JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Ziyue Wang,Lu Li,Wenliang Li,Haiyang Yan,Yuan Yuan
As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC–MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein–protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.
研究领域:
药理学
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微生物学
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免疫学
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毒理学
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胃肠病学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
He Shumei,Fan Hongyan,Sun Bin,Yang Meipan,Liu Hongxu,Yang Jianwei,Liu Jianxin,Luo Sizhu,Chen Zihan,Zhou Jing,Xia Lu,Zhang Shulin,Yan Bo
The treatment for tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), has a prolonged cycle which can last up to a year. This is partially due to the lack of effective therapies. The development of novel anti-TB drugs from the perspective of host immune regulation can provide an important supplement for conventional treatment strategies. Salidroside (SAL), a bioactive component from the Tibetan medicine Rhodiola rosea, has been used in the treatment of TB, although its mechanism remains unclear. Here, the bacteriostatic effect of SAL in vivo was first demonstrated using a zebrafish–M. marinum infection model. To further investigate the underlying mechanism, we then examined the impact of SAL on immune cell recruitment during wound and infection. Increased macrophage and neutrophil infiltrations were found both in the vicinity of the wound and infection sites after SAL treatment compared with control, which might be due to the elevated chemokine expression levels after SAL treatment. SAL treatment alone was also demonstrated to improve the survival of infected zebrafish larvae, an effect that was amplified when combining SAL treatment with isoniazid or rifampicin. Interestingly, the reduced bacterial burden and improved survival rate under SAL treatment were compromised in tnfα-deficient embryos which suggests a requirement of Tnfα signaling on the anti-mycobacterial effects of SAL. In summary, this study provides not only the cellular and molecular mechanisms for the host anti-mycobacterial effects of the Tibetan medicine SAL but also proof of concept that combined application of SAL with traditional first-line anti-TB drugs could be a novel strategy to improve treatment efficacy.
研究领域:
免疫学
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微生物学
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药理学
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传染病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2026
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IF 5.1
Xue-Ni Peng,Sheng-Jin Xiang,Yue-Xiao Wu,Jing Luo,Zai-Long Chi,Tong Li
Optic neuropathy is characterized by impaired optic nerve function resulting from various pathological processes, often leading to retinal ganglion cell (RGC) degeneration and irreversible vision loss. Several studies have demonstrated the neuroprotective effects of salidroside (Sal). However, its clinical application has been limited by the high dosage required and the short half-life of Sal. To enhance drug efficacy and prolong therapeutic effects, we developed engineered small extracellular vesicles (sEVs) loaded with Sal (sEVs-Sal) for intravitreal administration in a mouse model of optic nerve crush (ONC). Our findings demonstrate that sEV-mediated low-dose Sal administration significantly enhanced visual functional recovery in ONC mice by mitigating RGC degeneration and inhibiting microglial activation. Proteomic profiling indicated that sEVs-Sal concurrently modulate both the TNF-α/IL-1β inflammatory axis and the Caspase-3/Bcl-2 apoptotic pathway, thereby conferring dual anti-inflammatory and antiapoptotic effects. This study establishes an efficient sEV-based drug delivery platform and highlights the considerable therapeutic potential of sEVs-Sal in the treatment of optic nerve injury. By addressing the pharmacokinetic limitations of free Sal and augmenting neuroprotection, this nanoformulation represents a promising translational strategy for optic neuropathies.
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Zhong Zhi-feng,Han Jing,Zhang Ji-Zhou,Xiao Qing,Chen Jing-yan,Zhang Kai,Hu Juan,Chen Li-dian
Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Salidroside has prominent anti-stroke effects in cerebral ischemia/reperfusion models. However, the underlying mechanisms of its actions are poorly understood. This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the modified neurological severity scores (mNSS), the balance beam test, and the foot fault test. Moreover, enzyme-linked immunosorbent assay (ELISA) suggested that MCAO-induced reduction in monoamine oxidase (MAO) was inhibited by salidroside. Immunohistochemical and immunofluorescence analyses revealed high level of tyrosine hydroxylase (TH) in the ipsilateral striatal caudate putamen (CPu) after cerebral ischemia/reperfusion, which could be further elevated by salidroside. In addition, salidroside could reverse the decreased immunoreactivity of TH in the substantia nigra pars compacta (SNpc). These results suggest that the anti-stroke effects of salidroside in MCAO-induced cerebral ischemia/reperfusion may involve the modulation of monoamine metabolism in the striatum and SNpc, which may be related to the function of the dopaminergic system in the rat brain.
研究领域:
神经科学
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药理学
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神经病学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL BIOLOGY AND MEDICINE
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2020
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IF 3.139
Jiaqi Li,Yongguang Zhang,Zhimin Yang,Jingxian Zhang,Ren Lin,Daoshu Luo
Schwann cell and nerve conduit are crucial for nerve regeneration and re-myelination after peripheral nerves injury. To investigate the effects of Salidroside on autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on an animal model with 5 mm sciatic nerve defect injury in rat, motor function, muscle reinnervation, immunohistochemical staining, retrograded tracing and Western blot were used in this study. The results showed that Salidroside enhanced the compound effects of epimysium conduit mixed with BD matrigel and RSC96 Schwann cells to improve the sciatic functional index and the gastrocnemius muscle weight ratio, which were better than EPM group at 8 weeks and 12 weeks post operation. Immunofluorescence and Western blot results of P75NTR showed that Salidroside improved the sciatic nerve regeneration, and retrograded tracing of CTB-Alexa 488 also supported that Salidroside was better to promote CTB tracer transporting from the distal nerve defect to the ipsilateral dorsal root ganglion and ventral horn of L3-L5 spinal cord on post-operation 8 weeks and 12 weeks. Our results demonstrated that Salidroside improved the effect of autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on sciatic nerve regeneration in our study.Impact statementPeripheral nerve injury and regeneration remain a major challenge. Although nerve conduit and Schwann cells have been used to study the nerve regeneration, our results demonstrated that Salidroside improved the regenerative effect in a rat model with sciatic nerve injury model, following a combined application of autogenous epimysium conduit mixed with Schwann cells. Different concentrations of Salidroside combining autogenous epimysium conduit and Schwann cells were applied to compare the epimysium conduit group and the epimysium conduit combining Schwann cells group. Based on the results of motor function and muscle reinnervation evaluation, as well as neuronal tracing and expression of P75NTR, our study for the first time suggests that Salidroside may improve the regeneration effect on the sciatic nerve following a combined application of epimysium conduit and RSC96 Schwann cells in rats.
研究领域:
神经科学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chai Yuhui,Cai Yawen,Fu Yu,Wang Yingdi,Zhang Yiming,Zhang Xue,Zhu Lingpeng,Miao Mingxing,Yan Tianhua
Depression is a common and serious mental disorder. Data on its pathogenesis remain unclear and the options of drug treatments are limited. Here, we explored the role of pyroptosis, a novel pro-inflammatory programmed cell death process, in depression as well as the anti-depression effects and mechanisms of salidroside (Sal), a bioactive extract from Rhodiola rosea L. We established a corticosterone (CORT)-induced or lipopolysaccharide (LPS)-induced mice in vivo, and CORT, or nigericin (NLRP3 agonist)-induced PC12 cells in vitro. Our findings demonstrated that Sal profoundly mediated CORT or LPS-induced depressive behavior and improved synaptic plasticity by upregulating the expression of brain-derived neurotrophic factor (BDNF) gene. The data showed upregulation of proteins associated with NLRP3-mediated pyroptosis, including NLRP3, cleaved Caspase-1, IL-1β, IL-18, and cleaved GSDMD. The molecular docking simulation predicted that Sal would interact with P2X7 of the P2X7/NF-κB/NLRP3 signaling pathway. In addition, our findings showed that the NLRP3-mediated pyroptosis was regulated by P2X7/NF-κB/NLRP3 signaling pathway. Interestingly, Sal was shown to ameliorate depression via suppression of the P2X7/NF-κB/NLRP3 mediated pyroptosis, and rescued nigericin-induced pyroptosis in the PC12 cells. Besides, knock down of the NLRP3 gene by siRNA markedly increased the inhibitory effects of Sal on pyroptosis and proinflammatory responses. Taken together, our findings demonstrated that pyroptosis plays a crucial role in depression, and Sal ameliorates depression by suppressing the P2X7/NF-κB/NLRP3-mediated pyroptosis. Thus, our study provides new insights into the potential treatment options for depression.
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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免疫学
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精神病学
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产品关联
DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
2021
·Vol. 62
·期 9
·25-25
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IF 4.799
Xiaoling Shi,Nuo Dong,Qi Qiu,Shanhua Li,Jiaxing Zhang
Purpose:Retinopathies are associated with the injury of retinal microvascular endothelial cells. Salidroside (SAL) is a medicinal supplement that has antioxidative and cytoprotective properties. We hypothesized that SAL might have a protective function in retinopathies. This research aims to explore the function and mechanism of SAL in hypoxia-induced retinal microvascular endothelial cell injury.Methods:Human retinal microvascular endothelial cells (HRMECs) injury was induced by culturing under hypoxic condition. The function of SAL on HRMECs injury was investigated using cell counting kit-8, 5-ethynyl-2′-deoxyuridine (EdU) staining, flow cytometry, Western blotting, and enzyme linked immunosorbent assay. MicroRNA (miR)-138, roundabout 4 (ROBO4), and proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were examined using quantitative reverse transcription polymerase chain reaction or Western blotting. The target correlation was determined by dual-luciferase reporter analysis and RNA immunoprecipitation.Results:Hypoxia resulted in proliferation inhibition, cycle arrest, apoptosis, inflammatory reaction, and oxidative stress in HRMECs. SAL attenuated hypoxia-induced HRMECs injury via increasing cell proliferation, and mitigating cycle arrest, apoptosis, inflammatory reaction, and oxidative stress. MiR-138 expression was enhanced by hypoxia, and decreased via SAL stimulation. MiR-138 upregulation reversed the influence of SAL on hypoxia-induced HRMECs injury. ROBO4 was targeted via miR-138. ROBO4 overexpression weakened the role of miR-138 in HRMECs injury. The PI3K/AKT/mTOR pathway was inactivated under hypoxic condition, and SAL increased the activation of PI3K/AKT/mTOR pathways by decreasing miR-138.Conclusions:SAL protected against hypoxia-induced HRMECs injury through regulating miR-138/ROBO4 axis, indicating the protective potential of SAL in retinopathies.
研究领域:
眼科学
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分子生物学
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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
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
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IF 5.6
Qi Liang,Rongjie Guo,Jia-Ruei Tsao,Yun He,Chenchen Wang,Jiaxuan Jiang,Di Zhang,Taige Chen,Tingting Yue,Kai Hu
Dry eye disease (DED) is a multifactorial disease, and oxidative stress plays a crucial role in its pathogenesis. Recently, multiple studies have shown that upregulation of autophagy can protect the cornea from oxidative stress damage. The present study investigated the therapeutic effects of salidroside, the main component of Rhodiola crenulata , in both in vivo and in vitro dry eye models. The results showed that topical eye drop treatment with salidroside restored corneal epithelium damage, increased tear secretion, and reduced cornea inflammation in the DED mice. Salidroside activated autophagy through AMP-activated protein kinase (AMPK)-sirtuin-1 (Sirt1) signaling pathway, which promoted the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and increased the expression of downstream antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). This process restored antioxidant enzyme activity, reduced reactive oxygen species (ROS) accumulation, and alleviated oxidative stress. The application of autophagy inhibitor chloroquine and AMPK inhibitor Compound C reversed the therapeutic efficacy of salidroside, validating the above findings. In conclusion, our data suggest that salidroside is a promising candidate for DED treatment.
研究领域:
药理学
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眼科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NEUROIMMUNOLOGY
·
2025
·
IF 2.5
Weiwei Ji,Zengyu Zhang,Tingyu Jin,Danyang Meng,Xuyou Zhou,Jin Hu,Yong Wang
Background Chronic cerebral hypoperfusion (CCH) is a significant contributor to vascular cognitive impairment (VCI), often linked to cortical and hippocampal damage. This study investigates the therapeutic potential of salidroside (SLDS) in mitigating CCH-induced brain injury by modulating microglial activation and inflammatory responses. Methods We established a CCH model in mice using the 0.16/0.18 mm bilateral common carotid artery stenosis (BCAS) procedure. We assessed cerebral blood flow (CBF) via laser speckle contrast imaging, while neuropathology was evaluated through Nissl staining and immunofluorescence (IF) experiments. Cognitive deficits were measured using the Morris water maze test. Neuronal apoptosis and neuroinflammation were examined through IF, ELISA, and qRT-PCR. Results BCAS-induced hypoperfusion resulted in a marked reduction in CBF, increased neuronal apoptosis, and significant cognitive deficits. SLDS treatment effectively countered these effects by shifting microglial polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, reducing pro-inflammatory cytokine levels, and enhancing neuronal survival. Conclusion SLDS demonstrates strong neuroprotective potential against CCH-induced brain injury by reducing inflammation and preventing neuronal apoptosis. These findings highlight the promise of SLDS as a therapeutic agent for chronic cerebrovascular disorders, warranting further investigation into its molecular mechanisms and clinical applicability.
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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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Xiaoyu Wu,Chun Liu,Yuqing Jiang,Ting Dai,Linxiang Zhang,Jiafeng Wang,Hongbin Zhao
Background Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.Methods and Results This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane’s vascularization and osteogenic capacities involved transplantation onto a rat’s subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane’s outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.Conclusion Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Guiqin Huang,Yawen Cai,Menghui Ren,Xiaoyu Zhang,Yu Fu,Run Cheng,Yingdi Wang,Mingxing Miao,Lingpeng Zhu,Tianhua Yan
Introduction Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. Objective This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. Methods Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. Results The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe 2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe 2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. Conclusions Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.
研究领域:
肿瘤学
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药理学
·
分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
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
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）