FOOD AND CHEMICAL TOXICOLOGY
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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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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 24
·期 4
·1-7
·
IF 2.952
Yongpan Huang,Xiaodong Han,Jiayu Tang,Xian Long,Xiaoye Wang
Homocysteine (Hcy) was discovered to be an independent risk factor for the development of atherosclerosis (AS). Moreover, endothelial‑mesenchymal transition (EndMT) was found to be one of main mechanisms contributing to the pathogenesis of AS. Salidroside (SAL) has diverse pharmacological activities, including anti‑inflammatory, anti‑cancer, anti‑oxidative and anti‑fibrosis properties. However, whether SAL serves a beneficial role in Hcy‑induced EndMT remains unknown. The present study aimed to investigate whether SAL exerted its effects on Hcy‑induced EndMT via the Kruppel‑like factor 4 (KLF4)/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. HUVECs were pretreated with high and low doses (10 or 50 µmol/l) of SAL for 2 h, followed by 1 mmol/l Hcy for 48 h to induce EndMT. Western blotting was used to analyze the protein expression levels of the endothelial marker, VE‑cadherin, the mesenchymal cell marker, α‑smooth muscle actin (SMA), and the nuclear transcription factors, KLF4 and eNOS. Wound healing assays were used to determine the cell migratory ability, and the levels of NO in the cell culture supernatants were measured using a nitrate reductase assay. Cellular immunofluorescence was used to analyze the expression and localization of KLF4. Small interfering (si)RNA targeting KLF4 (siKLF4) was used to knock down KLF4 expression in HUVECs. The results of the present study revealed that treatment with SAL upregulated the expression levels of VE‑cadherin, downregulated the expression levels of α‑SMA, reduced cell migration and activated the eNOS/NO signaling axis, as well as downregulated KLF4 expression and translocation to the nucleus. Compared with the SAL + siKLF4 co‑administration group, no significant differences were observed in the expression levels of the phenotypic markers in the SAL or siKLF4 groups. In conclusion, the findings of the present study revealed that SAL may inhibit Hcy‑induced EndMT via regulation of the KLF4/eNOS signaling pathway.
研究领域:
心血管疾病
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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
BIOTECHNOLOGY AND BIOENGINEERING
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2020
·Vol. 117
·期 8
·2410-2419
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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
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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产品关联
DOI
PubMed
高影响因子
Systems Microbiology and Biomanufacturing
·
2026
·Vol. 6
·期 3
·98
·
IF 3.5
Li Caimei,Shen Wei,Yang Haiquan,Zhou Li,Xia Yuanyuan,Chen Xianzhong
Salidroside, the key active component of Rhodiola , possesses anti-hypoxia and anti-fatigue properties, making it valuable in medicine, health products, and cosmetics. This study focuses on efficiently synthesizing salidroside using a dual-enzyme cascade system with sucrose synthase AtSUS3 and glycosyltransferase AtUGT85A1 from Arabidopsis thaliana . This system facilitates the regeneration of UDPG and the conversion of tyrosol into salidroside. First, the two key enzymes AtSUS3 and AtUGT85A1 were expressed and purified with optimized His‑tag positions. Solubility enhancement via tag fusion and linker engineering yielded the fusion proteins TSu and ES85 with desirable activity. Subsequently, semi‑rational design on the poorly thermostable ES85 using the FireProt platform generated an S324R mutant with significantly improved thermostability. Ultimately, a recombinant strain TSR85 co‑expressing both enzymes was constructed. A one‑pot system employing this strain achieved 13.61 g/L salidroside with a conversion rate of 90% within 10 h (space‑time yield 1.36 g/L/h). This study thus integrates solubility enhancement, thermostability engineering, and one‑pot catalysis into a balanced, practical, and industrially relevant platform for salidroside biosynthesis.
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2014
·
IF 3.785
Yongtai Zhang,Kai Zhang,Zhonghua Wu,Teng Guo,Beini Ye,Mingyun Lu,Jihui Zhao,Chunyun Zhu,Nianping Feng
Span 40-based niosomes were employed as nanocarriers to improve cutaneous absorption of salidroside . The niosomal formulation with a molar proportion of Span 40 to cholesterol of 4:3 showed the highest transdermal flux and skin deposition of salidroside. The transdermal flux of the 4:3 niosomal formulation was significantly greater than that of the aqueous solution. Salidroside-loaded niosomes showed good biocompatibility with skin tissue, human epidermal immortal keratinocytes (HaCaT), and human embryonic skin fibroblasts (CCC-ESF). The fluorescence intensity of HaCaT cells after uptake of coumarin 6-labeled niosomes was similar to that observed after uptake of the aqueous suspension. The fluorescence intensity of CCC-ESF cells was greater than that of the aqueous suspension after incubation for 10 min, but was not significantly different after 60 min. Further investigation revealed that internalization of niosomes by HaCaT cells may be achieved through pinocytotic vesicles and macropinocytosis, which consumes energy, rather than via lysosomes. In CCC-ESF cells, pinocytotic vesicles and lysosomes were both important mediators of endocytosis. The niosome formulations reported here could improve the dermal and transdermal salidroside delivery, and the in vitro cell uptake evaluation results serve as a basis for further research into the mechanisms through which niosomes enhance drug permeability.
研究领域:
药剂学
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皮肤科学
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生物医学工程
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2023
·
IF 3.3
Minyan Li,Sha Wang,Chunmei Fu,Hongyu Chen,Yuxia Su,Peng Wu,Xinhao Yan,Juanjuan Gao
Parkinson's disease (PD) is the second-most common neurodegenerative disease, and the development and progression of PD is characterized by oxidative stress (OS). This study determined the neuroprotective effects of salidroside (Sal). We report that Sal with scavenging ROS capabilities could regulate oxidative stress for the prevention of pathologic α-synuclein (α-syn) transmission in 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells. Sal exhibits effective free radical quenching ability and safe use in biological systems. The protective effects of Sal against 6-OHDA-induced neurotoxicity in PC12 cells were investigated using the DPPH method for free radical scavenging, CCK8 for cell viability, DCFH-DA for ROS levels, immunohistochemical staining for α-syn, and western blot for SOD, CAT, and GPX4 protein detection. The results obtained through our studies showed that 6-OHDA-induced neurotoxicity significantly decreased cell viability, antioxidant enzyme (SOD, CAT, and GPX4) expression, increased ROS levels, and α-syn accumulation, while on Sal (50 mg mL−1) pretreatment obviously regulated the cellular redox balance and decreased α-syn accumulation. With further study, these findings may provide new insight into the protective mechanisms against neurodegenerative diseases and synucleinopathies.
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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DOI
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Qi Ouyang,Shengye Tian,Hengyu Zhou,Ying Mao,Xiang Li,Feng Yan,Ailong Liu,Xiang Hu,Changqiao You,Jun He
Background Melanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis. Methods Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry. Results We confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H 2 O 2 -induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro , and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth. Conclusion Salidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.
研究领域:
肿瘤学
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药理学
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生物化学
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细胞生物学
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分子生物学
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皮肤病学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2014
·Vol. 19
·期 6
·7757-7769
·
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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产品关联
DOI
PubMed
高影响因子
MEAT SCIENCE
·
2025
·
IF 6.1
Jiaying Duan,Qing Zhao,Chunbao Li,Yingqun Nian
This study used the Fenton reaction to simulate the oxidation process of porcine myofibrillar proteins (MPs), aiming to explore the regulatory effect of salidroside (SAL) on the structure and functional properties of MPs under oxidative conditions. Systematic characterization of MPs-SAL interactions through biochemical assays, physicochemical measurements, and multispectral structural analysis. The results demonstrated that SAL boosted the antioxidant prowess of MPs in a dose-dependent fashion. Oxidative stress caused a reduction in sulfhydryl levels and absolute Zeta potential values, while simultaneously increasing dimeric tyrosine formation. Compared to the control group, sulfhydryl and dimerized tyrosine levels decreased with increasing SAL concentration, while the absolute Zeta potential values exhibited a progressive augmentation. Furthermore, oxidation resulted in elevated surface hydrophobicity and reduced solubility, and SAL further promoted the exposure of hydrophobic residues, and SAL caused changes in both the secondary and tertiary structures of MPs. SDS-PAGE revealed no notable band variations in oxidized groups following SAL treatment. Scanning electron microscopy revealed that the pores of MPs became larger and the surface rough after oxidation, while the protein surface became less wrinkled and smoother after the addition of SAL. In summary, the interaction between MPs and SAL affects the structural and functional properties of proteins.
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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
ACTA NEUROPSYCHIATRICA
·
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
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
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