Microbial Cell Factories
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2020
·Vol. 19
·期 1
·1-12
·
IF 4.187
Yin Hua,Hu Tiandong,Zhuang Yibin,Liu Tao
Background The natural phenolic glycoside gastrodin is the major bioactive ingredient in the well-known Chinese herb Tianma and is widely used as a neuroprotective medicine in the clinic. Microbial production from sustainable resources is a promising method to replace plant extraction and chemical synthesis which were currently used in industrial gastrodin production. Saccharomyces cerevisiae is considered as an attractive host to produce natural plant products used in the food and pharmaceutical fields. In this work, we intended to explore the potential of S. cerevisiae as the host for high-level production of gastrodin from glucose. Results Here, we first identified the plant-derived glucosyltransferase AsUGT to convert 4-hydroxybenzyl alcohol to gastrodin with high catalytic efficiency in yeast. Then, we engineered de novo production of gastrodin by overexpressing codon-optimized AsUGT syn , the carboxylic acid reductase gene CAR syn from Nocardia species, the phosphopantetheinyl transferase gene PPTcg-1 syn from Corynebacterium glutamicum , the chorismate pyruvate-lyase gene UbiC syn from Escherichia coli , and the mutant ARO4 K229L . Finally, we achieved an improved product titer by a chromosomal multiple-copy integration strategy and enhancement of metabolic flux toward the aglycon 4-hydroxybenzyl alcohol. The best optimized strain produced 2.1 g/L gastrodin in mineral medium with glucose as the sole carbon source by flask fermentation, which was 175 times higher than that of the original gastrodin-producing strain. Conclusions The de novo high-level production of gastrodin was first achieved. Instead of chemical synthesis or plants extraction, our work provides an alternative strategy for the industrial production of gastrodin by microbial fermentation from a sustainable resource.
研究领域:
生物工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 29
·16701-16712
·
IF 3.049
Xiaofeng Li,Maohua Ma,Xuan Xin,Yuqian Tang,Guanglei Zhao,Xinglong Xiao
Gastrodin, a bioactive compound extracted from the plant source of Gastrodia elata Blume, has a wide range of therapeutic effects on central nervous system (CNS) diseases, but suffers from poor brain permeability and short half-life in plasma. In this study, fatty acid esters of gastrodin were successfully synthesized by a whole cell-based biocatalytic method. Aspergillus oryzae cells showed different catalytic activities in the organic solvent systems tested. Tetrahydrofuran was confirmed as the most suitable pure organic solvent, with the highest substrate conversion of 98.0%. Addition of ionic liquids (ILs) into pyridine dramatically accelerated the reaction with conversion increased from 5.9% to 84.2%, and also changed the selectivity of the cells, mainly due to the use of IL-containing systems altering cell permeability and contact of the enzymes with solvent molecules possessing different polarities. The ester products were characterized by 13C-NMR and ESI-MS as gastrodin monoester and diester.
研究领域:
药理学
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生物催化
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Kunkun Guo,Xin Wang,Baolin Huang,Xiaoyun Wu,Shuimei Shen,Zimin Lin,Jie Zhao,Zheng Cai
Gastrodin is the main active constituent of Tianma, a famous traditional Chinese herbal medicine. Our previous research has found that gastrodin is absorbed rapidly in the intestine by the sodium-dependent glucose transporter 1 (SGLT1). In the current report, gastrodin is the best glycoside compound absorbed via the glucose transport pathway. This study aimed to investigate the effect of the slight difference in chemical structure on the drug intestinal absorption via the glucose transport pathway. Traditional biopharmaceutical and computer-aided molecular docking methods were used to evaluate the intestinal absorption characteristics of three gastrodin analogues, namely, salicin , arbutin and 4-methoxyphenyl-β-D-glucoside (4-MG). The oil–water partition coefficient (log P ) experiments showed that the log P values of the gastrodin analogues followed the order: 4-MG > salicin > arbutin. In vitro Caco-2 cell transport experiments demonstrated that the apparent permeability coefficient ( P app ) value of arbutin was higher than those of salicin and 4-MG. In situ single-pass intestinal perfusion experiments showed that the absorption of arbutin and 4-MG was better than that of salicin and that the absorption of the three compounds in the colon was lower than that in the small intestine. Quantitative real-time polymerase chain reaction results confirmed that the SGLT1 mRNA expression in the small intestine of rats was obviously higher than that in the colon of rats. In vivo pharmacokinetic experiments demonstrated that the oral bioavailability of salicin was lower than those of arbutin and 4-MG. In vitro and in vivo experiments showed that glucose or phlorizin (SGLT1 inhibitor) could decrease the intestinal absorption of the three compounds. Contrary to the above biopharmaceutical experiments, the computer-aided molecular docking test showed that the affinity of salicin to the v SGLT receptor was stronger than those of arbutin and 4-MG. In conclusion, the SGLT1 can facilitate the intestinal absorption of salicin, arbutin and 4-MG, and the slight difference in chemical structure can affect absorption.
研究领域:
药理学
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生物医学工程
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Neuroscience
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2024
·
IF 3.2
Houminji Chen,Yuqing Miao,Haowen Duan,Shasha Yi,Zhengrong Lin,Yanwu Guo,Junjie Zou,Lili Niu
Both physiotherapy and medicine play essential roles in the treatment of epilepsy. The purpose of this research was to evaluate the efficacy of the combined therapy with focus ultrasound stimulation (FUS) and gastrodin (GTD) on seizures in a mouse model. Kainic acid-induced seizure mice were divided into five groups randomly: sham, FUS, saline + sham, GTD + sham and GTD + FUS. The results showed that combined therapy with ultrasound stimulation and gastrodin can significantly reduce the number and duration of seizures in GTD + FUS group. 9.4T magnetic resonance imaging and histologic staining results revealed the underlying mechanism of the combined therapy may be that ultrasound stimulation increases cell membrane permeability to increase GTD concentration in brain. In addition, we verified the safety of FUS combined with GTD therapy. This research provides a new strategy for neurological disorders combining treatment of physical neuromodulation and medicine.
研究领域:
神经科学
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药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
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2020
·Vol. 108
·期 8
·1713-1725
·
IF 3.525
Qing Li,Limei Li,Mali Yu,Meng Zheng,Yao Li,Jian Yang,Min Dai,Lianmei Zhong,Lin Sun,Di Lu
The extracellular matrix provides cells with a support structure and an attachment site in actual substrate. Its biochemical and surface properties play an important role in and have significant impact on cell attachment, proliferation, migration, differentiation, and gene expression. Leveraging the hydrophilicity and neuroprotective of gastrodin, a gastrodin/polyurethane (PU) elastomer was developed utilizing in situ polymerization and salt-leaching methods. The results showed that gastrodin/PU film had a good flexibility and supporting strength, as well as hydrophilicity. Thus film possessed highly surface area, interconnected porous structure with a pore size (10~60 μm) for cell attachment, and could provide surface cues to augment neurite extension. For PC12 cells cultured within the films, especially the 5gastrodin/PU group, presented a progressive increase with time, coupled with the upregulation of brain-derived neurotrophic factor and glial cell derived neurotrophic factor expression. This is the first report on the construction of a gastrodin/PU porous film, and the results reveal its promise as a scaffold material for neural tissue engineering.
研究领域:
生物材料学
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神经科学
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组织工程学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2012
·
IF 2.888
Li Jiang,Jundong Dai,Zhenlin Huang,Qinghua Du,Jiahao Lin,Yurong Wang
Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae , respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic ( i.g. )/intravenous ( i.v. ) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101–101 μg/mL for Gas and 0.0500–5.98 μg/mL for Pur ( r 2 > 0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4 ± 6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g. / i.v. administration of Gas and Pur alone or combined with each other ( i.g. : 40 mg/kg Gas, 400 mg/kg Pur; i.v. : 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C 18 column with a gradient mobile phase of ACN–H 2 O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C max , T max , T 1/2 , MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral bioavailability of Pur in combined administration was 10.7 times as much as that of single administration, whilst 1.52 folds in Gas. These results indicate that co-administration of Gas and Pur is a promising combination to gain higher bioavailability and it is suggested that doctors pay more attention to the dosages of the two when simultaneously using both of them.
研究领域:
药理学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 4
·1230
·
IF 4.927
Li Jiang,Yanling Xiong,Yu Tu,Wentong Zhang,Qiyun Zhang,Peng Nie,Xiaojun Yan,Hongning Liu,Ronghua Liu,Guoliang Xu
Puerarin (PUR) and gastrodin (GAS) are often used in combined way for treating diseases caused by microcirculation disorders. The current study aimed to investigate the absorption and transportation mechanism of PUR and GAS and their interaction via Caco-2 monolayer cell model. In this work, the concentration in Caco-2 cell of PUR and GAS was determined by HPLC method. The bidirectional transport of PUR and GAS and the inhibition of drug efflux including verapamil and cyclosporine on the transport of these two components were studied. The mutual influence between PUR and GAS, especially the effect of the latter on the former of the bidirectional transport were also investigated. The transport of 50 μg·mL−1PUR in Caco-2 cells has no obvious directionality. While the transport of 100 and 200 μg·mL−1PUR presents a strong directionality, and this directionality can be inhibited by verapamil and cyclosporine. When PUR and GAS were used in combination, GAS could increase the absorption of PUR while PUR had no obvious influence on GAS. Therefore, the compatibility of PUR and GAS is reasonable, and GAS can promote the transmembrane transport of PUR, the effect of which is similar to that of verapamil.Keywords:transport mechanism;puerarin;gastrodin;absorption;Caco-2 cell monolayer
研究领域:
药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 3
·547
·
IF 3.06
Minhui Hu,Hui Yan,Yuanyuan Fu,Yulan Jiang,Weifeng Yao,Sheng Yu,Li Zhang,Qinan Wu,Anwei Ding,Mingqiu Shan
Gastrodia elatatuber (GET) is a popular traditional Chinese medicines (TCMs). In this study, response surface methodology (RSM) with a Box–Behnken design (BBD) was performed to optimize the extraction parameters of gastrodin-type components (gastrodin, gastrodigenin, parishin A, parishin B, parishin C and parishin E). Different from the conventional studies that merely focused on the contents of phytochemical, we gave consideration to both quantitative analysis of the above six components by HPLC and representative bioactivities of GET, including antioxidation and protection of human umbilical vein endothelial cells (HUVEC). Four independent variables (ethanol concentration, liquid-material ratio, soaking time and extraction time) were investigated with the integrated evaluation index of phytochemical contents. With the validation experiments, the optimal extraction parameters were as follows: ethanol concentration of 41%, liquid–solid ratio of 28.58 mL/g, soaking time of 23.91 h and extraction time of 46.60 min. Under the optimum conditions, the actual standardized comprehensive score was 1.8134 ± 0.0110, which was in accordance with the predicted score of 1.8100. This firstly established method was proved to be feasible and reliable to optimize the extraction parameters of the bioactive components from GET. Furthermore, it provides some reference for the quality control and extraction optimization of TCMs.Keywords:Gastrodia elatatuber (GET);Response surface methodology;Antioxidation;HUVEC;Gastrodin-type components
研究领域:
中药学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Qiang Yin,Ran Yan,Yan Wang,Jia Yu
Gatrodin is an active compound with cardio-protective potentials. In the current study, the mechanism underlying the effects of gastrodin was explored. Myocardial infarction was induced and handled with gastrodin. The role of miR-30a-5p and its downstream effector, ATG5, in the cardio-protective effects of gastrodin was verified. Gastrodin induced the dys-expresseion of 72 miRs in oxygen/glucose deprivation (OGD) cardiomyocytes and miR-30a-5p was selected as the potential therapeutic target. Gastrodin increased viability and suppressed autophagy in OGD cardiomyocytes, which was associated with the induction of miR-30a-5p and deactivation of ATG5. In rat models, gastrodin attenuated structure deterioration and dysfunction in heart, and suppressed autophagy. At molecular level, miR-30a-5p was induced and ATG5 were down-regulated. After the suppression of miR-30a-5p or the overexpression of ATG5, the cardio-protective effects of gastrodin were compromised. Gastrodin induced the expression of miR-30a-5p, which contributed to the attenuation of autophagy in infarcted heart tissues.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Current Research in Toxicology
·
2024
·
IF 2.9
Yan Ma,Honggang Chen,Yuxin Jiang,Diya Wang,Michael Aschner,Wenjing Luo,Peng Su
Elevated manganese (Mn) exposure has been implicated in a broad spectrum of neurological disorders, including motor dysfunction and cognitive deficits. Previous studies have demonstrated that Mn induces neurotoxicity by disrupting the integrity of the blood–brain barrier (BBB), a critical regulator in maintaining central nervous system homeostasis and a contributing factor in the pathogenesis of numerous neurological disorders. However, the precise molecular mechanisms underlying Mn-induced BBB disruption and its role in facilitating neurotoxicity remain incompletely understood. The primary objectives of this study were to elucidate the mechanisms underlying the relationship between Mn exposure and BBB tight junction proteins (TJPs), and to further investigate potential neuroprotective strategies for mitigating Mn-induced cognitive impairments. In this investigation, we developed Mn exposure models utilizing both murine subjects and cell culture systems to elucidate the mechanisms underlying TJPs involvement and to assess the potential neuroprotective effects of gastrodin (GAS), a bioactive compound extracted from traditional Chinese medicine. Our findings revealed a significant reduction in TJPs expression, both in vivo and in vitro , in Mn-induced BBB disruption. The overexpression of Occludin (OCLN), a crucial component of TJPs, mitigated Mn-induced BBB damage. GAS administration effectively attenuated Mn-induced disruption of the BBB, enhanced the expression of TJPs, and mitigated Mn-induced cognitive dysfunctions, potentially through the modulation of the RhoA/ROCK2 signaling pathway. This research sought to advance our understanding of the molecular pathways involved in Mn-mediated BBB disruption and to identify novel therapeutic approaches for mitigating the deleterious effects of Mn exposure on cognitive function.
研究领域:
神经科学
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毒理学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 85
·期 4
·798-804
·
IF 2.043
Yang Yanfei,Li Yabin,Han Jinli,Wang Yanfen
Gastrodin has shown the potential as an anticonvulsant. Epilepsy is a neurological disease with significant effects in children. In the current study, the therapeutic potential of gastrodin in handling pediatric epilepsy was explored by focusing on the AMPK/PPARα pathway. Three-week-old Sprague–Dawley rats were subjected to lithium-pilocarpine method to induce epileptic symptoms and then administrated with gastrodin. The effects of gastrodin on rats were first assessed using electroencephalogram (EEG) recording, Racine classification, Morris water maze test, and histological staining. The levels of BDNF and NGF, and the activity of AMPK/PPARα were measured. Based on the results of EEG, behavior analyses, and histological staining, epileptic symptoms were significantly alleviated by gastrodin. Moreover, the administration of gastrodin also suppressed the levels of BDNF and NGF, and activated the AMPK/PPARα pathway. In conclusion, our results demonstrated that gastrodin contributed to the alleviation of pediatric epilepsy by activating AMPK/PPARα signaling transduction.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Yong-xin Chen,Hong Yang,Da-song Wang,Ting-ting Chen,Xiao-lan Qi,Ling Tao,Yan Chen,Xiang-chun Shen
Background Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. Purpose This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. Methods A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate TFAM was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. Results GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated mitochondrial transcription factor A (TFAM), mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. Conclusion The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.
研究领域:
神经科学
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药理学
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分子生物学
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病理生理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）