JOURNAL OF FOOD ENGINEERING
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2023
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IF 5.5
Juanjuan Wen,Ye Tian,Yibin Zhuang,Limin Gou,Wei Ke,Ling Jiang,Minghui Qiu,Yiqun Fan
The issues of flux decline and irreversible membrane fouling must be considered in membrane separation . In this paper, the culture medium, bacterial cells, and proteins were removed using a one-step tight ultrafiltration (UF) membrane separation process. Although the membrane resistance of the tight UF membranes increased owing to their smaller pore size, the stable flux of the 6 nm membrane during fermentation broth filtration of gastrodin was 28.0% higher than that of loose UF membranes, and the flux recovery ratio reached 97.3%. During purification, a higher filtration flux was obtained by retaining the operating pressure within the range of 2–3 bar and the operating temperature range of 50–60 °C. The average flux of a 6 nm 19-channel membrane reached 56 L·m −2 ·h −1 , and the total yield of gastrodin reached 96.2%. This study provides a basis for the large-scale application of tight UF membrane in food industry.
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高影响因子
METABOLIC ENGINEERING
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2016
·
IF 8.201
Yanfen Bai,Hua Yin,Huiping Bi,Yibin Zhuang,Tao Liu,Yanhe Ma
Gastrodin, a phenolic glycoside , is the key ingredient of Gastrodia elata , a notable herbal plant that has been used to treat various conditions in oriental countries for centuries. Gastrodin is extensively used clinically for its sedative, hypnotic, anticonvulsive and neuroprotective properties in China. Gastrodin is usually produced by plant extraction or chemical synthesis, which has many disadvantages. Herein, we report unprecedented microbial synthesis of gastrodin via an artificial pathway. A Nocardia carboxylic acid reductase , endogenous alcohol dehydrogenases and a Rhodiola glycosyltransferase UGT73B6 transformed 4-hydroxybenzoic acid, an intermediate of ubiquinone biosynthesis , into gastrodin in Escherichia coli. Pathway genes were overexpressed to enhance metabolic flux toward precursor 4-hydroxybenzyl alcohol. Furthermore, the catalytic properties of the UGT73B6 toward phenolic alcohols were improved through directed evolution. The finally engineered strain produced 545 mg l −1 gastrodin in 48 h. This work creates a new route to produce gastrodin, instead of plant extractions and chemical synthesis.
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JOURNAL OF BIOTECHNOLOGY
·
2026
·
IF 4
Lin Ge,Ruobing Jia,Wenxin Xu,Yu Xia,Jianjun Pei
A glycosyltransferase for efficiently converting p HBA into gastrodin was screened. • Enhancing UDP-glucose supply can significantly increase the gastrodin titer in E.coli . • Combinatorial optimization achieved 4578.03 mg/L gastrodin in engineered E. coli . Gastrodin is the principal bioactive component of Gastrodia elata , which is famous for its many remarkable pharmacological properties. In this study, several UDP-glycosyltransferases from different sources were used to evaluate and compare the biotransformation ability of p -hydroxybenzyl alcohol to gastrodin. The recombinant strain BL-RrUGT, expressing the UDP-glycosyltransferase (RrUGT) from Rhodiola rosea , exhibited the highest initial titer of 210.60 mg/L. To further augment production, we enhanced the intracellular UDP-glucose level in Escherichia coli ( E. coli ) K12 by overexpressing two pivotal biosynthetic enzymes: phosphoglucomutase and UDP-glucose pyrophosphorylase. This metabolic engineering strategy yielded the recombinant strain BL-Rr-PG, which boosted the gastrodin titer to 342.40 mg/L. Subsequently, the culture medium and fermentation conditions were optimized. This resulted in a maximum gastrodin titer of 4578.03 mg/L, with a specific productivity of 69.36 mg/L/h and a molar conversion rate of 82.72%. This output represents the highest yield of gastrodin reported in E. coli to date. Download: Download high-res image (198KB) Download: Download full-size image
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JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
·
2025
·
IF 3.1
Lin Ge,Yu Xia,Wenxin Xu,Ruobing Jia,Tingting Zhang
Gastrodin, the primary bioactive constituent of Gastrodia elata , possesses numerous remarkable pharmacological properties. In this investigation, UDP-glycosyltransferase from Rauvolfia serpentina (RsUGT) was expressed, subsequently purified and characterized. The maximum yield of the enzyme was 17.57 mU/ml and possessed a relative molecular weight of approximately 77.7 kDa. Utilizing GST affinity resin, RsUGT was purified 20.8-fold, with an overall recovery rate of 58.6% and specific activity of 79.2 mU/mg. The optimal temperature and pH for RsUGT was identified as 40°C and 10.0, respectively. Notably, 2% DMSO could increase the RsUGT activity by 12.15%. The Michaelis-Menten constants K M and V max were determined to be 0.50mM and 171.60 mU/mg. By optimizing the conditions for the enzymatic biosynthesis of gastrodin by RsUGT, the highest gastrodin production was 285.35 mg/l, accompanied by a molar conversion rate of 99.67%. In addition, the conditions of gastrodin biosynthesis by recombinant strain BL-RsUGT were also studied. The highest gastrodin production was 225.99 mg/l, and the corresponding p HBA conversion rate was 98.00%. These findings confirmed the promising potential of RsUGT in the production of gastrodin.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2020
·Vol. 108
·期 8
·1713-1725
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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.
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PROCESS BIOCHEMISTRY
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2012
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IF 2.627
Chao-Jun Pei,Jinhyuk Lee,Yue-Xiu Si,Sangho Oh,Wei-An Xu,Shang-Jun Yin,Guo-Ying Qian,Hong-Yan Han
We studied the inhibitory effect of gastrodin on tyrosinase using inhibition kinetics and computational simulation. Gastrodin reversibly inhibited tyrosinase in a mixed-type manner with K i = 123.8 ± 20.2 mM. Time-interval kinetics revealed the inhibition to be a first-order process with mono- and bi-phasic components. Using AutoDock Vina, we calculated a binding energy of −6.3 kcal/mol for gastrodin and tyrosinase, and we performed a molecular dynamics simulation of the tyrosinase–gastrodin interaction. The simulation results suggested that gastrodin interacts primarily with histidine residues in the active site. A 10-ns molecular dynamics simulation showed that one copper ion in the tyrosinase active site was responsible for the interaction with gastrodin. Our study provides insight into the inhibition of tyrosinase by the hydroxyl groups of gastrodin. A combination of inhibition kinetics and computational calculations may help to confirm the inhibitory action of gastrodin on tyrosinase and define the mechanisms of inhibition.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 10
·4593
·
IF 5.6
Xiaolin Zhang,Yushan Du,Penghui Yang,Shiji Li,Fengya Cui,Xinran Li,Xinyue Du,Bingyao Sun,Yulu Ma,Wenjie Sui,Min Zhang,Jing Meng
Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases.
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高影响因子
CATALYSIS LETTERS
·
2023
·
IF 2.8
Xia Hui,Zhang Zihan,Ding Ji,Jiang Kehan,Xue Feng
Gastrodin is an important plant-derived medicinal ingredient that has been used to treat various diseases. Biosynthesis is an effective strategy for gastrodin production, but the expression and activity of natural glycosyltransferases (GTs) is generally a limiting factor. To identify highly efficient GTs, four plant-derived enzymes were identified by homologous sequence analysis and expressed in Escherichia coli BL21 (DE3). A GT from Arabidopsis thaliana (At UGT) displayed the highest activity of 0.45 U/mg, with an optimal pH of 9.0 and high thermostability. Under optimized conditions, 10 mM p -hydroxybenzyl alcohol and uridine diphosphate glucose were converted into 2.67 g/L gastrodin, corresponding to a conversion rate of 94.34% in 12 h. Furthermore, molecular docking simulations were performed between At UGT and p -hydroxybenzyl alcohol, revealing the catalytic mechanism of At UGT. This study provides a novel and effective biocatalyst for the synthesis of gastrodin. Graphical Abstract
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高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Hongcai Yang,Qing Li,Limei Li,Shaochun Chen,Yu Zhao,Yingrui Hu,Lu wang,Xiaoqian Lan,Lianmei Zhong,Di Lu
Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti‐inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro , and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo . Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications.
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高影响因子
Frontiers in Neuroscience
·
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.
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高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Di Pan,Tian Zheng,Canping Chen,Jie Qiu,Zhijuan Deng,Zhaohui Jiang,Yan Chen,Chaoda Xiao,Yini Xu,Lingyun Fu,Kegang Linghu,Jiyu Chen,Fangfang Fan,Qingxiu Zhang,Ling Tao,Xiaoxia Hu,Li Zhao,Xiangchun Shen
Background Cholestatic liver diseases, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and biliary atresia (BA), are characterized by bile accumulation and frequently progress to liver fibrosis, cirrhosis, and organ failure. Objective Given its well-documented hepatoprotective and anti-inflammatory properties, this study aimed to investigate the therapeutic potential and underlying mechanisms of gastrodin (4-(hydroxymethyl) phenyl β-D-glucopyranoside, C 13 H 18 O 7 ), a primary bioactive compound from Gastrodia elata , for the treatment of cholestatic liver fibrosis. Methods Two established mouse models of cholestatic fibrosis were used: the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet model and the bile duct ligation (BDL) model. An integrated analysis of single-nucleus RNA sequencing (snRNA-seq) data was performed, combining an in-house dataset from the DDC model with a public dataset. Results Gastrodin treatment significantly alleviated liver injury, reduced serum levels of total bilirubin (TBIL) and total bile acids (TBA), decreased collagen deposition, and prolonged survival in mouse models. snRNA-seq analysis revealed that gastrodin promoted hepatocyte repair by regulating key sulfotransferases (Sult2a1 and Sult1e1), enhanced detoxification, reduced the proportion of Kupffer cells, and suppressed their production of inflammatory mediators (e.g., TNF-α, IL-6), potentially via upregulation of immunomodulatory genes ( Pilrb1, Ifi27l2a, Rtp4 ). Furthermore, gastrodin modulated hepatic stellate cell (HSC) heterogeneity by expanding a novel HSC subgroup characterized by Serpina expression and associated with anti-fibrotic traits. Conclusion Gastrodin alleviates cholestatic liver fibrosis through coordinated multi-cellular mechanisms involving hepatocytes, Kupffer cells, and HSCs. It represents a promising natural therapeutic candidate, with Sult2a1, Sult1e1, and Serpina1a identified as potential targets.
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高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Jin-Jin Song,Hui Li,Nan Wang,Xiao-Yan Zhou,Yan Liu,Zhen Zhang,Qian Feng,Yu-Ling Chen,Dan Liu,Jia Liang,Xiang-Yu Ma,Xiang-Ru Wen,Yan-Yan Fu
Background: Neuroinflammation plays a pivotal role in the pathogenesis of Central Nervous System (CNS) diseases. The phenolic glucoside gastrodin (GAS), has been known to treat CNS disorders by exerting anti-inflammatory activities. Our aim was to investigate the potential neuroprotective mechanisms of GAS on lipopolysaccharide (LPS)-induced mice. Methods: Male C57BL/6J mice were treated by LPS, before which GAS was adminisrated. The behavior tests such as forced swim test, tail suspension test, and elevated plus maze were performed to evaluate depressive-anxiety-like behaviors. A high-throughput sequencing (HTS) analysis was performed to screen out distinctive miRNAs which were validated using quantitative real-time PCR. Then, miRNA agomir or NC was injected stereotaxically into hippocampus of mice to explore the role of miRNA on GAS in response to LPS. Furthermore, Immunofluorescence and the hematoxylin and eosin (H&E) staining were employed to observe the cellular morphology. The protein levels of pro-inflammatory factors were evaluated by western blot. Finally, the target mRNA of miRNA was predicted using bioinformatics analysis. GO and KEGG enrichment analyses were conducted to clarify the potential function of target protein, which were visualized by bubble charts. Results: The behavioral data showed that mice in the LPS group had obvious depressive-anxiety-like behaviors, and 100 mg/kg GAS could improve these behavioral changes and alleviate the levels of pro-inflammatory cytokines in the hippocampus when mice were exposed to LPS for 6 h. Meanwhile, LPS-induced microglia and astrocyte activation in the CA1, CA2, CA3, and DG regions of the hippocampus were also reversed by GAS. Furthermore, miR-107-3p were screened out and verified for GAS in response to LPS. Importantly, miR-107-3p overexpression negatively abrogated the neuroprotective effects of GAS. Moreover, KPNA1 might be the target molecular of miR-107-3p. KPNA1 might regulate 12 neuroinflammation-related genes, which were mainly involved in cytokine-mediated signaling pathway. Conclusion: These results suggested that GAS might alleviate the LPS-induced neuroinflammation and depressive-anxiety-like behaviors in mice by downregulating miR-107-3p and upregulating the downstream target KPNA1. The indicates miR-107-3p may provide a new strategy for the treatment of CNS diseases.
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