Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salid...Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salidroside,the main active component of Rhodiola rosea,exhibits distinct pharmacological actions including an anti-fibrotic effect.The purpose of this study is to investigate the therapeutic effect of salidroside(SAL)on RIPF via Nr1d2 regulation,which may affect inflammation response and epithelial mesenchymal transformation(EMT).Methods The key genes involved in RIPF development were identified by combining differentially expressed gene(DEG)analysis(mRNA microarray dataset GSE41789 downloaded from the Gene Expression Ombibus database,GEO)with Quantitative real time polymerase chain reaction(qRT-PCR)validation.Mouse type II lung epithelial cells(MLE-12)were divided into control group(control),radiation-exposure group(IR),group with postradiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The MLE-12 cells in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single dose of 6 Gy X-rays,and the latter two groups were treated with SAL at three concentrations(5,10,and 20μg/mL)for 24 h.A total of 48 C57BL/6J mice were randomly allocated into control group(control),radiation-exposure group(IR),group with post-radiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The mice in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single thorax dose of 17 Gy X-rays.At 24 h after irradiation,the mice in the AIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 21 days.The mice in the ABIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 10 days before thorax irradiation and for 11 days after thorax irradiation.Results The mice in the IR group incurred lung injuries including haemorrhage,oedema,inflammatory cell infiltration,increased release of proinflammatory cytokines,and pulmonary fibrosis.SAL treatment evidently alleviated radiationinduced inflammation and pulmonary fibrosis in the irradiated MLE-12 and mice.Moreover,SAL hindered the expression of Nr1d2,which influencedα-SMA and E-cadherin expression.Notably,pre-treatment with SAL in the irradiated mice exhibited a significant preventive effect on RIPF development.Conclusions Salidroside alleviated pulmonary fibrosis development through multiple mechanisms,including relieving inflammation response.Moreover,the downregulation of Nr1d2 might suppressα-SMA and promote E-cadherin,which affected EMT.展开更多
This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in o...This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in osteoblasts.Luciferase reporter assay and chromatin immunoprecipitation(Ch IP)assay were employed to validate whether the receptor activator of nuclear factor-κB ligand(RANKL)is the downstream target gene of HIF-1αin osteoblasts.The study also utilized lipopolysaccharide(LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo.Furthermore,conditioned medium(CM)from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1αpathway.Hypoxic condition-induced overexpression of HIF-1αupregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells.In vivo,SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1αby downregulating the expression of RANKL,vascular endothelial growth factor(VEGF),interleukin 6(IL-6),and angiopoietin-like 4(ANGPTL4).In the paracrine experiment,conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.RANKL emerges as the downstream target gene regulated by HIF-1αin osteoblasts.SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.展开更多
Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NS...Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.展开更多
Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attribute...Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attributes.Notwithstanding these latent virtues,the ramifications of Sal on retinal ganglion cells(RGCs)impairment during the incipient stages of diabetic retinopathy(DR)remain equivocal.The purpose of this study was to investigate inhibitory effect of Sal on ferroptosis of RGCs in db/db mice.Within the research conducted,Sal was administered via gavage,and observations were made 8 weeks post-treatment.Retinal samples were collected for analysis.The results evidenced that Sal ameliorated blood glucose levels,attenuated RGCs destruction,and augmented visual functionality in db/db mice.Additionally,Sal exerted an anti-ferroptosis impact on the RGCs in the db/db mice.Successive discoveries have outlined the involvement of the HIF-1α/HO-1 signaling pathway in this protective mechanism.Ferroptosis of RGCs has a contributory effect on the development of DR,in part through the HIF-1α/HO-1 pathway.Intriguingly,Sal reversed the alterations in the HIF-1α/HO-1 pathway in db/db mice and displayed prospective advantageous effects on DR.Sal mitigated RGCs ferroptosis by reducing blood sugar and impeding the HIF-1α/HO-1 signaling pathway,thereby improving DR.Thus,Sal shows potential for use as a pharmaceutical and nutraceutical for DR.展开更多
Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM_(2.5) in mice and illuminate the function of SIRT1-PGC-1ɑaxis.Methods Specific pathogen-free(SPF)grade male...Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM_(2.5) in mice and illuminate the function of SIRT1-PGC-1ɑaxis.Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM_(2.5) group,SAL+PM_(2.5) group.On the first day,SAL was given by gavage,and on the second day,PM_(2.5) suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑproteins were detected by Western blotting.Results Exposure to PM_(2.5) leads to obvious morphological and pathologica changes in the lung of mice.PM_(2.5) caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM_(2.5) by activating the SIRT1-PGC-1α pathway.Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.展开更多
By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of interm...By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of intermediates, which allowed the scalable synthesis of salidroside. It included a reaction of penta-O-acetyl-β-D-glucose with acyl protected tyrosol in the presence of Lewis acid catalyst（ZnCl2）, followed by deacylation under basic condition（NaOMe/MeOH） to give the salidroside. The total yield of this three-step reaction was 47%. Final product and intermediates were purified by recrystallization, which significantly reduced the cost and made the large scale synthesis feasible.展开更多
Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-...Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein （GFAP） and neurotrophin-3 （NT-3） in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. Results D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 （IL-2） production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Conclusion Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.展开更多
Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In t...Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2（Nrf2）pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside（30 mg/kg）reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.展开更多
Objective：To test the effects of salidroside on formation and growth of glioma together with tumor microenvironment.Methods：Salidroside extracted from Rhodiola rosea was purified and treated on human glioma cells U2...Objective：To test the effects of salidroside on formation and growth of glioma together with tumor microenvironment.Methods：Salidroside extracted from Rhodiola rosea was purified and treated on human glioma cells U251 at the concentration of 20 μg/mL.3-（4,5-dimethylthiazol-2-yl）-2,5-dephenyltetrazolium bromide （MTT） assay for cytotoxicity and flow cytometry （FCM） for cell cycle analysis were performed.Then for in vivo study,xenotransplantation tumor model in nude mice was generated and treated with salidroside at the concentration of 50 mg/kg.d for totally 20 d.Body weight and tumor size were detected every 2 d after the treatment.The levels of 8-isoprostane,superoxide dismutase （SOD） and malondialdehyde （MDA）,special markers for oxidative stress,were detected while immunofluoresence staining was performed for astrocyte detection.Results：For in vitro study,salidroside could decrease the viability of human glioma cells U251 and the growth of U251 cells at G0/G1 checkpoint during the cell cycle.For in vivo study,salidroside could also inhibit the growth of human glioma tissue in nude mice.The body weight of these nude mice treated with salidroside did not decrease as quickly as control group.In the tumor xenotransplantation nude mice model,mice were found of inhibition of oxidative stress by detection of biomarkers.Furthermore,overgrowth of astrocytes due to the stimulation of oxidative stress in the cortex of brain was inhibited after the treatment of salidroside.Conclusions：Salidroside could inhibit the formation and growth of glioma both in vivo and in vitro and improve the tumor microenvironment via inhibition of oxidative stress and astrocytes.展开更多
AIM: The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin(OVA)-induced asthma model in mice. METHOD: BALB/c mice were sensitized with an intraperitoneal i...AIM: The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin(OVA)-induced asthma model in mice. METHOD: BALB/c mice were sensitized with an intraperitoneal injection of ovalbumin(OVA) to induce a mouse model of asthma in paracmasis. The mice were treated with dexamethasone as the positive control. At the end of the study, respiratory reactivity was detected, the numbers of various kinds of white blood cells in the bronchoalveolar lavage fluid(BALF) were counted, and the levels of IL-4 and INF-γ in BALF were determined. Quantitative PCR was used to detect the mRNA contents of IL-4 and INF-γ in lung tissue. Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS: Salidroside treatment virtually eliminated airway hyper-reactivity, markedly reduced the eosinophil percent, obviously reduced the levels of IL-4 and raised INF-γ in the bronchoalveolar lavage fluid(BALF) compared with the sham-treated group. Quantitative PCR on the mRNA content of IL-4 and INF-γ provided confirmation. Lung histologic observations showed that salidroside reduced inflammation and edema. These effects were equivalent to the effects of dexamethasone. CONCLUSION: Synthetic salidroside exhibits an anti-asthma effect which is related to the regulation of Th1/Th2 balance. This provides a new possibility for treatment of allergic asthma.展开更多
Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases.Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages....Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases.Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages.Salidroside (Sal),one of main bioactive components in Rhodiola crenulata (Hook.F.et Thoms) H.ohba,reportedly possesses anti-inflammatory activity and ameliorates inflammation in alcohol-induced hepatic injury.However,whether Sal regulates the activation of proinflammatory macrophages through Notch signaling pathway remains unknown.The present study investigated the effects of Sal on macrophage activation and its possible mechanisms by using both alcohol and lipopolysaccharide (LPS) to mimic the microenvironment of alcoholic liver.Detection of THP-1-derived macrophages exhibited that Sal could significantly decrease the expression of tumor necrosis factor-α(TNF-α),interleukinbeta (IL-1β)and IL-6 in the macrophages at both mRNA and protein levels.Furthermore,Sal significantly suppressed NF-kB activation via Notch-Hes signaling pathway in a dose-dependent manner.Moreover,in the microenvironment of alcoholic liver,the expression of Notch-dependent pyruvate dehydrogenase phosphatase 1 (PDP1) was elevated,and that of Ml gene expression [inducible NO synthase (NOS2)] was up-regulated.These changes could all be effectively ameliorated by Sal.The aforementioned findings demonstrated that Sal could inhibit LPS-ethanol-induced activation of proinflammatory macrophages via Notch signaling pathway.展开更多
Summary： Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside （Sal）, one of the main bioactive components ofRhodiola Sachalinensis, has been reported to possess anti-infla...Summary： Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside （Sal）, one of the main bioactive components ofRhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activa- tion of macrophages and the possible mechanism. The lipopolysaccharide （LPS）-stimulated phrobol 12-myristate 13-acetate （PMA）-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-l-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase （iNOS）, cyclooxygenase-2 （COX2）, interleukin-lbeta （IL-1β）, interleukin-6 （IL-6） and tumor necrosis fac- tor-or （TNF-a） at both mRNA and protein levels in THP-l-derived macrophages, and the effect was dose-depedent. Moreover, NF-B activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-a, and the mechanism involves the inhibition of NF-r,B activation and the phosphorylation of the MAPK signal pathway.展开更多
A simple,rapid and sensitive liquid chromatography-mass spectrometry（LC-MS）method was developed for the determination of salidroside in rat plasma and study of its pharmacokinetics after oral administration of suspe...A simple,rapid and sensitive liquid chromatography-mass spectrometry（LC-MS）method was developed for the determination of salidroside in rat plasma and study of its pharmacokinetics after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi into Wistar rats.Plasma sample of 200 μL was extracted with acetic ether-isopropanol（2∶1）and the extraction was performed on a Kromasil C18 column（150 mm×4.6 mm,5 μm）with the mobile phase of methanol-water（41∶59,v/v）within a run time of 6.0 min.The analyte was monitored with positive electrospray ionization（ESI）by selected ion monitoring（SIM）mode.The target ions were m/z 323.05 for salidroside and m/z 411.05 for internal standard（IS）geniposide.A good linear relationship was obtained over the range of 5.0-500.0 ng/mL and the lower limit of quantification was 5.0 ng/mL.The validated method was successfully applied to the pharmacokinetic study of salidroside in rat plasma after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi.展开更多
Salidroside(SAL),a major bioactive compound of Rhodiola crenulata,has significant anti-hypoxia effect,however,its underlying molecular mechanism has not been elucidated.In order to explore the protective mechanism of ...Salidroside(SAL),a major bioactive compound of Rhodiola crenulata,has significant anti-hypoxia effect,however,its underlying molecular mechanism has not been elucidated.In order to explore the protective mechanism of SAL,the lactate dehydrogenase(LDH),reactive oxygen species(ROS),superoxide dismutase(SOD)and hypoxia-induced factor 1α(HIF-1α)were measured to establish the PC12 cell hypoxic model.Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL.The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition.The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting.The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2,p-PTEN/PTEN,PI3K,p-Akt/Akt,NF-κB p65 and Bcl-2 were increased,suggesting that SAL could increase the expression of CK2,which induced the phosphorylation and inactivation of PTEN,reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway.Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.展开更多
Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on b...Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on body weight. The control group was given distilled water and the 4 intervention groups were given various doses of salidroside （60, 180, 360, 720 mg/kg） for 15 consecutive days, respectively. The levels of lactate, serum urea nitrogen, muscle and liver glycogen, the longest swimming time and hemoglobin were determined before and after swimming test. Results： Different doses of salidroside significantly lengthened the swimming time and increased the contents of hemoglobin and muscle and liver glycogen, while reducing that of lactate in blood significantly compared with control group, especially in the 180 mg/kg salidroside group. Conclusion： Salidroside has noticeable anti-fatigue effect on mice. These effects were dose-dependent, and the strongest effect on most biomarkers was seen with an intermediate dose.展开更多
Salidroside(SAL)is a phenolic substance with high solubility and low permeability,which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora,resulting in lower bioavailability....Salidroside(SAL)is a phenolic substance with high solubility and low permeability,which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora,resulting in lower bioavailability.The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL(w/o SAL-N)to explore its suitability in oral drug delivery systems.In this work,SAL-N was successfully prepared by water titration method at K_(m)=1 to construct the pseudo-ternary phase diagrams.Physical characterization including the average viscosity,pH,refractive index,particle size,PDI,TEM,DSC,the content of SAL,and stability study were performed.It was evaluated for drug release in vitro and pharmacokinetic studies in vivo.The optimized nanoemulsion formulation consisted of Labrafil M 1944 CS(63%),Span-80/Tween-80/EtOH(27%)and 200 mg·mL^(-1) SAL solution(SAL-SOL)(10%).Low viscosity and suitable pH were expected for the nanoemulsion.The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system.In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points.The pharmacokinetic studies exhibited that SAL-N had significantly higher in t_(1/2)(2.11-fold),AUC_(0-48 h)(1.75-fold)and MRT0-48 h(2.63-fold)than SAL-SOL(P<0.01).The w/o SAL-N prepared in this work can be effectively delivered via the oral route.It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release,enhance oral absorption and reduce metabolic rate.展开更多
Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic str...Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum （ER） stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti- oxidative stress properties and protects against DA neu- ronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine （6-OHDA）- induced cytotoxicity by attenuating ER stress. Further- more, treatment of a DA neuronal cell line （SN4741） and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results sug- gest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.展开更多
Salidroside is the active ingredient extracted from Rhodiola rosea,and has been reported to show protective effects in cerebral ischemia,but the exact mechanisms of neuronal protective effects are still unrevealed.In ...Salidroside is the active ingredient extracted from Rhodiola rosea,and has been reported to show protective effects in cerebral ischemia,but the exact mechanisms of neuronal protective effects are still unrevealed.In this study,the protective effects of salidroside(1 jimol/L)in ameliorating neuronal injuries induced by oxygen-glucose deprivation(OGD),which is a classical model of cerebral ischemia,were clarified.The results showed that after 8 h of OGD,the mouse hippocampal neuronal cell line HT22 cells showed increased cell death,accompanied with mitochondrial fragmentation and augmented mitophagy.However,the cell viability of HT22 cells showed significant restoration after salidroside treatment.Mitochondrial morphology and mitochondrial function were effectively preserved by salidroside treatment.The protective effects of salidroside were further related to the prevention of mitochondrial over-fission.The results showed that mTOR could be recruited to the mitochondria after salidroside treatment,which might be responsible for inhibiting excessive mitophagy caused by OGD.Thus,salidroside was shown to play a protective role in reducing neuronal death under OGD by safeguarding mitochondrial function,which may provide evidence for further translational studies of salidroside in ischemic diseases.展开更多
Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density li...Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor - deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Method Six-week old apoE-/- male mice were fed a high-fat diet for 8 weeks and then were ad- ministered with SAL for another 8 weeks. Atherosclerotic lesion and vascular function were analyzed. Primary cul- tured human umbilical vein endothelial cells （HUVECs） were prepared. Superoxide anion （O2^-）, NO produc- tion, mitochondrial membrane potential （△ψm） and intracellular ATP and AMP levels were measured. Expression of eNOS and AMPK were analyzed by Western blot. Result SAL significantly improved endothelial function asso- ciated with increasing eNOS activation thus reduced the atherosclerotic lesion area. SAL increased eNOS-Serl177 phosphorylation and decreased eNOS-Thr495 phosphorylation. SAL significantly activated AMP-activated protein ki- nase （AMPK）. Both AMPK inhibitor and AMPK small interfering RNA （siRNA） abolished SAL-induced Akt- Ser473 and eNOS-Serl177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. SAL decreased cellular ATP content and increased the cel- lular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease A^m, which is likely consequence of reduced ATP production. Conclusion The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide （NO） production, which was associated with mitochondria depolarization and subsequent activation of the AMPK/PI3 IC/ Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis.展开更多
As a main component of efficiency in Rhodiola plants, salidroside is a promising environmental acclamation medicine and possesses specific medical properties against symptoms of fatigue, old age, microwave radiation, ...As a main component of efficiency in Rhodiola plants, salidroside is a promising environmental acclamation medicine and possesses specific medical properties against symptoms of fatigue, old age, microwave radiation, viral infections and tumors. Salidroside plays important roles, especially in military, aerospace, sport and healthcare medicine and has, therefore, recently, drawn more and closer attention. This article probes mainly into the probable biosynthetic pathway of salidroside following a brief introduction of the exploitation and utilization values of Rhodiola plants and the current condition of its natural resources. We have come to the conclusion that tyrosol, the aglycon of salidroside, is biosynthesized through the well-characterized shikimic acid pathway. A molecule of glucose is transferred by the UDP-glucosyltransferase （or possibly by the β-D-glucosidase too） to the tyrosol to form salidroside. On the other hand, salidroside may be degraded into tyrosol and glucose by β-D-glucosidase. Progress in research of these two key-enzymes, involved in the metabolism of salidroside, is finally elaborated.展开更多
文摘Objective Radiation-induced pulmonary fibrosis(RIPF)is a dynamic,complex and long-term process involving multiple chemokines and cytokines that lead to irreversible and severe lung tissue damage and even failure.Salidroside,the main active component of Rhodiola rosea,exhibits distinct pharmacological actions including an anti-fibrotic effect.The purpose of this study is to investigate the therapeutic effect of salidroside(SAL)on RIPF via Nr1d2 regulation,which may affect inflammation response and epithelial mesenchymal transformation(EMT).Methods The key genes involved in RIPF development were identified by combining differentially expressed gene(DEG)analysis(mRNA microarray dataset GSE41789 downloaded from the Gene Expression Ombibus database,GEO)with Quantitative real time polymerase chain reaction(qRT-PCR)validation.Mouse type II lung epithelial cells(MLE-12)were divided into control group(control),radiation-exposure group(IR),group with postradiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The MLE-12 cells in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single dose of 6 Gy X-rays,and the latter two groups were treated with SAL at three concentrations(5,10,and 20μg/mL)for 24 h.A total of 48 C57BL/6J mice were randomly allocated into control group(control),radiation-exposure group(IR),group with post-radiation exposure plus SAL treatment(AIR+SAL),and group with pre/post-radiation exposure plus SAL treatment(ABIR+SAL).The mice in the IR,AIR+SAL,and ABIR+SAL groups were irradiated with a single thorax dose of 17 Gy X-rays.At 24 h after irradiation,the mice in the AIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 21 days.The mice in the ABIR+SAL group were intraperitoneally injected with SAL(10,20,and 40 mg/kg)for 10 days before thorax irradiation and for 11 days after thorax irradiation.Results The mice in the IR group incurred lung injuries including haemorrhage,oedema,inflammatory cell infiltration,increased release of proinflammatory cytokines,and pulmonary fibrosis.SAL treatment evidently alleviated radiationinduced inflammation and pulmonary fibrosis in the irradiated MLE-12 and mice.Moreover,SAL hindered the expression of Nr1d2,which influencedα-SMA and E-cadherin expression.Notably,pre-treatment with SAL in the irradiated mice exhibited a significant preventive effect on RIPF development.Conclusions Salidroside alleviated pulmonary fibrosis development through multiple mechanisms,including relieving inflammation response.Moreover,the downregulation of Nr1d2 might suppressα-SMA and promote E-cadherin,which affected EMT.
基金supported by grants from the National Natural Science Foundation of China(Nos.81572852 and 82104671)the Great Program of the Science Foundation of Tianjin(No.18JCZDJC33200)+1 种基金Heilongjiang Province Fund(No.LH2020H102)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-032A)。
文摘This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in osteoblasts.Luciferase reporter assay and chromatin immunoprecipitation(Ch IP)assay were employed to validate whether the receptor activator of nuclear factor-κB ligand(RANKL)is the downstream target gene of HIF-1αin osteoblasts.The study also utilized lipopolysaccharide(LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo.Furthermore,conditioned medium(CM)from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1αpathway.Hypoxic condition-induced overexpression of HIF-1αupregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells.In vivo,SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1αby downregulating the expression of RANKL,vascular endothelial growth factor(VEGF),interleukin 6(IL-6),and angiopoietin-like 4(ANGPTL4).In the paracrine experiment,conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.RANKL emerges as the downstream target gene regulated by HIF-1αin osteoblasts.SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
基金supported by the Scientific Research Project of Hubei Cancer Hospital(No.2024HBCHYN08)the Natural Science Foundation of Hubei Province(No.2023AFB988)+1 种基金the Scientific Research Project in the Field of Oncology(No.FB2024025225)the Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC007).
文摘Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.
基金supported by the Basic Research Project for Higher Education Institutions of Liaoning Provincial Department of Education(Youth Project)(LJ212410160055)Foundation of Education Department of Liaoning Province of China(LJKMZ20221241)+1 种基金The National Natural Science Foundation of China(81571383)Natural Science Foundation of Liaoning Province of China(2023-MS-312)。
文摘Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attributes.Notwithstanding these latent virtues,the ramifications of Sal on retinal ganglion cells(RGCs)impairment during the incipient stages of diabetic retinopathy(DR)remain equivocal.The purpose of this study was to investigate inhibitory effect of Sal on ferroptosis of RGCs in db/db mice.Within the research conducted,Sal was administered via gavage,and observations were made 8 weeks post-treatment.Retinal samples were collected for analysis.The results evidenced that Sal ameliorated blood glucose levels,attenuated RGCs destruction,and augmented visual functionality in db/db mice.Additionally,Sal exerted an anti-ferroptosis impact on the RGCs in the db/db mice.Successive discoveries have outlined the involvement of the HIF-1α/HO-1 signaling pathway in this protective mechanism.Ferroptosis of RGCs has a contributory effect on the development of DR,in part through the HIF-1α/HO-1 pathway.Intriguingly,Sal reversed the alterations in the HIF-1α/HO-1 pathway in db/db mice and displayed prospective advantageous effects on DR.Sal mitigated RGCs ferroptosis by reducing blood sugar and impeding the HIF-1α/HO-1 signaling pathway,thereby improving DR.Thus,Sal shows potential for use as a pharmaceutical and nutraceutical for DR.
基金supported by Shandong Provincial Natural Science Foundation,China(No.ZR2020MH336)Weifang Science and Technology Development Plan Project(NO.2022GX015,NO.2022GX010).
文摘Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM_(2.5) in mice and illuminate the function of SIRT1-PGC-1ɑaxis.Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM_(2.5) group,SAL+PM_(2.5) group.On the first day,SAL was given by gavage,and on the second day,PM_(2.5) suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑproteins were detected by Western blotting.Results Exposure to PM_(2.5) leads to obvious morphological and pathologica changes in the lung of mice.PM_(2.5) caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM_(2.5) by activating the SIRT1-PGC-1α pathway.Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.
基金the National Basic Research Program of China(973 Program,Grant No.2012CB822100)the National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2012ZX09502001-001)the National Natural Science Foundation of China(Grant No.21232002,21072016 and 21072017)
文摘By analyzing the key steps that restricted the industrial synthesis of salidroside, selective protection of tyrosol with different acylation reagents was adopted. The strategy facilitated the crystallization of intermediates, which allowed the scalable synthesis of salidroside. It included a reaction of penta-O-acetyl-β-D-glucose with acyl protected tyrosol in the presence of Lewis acid catalyst（ZnCl2）, followed by deacylation under basic condition（NaOMe/MeOH） to give the salidroside. The total yield of this three-step reaction was 47%. Final product and intermediates were purified by recrystallization, which significantly reduced the cost and made the large scale synthesis feasible.
基金supported by the National Grand Fundamental Research 973 Program of China(2007CB507406)the National NaturalScience Foundation of China(30600659)the Central and Non-profitable Basic R&D Funds for Scientific Research Institutes(IMBF200913)
文摘Objective To investigate the protective effects of putative AGEs （advanced glycation endproducts） inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. Methods A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein （GFAP） and neurotrophin-3 （NT-3） in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. Results D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 （IL-2） production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. Conclusion Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.
基金supported by the Independent Research Project of Fujian Academy of Traditional Chinese Medicine in China,No.2012fjzyyk-4the Natural Science Foundation of Fujian Province in China,No.2014J01340+1 种基金the Research Project of Fujian Provincial Health and Family Planning Commission,No.2014-ZQN-JC-32a grant from the Platform for Preclinical Studies of Traditional Chinese Medicine and Quality Control Engineering Technology Research Center of Fujian Province in China,No.2009Y2003
文摘Salidroside,the main active ingredient extracted from Rhodiola crenulata,has been shown to be neuroprotective in ischemic cerebral injury,but the underlying mechanism for this neuroprotection is poorly understood.In the current study,the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2（Nrf2）pathway was investigated in a rat model of middle cerebral artery occlusion.Salidroside（30 mg/kg）reduced infarct size,improved neurological function and histological changes,increased activity of superoxide dismutase and glutathione-S-transferase,and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion.Furthermore,salidroside apparently increased Nrf2 and heme oxygenase-1 expression.These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved.The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.
基金supported by the National Natural Science Foundation of China(No.81141080)Jiangsu Provincial Natural Science Foundation(SBK201340596)
文摘Objective：To test the effects of salidroside on formation and growth of glioma together with tumor microenvironment.Methods：Salidroside extracted from Rhodiola rosea was purified and treated on human glioma cells U251 at the concentration of 20 μg/mL.3-（4,5-dimethylthiazol-2-yl）-2,5-dephenyltetrazolium bromide （MTT） assay for cytotoxicity and flow cytometry （FCM） for cell cycle analysis were performed.Then for in vivo study,xenotransplantation tumor model in nude mice was generated and treated with salidroside at the concentration of 50 mg/kg.d for totally 20 d.Body weight and tumor size were detected every 2 d after the treatment.The levels of 8-isoprostane,superoxide dismutase （SOD） and malondialdehyde （MDA）,special markers for oxidative stress,were detected while immunofluoresence staining was performed for astrocyte detection.Results：For in vitro study,salidroside could decrease the viability of human glioma cells U251 and the growth of U251 cells at G0/G1 checkpoint during the cell cycle.For in vivo study,salidroside could also inhibit the growth of human glioma tissue in nude mice.The body weight of these nude mice treated with salidroside did not decrease as quickly as control group.In the tumor xenotransplantation nude mice model,mice were found of inhibition of oxidative stress by detection of biomarkers.Furthermore,overgrowth of astrocytes due to the stimulation of oxidative stress in the cortex of brain was inhibited after the treatment of salidroside.Conclusions：Salidroside could inhibit the formation and growth of glioma both in vivo and in vitro and improve the tumor microenvironment via inhibition of oxidative stress and astrocytes.
基金supported by major drugdiscovery projects during the 12th five year plan(No.2011ZX09102-002-01)
文摘AIM: The aim of the study was to investigate the effect and mechanism of action of synthetic salidroside in an ovalbumin(OVA)-induced asthma model in mice. METHOD: BALB/c mice were sensitized with an intraperitoneal injection of ovalbumin(OVA) to induce a mouse model of asthma in paracmasis. The mice were treated with dexamethasone as the positive control. At the end of the study, respiratory reactivity was detected, the numbers of various kinds of white blood cells in the bronchoalveolar lavage fluid(BALF) were counted, and the levels of IL-4 and INF-γ in BALF were determined. Quantitative PCR was used to detect the mRNA contents of IL-4 and INF-γ in lung tissue. Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS: Salidroside treatment virtually eliminated airway hyper-reactivity, markedly reduced the eosinophil percent, obviously reduced the levels of IL-4 and raised INF-γ in the bronchoalveolar lavage fluid(BALF) compared with the sham-treated group. Quantitative PCR on the mRNA content of IL-4 and INF-γ provided confirmation. Lung histologic observations showed that salidroside reduced inflammation and edema. These effects were equivalent to the effects of dexamethasone. CONCLUSION: Synthetic salidroside exhibits an anti-asthma effect which is related to the regulation of Th1/Th2 balance. This provides a new possibility for treatment of allergic asthma.
基金This study was supported by the National Natural Science Foundation of China (No.81572274).
文摘Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases.Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages.Salidroside (Sal),one of main bioactive components in Rhodiola crenulata (Hook.F.et Thoms) H.ohba,reportedly possesses anti-inflammatory activity and ameliorates inflammation in alcohol-induced hepatic injury.However,whether Sal regulates the activation of proinflammatory macrophages through Notch signaling pathway remains unknown.The present study investigated the effects of Sal on macrophage activation and its possible mechanisms by using both alcohol and lipopolysaccharide (LPS) to mimic the microenvironment of alcoholic liver.Detection of THP-1-derived macrophages exhibited that Sal could significantly decrease the expression of tumor necrosis factor-α(TNF-α),interleukinbeta (IL-1β)and IL-6 in the macrophages at both mRNA and protein levels.Furthermore,Sal significantly suppressed NF-kB activation via Notch-Hes signaling pathway in a dose-dependent manner.Moreover,in the microenvironment of alcoholic liver,the expression of Notch-dependent pyruvate dehydrogenase phosphatase 1 (PDP1) was elevated,and that of Ml gene expression [inducible NO synthase (NOS2)] was up-regulated.These changes could all be effectively ameliorated by Sal.The aforementioned findings demonstrated that Sal could inhibit LPS-ethanol-induced activation of proinflammatory macrophages via Notch signaling pathway.
基金supported by grants from the National Natural Science Foundation of China(Nos.81100282,81030007,81171558,81271808)Program for Changjiang Scholars and Innovative Research Team in University(No.PCSIRT1131)China Postdoctoral Science Foundation(No.2013M531700)
文摘Summary： Excessive activation of macrophages is implicated in various inflammatory injuries. Salidroside （Sal）, one of the main bioactive components ofRhodiola Sachalinensis, has been reported to possess anti-inflammatory activities. This study aimed to examine the effect of Sal on the activa- tion of macrophages and the possible mechanism. The lipopolysaccharide （LPS）-stimulated phrobol 12-myristate 13-acetate （PMA）-differentiated THP-1 macrophage models were established. The changes in the inflammatory profiles of THP-l-derived macrophages were determined. The results showed that Sal significantly decreased the expression of inducible nitric oxide synthase （iNOS）, cyclooxygenase-2 （COX2）, interleukin-lbeta （IL-1β）, interleukin-6 （IL-6） and tumor necrosis fac- tor-or （TNF-a） at both mRNA and protein levels in THP-l-derived macrophages, and the effect was dose-depedent. Moreover, NF-B activation was significantly suppressed and the phosphorylation of ERK, p38 and JNK was substantially down-regulated after Sal treatment. The findings suggested that Sal can suppress the activation of LPS-stimulated PMA-differetiated THP-1 cells, as evidenced by the decreased expression of iNOS, COX2, IL-1β, IL-6 and TNF-a, and the mechanism involves the inhibition of NF-r,B activation and the phosphorylation of the MAPK signal pathway.
文摘A simple,rapid and sensitive liquid chromatography-mass spectrometry（LC-MS）method was developed for the determination of salidroside in rat plasma and study of its pharmacokinetics after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi into Wistar rats.Plasma sample of 200 μL was extracted with acetic ether-isopropanol（2∶1）and the extraction was performed on a Kromasil C18 column（150 mm×4.6 mm,5 μm）with the mobile phase of methanol-water（41∶59,v/v）within a run time of 6.0 min.The analyte was monitored with positive electrospray ionization（ESI）by selected ion monitoring（SIM）mode.The target ions were m/z 323.05 for salidroside and m/z 411.05 for internal standard（IS）geniposide.A good linear relationship was obtained over the range of 5.0-500.0 ng/mL and the lower limit of quantification was 5.0 ng/mL.The validated method was successfully applied to the pharmacokinetic study of salidroside in rat plasma after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi.
基金supported by the National Natural Science Foundation of China(Nos.81573683,81173121,81773803).
文摘Salidroside(SAL),a major bioactive compound of Rhodiola crenulata,has significant anti-hypoxia effect,however,its underlying molecular mechanism has not been elucidated.In order to explore the protective mechanism of SAL,the lactate dehydrogenase(LDH),reactive oxygen species(ROS),superoxide dismutase(SOD)and hypoxia-induced factor 1α(HIF-1α)were measured to establish the PC12 cell hypoxic model.Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL.The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition.The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting.The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2,p-PTEN/PTEN,PI3K,p-Akt/Akt,NF-κB p65 and Bcl-2 were increased,suggesting that SAL could increase the expression of CK2,which induced the phosphorylation and inactivation of PTEN,reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway.Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.
基金the Foundation of the Gym Sport Bureau of Shanghai (04JT017)
文摘Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on body weight. The control group was given distilled water and the 4 intervention groups were given various doses of salidroside （60, 180, 360, 720 mg/kg） for 15 consecutive days, respectively. The levels of lactate, serum urea nitrogen, muscle and liver glycogen, the longest swimming time and hemoglobin were determined before and after swimming test. Results： Different doses of salidroside significantly lengthened the swimming time and increased the contents of hemoglobin and muscle and liver glycogen, while reducing that of lactate in blood significantly compared with control group, especially in the 180 mg/kg salidroside group. Conclusion： Salidroside has noticeable anti-fatigue effect on mice. These effects were dose-dependent, and the strongest effect on most biomarkers was seen with an intermediate dose.
基金supported by Tianjin City High School Science Technology Fund Planning Project(No.2017KJ134)。
文摘Salidroside(SAL)is a phenolic substance with high solubility and low permeability,which make it easy to cause the efflux effect of P-glycoprotein and degradation of intestinal flora,resulting in lower bioavailability.The aim of this study was to develop and optimize a water-in-oil nanoemulsion of SAL(w/o SAL-N)to explore its suitability in oral drug delivery systems.In this work,SAL-N was successfully prepared by water titration method at K_(m)=1 to construct the pseudo-ternary phase diagrams.Physical characterization including the average viscosity,pH,refractive index,particle size,PDI,TEM,DSC,the content of SAL,and stability study were performed.It was evaluated for drug release in vitro and pharmacokinetic studies in vivo.The optimized nanoemulsion formulation consisted of Labrafil M 1944 CS(63%),Span-80/Tween-80/EtOH(27%)and 200 mg·mL^(-1) SAL solution(SAL-SOL)(10%).Low viscosity and suitable pH were expected for the nanoemulsion.The spherical morphology and nanoscale size of SAL-N enhanced the stability of the nanoemulsion system.In vitro drug release showed that SAL-N had a better controlled release property than SAL-SOL at earlier time points.The pharmacokinetic studies exhibited that SAL-N had significantly higher in t_(1/2)(2.11-fold),AUC_(0-48 h)(1.75-fold)and MRT0-48 h(2.63-fold)than SAL-SOL(P<0.01).The w/o SAL-N prepared in this work can be effectively delivered via the oral route.It can be seen w/o nanoemulsion is a strategy for the drug with polyphenols to delay the release,enhance oral absorption and reduce metabolic rate.
基金supported by the National Basic Research Development Program(973 Program)of China(2011CB510000)the National Natural Science Foundation of China(31371400)
文摘Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum （ER） stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti- oxidative stress properties and protects against DA neu- ronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine （6-OHDA）- induced cytotoxicity by attenuating ER stress. Further- more, treatment of a DA neuronal cell line （SN4741） and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results sug- gest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.
基金supported by grants from the National Natural Science Foundation of China(Nos.81873725,81371416,and 31670778)Hubei Province’s Outstanding Medical Academic Leader Program.
文摘Salidroside is the active ingredient extracted from Rhodiola rosea,and has been reported to show protective effects in cerebral ischemia,but the exact mechanisms of neuronal protective effects are still unrevealed.In this study,the protective effects of salidroside(1 jimol/L)in ameliorating neuronal injuries induced by oxygen-glucose deprivation(OGD),which is a classical model of cerebral ischemia,were clarified.The results showed that after 8 h of OGD,the mouse hippocampal neuronal cell line HT22 cells showed increased cell death,accompanied with mitochondrial fragmentation and augmented mitophagy.However,the cell viability of HT22 cells showed significant restoration after salidroside treatment.Mitochondrial morphology and mitochondrial function were effectively preserved by salidroside treatment.The protective effects of salidroside were further related to the prevention of mitochondrial over-fission.The results showed that mTOR could be recruited to the mitochondria after salidroside treatment,which might be responsible for inhibiting excessive mitophagy caused by OGD.Thus,salidroside was shown to play a protective role in reducing neuronal death under OGD by safeguarding mitochondrial function,which may provide evidence for further translational studies of salidroside in ischemic diseases.
文摘Aim Salidroside （SAL） is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor - deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Method Six-week old apoE-/- male mice were fed a high-fat diet for 8 weeks and then were ad- ministered with SAL for another 8 weeks. Atherosclerotic lesion and vascular function were analyzed. Primary cul- tured human umbilical vein endothelial cells （HUVECs） were prepared. Superoxide anion （O2^-）, NO produc- tion, mitochondrial membrane potential （△ψm） and intracellular ATP and AMP levels were measured. Expression of eNOS and AMPK were analyzed by Western blot. Result SAL significantly improved endothelial function asso- ciated with increasing eNOS activation thus reduced the atherosclerotic lesion area. SAL increased eNOS-Serl177 phosphorylation and decreased eNOS-Thr495 phosphorylation. SAL significantly activated AMP-activated protein ki- nase （AMPK）. Both AMPK inhibitor and AMPK small interfering RNA （siRNA） abolished SAL-induced Akt- Ser473 and eNOS-Serl177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. SAL decreased cellular ATP content and increased the cel- lular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease A^m, which is likely consequence of reduced ATP production. Conclusion The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide （NO） production, which was associated with mitochondria depolarization and subsequent activation of the AMPK/PI3 IC/ Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis.
文摘As a main component of efficiency in Rhodiola plants, salidroside is a promising environmental acclamation medicine and possesses specific medical properties against symptoms of fatigue, old age, microwave radiation, viral infections and tumors. Salidroside plays important roles, especially in military, aerospace, sport and healthcare medicine and has, therefore, recently, drawn more and closer attention. This article probes mainly into the probable biosynthetic pathway of salidroside following a brief introduction of the exploitation and utilization values of Rhodiola plants and the current condition of its natural resources. We have come to the conclusion that tyrosol, the aglycon of salidroside, is biosynthesized through the well-characterized shikimic acid pathway. A molecule of glucose is transferred by the UDP-glucosyltransferase （or possibly by the β-D-glucosidase too） to the tyrosol to form salidroside. On the other hand, salidroside may be degraded into tyrosol and glucose by β-D-glucosidase. Progress in research of these two key-enzymes, involved in the metabolism of salidroside, is finally elaborated.
