elata Bl., Orchidaceae). Gastrodin (GAS), a bioactive component of tianma, its pharmacokinetic (PK) behavior significantly changed after oral administration of DCXDCP compared with the extract of tianma. However, little is known about how the ingredients of chuanxiong influenced on the PK of GAS.To study the possible PK behavior differences of GAS after individually oral administration of tianma extract and tianma extract mixed with different active ingredients of chuanxiong to rats, as well as explore whether there were some herb-herb interactions.Different DCXDCP suspensions were prepared by mixing tianma extract with different active ingredients of chuanxiong. The rats were randomly assigned to six groups and were orally treated with different DCXDCP. At different predetermined time points after administration, the concentrations of GAS in the rat plasma were determined using HPLC, and the main PK parameters were investigated.The results showed that tetramethylpyrazine had no significant effects on the PK parameters of GAS (p0.05), whereas ferulic acid (FA), total phenolic acids and total alkaloids significantly increased AUC0-∞ (p0.05). In general the observed changes in the PK parameters of GAS in DCXDCP could be closely related to the total phenolic acids and total alkaloids.It could be shown that total phenolic acids and total alkaloids present in Ligusticum chuanxiong in addition to other components not tested yet play an important role in affecting the PK of gastrodin in DCXDCP.

In this study, direct ionization mass spectrometry (DI-MS) for rapid authentication of Gastrodiae rhizoma (known as Tianma in Chinese), a popular herbal medicine, has been developed. This method is rapid, simple and allows direct generation of characteristic mass spectra from the raw herbal medicines with the application of some solvents and a high voltage. The acquired DI-MS spectra showed that gastrodin, parishin B/parishin C and parishin, the major active components of Gastrodiae rhizoma, could be found only in genuine Gastrodiae rhizoma samples, but not in counterfeit samples, thus allowing rapid authentication of Gastrodiae rhizoma. Moreover, wild and cultivated Gastrodiae rhizoma could be classified and Gastrodiae rhizoma from different geographical locations could be differentiated based on their different intensity ratios of characteristic ions or principal component analysis (PCA). This method is simple, rapid, reproducible, and can be extended to analyze other herbal medicines.

Rapid discovery of novel compounds of a traditional herbal medicine is of vital significance for pharmaceutical industry and plant metabolic pathway analysis. However, discovery of unknown or trace natural products is an ongoing challenge. This study presents a universal targeted data-independent acquisition and mining strategy to globally profile and effectively match novel natural product analogues from an herbal extract. The famous medical plant Gastrodia elata was selected as an example. This strategy consists of three steps: (i) acquisition of accurate parent and adduct ions (PAIs) and the product ions data of all eluting compounds by untargeted full-scan MS(E) mode; (ii) rapid compound screening using diagnostic product ions (DPIs) network and in silico analogue database with SUMPRODUCT function to find novel candidates; and (iii) identification and isomerism discrimination of multiple types of compounds using ClogP and ions fragment behavior analyses. Using above data mining methods, a total of 152 compounds were characterized, and 70 were discovered for the first time, including series of phospholipids and novel gastroxyl derivatives. Furthermore, a number of gastronucleosides and phase II metabolites of gastrodin and parishins were discovered, including glutathionylated, cysteinylglycinated and cysteinated compounds, and phosphatidylserine analogues. This study extended the application of classical DPIs filter strategy and developed a structure-based screening approach with the potential for significant increase of efficiency for discovery and identification of trace novel natural products.

Ethnopharmacology relevance Gastrodia elata Blume (GE) is a traditional herbal medicine belonging to the Orchidaceae family, and has been used to manage neurological disorders for centuries. We have previously reported that its water extract (WGE) could improve the depressive-like behaviours in the forced swimming test (FST), an animal model of depression. Aim of the study To investigate the antidepressant-like effects of WGE in rats exposed to unpredictable chronic mild stress (UCMS) model, and to explore its possible molecular mechanisms. Materials and methods UCMS rats were orally administered with WGE (0.5 g/kg body weight) daily within the 4 weeks UCMS procedure. The sucrose preference test and the open field test were conducted to assess anhedonia and spontaneous behaviours, respectively. The cerebral turnover rates of monoamine neurotransmitters and the serum corticosterone levels were measured. In vitro direct and indirect monoamine oxidase A (MAO-A) inhibitory assays were employed to assess the possible antidepressant-like mechanisms of WGE (0.5 mg/mL) and its major component, gastrodin (GAS, 15, 30 and 60 μg/mL). Western blot was used to examine the expression of protein related to monoamine regulation, such as MAO-A and tyrosine hydroxylase (TH). Results WGE significantly reversed the sucrose preference and other abnormal behaviours induced by 4 weeks of UCMS. WGE significantly restored the cerebral turnover rates of serotonin and dopamine and decreased serum corticosterone levels. WGE and gastrodin inhibited the activity and protein expression of MAO-A, and increased TH levels in PC12 cells. Conclusion The antidepressant-like effects of WGE and gastrodin might be mediated by the regulation of monoamine neurotransmitters, and therefore were beneficial in depression treatment as a complementary approach.

Gastrodia elata tuber (GET) has been widely used as a famous herbal medicine in China and other East Asian countries. In this work, we developed a comprehensive strategy integrating targeted and non-targeted analyses for quality evaluation and discrimination of GET from different geographical origins and cultivars. Firstly, 43 batches of GET samples of five cultivars from three regions in China were efficiently quantified by a "single standard to determine multi-components" (SSDMC) method. Six marker compounds were simultaneously determined within 11min using gastrodin as the internal standard. It showed that samples from different regions and cultivars could not be differentiated by the contents of six marker compounds. Secondly, a non-targeted metabolite profiling analysis was performed by ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Samples from different geographical origins and cultivars were clearly discriminated by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). 147 discriminant ions contributing to the group separation were selected from 1194 aligned variables. Furthermore, based on the relative intensities of discriminant ions, support vector machines (SVM) was employed to predict the geographical origins of GET. The obtained SVM model showed excellent prediction performance with an average prediction accuracy of 100%. These results demonstrated that the UHPLC-QTOF/MS-based non-targeted metabolite profiling analysis, as a vital supplement to targeted analysis, can be used to discriminate the geographical origins and cultivars of GET.

Ethnopharmacological relevance Gastrodia elata Blume, a traditional Chinese herb, was widely used against convulsant, vertigo, paralysis, epilepsy, tetanus, asthma and immune dysfunctions. Gastrodin is one of the major bioactive components of G. elata and it is known for its anticonvulsive, anti-inflammatory, antiepileptic and neuroprotective effects. Materials and methods An ultra high performance liquid chromatography-fluorescence detection (UHPLC-FLD) method was developed to determine gastrodin in rat plasma. Gastrodin and Thiamphenicol (internal standard, IS) were extracted from rat plasma by immediately protein precipitation. The pharmacokinetics of gastrodin in rats by following differently administered types was studies: intragastric administration of gastrodin (100 mg/kg), parishin (116 mg/kg, with the same mole of gastrodin moiety) and G. elata extract (2.3 g/kg, with the same mole of gastrodin moiety). Non-compartmental pharmacokinetic profiles were constructed using the software of WinNonlin (Phoenix, version 6.3), and the pharmacokinetic parameters were compared using unpaired Student’s t-test. Results The results showed that the pharmacokinetic parameters, including Cmax, Tmax, AUC0–∞, t1/2, MRT, Vd, CL, were quite different among the three types of gastrodin administration. The administration of parishin and G. elata extract, which either could convert to gastrodin in vivo or contained free gastrodin and abundant gastrodin conjugates, gave rise to higher elimination half-life (t1/2) and mean residence time (MRT) values for gastrodin compared to free gastrodin administered. Conclusion The comparison of the pharmacokinetics of gastrodin among three different administered types of gastrodin in rats suggested that administration of parishin or G. elata extract in clinic may result in a longer duration time of action than that of the administration of free gastrodin. The results may provide some guidance for the clinical applications of parishin and G. elata.

Fulminant hepatitis (FH), characterized by overwhelmed inflammation and massive hepatocyte apoptosis, is a life-threatening and high mortality rate. Gastrodin (GTD), a phenolic glucoside extracted from Gastrodiaelata Blume, exerts anti-apoptosis, and anti-inflammatory activities. In the present study, we aimed to evaluate whether GTD treatment could alleviate lipopolysaccharide and d-galactosamine (LPS/GalN)-induced FH in mice and its potential mechanisms. These data suggested that GTD treatment remarkably protected against LPS/GalN-induced FH by enhancing the survival rate of mice, reducing ALT and AST levels, attenuating histopathological changes, and suppressing interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α secretion. In addition, GTD treatment relieved hepatic apoptosis by the regulation of peroxisome proliferator-activated receptors (PPARs), P53 and caspase-3/9. Furthermore, GTD treatment could significantly inhibit inflammation-related signaling pathways activated by LPS/GalN, including the suppression of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) and nuclear factor-kappa B (NF-κB) activation. Importantly, GTD treatment effectively restored but not induced LPS/GalN-reduced the expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, as well as the level of pro-autophagy proteins. Taken together, our investigation indicated that GTD played an essential role in liver protection by relieving hepatocyte apoptosis and inflammation reaction, which may be closely involved in the inhibition of NLRP3 inflammasome and NF-κB activation, regulation of apoptosis-related proteins expression, and the recovery of AMPK/ACC/autophagy.

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.

Parishins, important constituents of Gastrodia elata (G. elata), are known to exhibit a number of biological and pharmacological properties. However, their role and mechanisms of action in myocardial ischemia are unknown. The present study investigated the potential protective effects and mechanisms of parishins extracted from G. elata on hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. The results demonstrated that parishins had significant protective effects on myocardial cells with parishins J and B providing greater cardioprotection through down-regulation of the level of cleaved-caspase-3 and cytochrome c in the cytoplasm and Bax, and up-regulation of cytochrome c in the mitochondria and Bcl-2 than induced by the positive control gastrodin. Additional study of the mechanisms of action indicated that the myocardial protection provided by parishin J was due to inhibition of JNK1 phosphorylation levels, down-regulation of c-jun and ATF-2 phosphorylation levels, a decrease in the phosphorylation of 14-3-3 and an increase in its binding to Bax. Therefore, parishin J was revealed to be a promising candidate as a novel treatment for myocardial protection.

Depression is a widespread psychological disorder that affects up to 20% of the world's population. Traditional Chinese medicine (TCM), with its unique curative effect in depression treatment, is gaining increasing attention as the discovery of novel antidepressant drug has become the pursuit of pharmaceutical. This article summarizes the work done on the natural products from TCM that have been reported to conceive antidepressant effects in the past two decades, which can be classified according to various mechanisms including increasing synaptic concentrations of monoamines, alleviating the hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, lightening the impairment of neuroplasticity, fighting towards immune and inflammatory dysregulation. The antidepressant active ingredients identified can be generally divided into saponins, flavonoids, alkaloids, polysaccharides and others. Albiflorin, Baicalein, Berberine chloride, beta-Asarone, cannabidiol, Curcumin, Daidzein, Echinocystic acid (EA), Emodin, Ferulic acid, Gastrodin, Genistein, Ginsenoside Rb1, Ginsenoside Rg1, Ginsenoside Rg3, Hederagenin, Hesperidin, Honokiol, Hyperoside, Icariin, Isoliquiritin, Kaempferol, Liquiritin, L-theanine, Magnolol, Paeoniflorin, Piperine, Proanthocyanidin, Puerarin, Quercetin, Resveratrol (trans), Rosmarinic acid, Saikosaponin A, Senegenin, Tetrahydroxystilbene glucoside and Vanillic acid are Specified in this review. Simultaneously, chemical structures of the active ingredients with antidepressant activities are listed and their sources, models, efficacy and mechanisms are described. Chinese compound prescription and extracts that exert antidepressant effects are also introduced, which may serve as a source of inspiration for further development. In the view of present study, the antidepressant effect of certain TCMs are affirmative and encouraging. However, there are a lot of work needs to be done to evaluate the exact therapeutic effects and mechanisms of those active ingredients, specifically, to establish a unified standard for diagnosis and evaluation of curative effect.

Tourette's syndrome (TS) occurs commonly in children, and dysfunction of dopaminergic system has long been postulated to underlie the disorder. Here, we used two TS rat models induced by 3,3'-iminodipropionitrile (IDPN) and Apomorphine (Apo) to assess an unique dopamine (DA) modulating property of gastrodin (GAS), the main bioactive component isolated from Gastrodia elata Blume, which has been widely used for treating various neurological disorders. By using high-performance liquid chromatography (HPLC), the dual restoring effects of gastrodin, at least partially, has been observed: on the one hand, gastrodin increased the down-regulated striatal DA content in IDPN-induced rats; on the other hand, gastrodin decreased the up-regulated striatal DA content in Apo-induced rats. Taken together, our data corroborated that gastrodin could restore the abnormal striatal DA dually, and this therapeutic potential might be meaningful for the anti-tic treatment.

A simple, rapid and sensitive ultra high performance liquid chromatography with fluorescence detection (UHPLC-FLD) method was developed and validated for quantification of parishin and its metabolites in rats. Plasma samples were prepared by protein precipitation and then analyzed using UHPLC-FLD system. Repeated optimization showed that parishin and its metabolites, including gastrodin, p-hydroxybenzyl alcohol, parishin B and parishin C, could be sensitively detected based on the autofluorescence when excitation and emission wavelengths were set at 225nm and 295nm, respectively. The limit of detections (LODs) of GAS, HBA, PB, PC and PA reached 0.6, 0.8, 1, 1 and 1ng/mL, respectively. The linearity for all targets was within the range 2.5-5000ng/mL and the correlation coefficient (r2) was larger than 0.999. Importantly, our method was almost free from matrix effects and the recoveries were higher than 80%. Additionally, our method also had high precision and accuracy for all analytes, presenting RSDs and REs within ±6% and ±14%, respectively. Finally, the validated UHPLC-FLD method was successfully applied for studying the pharmacokinetics of parishin following intragastrically administration in rats.

A simple, sensitive and reliable ultra fast liquid chromatography-electrospray ionization-tandem mass spectrometry (UFLC-ESI-MS/MS) method was developed for simultaneously quantifying gastrodin (p-hydroxy-methyl-phenol-β-d-glucoside) and its metabolite p-hydroxybenzyl alcohol (HBA) in dog plasma. Separation was performed on an ultra fast liquid chromatography (UFLC) system. Detection was carried out on a tandem mass spectrometry (MS/MS) in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) interface. MRM mode of precursor-product ion transitions was used for gastrodin, HBA and the internal standard (IS, bergeninum) at m/z 285.0→123.0, 123.0→105.0 and 326.9→192.2, respectively. The lower limits of quantification (LLOQ) of this method for both gastrodin and HBA were 1ng/mL, with their linear concentration ranging from 0.001 to 10μg/mL. The methods were validated for selectivity, calibration curves, accuracy and precision, extraction recoveries, matrix effects, carry-over, cross talk, dilution integrity, stability and incurred sample reanalysis (ISR). Using this validated method, pharmacokinetic behaviors of gastrodin and HBA after intragastric administration (ig) of gastrodin to dogs were studied for the first time.

Objectives To explore 1 H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats. Methods In this research, 1 H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats. Results 24 endogenous metabolites were identified. Body weight, daily diet and the total volume of urine in in each day of each rat were measured synchronously. Modifications in 12 metabolites were observed following gastrodin intervention, indicating gastrodin-induced alterations in carbohydrate and energy metabolism. Interestingly, these metabolic changes were not totally identical in female and male rats. Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male, together with arginine/ornithine, creatine, and glycerol which were on the increase in the female but on the decrease in the male. While the decrease in pyruvate, succinate and glutamate was only shown in the male and the increase in valine, α-ketoglutarate, glycine and glucose was only in the female. Conclusions This research shows the sex-specific metabolic response to GAS intervention, weather GAS is a healthy dietary supplement for the male merits further investigation.

Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine Gastrodia elata (GE) Blume, has been known to display antioxidant activity. The present study aimed to investigate the protective effects of gastrodin on 1-methyl-4-phenylpyridinium (MPP + )-induced oxidative cytotoxicity in human dopaminergic SH-SY5Y cells and the underlying mechanism for this neuroprotection. Results indicate that pre-treatment with gastrodin for 1 h significantly reduced the MPP + -induced viability loss, apoptotic rate and attenuated MPP + -mediated ROS production. In addition, gastrodin inhibited MPP + -induced lowered membrane potential, decreased Bcl-2/Bax ratio. Moreover, we have revealed the gastrodin increased Nrf2 nuclear translocation, which is upstream of heme oxygenase-1 (HO-1) expression and for the first time revealed gastrodin could increased antioxidant enzyme HO-1 expression in concentration-dependent and time-dependent manners. HO-1 siRNA transfection was employed, and confirmed gastrodin could active the expression of HO-1. And the increase in HO-1 expression was correlated with the protective effect of gastrodin against MPP + -induced injury. Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of gastrodin against MPP + -induced cell death. We also demonstrated that the specific p38 MAPK inhibitor, SB203580, concentration-dependently blocked on gastrodin-induced HO-1 expression, and meanwhile SB203580 reversed the protective effect of gastrodin against MPP + -induced cell death. Taken together, these findings suggest that gastrodin can induce HO-1 expression through activation of p38 MAPK/Nrf2 signaling pathway, thereby protecting the SH-SY5Y cells from MPP + -induced oxidative cell death. Thus our study indicates that gastrodin has a partial cytoprotective role in dopaminergic cell culture systems and could be of importance for the treatment of PD and other oxidative stress-related diseases.

Molecular imprinted polymers (MIPs) with high selectivity and affinity to gastrodin in water were designed using allyl 2,3,4,6-tetra-O-acetyl-glucopyranoside (TAGL) and 1,2,3,4,5-pentafluoro-6-vinylbenzene (PFVB) as novel functional monomers. Binding characterization of pre-polymerization complexes was researched by nuclear magnetic resonance (NMR) and the MIPs were characterized by scanning electron microscopy (SEM). The properties involving adsorption isotherm, adsorption kinetics and selective recognition capacity were evaluated. The MIPs/TAGL exhibited good site accessibility in which it only took 30min to achieve adsorption equilibrium and highly selective recognition for the template. Furthermore, the performance of the MIPs/TAGL as solid phase extraction material was investigated in detail and hot water at 50°C served as the eluting solvent. Pure gastrodin with the recovery of 76.6% was obtained from the aqueous extract of Gastrodia elata roots.

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug “Tianma” (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery., Graphical abstract Although the brain targeting of the sustained-release solid dispersions was slightly weaker (brain targeting index: 1.83 vs. 2.09) compared with the free mixture of gastrodin and borneol, stomach irritation caused by borneol obviously reduced. Sustained-release technology can be used to reduce stomach irritation by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

Gastrodin (GAS) is a Chinese medicine with wide application for the treatment of nervous system disease. Previous studies reported that GAS exhibited non-specific immunomodulatory activities. To explore the effects of GAS as a vaccine adjuvant, the expression levels of CD80, CD86, MHCI and MHCII activated markers were detected after GAS treatment in vitro and in vivo, and the expression levels of IL-2 and TNF-α in splenocytes were detected after GAS treatment in vivo. Besides, the expression levels of IL-2 and IFN-γ in CD4+T cells and perforin, TNF-α and IFN-γ in CD8+T cells were detected. The effects of GAS on the survival rate and tumor size of tumor-challenged mice and the effect of cytotoxicity on CD8+T cells were also investigated. Our data showed that GAS ameliorated CD8+T cell mediated immune response and significantly improved protection of tumor-challenged animals. The results demonstrated that GAS is a potential adjuvant contributing to anticancer immunomodulation.

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.

Eleven previously unknown compounds and 23 known compounds, including 20 phenanthrene or 9,10-dihydrophenanthrene derivatives, five bibenzyls, seven malate or tartrate benzyl ester glucosides, adenosine and gastrodin were isolated from tubers of Cremastra appendiculata. Among the obtained compounds, two are the first isolated dimers with one phenanthrene or bibenzyl unit connected to C-3 of 2,3,4,5-tetrahydro-phenanthro[2,1-b]furan moiety. In addition, 33 of these compounds were evaluated in vitro for their cytotoxic activity against two cancer cell lines. Among the compounds examined, one compound showed moderate cytotoxic activity, while five showed weak cytotoxic activity against the A549 cell line.

A new series of glycosyl oxadiazoles compounds were synthesized and characterized through (1)H NMR, (13)C NMR, IR and HRMS. The anti-tumor activities for MDA-MB-231 of all these new compounds were screened in vitro by MTT assay. Due to the modification of gastrodin analogues, the anti-tumor activities of these 1,3,4-oxadiazoles derivatives were greatly improved. Six compounds (6 c, 6 d, 6 i, 6 j, 6 k and 6 l) displayed relatively higher MDA-MB-231 potency with IC50 values (0.89, 0.26, 1.35, 3.60, 0.95 and 1.08 μM) compared with the reference medicine Rosiglitazone (5.23 μM).

Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4+ T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8+ T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4+ T cells but not in CD8+ T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4+ T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4+ T cells is implicated in its immunomodulatory activity.

The phenolic glucoside gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties. However, the role and precise molecular mechanisms explaining how gastrodin suppresses the inflammatory response in septic cardiac dysfunction are unknown. To study this, rat H9c2 cardiomyocytes were treated with gastrodin and/or lipopolysaccharide (LPS). Our results showed that gastrodin treatment strongly suppressed nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) family activation and upregulation of the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated H9c2 cardiomyocytes. Simultaneously, gastrodin obviously upregulated the phosphatidylinositol 3-kinase (PI3-K)/Akt signaling in a dose-dependent manner. However, wortmannin, a specific PI3-K inhibitor, blocked the inhibitory effects of gastrodin on LPS-stimulated H9c2 cardiomyocytes. Furthermore, PI3-K/Akt inhibition partially abolished the inhibitory effects of gastrodin on the phosphorylation of inhibitor κB-α (IκB-α), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and activity of NF-κB. Here we report activation of the PI3-K/Akt signaling by gastrodin and that inhibition of this pathway reverses the inhibitory effects of gastrodin on NF-κB and MAPKs activation in H9c2 cardiomyocytes.

One hallmark of Alzheimer's disease (AD) is amyloid-beta (Aβ) deposition, which can initiate a cascade of oxidative events that may result in neuronal death. The present study aimed to investigate the protective effects of gastrodin, a phenolic compound which shows antioxidant activity, on Aβ(1-42)-induced neurotoxicity and the underlying mechanism for this neuroprotection. Results indicate that Aβ(1-42)-induced neuronal toxicity as measured by cell viability, which was correlated with decreased catalase (CAT) content and superoxide dismutase (SOD) activity. Pre-treatment of primary hippocampal neurons with gastrodin significantly attenuated Aβ(1-42)-induced neurotoxicity and changes in SOD and CAT, and upregulated gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation. Pharmacological blockade of ERK1/2 abrogation this action of gastrodin. The ERK1/2 pathway may be involved in the neuroprotective effect of gastrodin against Aβ(1-42)-induced oxidative in primary cultured rat hippocampal neurons. These findings suggest that gastrodin could be of importance for the treatment of AD and other oxidative stress-related diseases.

Ethnopharmacological relevance Da Chuan Xiong Decoction Compound preparation (DCXDCP), the formulation of a classical Chinese prescription recorded in “Xuanminglunfang”, was clinically employed to treat migraine's disease. Aim of the study In order to investigate the influence of compatibility on the pharmacokinetics of the active ingredient Gastrodin (GAS), the comparative evaluations on pharmacokinetics of DCXDCP with various combinations of its constituent herbs in plasma after oral administration were studied. Materials and methods The rats were randomly assigned to four groups and orally administered with different prescription proportion of Gastrodia elata Bl. and Ligusticum chuanxiong Hort. (1:0; 1:0.25; 1:2.1; 1:4.2), respectively. At different predetermined time points after administration, the concentrations of GAS in rat plasma were determined by using HPLC, and main pharmacokinetic parameters were investigated. Results The results showed that the pharmacokinetic parameters, AUC and Cmax of GAS were dramatically different (p Conclusions These indicated that the compatibility effects of other ingredients present in DCXDCP could affect the pharmacokinetics of the prescription.

Gastrodin is a pharmacologically active substance isolated from Gastrodia elata Blume with sedation, anti-convulsion and anti-epilepsy activities. A rapid and sensitive liquid chromatography technique coupled to tandem mass spectrometry (LC-MS/MS) system was developed to determine gastrodin and its metabolite p-hydroxybenzyl alcohol (HBA) in rat blood, brain and bile collected using microdialysis technique. The analytes were separated using a reversed phase column (4.6 mm x 150 mm, 5 microm). The mobile phase for column separation was 30% methanol with a flow rate of 0.6 mL/min. As a post-column addition, 1% ammonium hydroxide solution (in methanol) was additionally pumped via a T-connection using a chromatographic pump (BAS PM-80, USA) at a flow rate of 0.2 mL/min after the column separation. A LC-MS/MS system equipped with a negative electrospray ionization (ESI) source in multiple reaction monitoring (MRM) mode was used to monitor m/z 285.0-->122.9 and m/z 123.0-->105.0 transitions for gastrodin and HBA, respectively. The lower limit of quantification (LLoQ) for gastrodin and HBA were 0.5 and 2 ng/mL, respectively. The calibration curves were linear over the range of 0.5-5,000 ng/mL and 2-1,000 ng/mL for gastrodin and HBA with a coefficient of determination >0.995, respectively. This selective and sensitive method is useful for the determination of gastrodin and HBA and in the pharmacokinetic studies of these compounds.

Gastrodin is the important ingredients of Gastrodia elata Blume owing to its important pharmacological properties. The aim of the current research is to introduce one-step microbial bioconversion of p -2-hydroxybenzyl alcohol (HBA) to gastrodin instead of chemical synthesis. The method of gastrodin measurement was firstly constructed. Structural elucidation of biotransformed compounds was based on one-dimensional and two-dimensional NMR. Nine resting-filamentous cells suspension are screened for their transforming capabilities to produce gastrodin. The microorganisms used were Armillaria luteo-virens Sacc (CGMCC no. 1884), Aspergillus foetidus ZU-G1 (CGMCC no. 1628), Peniciuium cyclopium AS 3.4513, Aspergillus niger AS 3.40, A. niger AS 3.429, Trichoderma viride AS 3.4005, Trichoderma sp., Penicillium notatum , Mucor sp., Rhizopus sp. A. luteo-virens Sacc U gave the highest gastrodin concentration. The optimized bioconversion conditions for A. luteo-virens Sacc U consisted of inoculums size 160.0 ± 10.5 g resting cells/L, amounts of precursor (HBA) 10.0 mg/ml, bioconversion system pH 6.0, 1% (v/v) Tween 80 or 0.1% oleic acid, bioconversion temperature 23 °C, shaking speed 120 rpm in darkness. Under the optimized transformation conditions, the highest gastrodin concentration was 750 ± 38 μg/100 ml at 5 days. The results of current study cannot only apply to replace the chemical synthesis process that involves the glycosylation reaction, but also apply to scale-up production.