BIOTECHNOLOGY AND BIOENGINEERING
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2020
·Vol. 117
·期 8
·2410-2419
·
IF 4.002
Wei Guo,Qiulan Huang,Yuhui Feng,Taicong Tan,Suhao Niu,Shaoli Hou,Zhigang Chen,Zhi-Qiang Du,Yu Shen,Xu Fang
Metabolic engineering of Saccharomyces cerevisiae for high-level production of aromatic chemicals has received increasing attention in recent years. Tyrosol production from glucose by S. cerevisiae is considered an environmentally sustainable and safe approach. However, the production of tyrosol and salidroside by engineered S. cerevisiae has been reported to be lower than 2 g/L to date. In this study, S. cerevisiae was engineered with a push-pull-restrain strategy to efficiently produce tyrosol and salidroside from glucose. The biosynthetic pathways of ethanol, phenylalanine, and tryptophan were restrained by disrupting PDC1 , PHA2 , and TRP3 . Subsequently, tyrosol biosynthesis was enhanced with a metabolic pull strategy of introducing PcAAS and EcTyrA M53I/A354V . Moreover, a metabolic push strategy was implemented with the heterologous expression of phosphoketolase (Xfpk), and then erythrose 4-phosphate was synthesized simultaneously by two pathways, the Xfpk-based pathway and the pentose phosphate pathway, in S. cerevisiae . Furthermore, the heterologous expression of Xfpk alone in S. cerevisiae efficiently improved tyrosol production compared with the coexpression of Xfpk and phosphotransacetylase. Finally, the tyrosol yield increased by approximately 135-folds, compared with that of parent strain. The total amount of tyrosol and salidroside with glucose fed-batch fermentation was over 10 g/L and reached levels suitable for large-scale production.
研究领域:
生物技术
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代谢工程
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DOI
PubMed
高影响因子
MOLECULES
·
2014
·Vol. 19
·期 6
·7757-7769
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IF 2.095
Lingyun Xiao,Haifeng Li,Ju Zhang,Fan Yang,Aizhen Huang,Jingjing Deng,Ming Liang,Fangli Ma,Minghua Hu,Zebo Huang
Polyglutamine (polyQ) aggregation plays a pivotal role in the pathological process of Huntington’s disease and other polyQ disorders. Therefore, strategies aiming at restoring dysfunction and reducing stresses mediated by polyQ toxicity are of therapeutic interest for proteotoxicity diseases. Salidroside, a glycoside fromRhodiola rosea, has been shown to have a variety of bioactivities, including antioxidant activity. Using transgenicCaenorhabditis elegansmodels, we show here that salidroside is able to reduce neuronal death and behavioral dysfunction mediated by polyQ expressed in ASH neurons, but the neuroprotective effect is not associated with prevention of polyQ aggregationper se. Further experiments reveal that the neuroprotective effect of salidroside inC. elegansmodels involves its antioxidant capabilities, including decrease of ROS levels and paraquat-induced mortality, increase of antioxidant enzyme activities and reduction of lipid peroxidation. These results demonstrate that salidroside exerts its neuroprotective function against polyQ toxicity via oxidative stress pathways.Keywords:salidroside;polyglutamine;neurotoxicity;oxidative stress;C. elegans;chemoavoidance
研究领域:
神经科学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 20
·期 1
·529-538
·
IF 1.851
Shasha Chen,Feng Cai,Jirong Wang,Zhouxin Yang,Chi Gu,Guofu Wang,Genxiang Mao,Jing Yan
The abnormal aggregation of α‑synuclein (α‑syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild‑type and the A53T mutation of α‑syn to induce a neuronal model of PD in SH‑SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose‑dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) α‑syn expression as well as the ratio of microtubule‑associated proteins 1A/1B light chain 3 (LC3)‑I to LC3‑II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL‑induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of α‑syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway.
研究领域:
神经科学
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药理学
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细胞生物学
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PubMed
高影响因子
CHINESE JOURNAL OF CATALYSIS
·
2012
·
IF 1.171
Yanhong BI,Zhaoyu WANG,Yanyong MAO,Shangyong ZHENG,Haijiang ZHANG,Hao SHI
The preparation of salidroside was successfully carried out in fourteen ionic liquids (ILs)-containing systems using β-glycosidase from black plum seeds for the first time. The optimum conditions were determined for C 6 MIm·BF 4 , pH, phosphate buffer content, and molar ratio of tyrosol to D-glucose to be 1% (v/v), 5.9, 20% (v/v), and 8:1, under which the initial reaction rate and yield were 3.3 mmol/(L·h) and 24.5%, respectively. Moreover, the effects of 1-alkylimidazolium-based ILs possessing different alkyl chain lengths from C 2 to C 10 and a variety of anions including BF 4 − , PF 6 − , Cl − , Br − , and I − on enzyme activity in co-solvent systems were investigated. The results indicate that the optimal chain length of the alkyl substituent on the imidazolium ring of the cation was C 6 . 摘要 研究了混合溶剂体系中阴离子分别为 BF 4 − , PF 6 − , Cl − , Br − 和 I − 的 14 种离子液体对来源于黑布林糖苷酶催化合成红景天苷反应的影响. 结果表明, 在最佳反应条件下, β-糖苷酶的反应初速度和红景天苷的产率分别为 3.3 mmol/(L·h) 和 24.5%. 离子液体咪唑阳离子的烷基链长 (C 2 ∼C 10 ) 对 β-糖苷酶的活性影响较大, 当烷基链长为 C 6 时, 糖苷酶表现出较高的催化活性.
研究领域:
生物化学
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酶工程
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产品关联
DOI
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Qian Zhang,Yu-Qiao Wang,Lin Li,Hao-Lin Song,Hai-Tao Wu,Bei-Wei Zhu
Salidroside (Sal), the main bioactive substance in Rhodiola rosea , is a promising functional food component with a wide range of pharmacological effects, but its biological activity is challenging to sustain due to its short half-life, low oral bioavailability, and susceptibility to environmental factors. The aim of this study was to investigate the effect of sodium alginate (SA) concentration on the construction of W/O/W emulsion in the protection of Sal. With the escalation of SA concentrations, the range of droplet size distribution was smaller and the droplets were more uniform. When the concentration of SA was 2 %, the average droplet size reached 9.1 ± 0.1 μm, and the encapsulation efficiency of Sal was 77.8 ± 1.8 %. Moreover, the double emulsion with 2 % SA was the most stable for 28 days at 4 °C since the oil droplets were embedded in the network structure of SA.
研究领域:
药学
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食品科学
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材料科学
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DOI
PubMed
高影响因子
ACTA NEUROPSYCHIATRICA
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2024
·
IF 2.6
Shan Xing,Shuyi Xu,Linjiao Wang,Liyuan Guo,Xin Zhou,Haoxin Wu,Wei Wang,Lanying Liu
Depression is one of the major mental disorders, which seriously endangers human health, brings a serious burden to patients’ families. In this study, we intended to further explore the antidepressant-like effect and possible molecular mechanisms of Salidroside (SAL). We built corticosterone (CORT)-induced depressive mice model and used behavioural tests to evaluate depression behaviour. To explore the molecular mechanisms of SAL, we employed a variety of methods such as immunofluorescence, western blot, pharmacological interference, etc. The results demonstrated that SAL both at 25 mg/kg and 50 mg/kg can reduce immobility time in the tail suspension test (TST). At the same time, SAL treatment could restore the reduced sugar water intake preference in the sucrose preference test (SPT) in CORT-induced depressive mice and reduce the immobility time in TST and forced swimming experiments (FST). In addition, SAL treatment reversed the reduction in the number of Ki-67, BrdU, and NeuN in the hippocampus due to CORT treatment. SAL treatment also restored the expression of SIRT1, PGC-1α, brain-derived neurotrophic factor (BDNF) and other proteins in the hippocampus. In addition, after blocking SIRT1 signalling with EX527, we found that the treatment with SAL failed to reduce the immobility time in TST and FST, the level of SIRT1 and PGC-1α activity were correspondingly downregulated, and the expression of DCX and Ki-67 in the hippocampus failed to be activated. These findings suggested that SAL exerts antidepressant-like effects by promoting hippocampal neurogenesis through the SIRT1/PGC-1α signalling pathway.
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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产品关联
DOI
PubMed
高影响因子
Diabetes Metabolic Syndrome and Obesity-Targets and Therapy
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2019
·
IF 3.319
Qi Feng,Chen Liu,Wei Gao,Xiao-ling Geng,Ning Dai
Purpose Oxidative stress plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). TRPM2 ion channel functions as a molecular sensor for oxidative stress. The aim of this study was to examine the protective effects of Salidroside, a powerful antioxidative plant, on TRPM2 in an established in vitro model of NAFLD. Methods NAFLD model was established by palmitic acid (PA) in hepatic L02 cell lines and was added to the media at a final concentration of 400 μM. Cells were used as normal group, PA group and PA receiving varied concentrations of Salidroside (75μg/mL, 150μg/mL, 300μg/mL). After treating 24 hrs, MTT assay was used to detect cell viability, and ALT level was measured using an appropriate kit assay. Intracellular lipid accumulation was observed by Oil red O staining. Cytosolic Ca 2+ concentrations were evaluated by flow cytometer with Fluo-3/AM. Quantitative RT-PCR was used to measure the mRNA expression of TRPM2, IL-1β and IL-6, and the protein expressions of TRPM2, p-CaMKII and autophagy (LC3B, p62) were determined using Western blot. Results Treatment with Salidroside effectively restored liver injury and alleviated lipid droplet deposition in a dose-dependent manner, which was associated with inhibition of TRPM2/Ca 2+ /CaMKII pathway. Additionally, autophagic clearance was enhanced by intervention with Salidroside in a dose-dependent manner. Further investigation indicated that Salidroside down-regulated the mRNA expression of IL-1β and IL-6-pro-inflammatory cytokines. Conclusion These results suggest that Salidroside could alleviate inflammatory injury and steatosis via autophagy activation mediated by downregulation of the TRPM2/Ca 2+ /CaMKII pathway. Targeting the TRPM2 ion channel is a novel treatment strategy for oxidative stress-induced liver in NAFLD.
研究领域:
药理学
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细胞生物学
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分子生物学
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肝病学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2024
·
IF 2.5
Qian Sun,Li Zhang,Xiuyan Huang,Min Wang
Background Salidroside (Sal) has been found to protect against multiple impairments caused by diabetes, and we designed this study to investigate the effect of Sal on gestational hypertension (GHP)-induced impairment of offspring learning and memory. Methods We established a GHP rat model by intraperitoneal injection of NG-nitro-L-arginine methyl ester (L-NAME), and treated with Sal by daily gavage. We used Morris Water Maze test to evaluate the learning and memory ability of offspring rats. HE staining was used to measured the pathological changes in hippocampus of offspring. Immunohistochemistry, cellular immunofluorescence and western blot were used to detect the protein expression. Results The learning and memory abilities of GHP offspring rats were significantly lower than those of normal rat offspring, while Sal treatment could significantly improve the learning and memory abilities of GHP offspring rats. HE staining did not reveal pathological differences in the hippocampus of normal rats, GHP rats and Sal-treated GHP offspring rats. However, Sal treatment can significantly increase the expression of Wnt1 and Skp2 protein, and decrease the expression of P27kiwf and P21waf1 protein in the hippocampus of GHP offspring rats. In vitro, Sal significantly promoted the proliferation and differentiation on neural stem cell, while Wnt1 knockdown could reverse these promotions by Sal. In the hippocampus of GHP offspring rats, Sal treatment significantly increased the expression of Tuj1, SOX2, Ki67 and DCX protein. Conclusion Salidroside significantly improves the learning and memory impairment of offspring caused by GHP, and its mechanism may be related to the fact that Salidroside promotes the proliferation and differentiation of neural stem cells by activating the Wnt1/Skp2 signaling pathway.
CAS / MDL:
研究领域:
药理学
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神经科学
·
发育生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Nan Wang,Zhengshan Gao,Honghong Zhan,Lin Jing,Fancheng Meng,Min Chen
Doxorubicin (DOX) is a potent anticancer drug, while its toxic side effects involve multi-organ toxicity, including hepatotoxicity. This study aims to investigate the therapeutic potential of salidroside against DOX-induced hepatotoxicity and elucidate its underlying mechanisms. Result showed that salidroside exhibited a liver protective effect in DOX-induced hepatotoxicity in mice, represented by the decreased serum ALT, AST and LDH levels, as well as the rescue of pathological changes in mice livers. Further study showed salidroside reduced the expression level of pyroptosis-associated proteins, including NLRP3, cleaved- caspase 1, gasdermin D (GSDMD-N) and mature IL-1β in mice liver tissues. In vitro study confirmed salidroside exerted a similar effect in AML12 cells. Mechanistically, salidroside alleviated mitochondrial dysfunction by activating the PGC-1α /Mfn2 signaling pathway, and restrained the endoplasmic reticulum (ER) stress, represented by the downregulation of GRP78 and p-PERK/PERK level. Subsequent investigations revealed that salidroside activated the Sestrin2/AMPK pathway, while the application of AMPK inhibitors, PGC-1α siRNA or Sestrain2 siRNA reversed the effects of salidroside on ameliorating mitochondrial dysfunction and ER stress, suggesting salidroside could be a promising therapeutic strategy for alleviating DOX-induced hepatotoxicity.
研究领域:
药理学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Functional Biomaterials
·
2023
·Vol. 14
·期 3
·150
·
IF 4.8
Shengnan He,Fang Xie,Wuyue Su,Haibin Luo,Deliang Chen,Jie Cai,Xuechuan Hong
Atopic dermatitis (AD) is the most common heterogeneous skin disease. Currently, effective primary prevention approaches that hamper the occurrence of mild to moderate AD have not been reported. In this work, the quaternized β-chitin dextran (QCOD) hydrogel was adopted as a topical carrier system for topical and transdermal delivery of salidroside for the first time. The cumulative release value of salidroside reached ~82% after 72 h at pH 7.4, while in vitro drug release experiments proved that[email protected]([email protected]) has a good, sustained release effect, and the effect of[email protected]on atopic dermatitis mice was further investigated.[email protected]could promote skin repair or AD by modulating inflammatory factors TNF-α and IL-6 without skin irritation. The present study also evaluated NIR-II image-guided therapy (NIR-II, 1000–1700 nm) of AD using[email protected]The treatment process of AD was monitored in real-time, and the extent of skin lesions and immune factors were correlated with the NIR-II fluorescence signals. These attractive results provide a new perspective for designing NIR-II probes for NIR-II imaging and image-guided therapy with[email protected]Keywords:the quaternized β-chitin/dextran hydrogel;imaging in the second near-infrared window (NIR-II);atopic dermatitis;Rhodiola rosea;treatment
研究领域:
药学
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生物医学工程
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材料科学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2015
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IF 1.88
Yibo Feng,Xiaojuan Zhao,Fang Lv,Jinqiu Zhang,Bihua Deng,Yanhong Zhao,Yuanliang Hu,Deyun Wang,Jiaguo Liu,Yu Lu,Ruonan Bo,Zhenguang Liu
The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE) and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2) vaccine adjuvant. Response surface methodology (RSM) was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 molL−1, ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mLmin−1, and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.
研究领域:
药剂学
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免疫学
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病毒学
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药物递送系统
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DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
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2012
·Vol. 34
·期 9
·1673-1678
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IF 1.683
Chen Lei,Hu Ying-Dan,Li Ning,Zong Min-Hua
Cross-linked enzyme aggregates (CLEAs) of β -glucosidase were prepared and characterized. Under the optimum conditions, the activity recovery of CLEAs reached 84 %. The reduction by NaBH 4 resulted in slightly lower activities of CLEAs, while their thermostability was enhanced. CLEAs were more thermally stable than free enzyme (half lives, 973 vs. 518 min at 50 °C), while less stable than seed meal (half life, 1,090 min). In 90 % (v/v) t -butanol, the half lives of CLEAs and free enzyme were 53 and 6.7 h, respectively. Besides, the catalytic efficiency ( V
max / K
m ) of CLEAs was comparable to free enzyme (0.42 vs. 0.47 min −1 mg −1 ). This carrier-free immobilized enzyme had a network structure with multiple layers. The productivity of salidroside using CLEAs reached 150 g/l g catalyst, while being 6.3 g/l g with seed meal.
研究领域:
生物化学
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酶学
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食品科学
✓ 已验证
DOI
PubMed
高影响因子