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Major depressive disorder (MDD) is a prevalent condition that affects approximately 350 million people worldwide. Several studies have identified changes in amino acids in the blood of MDD patients, suggesting their potential as biomarkers to better understand their role in depression. Gastrodia elata Blume (GEB) and its active compound gastrodin (GAS) are recognized for their antidepressant properties. However, their effects on amino acid profiles and their potential role in alleviating depression remain poorly understood. Understanding how GEB and GAS influence amino acid metabolism may offer novel insights into their mechanisms in alleviating depression, potentially leading to more targeted therapeutic strategies. This study aimed to investigate the potential role of supplementing GEB and its active compound GAS to reverse altered amino acid profiles in depressed rats. To achieve this, six-week-old SD rats were induced depressive-like behaviors by the UCMS rat model for 5 weeks. Groups receiving GEB or GAS were administered orally via gavage daily within the UCMS model. Serum samples were collected and analyzed using a targeted metabolomics approach employing LC-MS for amino acid profiling. A total of 38 amino acid metabolites were identified, 17 of which were significantly altered following UCMS. UCMS rats exhibited perturbed arginine biosynthesis, arginine and proline metabolism pathways. Changes in key amino acids in these metabolic pathways were reversed following supplementation with GEB and GAS, which also alleviated depressive symptoms. In conclusion, UCMS-induced depression in rats causes changes in some amino acid metabolites similar to those found in human depression, validating its relevance as a model for studying depression. Additionally, the research suggests that GEB and GAS may exert antidepressant effects by regulating amino acid metabolism. [Display omitted] • Gastrodia elata Blume and gastrodin restores sucrose preference in rats subjected to unpredictable chronic mild stress (UCMS). • Amino acid profile alterations observed in rats subjected to UCMS. • Amino acid metabolism could be a therapeutic target for the invention of novel antidepressants. • Gastrodia elata Blume and gastrodin exerts antidepressant effects by reversing perturbations in the arginine and proline metabolic pathway. [ABSTRACT FROM AUTHOR]

Cisplatin (CP) results in acute kidney injury (AKI) and negatively affects patients' therapy and survival. The dried rhizome of Gastrodia elata Blume has been used to treat clinical kidney diseases. Gastrodin (GAS) is an active ingredient of the G. elata tuber. It is unknown whether GAS can alleviate CP-induced AKI. This study aimed to investigate whether GAS, an active ingredient of G. elata Blume, can alleviate CP-induced AKI and to explore its underlying mechanisms. Experiments were conducted with a CP-induced AKI mouse model and an immortalized human renal tubular epithelial cell line (HK-2). Serum creatinine, Periodic acid–Schiff staining, tissue iron, glutathione, malondialdehyde, and 4-Hydroxynonenal were detected in serum and kidney samples to observe whether GAS inhibits CP-induced tubule ferroptosis. The drug target was verified by detecting the effects of GAS on sirtuin-1 (SIRT1) activity in vitro. Transcriptional regulation of glutathione peroxidase 4 (GPX4) by forkhead box O3A (FOXO3A) was verified by siRNA knockdown, overexpression, and chromatin immunoprecipitation. The effects of FOXO3A, SIRT1, and GAS on CP-induced ferroptosis were measured with propidium iodide, dihydroethidium, monobromobimane, and dipyrromethene boron difluoride staining in HK-2 cells. The relationship between GAS and the SIRT1/FOXO3A/GPX4 pathway was studied using Western blotting. GAS treatment inhibited CP-induced reactive oxygen species, lipid peroxidation, and tubule death in the cell and animal models. GAS activated SIRT1 in vitro. The SIRT1 inhibitor blocked the protective role of GAS in reducing lipid peroxidation in HK-2 cells. FOXO3A transcriptionally regulated GPX4 expression and inhibited CP-induced cell ferroptosis. Compared to CP-damaged mouse kidneys, GAS-treated mice demonstrated significantly increased SIRT1 and GPX4 expression levels, decreased CP-induced acetylation of FOXO3A, and inhibited lipid peroxidation and cell death. GAS alleviated CP-induced AKI by inhibiting ferroptosis via the SIRT1/FOXO3A/GPX4 signaling pathway. The results offer new insights into the development of new anti-AKI drugs from traditional Chinese medicine. Gastrodin is the main active ingredient of the perennial herb Gastrodia elata Blume, and exerts anti-ferroptosis effects in CP-injured HK-2 cells and mice by regulating the SIRT1/FOXO3A/GPX4 signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance 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. Aim of the study 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. Materials and methods 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. Results The results showed that tetramethylpyrazine had no significant effects on the PK parameters of GAS ( p >0.05), whereas ferulic acid (FA), total phenolic acids and total alkaloids significantly increased AUC 0-∞ ( p <0.05). 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ethnopharmacology relevance Gastrodia elata Blume is a highly valuable traditional Chinese medicine used in the treatment of depression. However, compounds with antidepressant effects in water extracts of G. elata Bl. (WGE) have not been identified. The aims of this study were to determine the major antidepressant compound in WGE and to evaluate the antidepressant effects of WGE and its active compounds which involved the monoaminergic system and neuronal cytoskeletal remodeling. Materials and methods Gastrodin (GAS) and 4-hydroxybenzyl alcohol (HBA) in WGE, were analyzed with high-performance liquid chromatography (HPLC)-ultraviolet detection. The forced swimming test (FST) was used to induce depression-like symptoms in 9 weeks old male Sprague-Dawley rats. The open field test (OFT) was used to measure anxiety after WGE, GAS, and HBA treatments. The levels of monoamine such as serotonin (5-HT), dopamine (DA), and their metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using HPLC-electrochemical detection. Western blotting was used to examine the 5-HT1A receptor and the neuronal cytoskeleton remodeling-related proteins, Slit, dihydropyrimidinase-related protein 2 (DPYSL2, also called CRMP2), Ras homologous member A (RhoA), and profilin 1 (PFN1) in vivo. Slit1 expression was evaluated in Hs683 cell line after treated with WGE (0.5 mg/mL), GAS (50, 100 and 100 μM), and HBA (50, 100 and 100 μM). Results Oral administration of WGE (500 mg/kg bw), GAS (100 mg/kg bw), and HBA (100 mg/kg bw) exhibited the anti-depressant effect by significantly reducing the immobility time in FST, monoamine metabolism including the 5-HT to 5-HIAA in the hippocampus and DA to DOPAC and HVA ratios in the frontal cortex, amygdala, and hippocampus. In the hippocampus, the expression of the neuronal cytoskeleton remodeling-related negative regulators Slit1 and RhoA were significantly down-regulated. In addition, the positive regulators CRMP2 and PFN1 were significantly up-regulated following GAS, HBA, and WGE treatments. Moreover, WGE, GAS, and HBA were directly down-regulated Slit1 expression in Hs683 cells. Conclusion WGE, GAS, and HBA exhibited potential anti-depressant effects in rats by decreasing monoamine metabolism and modulated cytoskeleton remodeling-related protein expression in the Slit-Robo pathway. These results suggest that WGE can be used as agent for depressive prevention. [ABSTRACT FROM AUTHOR]

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 C max , T max , AUC 0–∞ , t 1/2 , MRT, V d , 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 ( t 1/2 ) 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 . [ABSTRACT FROM AUTHOR]

Abstract: 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 C max of GAS were dramatically different (p <0.05) after oral administration of G. elata Bl. and the different combinations of its constituent herbs. Conclusions: These indicated that the compatibility effects of other ingredients present in DCXDCP could affect the pharmacokinetics of the prescription. [Copyright &y& Elsevier]

Gastrodia elata Blume (GEB), known as Tianma in China, is a traditional medicinal herb that has been reported to have various pharmacological effects and neuroprotection, has long been used for treating dizziness, epilepsy, stroke. However, explanation of its underlying mechanisms remains a great challenge. The neuroprotective mechanism of GEB on hypoxia-induced neuronal injury in cultured mouse embryonic neural progenitor cells (eNPCs) was investigated, with emphasis on the eNPCs proliferation and DNA damage repair. In this study, hypoxia was focused, which may be caused by stroke or acute cerebral ischemia and is considered as one of the important factors contributing to the Central Nervous System diseases. CoCl 2 was adopted to construct a hypoxic/ischemic condition in eNPCs. eNPCs proliferation analysis validated GEB neuroprotective effect under hypoxic/ischemic condition. Transcriptome and weighted gene co-expression network analysis (WGCNA) screened the special gene-network module correlated with what appeared to have significant positive correlation with GEB. Then, Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to explore the biological functions of selected genes in the modules that had high correlation with GEB. GEB has neuroprotective effect and could rescue eNPCs proliferation under hypoxic/ischemic condition induced by CoCl 2. Transcriptome and WGCNA unveil the neuroprotective mechanism of GEB on improving DNA damage repair ability by increasing the expression of genes associated with DNA repair and replication. Western blotting and qPCR showed that GEB could improve DNA damage repair ability by increasing the expression of Mcm2 , Mcm6 , Pold2, Pole , Pole2 , Rfc1 , Pole4 , Dna2 and Rpa2 , which were associated with DNA damage and replication. Through transcriptome and WGCNA, this study unveiled Gastrodia elata Blume could increase the cell viability of eNPCs under hypoxic condition by improving DNA damage repair ability. [Display omitted] • Gastrodia elata Blume could increase the cell viability of eNPCs under Hypoxic/Ischemic condition. • WGCNAs identified Gene-Network Modules rescuing eNSCs proliferation. • Gastrodia elata could improving DNA damage repair ability. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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 GABA A receptor after pilocarpine-induced seizures. In the experimental seizure model, gastrodin showed anti-seizure and neuroprotective abilities. Enhancing the expression of GABA A receptor plays an important role in its antiepileptic mechanism. The results offer a new insight of developing new antiepileptic drugs from traditional Chinese medicine. Image 1 • Gastrodin alleviated the acute seizure severity and epileptiform discharge in lithium-pilocarpine model. • Gastrodin showed neuroprotective effect against the seizure related hippocampal neuronal damage. • The treatment of gastrodin reversed the degradation of GABA A receptor after pilocarpine-induced seizures. [ABSTRACT FROM AUTHOR]