Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 ce...Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGDtreated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside.Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside.Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.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
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
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
Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokin...Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.展开更多
Salidroside(8-O-β-D-glucoside of tyrosol),a plant-derived natural product,is used for treatment of hypoxia,fatigue and aging diseases.The availability of salidroside is restricted since it is extracted from3-5 years ...Salidroside(8-O-β-D-glucoside of tyrosol),a plant-derived natural product,is used for treatment of hypoxia,fatigue and aging diseases.The availability of salidroside is restricted since it is extracted from3-5 years old Rhodiola roots,which grow very slowly in the cold region of northern hemisphere of Earth.Our laboratory has constructed an engineered Escherichia coli and established a fermentation process to produce salidroside from glucose.In this article,nine macroporous resins from polarity to non-polarity,including NKA-9,S-8,AB-8,SP825,D101,LSA-8,LX-12,LX-18 and LX-68 resins,were tested to separate salidroside from fermentation broth.After static and dynamic experiments,the weakly polar SP825 resin had a better separation efficiency among nine resins.The adsorption kinetic and isotherm of salidroside on the SP825 resin were determined,and the pseudo-second-order kinetic model and Langmuir model could be fitted well.The effects of the pH on adsorption and ethanol concentration on desorption were investigated,and an optimal separation process was established.The adsorption for salidroside in the SP825 resin column was conducted with loading 150 ml at pH 7,and desorpted by washing 50 ml of80%ethanol solution.Under the best process conditions,the purity and yield of salidroside in the final product were 91.6%and 74.0%,respectively.The results showed that the macroporous SP825 resin would be feasible and effective to prepare salidroside and has promising application in the downstream process of microbial fermentation.展开更多
OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms.METHODS The Caco-2 cell monolayer was exposed to 1% oxygen(O_2) concentratio...OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms.METHODS The Caco-2 cell monolayer was exposed to 1% oxygen(O_2) concentration for 24 h to build the hypoxiccell model.The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(P app).Healthy Sprague Dawley(SD) rats were exposed to 9% O_2 for 72 h for the construction of hypoxic rat model.Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism.The expression levels of salidroside-transporting and salidroside-metabolizing enzymes,including Sodium-dependent glucose cotransporters(SGLT1),β-glucosidase(GBA3)and sulfotransferase(SULT2A1),were thereafter detected by RT-PCR and Western blot.The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition,the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine.RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled,while the in vivo clearance was significantly reduced.Mechanistic study demonstrated that the Papp A-B/Papp B-A eualsto 10.3,indicating the potential active transport of salidrosile.The expression of SGLT1 and GBA3 was significantly decreased,which indicated a reduced metabolism of salidroside under hypoxia.Moreover,rat under hypoxia was found to suffer from renal dysfunction,with an abnormal value of blood urea nitrogen.CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia,the systemic exposure of salidroside in rats was significantly enhanced.展开更多
[Objectives]To use poly(lactic-co-glycolic acid)(PLGA)nanoparticles to improve the bioavailability and brain entrance capability of Salidroside(Sal).[Methods]An emulsion solvent evaporation approach was used to create...[Objectives]To use poly(lactic-co-glycolic acid)(PLGA)nanoparticles to improve the bioavailability and brain entrance capability of Salidroside(Sal).[Methods]An emulsion solvent evaporation approach was used to create PLGA nanoparticles(Sal-NP).The preparation parameters were optimized using a single factor experiment.The particle size and zeta potential were determined using the laser particle analyzer,and the morphology of the nanoparticles was observed using transmission electron microscopy.The encapsulation efficiency and drug loading were determined using HPLC.Subsequently,the in vitro drug release was determined using a dynamic dialysis method,and the cellular uptake and cytotoxicity were determined using the bEnd3 cell model.[Results]The ultrasonic time and power for preparing Sal-NP were 6 min and 100 W,respectively.The size of the nanoparticles was 162.0±74.86 nm,and the morphology of Sal-NP was spherical like.After 48 h,the cumulative release of Sal-NP was 62%,indicating that Sal showed a controlled release property in Sal-NP.Cellular uptake study showed that the PLGA nanoparticles remarkably increased the internalization than control group(P<0.001).In addition,Sal-NPs were non-toxic to cells at concentrations ranging from 12.5 to 100μM.[Conclusions]PLGA nanoparticles is promising to be exploited in Alzheimer's disease research due to the increasing absorption and controlled release advantages for Sal.展开更多
Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the...Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.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
Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.Thi...Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast,ovarian,cervical,colorectal,lung,liver,gastric,bladder,renal,and skin cancer as well as gliomas and fibrosarcomas.Thus,it provides a reference for the further development and utilization of salidroside.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
Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment a...Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment against AD.Salidroside(Sal)is the main effective component of Rhodiola rosea L.,which has several pharmacological activities.The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms.Methods:We used tau transgenic Drosophila line(TAU)in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system.After feeding flies with Sal,the lifespan and locomotor activity were recorded.We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry,and detected the levels of total glycogen synthase kinase 3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),t-tau and p-tau in the brain by western blot analysis.Results:Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity.We also observed less vacuoles in the mushroom body,upregulated level of p-GSK-3βand downregulated p-tau following Sal treatment.Conclusion:Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss.The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3βand down-regulation of the p-tau.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
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
Rhodiola quadrifida is a rare mountain medicinal plant whose root extracts are used in traditional Chinese medicine as a hemostatic,antitussive,and tonic in the treatment of gynecological diseases.The aim of the study...Rhodiola quadrifida is a rare mountain medicinal plant whose root extracts are used in traditional Chinese medicine as a hemostatic,antitussive,and tonic in the treatment of gynecological diseases.The aim of the study was to obtain R.quadrifida cultures at different degrees of differentiation in vitro and compare their growth characteristics and the content of salidroside and rosavin.Hairy roots were obtained by incubating cotyledons and hypocotyls in a suspension of Agrobacterium rhizogenes strain A4.The presence of the rolB and rolC genes was proven by polymerase chain reaction.The obtained roots were cultivated in Murashige-Skoog medium(MS).Calluses were obtained from the hairy roots in MS medium with the addition of hormones:3 mg/L 2,4 D and 0.5 mg/L BAP.The presence of the main secondary metabolites of R.quadrifida,salidroside and rosavin,in calluses and salidroside in hairy roots by HPLC/MS was confirmed.The content of salidroside in callus culture was significantly higher than in hairy roots,0.158 and 0.047%,respectively.The content of rosavin in callus culture was 0.07%.The content of rosavin and salidroside in callus culture was close to the level of these substances in the rhizomes of R.quadrifida plants growing in vivo,making this culture promising for its possible biotechnological use.展开更多
Objective: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas(HNSC). Methods: Gene expression data of HNSC samples and peripher...Objective: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas(HNSC). Methods: Gene expression data of HNSC samples and peripheral blood mononuclear cells(PBMCs) of HNSC patients were collected from Gene Expression Omnibus(GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres(DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. Results: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expressions of all 110 commonly DEGs were altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. Conclusions: This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.展开更多
Objective To study the constituents in the whole plant of Boschniakia rossica. Methods The constituents were separated and purified with chromatographic methods. Their structures were elucidated by spectroscopic metho...Objective To study the constituents in the whole plant of Boschniakia rossica. Methods The constituents were separated and purified with chromatographic methods. Their structures were elucidated by spectroscopic methods (1D, 2D NMR, UV, IR, and HRESI-TOF-MS) and chemical analyses. Results One new phenylpropanol glycoside (1) and its five known analogues were obtained from B. rossica. They were identified as trans-p-coumaryl- (2′-O-β-D-glucopyranosyl)-β-D-glucopyranoside (1), salidroside I (2), rossicasin A (3), trans-p-coumaryl alcohol 1-O-β-glucopyranosyl(1→4)-α-rhamnopyranosyl(1→3)-β-glucopyranoside (4), salidroside (5), and acetoside (6). Conclusion Among the known compounds, compound 2 is firstly isolated from the plants in genus Boschniakia C. A. Mey. ex Bongard. Meanwhile, the 13 C-NMR data of 9 and 4′ positions in compound 4 are corrected.展开更多
Objective To develop an effective method for simultaneous determination of eight major components in Liuwei Wuling Tablet(LWT). Methods Reversed phase HPLC method was used with variously improved conditions. Results S...Objective To develop an effective method for simultaneous determination of eight major components in Liuwei Wuling Tablet(LWT). Methods Reversed phase HPLC method was used with variously improved conditions. Results Salidroside, forsythoside A, specnuezhenide, phillyrin, schisandrol A, schizandrol A, schizandrin A, and schizandrin B in LWT were successfully separated on a Kromasil 100-5-C_(18) reverse phase column(250 mm × 4.6 mm, 5 μm) using acetonitrile -0.1% phosphoric acid(gradient elution) as mobile phase. The detection wavelength was 275 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 35 ℃. The recovery rate of the method was within the range of 95.13%-104.56% and the precision(RSD) was less than 3% for all eight analytes. All the compounds showed good linearities(r^2>0.9980) in a relatively wide concentration range. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation of LWT.展开更多
基金supported by the Zhejiang Traditional Chinese Medicine Science and Technology Plan Project(2021ZB027,2023ZL267)Zhejiang Medical and Health Platform Project of China(2019KY002,2019RC092).
文摘Objective: To evaluate the effect of salidroside on oxygen and glucose deprivation(OGD)-treated NT2 cells and its underlying mechanisms of action.Methods: Retinoic acid was used to induce the differentiation of NT2 cells into neurons. The effects of salidroside on survival, apoptosis, inflammatory response, and oxidative stress of neurons undergoing OGD were evaluated. Using precursor cells as controls, the effect of salidroside on the differentiation progression of OGDtreated cells was evaluated. In addition, the effect of erastin, a ferroptosis inducer, on NT2 cells was examined to investigate the underlying mechanisms of neuroprotective action of salidroside.Results: Salidroside alleviated the effects of OGD on neuronal survival, apoptosis, inflammation, and oxidative stress, and promoted NT2 cell differentiation. Moreover, salidroside prevented ferroptosis of OGD-treated cells, which was abolished following erastin treatment, indicating that ferroptosis mediated the regulatory pathway of salidroside.Conclusions: Salidroside attenuates OGD-induced neuronal injury by inhibiting ferroptosis and promotes neuronal differentiation.
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.
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.
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.
基金Supported by grants from the National Natural Science Foundation of China ( 81372202,81872273, 31871367)
文摘Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.
基金supported by The Key-Area Research and Development Program of Guangdong Province(2020B0303070002),China。
文摘Salidroside(8-O-β-D-glucoside of tyrosol),a plant-derived natural product,is used for treatment of hypoxia,fatigue and aging diseases.The availability of salidroside is restricted since it is extracted from3-5 years old Rhodiola roots,which grow very slowly in the cold region of northern hemisphere of Earth.Our laboratory has constructed an engineered Escherichia coli and established a fermentation process to produce salidroside from glucose.In this article,nine macroporous resins from polarity to non-polarity,including NKA-9,S-8,AB-8,SP825,D101,LSA-8,LX-12,LX-18 and LX-68 resins,were tested to separate salidroside from fermentation broth.After static and dynamic experiments,the weakly polar SP825 resin had a better separation efficiency among nine resins.The adsorption kinetic and isotherm of salidroside on the SP825 resin were determined,and the pseudo-second-order kinetic model and Langmuir model could be fitted well.The effects of the pH on adsorption and ethanol concentration on desorption were investigated,and an optimal separation process was established.The adsorption for salidroside in the SP825 resin column was conducted with loading 150 ml at pH 7,and desorpted by washing 50 ml of80%ethanol solution.Under the best process conditions,the purity and yield of salidroside in the final product were 91.6%and 74.0%,respectively.The results showed that the macroporous SP825 resin would be feasible and effective to prepare salidroside and has promising application in the downstream process of microbial fermentation.
基金supported by National Natural Science Foundation of China(81573683 and 81173121)
文摘OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms.METHODS The Caco-2 cell monolayer was exposed to 1% oxygen(O_2) concentration for 24 h to build the hypoxiccell model.The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(P app).Healthy Sprague Dawley(SD) rats were exposed to 9% O_2 for 72 h for the construction of hypoxic rat model.Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism.The expression levels of salidroside-transporting and salidroside-metabolizing enzymes,including Sodium-dependent glucose cotransporters(SGLT1),β-glucosidase(GBA3)and sulfotransferase(SULT2A1),were thereafter detected by RT-PCR and Western blot.The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition,the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine.RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled,while the in vivo clearance was significantly reduced.Mechanistic study demonstrated that the Papp A-B/Papp B-A eualsto 10.3,indicating the potential active transport of salidrosile.The expression of SGLT1 and GBA3 was significantly decreased,which indicated a reduced metabolism of salidroside under hypoxia.Moreover,rat under hypoxia was found to suffer from renal dysfunction,with an abnormal value of blood urea nitrogen.CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia,the systemic exposure of salidroside in rats was significantly enhanced.
基金Special Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2021MS121).
文摘[Objectives]To use poly(lactic-co-glycolic acid)(PLGA)nanoparticles to improve the bioavailability and brain entrance capability of Salidroside(Sal).[Methods]An emulsion solvent evaporation approach was used to create PLGA nanoparticles(Sal-NP).The preparation parameters were optimized using a single factor experiment.The particle size and zeta potential were determined using the laser particle analyzer,and the morphology of the nanoparticles was observed using transmission electron microscopy.The encapsulation efficiency and drug loading were determined using HPLC.Subsequently,the in vitro drug release was determined using a dynamic dialysis method,and the cellular uptake and cytotoxicity were determined using the bEnd3 cell model.[Results]The ultrasonic time and power for preparing Sal-NP were 6 min and 100 W,respectively.The size of the nanoparticles was 162.0±74.86 nm,and the morphology of Sal-NP was spherical like.After 48 h,the cumulative release of Sal-NP was 62%,indicating that Sal showed a controlled release property in Sal-NP.Cellular uptake study showed that the PLGA nanoparticles remarkably increased the internalization than control group(P<0.001).In addition,Sal-NPs were non-toxic to cells at concentrations ranging from 12.5 to 100μM.[Conclusions]PLGA nanoparticles is promising to be exploited in Alzheimer's disease research due to the increasing absorption and controlled release advantages for Sal.
文摘Salidroside is extensively used as a herbal medicine worldwide, and it has been shown to protect against disruption of endothelial homeostasis and act as an anti-aging agent. The present study aimed to investigate the ameliorative effects of salidroside on homocysteine (Hcy)-induced cell senescence in human umbilical vein endothelial cells (HUVECs) that were mediated via inhibition of Krüppel-like factor 4 (KLF4). An endothelial cell senescence model was induced by Hcy. The cell viability, activities of telomerase and lactate dehydrogenase (LDH), and the level of reactive oxygen species were determined using commercial kits. The expression levels of KLF4, p53 and p21 were determined via western blot analysis, whereas the mRNA expression levels of KLF4 were detected by reverse transcription-quantitative PCR. Small interfering RNA-mediated knockdown of KLF4 was found to reverse Hcy-induced cell senescence. Hcy treatment led to an accelerated cell senescence, as evidenced by decreases in both cell viability and telomerase activity, whereas increases were noted in the leakage of LDH and the level of reactive oxygen species, in addition to an up-regulation of the protein levels of p53 and p21, and up-regulation of KLF4 at both the mRNA and protein level. Treatment with salidroside ameliorated Hcy-induced cell senescence in a dose-dependent manner. Taken together, these results suggested that Hcy may induce cell senescence through upregulation of KLF4, and this may be reversed by treatment with salidroside. Therefore, salidroside was shown to inhibit Hcy-induced cell senescence through KLF4 inhibition.
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.
文摘Salidroside is a phenolic secondary metabolite present in plants of the genus Rhodiola,and studies investigating its extensive pharmacological activities and mechanisms have recently attracted increasing attention.This review summarizes the progress of recent research on the antiproliferative activities of salidroside and its effects on breast,ovarian,cervical,colorectal,lung,liver,gastric,bladder,renal,and skin cancer as well as gliomas and fibrosarcomas.Thus,it provides a reference for the further development and utilization of salidroside.
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 work was supported by grants from the National Natural Science Fund(91332107,81430022,81371407).
文摘Background:Alzheimer’s disease(AD)is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens.Intensive efforts have been made to find effective and safe treatment against AD.Salidroside(Sal)is the main effective component of Rhodiola rosea L.,which has several pharmacological activities.The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms.Methods:We used tau transgenic Drosophila line(TAU)in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system.After feeding flies with Sal,the lifespan and locomotor activity were recorded.We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry,and detected the levels of total glycogen synthase kinase 3β(t-GSK-3β),phosphorylated GSK-3β(p-GSK-3β),t-tau and p-tau in the brain by western blot analysis.Results:Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity.We also observed less vacuoles in the mushroom body,upregulated level of p-GSK-3βand downregulated p-tau following Sal treatment.Conclusion:Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss.The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3βand down-regulation of the p-tau.
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This work was supported by the Ministry of Education and Science of the Russian Federation(Topic No.АААА-А19-119041890054-8).
文摘Rhodiola quadrifida is a rare mountain medicinal plant whose root extracts are used in traditional Chinese medicine as a hemostatic,antitussive,and tonic in the treatment of gynecological diseases.The aim of the study was to obtain R.quadrifida cultures at different degrees of differentiation in vitro and compare their growth characteristics and the content of salidroside and rosavin.Hairy roots were obtained by incubating cotyledons and hypocotyls in a suspension of Agrobacterium rhizogenes strain A4.The presence of the rolB and rolC genes was proven by polymerase chain reaction.The obtained roots were cultivated in Murashige-Skoog medium(MS).Calluses were obtained from the hairy roots in MS medium with the addition of hormones:3 mg/L 2,4 D and 0.5 mg/L BAP.The presence of the main secondary metabolites of R.quadrifida,salidroside and rosavin,in calluses and salidroside in hairy roots by HPLC/MS was confirmed.The content of salidroside in callus culture was significantly higher than in hairy roots,0.158 and 0.047%,respectively.The content of rosavin in callus culture was 0.07%.The content of rosavin and salidroside in callus culture was close to the level of these substances in the rhizomes of R.quadrifida plants growing in vivo,making this culture promising for its possible biotechnological use.
文摘Objective: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas(HNSC). Methods: Gene expression data of HNSC samples and peripheral blood mononuclear cells(PBMCs) of HNSC patients were collected from Gene Expression Omnibus(GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres(DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. Results: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expressions of all 110 commonly DEGs were altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. Conclusions: This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.
基金Program for New Century Excellent Talents in University (NCET-10-0958)Important Drug Development Fund,Ministry of Science and Technology of China (2011ZX09307-002-01)Applied Basic and Advanced Research Program of Tianjin (10SYSYJC28900,10ZCKFSY09300)
文摘Objective To study the constituents in the whole plant of Boschniakia rossica. Methods The constituents were separated and purified with chromatographic methods. Their structures were elucidated by spectroscopic methods (1D, 2D NMR, UV, IR, and HRESI-TOF-MS) and chemical analyses. Results One new phenylpropanol glycoside (1) and its five known analogues were obtained from B. rossica. They were identified as trans-p-coumaryl- (2′-O-β-D-glucopyranosyl)-β-D-glucopyranoside (1), salidroside I (2), rossicasin A (3), trans-p-coumaryl alcohol 1-O-β-glucopyranosyl(1→4)-α-rhamnopyranosyl(1→3)-β-glucopyranoside (4), salidroside (5), and acetoside (6). Conclusion Among the known compounds, compound 2 is firstly isolated from the plants in genus Boschniakia C. A. Mey. ex Bongard. Meanwhile, the 13 C-NMR data of 9 and 4′ positions in compound 4 are corrected.
基金National Natural Science Foundation of China(No.81330090)National Natural Science Foundation of China(No.81274026)National Natural Science Foundation of China(No.03772888)
文摘Objective To develop an effective method for simultaneous determination of eight major components in Liuwei Wuling Tablet(LWT). Methods Reversed phase HPLC method was used with variously improved conditions. Results Salidroside, forsythoside A, specnuezhenide, phillyrin, schisandrol A, schizandrol A, schizandrin A, and schizandrin B in LWT were successfully separated on a Kromasil 100-5-C_(18) reverse phase column(250 mm × 4.6 mm, 5 μm) using acetonitrile -0.1% phosphoric acid(gradient elution) as mobile phase. The detection wavelength was 275 nm with flow rate of 1.0 mL/min, and the column temperature was maintained at 35 ℃. The recovery rate of the method was within the range of 95.13%-104.56% and the precision(RSD) was less than 3% for all eight analytes. All the compounds showed good linearities(r^2>0.9980) in a relatively wide concentration range. Conclusion Simultaneous quantification of the multiple components by HPLC would be a better strategy for the quality evaluation of LWT.
