APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2026
·
IF 3.5
Awang Danzeng,La Zong,Baima Kangzhuo,Xie Hongjun,Wang Li,Liu Xinyao,Wang Yueying,Shi Yan,Zhao Yicheng,Gongga Lanzi
Hypoxia-related myocardial injury is characterized by oxidative stress, mitochondrial dysfunction, and apoptosis, ultimately resulting in impaired cardiac structure and function. Salidroside (SAL), a major bioactive component of Rhodiola, has been shown to have antioxidant and cardioprotective effects, but its role in hypoxia-related myocardial injury remains incompletely understood. In this study, we combined network pharmacology, molecular docking, and experimental validation to investigate the protective effect of SAL in CoCl 2 -induced hypoxia-mimetic models. In vitro, SAL improved cell viability, reduced ROS accumulation, restored mitochondrial membrane potential and ATP production, and attenuated apoptosis in CoCl 2 -treated H9C2 cells. In vivo, SAL alleviated electrocardiographic abnormalities, myocardial histopathological injury, cardiomyocyte hypertrophy, and associated lung and liver damage in CoCl 2 -treated rats. Mechanistically, SAL modulated the Akt/GSK-3β signaling axis under CoCl 2 -induced stress. Notably, Akt inhibition experiments revealed that SAL promotes protective GSK-3β phosphorylation and exerts its anti-apoptotic effects through a largely Akt-independent mechanism. Collectively, these findings indicate that SAL alleviates hypoxia-induced myocardial injury through the attenuation of oxidative stress, the preservation of mitochondrial function, the suppression of apoptosis, and the robust, Akt-independent regulation of GSK-3β. Graphical The alternative text for this image may have been generated using AI.
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 10
·5767-5780
·
IF 5.882
Lin Zhu,Zhenchao Liu,Yuqian Ren,Xiaolin Wu,Yingjuan Liu,Tingting Wang,Yizhao Li,Yusheng Cong,Yunliang Guo
Studies have found that salidroside, isolated from Rhodiola rosea L , has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced β-galactosidase (β-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.
研究领域:
神经科学
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药理学
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衰老研究
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分子生物学
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PubMed
高影响因子
CHINESE JOURNAL OF CATALYSIS
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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
·
酶工程
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DOI
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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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2025
·Vol. 50
·期 5
·1-12
·
IF 3.8
Huang Manqian,Tang Meiling,Liu Lu
Epilepsy is a chronic neurological disorder featured by abnormal neural discharges that can lead to cognitive impairment. Salidroside (Sal), a biologically active component, protects neurons against various insults. The current study aims to explore the therapeutic potential of Sal in epilepsy and elucidate the mechanisms underlying its effects. We established a rat model of status epilepticus (SE) using pentylenetetrazol-kindling. SE rats were treated with Sal. Assessment of seizure latency and epileptic stage scores were performed. Cognitive function of rats was evaluated using a novel object recognition test and a Morris water maze test. Neuronal damage and hippocampal pathology were examined, alongside microglial and astrocyte activation, complement C3-C3a receptor (C3-C3aR) pathway involvement, and inflammatory factor levels. Sal prolonged seizure latency, decreased epilepsy stage scores, and improved cognitive performance compared to untreated SE rats. Furthermore, Sal suppressed the activation of C3-C3ar, microglia, and astrocytes, while decreasing the levels of inflammatory factors, which ameliorated hippocampal damage and neuronal loss. Sal may attenuate epilepsy and cognitive dysfunction by downregulating complement C3-C3aR pathway-mediated activation of microglia and astrocytes.
研究领域:
神经病学
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药理学
·
神经药理学
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免疫学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Yu Fu,Guiqin Huang,Yawen Cai,Menghui Ren,Run Cheng,Yuhui Chai,Yingdi Wang,Yunqi An,Tianhua Yan,Lingpeng Zhu,Xinxin Liu
Gastric cancer (GC) is a highly aggressive and heterogeneous malignancy. The process of ferroptosis regulates tumor growth and represents a promising therapeutic target for GCs. Despite Salidroside (Sal) being able to regulate ferroptosis in a variety of diseases, there are still limited reports on its therapeutic effects and potential targets in treating GC. This study aimed to investigate the potential mechanism of Sal-induced ferroptosis in GC. Our analysis, integrating databases like PharmMapper, Swiss Target Prediction, TargetNet, GeneCards, TTD, OMIM, STRING, and DAVID. Human gastric cancer MGC803 cells and tumor-bearing mice were used to evaluate the anti-tumor effect of Sal on GC in vitro and in vivo. CCK-8, LDH, and Calcein-AM/ PI were used to assess cell viability and damage. FerroOrange, Lillie’s Ferrous Iron Stain, MDA, ROS, BODIPY™ 581/591 C11, GSH, and GPxs were used to detect intracellular Fe 2+ concentration, lipid peroxidation level, and antioxidant defense system. qRT-PCR and western blot were performed to explore relevant mechanism studies. Network pharmacology results showed that Sal shares 322 targets with GC, which have biological functions related to lipid metabolism, cell death, and lipid peroxidation. Experiments further confirmed that Sal inhibits MGC803 cells by inducing ferroptosis, as evidenced by the induction of elevated Fe 2+ and increased lipid peroxidation. Fer-1, an inhibitor of ferroptosis, reversed the anti-GC effect of Sal in MGC803 cells and GC tumor-bearing mice. Further confirmation of the association between Sal and ferroptosis in GC. Subsequently, bioinformatics and machine learning algorithms identified nuclear receptor coactivator 4 (NCOA4) as a candidate signature gene associated with ferroptosis in GC, and molecular docking shows that NCOA4 binds Sal. We then performed in vivo and in vitro experiments to elucidate that Sal targeting NCOA4, a cargo receptor mediating ferritinophagy, mediates autophagic degradation of ferritin heavy chain 1 (FTH1, Fe 2+ storage protein), which further increases Fe 2+ and lipid peroxidation. In addition, Sal induces mitochondrial dysfunction and increases mitochondrial ROS levels, which activates autophagy and triggers autophagic degradation of FTH1. Taken together, we revealed that NCOA4 is a new target for Sal-anchored GC and that Sal may be a potential therapeutic drug for the treatment of GC.
研究领域:
肿瘤学
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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
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zhun Li,Sixia Yang,Wei Liu,Long Ling,Hailan Hu,Yanming Cao,Shouyu Xiang
Salidroside, one of the main active compounds extracted from Rhodiola, has shown promising potential for the treatment of osteoporosis. Our previous study demonstrated that salidroside alleviated cognitive dysfunction in senescence-accelerated mouse prone 8(SAMP8) mice. In this study, we further investigated the effect of salidroside on osteoporosis in SAMP8 mice and explored the mechanism. The results of micro-computed tomography(micro-CT) and histology showed that salidroside significantly increased trabecular bone formation and improved bone microstructure in senile osteoporotic SAMP8 mice, and upregulated the protein expression levels of phosphatidylinositol-3-kinase(PI3K), glutathione peroxidase 4(GPX4), and Runt-related transcription factor 2(RUNX2) in the distal femur. Cell-based assays, including the Cell Counting Kit-8(CCK-8) assay, senescence-associated β-galactosidase (SA-β-galactosidase) staining, alkaline phosphatase (ALP) staining, Alizarin Red staining, and lipid peroxide detection, demonstrated that salidroside significantly promoted the proliferation and osteogenic differentiation of senile osteoporotic bone marrow stromal cells (BMSCs) and decreased lipid peroxide levels. Furthermore, real-time polymerase chain reaction (RT-PCR) and Western blotting analysis showed that salidroside increased protein and gene expression levels of solute carrier family 7 member 11(SLC7A11), GPX4, and ferroptosis suppressor protein 1(FSP1). Additionally, salidroside also increased the phosphorylation of PI3K, AKT, and mTOR, an effect reversed by LY294002.In conclusion, our investigation showed that salidroside could prevent ferroptosis, promote proliferation, and enhance osteogenic differentiation in senile osteoporotic BMSCs, thereby alleviating senile osteoporosis in SAMP8 mice. The PI3K/AKT/mTOR signaling pathway might play a crucial role in this mechanism. These findings suggest that salidroside has the potential to prevent senile osteoporosis and may serve as a candidate for therapeutic development.
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2020
·
IF 5.573
Zelin Yang,Xin Huang,Wenfang Lai,Yuheng Tang,Junjie Liu,Yingzheng Wang,Kedan Chu,John Brown,Guizhu Hong
Salidroside [(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-hydroxyphenethoxy)tetrahy-dro-2H-pyran-3,4,5-triol] is an antioxidant , anti-inflammatory and neuroprotective agent , but its drug-like properties are unoptimized and its mechanism of actions is uncertain. We synthesized twenty-six novel derivatives of salidroside and examined them in CoCl 2 -treated PC12 cells using MTT assay . pOBz, synthesized by esterifying the phenolic hydroxyl group of salidroside with benzoyl chloride , was one of five derivatives that were more cytoprotective than salidroside, with an EC 50 of 0.038 μM versus 0.30 μM for salidroside. pOBz was also more lipophilic , with log P of 1.44 versus −0.89 for salidroside. Reverse virtual docking predicted that pOBz would bind strongly with monoamine oxidase (MAO) B by occupying its entrance and substrate cavities, and by interacting with the inter-cavity gating residue Ile199 and Tyr435 of the substrate cavity. Enzymatic studies confirmed that pOBz competitively inhibited the activity of purified human MAO-B (K i = 0.041 μM versus K i = 0.92 μM for salidroside), and pOBz was highly selective for MAO-B over MAO-A. In vivo, pOBz inhibited cerebral MAO activity after middle cerebral artery occlusion with reperfusion in rats, and it reduced cerebral infarct volume, improved neurological function and NeuN expression, and inhibited complement C3 expression and apoptosis . Our results suggest that pOBz is a structurally novel type of competitive and selective MAO-B inhibitor, with potent neuroprotective properties after cerebral ischemia-reperfusion injury in rats.
CAS / MDL:
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高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2013
·
IF 3.458
Hailong Peng,Ruichen Dong,Shenqi Wang,Zhong Zhang,Mei Luo,Chunqing Bai,Qiang Zhao,Jinhua Li,Lingxin Chen,Hua Xiong
A novel pH-responsive nano-carrier MSNs–PAA, possessing mesoporous silica nanoparticles (MSNs) cores and poly(acrylic acid) (PAA) shell-layers, was developed for controlled release of salidroside . The vinyl double bonds modified MSNs were synthesized by using cetyltrimethylammonium bromide (CTAB) as templates, tetraethyl orthosilicate (TEOS) as silicon source, and 3-(trimethoxylsilyl) propyl methacrylate (MPS) as surface modification functionalities. The pH-responsive layers of PAA were grafted onto the vinyl double bonds of the MSNs via precipitation polymerization, producing the MSNs–PAA with a hollow cubic core and mesoporous shell with penetrating pore channels. The characteristic results also showed that PAA was successfully grafted onto the surface of the MSNs. The MSNs–PAA was investigated as carriers for loading and regulating the release of salidroside in different pH solutions for the first time. The results demonstrated that the PAA layers on the surface of MSNs–PAA exhibited opened and closed states at different pH values, and thus could regulate the uptake and release of salidroside. The application of such pH-responsive nano-carrier might offer a potential platform for controlled delivery and increasing the bioavailability of drugs.
研究领域:
药剂学
·
材料科学
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DOI
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Shan Shan Qi,Meng Li Shao,Sun Ze,Hong Xing Zheng
Salidroside from Rhodiola rosea L. has hypoglycemic effects, and has anti-osteoporosis effect in diabetic rats. Whether it has beneficial effects on diabetic nephropathy (DN) has not been fully reported. Here, a DN rat model was established by streptozotocin (STZ). Salidroside (10, and 20 mg kg −1 d −1 ) were orally giving for eight weeks. The purity of salidroside was 99%. The results showed that eight weeks salidroside supplementation dose-dependently decreased blood glucose, serum insulin, serum creatinine, blood urea nitrogen (BUN), as well as urinary albumin of DN rats, repaired the pathological changes of kidney tissue, the renal sclerosis and fibrosis in the kidney of DN rats were improved, and the activities of oxidative defense system associated enzyme such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were also improved. Serum inflammatory cytokines (including tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1β, and interleukin-6) were decreased significantly in DN rats after eight weeks salidroside supplementation. Immunohistochemical results showed that fibrosis related proteins such as transforming growth factor-β1 (TGF-β1), phospho-Smad2 (p-Smad2), and phospho-Smad3 (p-Smad3) expression levels were decreased significantly in the kidney of salidroside treated group. Our results indicate that daily salidroside consumption could alleviate DN in rats, the main mechanisms are anti-inflammatory, anti-oxidative stress, and inhibition of the TGF-β1/Smad2/3 pathway. This study suggested that salidroside could be used as a nutrient against DN, as well as diabetes.
研究领域:
药理学
·
糖尿病学
·
肾病学
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产品关联
DOI
高影响因子
JOURNAL OF NATURAL PRODUCTS
·
2022
·
IF 4.803
Qi Zeng,Xu Nie,Li Li,Hui-Fang Liu,Yang-Yao Peng,Wang-Ting Zhou,Xiao-Jia Hu,Xin-Yi Xu,Xue-Li Chen
Salidroside (Sal), the major active constituent of Rhodiola rosea L., is considered as a potential pro-drug with various activities; however, its role in tumor therapy is not clear. Here, we demonstrated in vitro and in vivo that Sal enhanced the inhibitory activity of doxorubicin (DOX) in drug-resistant cancer cell lines. Our results showed that combination drug treatment (Sal and DOX) significantly decreased cell proliferation, migration, and motility. Besides biological validation, a luciferase-labeled animal tumor xenograft model and bioluminescence imaging (BLI) were applied for assessing the tumor progression. Sal combined with DOX inhibited the growth of HeLa-ADR-luc cells in vivo and downregulated the DOX-induced high expression of MDR1. Also, Sal downregulated the Bcl-2, MMP-2, MMP-9, PI3K, and AKT and upregulated BAX proteins. Sal demonstrated high safety and cardiac protection activity. We discovered that Sal enhances DOX sensitivity through the regulation of PI3K/Akt/HIF-1α and DOX-induced resistance pathways. Our results suggest that Sal could be a novel chemosensitization agent for the treatment of multi-drug-resistance tumors.
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高影响因子
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