Two new aromatic compounds, namely gastupdin A (1), and gastupdin B (2), together with three known compounds, arundin(3), phomosines B (4) and monocillin IV (5), were isolated from the aerial parts of Gastrodia elata Blume. The structures of the new compounds were confirmed through spectral analyses including NMR, HR-ESI-MS, ECD, UV, and IR. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death in Human Neuroblastoma Cells, with curcumin as the positive control, however, the activity of all compounds was weaker than the positive control, showing no significant activity.

BACKGROUND: Identifying the geographical origin of Gastrodia elata Blume contributes to the scientific and rational utilization of medicinal materials. In this study, infrared spectroscopy was combined with machine learning algorithms to distinguish the origin of G. elata BI.
OBJECTIVE: Realization of rapid and accurate identification of the origin of G. elata BI.
METHODS: Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra and Fourier transform near-infrared (FT-NIR) spectra were collected for 306 samples of G. elata BI.
METHODS: Firstly, a support vector machine (SVM) model was established based on the single-spectrum and the full-spectrum fusion data. To investigate whether feature-level fusion strategy can enhance the model\'s performance, the sequential and orthogonalized partial least squares discriminant analysis (SO-PLS-DA) model was established to extract and combine two types of spectral features. Next, six algorithms were employed to extract feature variables, SVM model was established based on the feature-level fusion data. To avoid complicated preprocessing and feature extraction processes, a residual convolutional neural network (ResNet) model was established after converting the raw spectral data into spectral images.
RESULTS: The accuracy of the feature-level fusion model is better as compared to the single-spectrum model and the fusion model with full-spectrum, and SO-PLS-DA is simpler than feature-level fusion based on the SVM model. The ResNet model performs well in classification but requires more data to enhance its generalization capability and training effectiveness.
CONCLUSIONS: Sequential and orthogonalized data fusion approaches and ResNet models are powerful solutions for identifying the geographic origin of G. elata BI.

Gastrodia elata (G. elata) Blume is widely used as a health product with significant economic, medicinal, and ecological values. Due to variations in the geographical origin, soil pH, and content of organic matter, the levels of physiologically active ingredient contents in G. elata from different origins may vary. Therefore, rapid methods for predicting the geographical origin and the contents of these ingredients are important for the market. This paper proposes a visible-near-infrared (Vis-NIR) spectroscopy technology combined with machine learning. A variety of machine learning models were benchmarked against a one-dimensional convolutional neural network (1D-CNN) in terms of accuracy. In the origin identification models, the 1D-CNN demonstrated excellent performance, with the F1 score being 1.0000, correctly identifying the 11 origins. In the quantitative models, the 1D-CNN outperformed the other three algorithms. For the prediction set of eight physiologically active ingredients, namely, GA, HA, PE, PB, PC, PA, GA + HA, and total, the RMSEP values were 0.2881, 0.0871, 0.3387, 0.2485, 0.0761, 0.7027, 0.3664, and 1.2965, respectively. The Rp2 values were 0.9278, 0.9321, 0.9433, 0.9094, 0.9454, 0.9282, 0.9173, and 0.9323, respectively. This study demonstrated that the 1D-CNN showed highly accurate non-linear descriptive capability. The proposed combinations of Vis-NIR spectroscopy with 1D-CNN models have significant potential in the quality evaluation of G. elata.

UNASSIGNED: Based on our previous research on the specific miRNAs identified from Gastrodia elata, we selected Gas-miR2-3p to investigate its effects on neuroinflammation via in vitro and in vivo experiments.
UNASSIGNED: RT-qPCR analysis indicated that G. elata specific Gas-miR2-3p was detected in all murine tissues post-oral administration, suggesting their potential as orally bioavailable miRNA. The analysis of RT-qPCR, Western blotting and ELISA assays consistently demonstrate that the expression of inflammatory factors as TNF-α, IL-6, IL-1β was decreased and the expression levels of p-p65 and p-IκBα were downregulated after the action of Gas-miR2-3p in both cell and animal experiments.
UNASSIGNED: Gas-miR2-3p can attenuate neuroinflammation by regulating the inflammation factors and suppressing the activation of the NF-κB signaling pathway. Our findings indicate that G. elata miRNAs, as novel active components, perform a modulatory role in the NF-κB signaling pathway associated with neuroinflammation in a cross-species way.

BACKGROUND: Gastrodia elata Blume (G. elata) has a long historical application in Asian countries and its tubers, seeds, and stalks are capable of being utilized for medicine, food, or health care products.
OBJECTIVE: This study aimed to offer a systematic and up-to-date analysis of the current review of the G. elata research advances in traditional uses, phytochemistry, pharmacology, applications, and quality control, as well as a scientific reference for the development and utilization of this plant.
METHODS: Electronic databases including PubMed, Web of Science, Google Scholar, ScienceDirect, SciFinder, and CNKI were used for the collection of publications on G. elata. The following keywords of G. elata were used truncated with other relevant topic terms, such as phenolic compounds, polysaccharides, glycosides, neuroprotection, learning and memory improvement effects, cardioprotection, applications, and quality control.
CONCLUSIONS: Approximately 134 chemical components mainly categorizing as phenolic compounds, polysaccharides, glycosides, organic acids, and sterols were reported from this plant. Moreover, preclinical studies indicated that G. elata performs several functions, including neuroprotection, learning and memory improvement effects, cardioprotection, vaso-modulatory effect, anti-depression, anti-cancer, and other effects. Currently, G. elata has been widely applied to clinics and foods. The available literature shows that the quality of G. elata might be affected by factors such as origin, fungus, and harvest time, which will have an impact on the drug efficacy. According to past research, G. elata is a potential medicinal and edible plant with several active components and pharmacological activity that has a high application value in medicine and the food business. Nevertheless, few studies have concentrated on characterization of polysaccharides structure and study of non-medicinal parts, implying that further comprehensive research on its polysaccharides structure and non-medicinal parts is critical for full utilization of resources of G. elata.

Gastrodia elata Blume is a traditional Chinese medicine with a long history, which has numerous pharmacological activities, such as anti-inflammation, anti-oxidation and protection of nerves. The present study investigated the regulatory effect of ethyl acetate extract of Gastrodia elata (EEGE) on the β-amyloid (Aβ) toxicity of Caenorhabditis elegans (C. elegans). First, the main components of EEGE were analyzed using high-performance liquid chromatography, and the total phenols, total flavonoids and total antioxidant capacity of EEGE were determined. Next, the regulation effect of EEGE on Aβ-induced toxicity of C. elegans was evaluated through experiments on nematode paralysis, lifespan, oxidative and heat stress, locomotor ability, reproductive ability, reactive oxygen species (ROS) level, Aβ aggregation test, malondialdehyde (MDA) level, catalase (CAT) activity and superoxide dismutase (SOD) activity. Finally, the mechanism of EEGE was elucidated using RNA sequencing (RNA-Seq) and the expression levels of related genes were verified using quantitative PCR. The present study revealed that the main components of EEGE included phosphorylated (p)-hydroxybenzyl alcohol, p-hydroxybenzaldehyde and 4,4\'-dihydroxydiphenylmethane, possessing strong in vitro free radical scavenging and reducing abilities. In addition, after the intervention of EEGE, the paralysis of nematodes could be delayed, the survival time of the nematodes was prolonged, the survival rate of the nematodes under stress (high temperature and oxidation) conditions was improved, the activity capacity and reproductive capacity of the nematodes were improved, the activities of SOD and CAT were improved and the levels of ROS and MDA were reduced. Notably, EEGE directly inhibited Aβ plaque aggregation in nematodes. RNA-Seq analysis showed that EEGE regulated metabolism and longevity-related genes, and these genes were regulated by the insulin/IGF-1 signaling (IIS) pathway. Therefore, the present study hypothesized that the regulatory mechanism of EEGE was significantly related to the IIS pathway. The present research results demonstrated that the protective effect of EEGE on transgenic C. elegans was to reduce Aβ protein aggregation, improve the in vivo antioxidant level, effectively remove free radicals and to regulate the expression of genes related to IIS pathway, thereby reducing Aβ-induced toxicity and delaying nematode paralysis.

The variety is one of the most important factors to generate difference of chemical compositions, which unavoidably influences the quality of natural medicine. Thus, simple and rapid authentication of different variants has great academic and practical significance. In this study, the goal was achieved with the help of near infrared spectroscopy (NIR) and chemometrics by using Gastrodia elata Blume as an example. A total of 540 samples including two classes of variants and their forms were investigated as a whole. The mean spectra of samples of each class and their 2-D synchronous correlation spectra were simultaneously applied to discover the difference of chemical characteristics. After hybrid pre-processing of the first and second derivative combined with Savitzky-Golay and Norris filtering, partial least squares discrimination analysis (PLS-DA) on the basis of latent variable projection was used to assess the feasibility for classification. The results show higher prediction accuracy in both internal test set and external prediction set. In order to further improve the robustness for modeling, three methods for wavelength selection were comprehensively compared to optimize PLS-DA models, including variable importance in the projection (VIP), random frog (RF), and Monte Carlo uninformative variable elimination (MC-UVE). The prediction accuracy of combination of the 2nd derivative, Norris, MC-UVE and PLS-DA achieved to 99.11% and 98.89% corresponding to the internal test set and external prediction set, respectively. The strategies proposed in this work perform effectiveness for rapid and accurate authentication of variants of plants with high chemical complexity.

In aerospace medicine, the influence of microgravity on cognition has always been a risk factor threatening astronauts\' health. The traditional medicinal plant and food material Gastrodia elata Blume has been used as a therapeutic drug for neurological diseases for a long time due to its unique neuroprotective effect. To study the effect of fresh Gastrodia elata Blume (FG) on cognitive impairment caused by microgravity, hindlimb unloading (HU) was used to stimulate weightlessness in mice. The fresh Gastrodia elata Blume (0.5 g/kg or 1.0 g/kg) was intragastrically administered daily to mice exposed to HU and behavioral tests were conducted after four weeks to detect the cognitive status of animals. The behavioral tests results showed that fresh Gastrodia elata Blume therapy significantly improved the performance of mice in the object location recognition test, Step-Down test, and Morris Water Maze test, including short-term and long-term spatial memory. According to the biochemical test results, fresh Gastrodia elata Blume administration not only reduced serum factor levels of oxidative stress but also maintained the balance of pro-inflammatory and anti-inflammatory factors in the hippocampus, reversing the abnormal increase of NLRP3 and NF-κB. The apoptosis-related proteins were downregulated which may be related to the activation of the PI3K/AKT/mTOR pathway by fresh Gastrodia elata Blume therapy, and the abnormal changes of synapse-related protein and glutamate neurotransmitter were corrected. These results identify the improvement effect of fresh Gastrodia elata Blume as a new application form of Gastrodia elata Blume on cognitive impairment caused by simulated weightlessness and advance our understanding of the mechanism of fresh Gastrodia elata Blume on the neuroprotective effect.

Epilepsy is a serious public health problem in the world. At present, over 30% of affected patients remain refractory to currently available treatment. Medicinal plants as pharmaceuticals and healthcare treatments have been frequently used in the management of epilepsy in China for many centuries. Gastrodia elata-Acous tatarinowii (GEAT), as a classic and most commonly used herb pair in traditional Chinese medicine (TCM), has been employed to control seizures for thousands of years. However, the animal experiment data on its anticonvulsant effect is limited in the literature. Thus, this study aimed to reveal the therapeutic actions of GEAT decoction against seizures in mice. UHPLC-MS/MS was performed to analyze the chemical components of GEAT decoction. The mice were given GEAT decoction for 7 days, and MES, PTZ, and 3-MP injection was given 30 min after the last administration. Video monitoring was performed for comparisons. In addition, the PTZ-induced kindling models were conducted to investigate the seizure severity, anxiety and cognitive profile, inflammation, and oxidative stress parameters in mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP, and PTZ-induced acute seizures. Furthermore, GEAT decoction significantly ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1β, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. These results suggest that GEAT decoction possesses certain anticonvulsant properties, which might be clinically useful as phytotherapy alone or as an adjunct therapy for the prevention and treatment of seizures and epilepsy.

Rhizoma Gastrodia (Orchidaceae; Gastrodia elata Blume), the rhizome of Gastrodia elata Blume (GE), is traditionally used as both a medicinal and functional food, with proven efficacy in treating mental disorders. In traditional processing, GE is washed, steamed with water, dried, and sliced. In this study, a novel processing technology-alcohol steamed GE (AGE) was proposed as an alternative. Totally, 17 compounds were identified in fresh GE and AGE. Compared with fresh GE, the relative content of parishin A and parishin E decreased after alcohol steaming, whereas gastrodin (GAS), p-hydroxylbenzyl alcohol (HBA), Parishin B, and Parishin C were increased. Additionally, the pentobarbital-induced sleep mice model and Chronic Restraint Stress (CRS) model were applied to evaluate the pharmacological effects of fresh GE and steamed GE, and both fresh and steamed GE showed an intensive hypnotic and anti-anxiety effect. Furthermore, the anti-anxiety mechanism based on serum metabolic was investigated and the tryptophan metabolic pathway was considered the response to the anti-anxiety effect of GE. Although the optimization of the processing technology of AGE still needs to be further explored, the current results have provided new thoughts for the processing technology and clinical application of GE.