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Preparative isolation and purification of salidroside from the
Chinese medicinal plant Rhodiola sachalinensis by high-speed
counter-current chromatograph
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Synonyms
Rhodioloside
Formal Name 2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside
CAS Number 10338-51-9
Molecular Formula C14H20O7
Formula Weight 300.3
Formulation A crystalline solid
Purity ≥97%
Stability 2 years
Storage -20°C
Shipping Room temperature in continental US; may vary elsewhere
SMILES Copy OC1=CC=C(C=C1)CCO[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2
Helpful references!
^ Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytotherapy Research. 2007 Jan;21(1):37-43. doi:10.1002/ptr.2013 PMID 17072830
^ Mattioli L, Funari C, Perfumi M. Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats. Journal of Psychopharmacology. 2008 May 30. doi:10.1177/0269881108089872 PMID 18515456
^ Panossian A, Nikoyan N, Ohanyan N, Hovhannisyan A, Abrahamyan H, Gabrielyan E, Wikman G. Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine. 2008 Jan;15(1-2):84-91. doi:10.1016/j.phymed.2007.10.003 PMID 18054474
Binge Eating:
Physiol Behav. 2010 Dec 2;101(5):555-62. Epub 2010 Sep 15.
Effect of salidroside, active principle of Rhodiola rosea extract, on binge eating.
Cifani C, Micioni Di B MV, Vitale G, Ruggieri V, Ciccocioppo R, Massi M.
Source
School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino (MC), Italy. carlo.cifani@unicam.it
Abstract
Stress is a key determinant of binge eating (BE). Since Rhodiola rosea is known to modulate stress responses, its effect in a model of BE was investigated. BE for highly palatable food (HPF) was evoked in female rats by three 8-day cycles of food restriction/re-feeding (for 4days 66% of the usual chow intake; for 4days food ad libitum) and acute stress on the test day (day 25). R. rosea dry extract (3% rosavin, 3.12% salidroside) or its active principles were given by gavage 1h before access to HPF. Only rats exposed to both food restrictions and stress exhibited BE in the first 15-60min after the stressful procedure. R. rosea extract 10mg/kg significantly reduced and 20mg/kg abolished the BE episode. R. rosea extract 20mg/kg abolished also stress-induced increase in serum corticosterone levels. The R. rosea active principle salidroside, but not rosavin, at doses present in the extract, dose-dependently reduced or abolished BE for the period in which it was elicited. In conclusion results indicate that R. rosea extracts may have therapeutic properties in bingeing-related eating disorders and that salidroside is the active principle responsible for this effect.
Wu, Y., Piao, D., Han, X., et al. Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biol Pharm Bull 31(8) 1523-1529 (2008).
Han, X., Zhang, T., Wei, Y., et al. Separation of salidroside from Rhodiola crenulata by high-speed counter-current chromatography. J Chromatogr A 971 237-241 (2002).
Tan, C., Gao, M., Xu, W., et al. Protective effects of salidroside on endothelial cell apoptosis induced by cobalt chloride. Biol Pharm Bull 32(8) 1359-1363 (2009).
Panossian, A., and Wikman, G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol 4 198-219 (2009).
Cai, L., Wang, H., Li, Q., et al. Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochim Biophys Sin 40(9) 796-802 (2008).
Ma, C., Tang, J., Wang, H., et al. Preparative purification of salidroside from Rhodiola rosea by two-step adsorption chromatography on resins. J Sep Sci 32 185-191 (2009).
Here are some abstracts from recent research:
Li, X., J. Sipple, et al. (2012). "Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance." Blood.
Salidroside is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea that has potent antioxidant properties. Here we show that Salidroside prevented the loss of hematopoietic stem cells (HSCs) in mice under oxidative stress. Quiescent HSCs were recruited into cell cycling upon in vivo challenge with oxidative stress, which was blocked by Salidroside. Surprisingly, Salidroside does not prevent the production of reactive oxygen species (ROS) but reduces hydrogen peroxide-induced DNA-strand breaks in bone marrow cells enriched for HSCs. We tested whether Salidroside enhances oxidative DNA damage repair (ODDR) in mice deficient for five DNA repair pathways known to be involved in oxidative DNA damage repair; we found that Salidroside activated poly(ADP-ribose)polymerase-1 (PARP-1), a component of the base excision repair pathway, in mouse bone marrow HSCs as well as primary fibroblasts and human lymphoblasts. PARP-1 activation by Salidroside protects quiescent HSCs from oxidative stress-induced cycling in native animals and self-renewal defect in transplanted recipients, which was abrogated by genetic ablation or pharmacologic inhibition of PARP-1. Together, these findings suggest that activation of PARP-1 by Salidroside could affect the homeostasis and function of HSCs and contribute to the antioxidant effects of Salidroside.
Zhang, M., H. Zhao, et al. (2012). "[Effect of salidroside on rat bone marrow mesenchymal stem cells differentiation into cholinergic nerve cells]." Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 26(2): 158-165.
OBJECTIVE: To investigate the effect of salidroside on rat bone marrow mesenchymal stem cells (BMSCs) differentiation into the cholinergic nerve cells, so as to provide the theory basis of the combination of salidroside and stem cells for clinical therapy of nervous system diseases. METHODS: BMSCs were isolated from 2 Wistar rats (aged 4-6 weeks,weighing 120 g), which were identified by CD34, CD45, CD90, and CD106 with flow cytometry. According to inducing method, BMSCs at passage 2 were divided into 3 groups: In groups A and B, BMSCs were induced by salidroside (20 microg/mL) and retinoicacid (5 micromol/mL) respectively for 1, 3, 6, and 9 days, in group C, BMSCs were cultured with serum-free DMEM/F12 medium as control. MTT assay was used to detect the cellular proliferation activity. The immunofluorescence chemical technology was used to detect the expressions of nerver growth factor (NGF) and relevant marker molecule of nerve cells, including neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), beta-Tubulin III, glial fibrillary acidic protein (GFAP), and the marker of chol inergic neuron, such as Acetylcholine (Ach) and NGF. RT-PCR was used to detect mRNA expressions of NSE, beta-Tubulin III, GFAP,brain derived neurotrophic factor (BDNF),and gamma-aminobutyric acid (GABA). ELISA was used to detect the levels of BDNF and NGF, and the expression level of NGF protein was analyzed by Western blot. RESULTS: The results of the flow cytometry showed that the cultured cells were CD90 and CD106 positive, and CD34 and CD45 negative,which indicated that the cells were BMSCs. The cellular proliferation activity in groups A and B were significantly higher than that in group C at 6 days and 9 days (P < 0.05). RT-PCR results showed that the expression level of NSE,BDNF, beta-Tubulin III,GFAPmRNA were increased in group A at 6 days; In group B, that expression level of NSE mRNA was up-regulated at 6 days, that expression level of BDNF mRNA increased at 1 days and reached the peak at 6 days, and that expression level of beta-Tubulin III mRNA was up-regulated at 3 days, which was significantly higher than that at the other time points, and than that in group C (P < 0.01). But no GABA mRNA expression was detected in each group. Immunofluorescence chemical technology staining showed that the positive rates of NSE, MAP2, beta-Tubulin III, and GFAP were significantly higher in group A than those in group C at 3 days; the positive rates of Ach were significantly higher at 3, 6, and 9 days than those at 1 day in groups A and B, and in groups A and B than in group C (P < 0.01); the positive rates of NGF in groups A and B were significantly higher than those in group C (P < 0.01). The levels of BDNF and NGF in groups A and B were significantly higher than those in group C at 1, 3, 6, and 9 days (P < 0.01), but no significant difference of BDNF was found between groups A and B (P > 0.05). The expression level of NGF protein in groups A and B were significantly higher than that in group C (P < 0.01). The NGF expression reached the peak at 6 days in group A and at 3 days in group B. CONCLUSION: Salidroside could induce rat BMSCs differentiate into cholinergic nerve cells in vitro.
Lu, L., J. Yuan, et al. (2012). "Rejuvenating activity of salidroside (SDS): dietary intake of SDS enhances the immune response of aged rats." Age (Dordr).
It is well known that immune response decreases with aging. Salidroside (SDS), an antioxidant component isolated from the traditional Chinese medicine roseroot Rhodiola rosea, has been demonstrated to possess potent anti-aging and health-promoting activities. However, the mechanism underlying these activities is poorly understood. In this study, we clearly demonstrated that (1) dietary intake of SDS induced a considerable increase in total T cells (CD3(+)) and T helper cells (CD4(+)) in aged (21 months old) Wistar male rats; (2) SDS supplementation significantly increased the DTH response, a T cell-mediated immune response, in aged rats; and (3) SDS supplementation remarkably promoted the production of total anti-KLH IgG, anti-KLH IgG(1), and anti-KLH IgG(2alpha) in aged rats without disturbing immune homeostasis. These indicate that SDS is able to counteract immunosenescence, thereby resulting in rejuvenation. Practically, SDS may be used to help the elderly to generate an improved response to vaccine with stronger humoral and cell-mediated immune responses.
Panossian, A., G. Wikman, et al. (2012). "Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells." Front Neurosci 6: 6.
The beneficial stress-protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress-protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress.
Zheng, K. Y., Z. X. Zhang, et al. (2012). "Salidroside stimulates the accumulation of HIF-1alpha protein resulted in the induction of EPO expression: A signaling via blocking the degradation pathway in kidney and liver cells." Eur J Pharmacol 679(1-3): 34-39.
Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance to mountain sickness in preventing hypoxia; however, the functional ingredient responsible for this adaptogenic effect has not been revealed. Here, we have identified salidroside, a glycoside predominantly found in Rhodiola, is the chemical in providing such anti-hypoxia effect. Cultured human embryonic kidney fibroblast (HEK293T) and human hepatocellular carcinoma (HepG2) were used to reveal the mechanism of this hematopoietic function mediated by salidroside. The application of salidroside in cultures induced the expression of erythropoietin (EPO) mRNA from its transcription regulatory element hypoxia response element (HRE), located on EPO gene. The application of salidroside stimulated the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) protein, but not HIF-2alpha protein: the salidroside-induced HIF-1alpha protein was via the reduction of HIF-1alpha degradation but not the mRNA induction. The increased HIF-1alpha could account for the activation of EPO gene. These results supported the notion that hematopoietic function of Rhodiola was triggered, at least partially, by salidroside.
Coenye, T., G. Brackman, et al. (2012). "Eradication of Propionibacterium acnes biofilms by plant extracts and putative identification of icariin, resveratrol and salidroside as active compounds." Phytomedicine 19(5): 409-412.
Propionibacterium acnes is a Gram-positive bacterium that plays an important role in the pathogenesis of acne vulgaris. This organism is capable of biofilm formation and the decreased antimicrobial susceptibility of biofilm-associated cells may hamper efficient treatment. In addition, the prolonged use of systemic antibiotic therapy is likely to lead to the development and spread of antimicrobial resistance. In the present study we investigated whether P. acnes biofilms could be eradicated by plant extracts or their active compounds, and whether other mechanisms besides killing of biofilm cells could be involved. Out of 119 plant extracts investigated, we identified five with potent antibiofilm activity against P. acnes (extracts from Epimedium brevicornum, Malus pumila, Polygonum cuspidatum, Rhodiola crenulata and Dolichos lablab). We subsequently identified icariin, resveratrol and salidroside as active compounds in three of these extracts. Extracts from E. brevicornum and P. cuspidatum, as well as their active compounds (icariin and resveratrol, respectively) showed marked antibiofilm activity when used in subinhibitory concentrations, indicating that killing of microbial cells is not their only mode of action.
Chu, H., W. He, et al. (2011). "[Flavonoids and nor-sesquiterpenes of Pedicularis densispica]." Zhongguo Zhong Yao Za Zhi 36(19): 2672-2675.
OBJECTIVE: To study the chemical constituents of the whole plants of Pedicularis densispica. METHOD: The chemical constituents were isolated by various chromatographic methods and their structures were determined by chemical evidences and spectral data. RESULT: Ten compounds were isolated and identified as acacetin (1), apigenin-7-0-beta-glucopyranoside (2), kaempferol-3,7-O-alpha-dirhamnopyranoside (3), scutellarein-7-0-beta-glucopyranoside (4), chrysoeriol-7-O-beta-glucopyranoside (5), pedicutricone A (6), dearabinosyl pneumonanthoside (7), salidroside (8), darendoside B (9), and maltol-beta-D-glucopyranoside (10). CONCLUSION: These compounds were isolated from the titled plant for the first time. Except compounds 6 and 8, the others were obtained for the first time from the genus Pedicularis.
Qu, Z. Q., Y. Zhou, et al. (2012). "Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis against streptozotocin-induced neural injury in the rat." PLoS One 7(1): e29641.
Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS.
Li, F., H. Tang, et al. (2011). "Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice." Molecules 16(12): 9912-9924.
It has been confirmed that diabetes mellitus (DM) carries increased oxidative stress. This study evaluated the effects of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice. After induction of diabetes, diabetic mice were administered daily doses of 50, 100 and 200 mg/kg salidroside for 28 days. Body weights, fasting blood glucose (FBG), serum insulin, TC (total cholesterol), TG (triglyceride), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. Results showed that salidroside possessed hypoglycemic activity and protective effects against diabetes-induced oxidative stress, which could significantly reduce FBG, TC, TG and MDA levels, and at same time increase serum insulin levels, SOD, GPx and CAT activities. Therefore, salidroside should be considered as a candidate for future studies on diabetes.
Shi, T. Y., S. F. Feng, et al. (2012). "Neuroprotective effects of salidroside and its analogue tyrosol galactoside against focal cerebral ischemia in vivo and h(2)o (2)-induced neurotoxicity in vitro." Neurotox Res 21(4): 358-367.
Salidroside (Sal) is a natural antioxidant extracted from the root of Rhodiola rosea L. that elicits neuroprotective effects in vivo and in vitro. Tyrosol galactoside (Tyr), an analog of Sal, was recently synthesized in our laboratory. The purpose of the current study was to investigate and compare the neuroprotective effects of Sal and Tyr against focal cerebral ischemia in vivo and H(2)O(2)-induced neurotoxicity in vitro. Sal and Tyr significantly prevented a cerebral ischemic injury induced by a 2 h middle cerebral artery occlusion and a 24 h reperfusion in rats in vivo. Furthermore, the oxidative insult was markedly attenuated by treatments of Sal and Tyr in the cultured rat cortical neurons after a 30 min exposure to 50 muM of H(2)O(2). Western blot analysis revealed that Sal and Tyr decreased the expression of Bax and restored the balance of pro- and anti-apoptotic proteins. The neuroprotective effects of these two analogues show that Tyr has a better antioxidative action compared with Sal both in vivo and in vitro, and suggest that the antioxidant activity of Sal and Tyr may be partly due to their different substituents in their glycosyl groups. This gives a new insight into the development of therapeutic natural antioxidants against oxidative stress.
Wang, C. Q., J. Chen, et al. (2011). "[Study on preparation of salidroside and polysaccharide in Rhodiola crenulata]." Zhong Yao Cai 34(7): 1122-1125.
OBJECTIVE: To optimize the preparation process of salidroside and polysaccharide in Rhodiola crenulata. METHODS: Water-extraction and alcohol-precipitation was used. The effect of added water volume, decoction time and frequency on water-extracting process was investigated by L9 (3(4)) orthogonal design using extraction rate, content of salidroside and polysaccharide as the assessment indexes. The effect of liquor strength and ethanol concentration on alcohol-precipitating process was investigated as well, using content of salidroside and polysaccharide as the assessment indexes. RESULTS: The optimum conditions for water-extracting process were as follows: decocting 3 times, and each time adding 8 fold of water and extracting 2 h. For alcohol-precipitating process,it was that liquor strength was 0.4 g/mL, and ethanol concentration in liquor was 70%. CONCLUSION: The optimized process has guidance for the development and comprehensive utilization of this plant.
Guan, S., H. Feng, et al. (2011). "Salidroside attenuates LPS-induced pro-inflammatory cytokine responses and improves survival in murine endotoxemia." Int Immunopharmacol 11(12): 2194-2199.
Salidroside is a major component isolated from the Rhodiola rosea. In the present study, we investigated the anti-inflammatory effects of salidroside on cytokine production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro, and the results showed that salidroside reduced tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) secretions. This inspired us to further study the effects of salidroside in vivo. Salidroside significantly attenuated TNF-alpha, IL-1beta and IL-6 productions in serum from mice challenged with LPS, and consistent with the results in vitro. In the murine model of endotoxemia, mice were treated with salidroside prior to or after LPS challenge. The results showed that salidroside significantly increased mouse survival. Further studies revealed that salidroside could downregulate LPS-induced nuclear transcription factor-B (NF-B) DNA-binding activation and ERK/MAPKs signal transduction pathways production in RAW 264.7 macrophages. These observations indicated that salidroside modulated early cytokine responses by blocking NF-B and ERK/MAPKs activation, and thus, increased mouse survival. These effects of salidroside may be of potential usefulness in the treatment of inflammation-mediated endotoxemia.
Sun, C., Z. Wang, et al. (2012). "Salidroside inhibits migration and invasion of human fibrosarcoma HT1080 cells." Phytomedicine 19(3-4): 355-363.
Oxidative stress plays an important role in tumorigenesis and metastasis. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Here we investigated the inhibitory effects of salidroside on tumor metastasis in human fibrosarcoma HT1080 cells in vitro. The results indicated that salidroside significantly reduced wound closure areas of HT1080 cells, inhibited HT1080 cells invasion into Matrigel-coated membranes, suppressed matrix metalloproteinases (MMP-2 and MMP-9) activity, and increased tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in a dose-dependent manner in HT1080 cells. Salidroside treatment upregulated the E-cadherin expression, while downregulated the expression of beta1-integrin. As an antioxidant, salidroside inhibited the intracellular reactive oxygen species (ROS) formation in a dose-dependent manner. The results also showed that salidroside could inhibit the activation of protein kinase C (PKC) and the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in a dose-dependent manner. In conclusion, these results suggest that salidroside inhibits tumor cells metastasis, which may due to its interfere in the intracellular excess ROS thereby down-regulated the ROS-PKC-ERK1/2 signaling pathway.
Guan, S., J. He, et al. (2011). "Adjuvant effects of salidroside from Rhodiola rosea L. on the immune responses to ovalbumin in mice." Immunopharmacol Immunotoxicol 33(4): 738-743.
Salidroside, a major component of Rhodiola rosea L., was evaluated for its adjuvant effects on the immune responses in mice by ovalbumin (OVA) stimulation. BALB/c mice were immunized subcutaneously with OVA 100 mug or OVA 100 mug dissolved in saline containing alum (100 mug) or salidroside (12.5, 25, or 50 mug) on Days 1 and 15. Two weeks later (Day 28), blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies. Meanwhile, splenocytes were harvested to assess lymphocyte proliferation, cytokines (IL-2, IL-4, and IFN-gamma) production, and CD4(+), CD8(+) lymphocyte subsets. The results indicated that co-administration of salidroside with OVA significantly enhanced the ConA-, LPS-, and OVA-induced splenocyte proliferation, produced more IL-2, IL-4, IFN-gamma, and IgG, IgG1, and IgG2b antibody levels, and increased the percentage of CD4(+), CD8(+) lymphocyte subsets than OVA alone. Thus, salidroside possess immunological adjuvant activity by regulating humoral and cellular immune responses in mice.
Zhu, Y., Y. P. Shi, et al. (2011). "Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway." DNA Cell Biol 30(10): 809-819.
Oxidative stress induces serious tissue injury in cardiovascular diseases. Salidroside, with its strong antioxidative and cytoprotective actions, is of particular interest in the development of antioxidative therapies for oxidative injury in cardiac diseases. We examined the pharmacological effects of salidroside on H9c2 rat cardiomyoblast cells under conditions of oxidative stress induced by hydrogen peroxide (H2O2) challenge. Salidroside attenuated H2O2-impaired cell viability in a concentration-dependent manner, and effectively inhibited cellular malondialdehyde production, lethal sarcolemmal disruption, cell necrosis, and apoptosis induced by H2O2 insult. Salidroside significantly augmented Akt phosphorylation at Serine 473 in the absence or presence of H2O2 stimulation; wortmannin, a specific inhibitor of PI3K, abrogated salidroside protection. Salidroside increased the intracellular mRNA expression and activities of catalase and Mn-superoxide dismutases in a PI3K-dependent manner. Our results indicated that salidroside protected cardiomyocytes against oxidative injury through activating the PI3K/Akt pathway and increasing the expression and activities of endogenous PI3K dependent antioxidant enzymes.
Liu, Z., X. Li, et al. (2012). "Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy." Mol Carcinog 51(3): 257-267.
The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53-/- MEFs) compared to their wild-type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2-/-, p53-/- MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-alpha phosphorylation and a decrease of 4E-BP1 phosphorylation, leading to increased binding of 4E-BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis.
Guan, S., W. Wang, et al. (2011). "Salidroside attenuates hydrogen peroxide-induced cell damage through a cAMP-dependent pathway." Molecules 16(4): 3371-3379.
Salidroside, a major component of Rhodiola rosea L., has shown various pharmacological functions, including antioxidant effects, but the signal transduction pathway of its antioxidant effects is not very clear. In this study, we found that salidroside could attenuate hydrogen peroxide (H(2)O(2))-induced HL-7702 cell damage, inhibit H(2)O(2)-induced cytosolic free Ca2+ ([Ca2+]i) elevation, scavenge reactive oxygen species (ROS) and increase 3'-5'-cyclic adenosine monophosphate (cAMP) level in a dose-dependent manner, but it couldn't influence 3'-5'-cyclic guanosine monophosphate (cGMP) levels. Therefore, these results indicated that the antioxidant effects of salidroside were associated with down-regulation of [Ca2+]i, ROS occur via a cAMP-dependent pathway.
Ye, S. S., Y. Y. Zeng, et al. (2011). "[Effects of salidroside on proliferation, apoptosis, phagocytosis, ROS and NO production of murine peritoneal macrophages in vitro]." Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 27(3): 237-241.
AIM: To investigate the effects of salidroside(Sal) on proliferation, apoptosis, phagocytosis, the production of ROS and NO of murine peritoneal macrophages in vitro as well as its immunoregulation. METHODS: The single cell suspension of murine peritoneal macrophages was prepared under sterile condition, then co-cultured with different concentrations of Sal(80, 160 and 320 mumol/L)for 4 hours prior to stimulation with LPS and IFN-gamma, the proliferation of macrophages was measured by MTT colorimetry. The effect of Sal on the apoptosis of Sytox(R) Green-labelled peritoneal macrophages induced by CHX was detected by Fluorescence enzyme-labelled meter. FCM was used to detect the effect of Sal on phagocytosis of peritoneal macrophages. Fluorescence enzyme-labelled meter was used to measure the effects of Sal on ROS of H(2);DCFDA-labelled macrophages induced by LPS and IFN-gamma. Griess Gragent was used to detect the role of Sal in production of NO in peritoneal macrophages activated by LPS and IFN-gamma. RESULTS: MTT result demonstrated that Sal could promote the proliferation of peritoneal macrophages activated by LPS and IFN-gamma at the final concentrations of 80, 160, 320 mumol/L, respectively (P<0.05). The result of Fluorescence enzyme-labelled meter detected showed that Sal at the final concentration of 160 mumol/L could inhibit apoptosis of peritoneal macrophages induced by CHX(P<0.01). FCM analysis showed that different concentrations of Sal significantly promoted the phagocytosis of peritoneal macrophages which include un-activated and activated by LPS and IFN-gamma(P<0.05). Fluorescence enzyme-labelled meter showed that Sal could reduce the production of ROS in activated peritoneal macrophages induced by LPS and IFN-gamma(P<0.05). Sal also increased the production of NO in activated peritoneal macrophages induced by LPS and IFN-gamma(P<0.05). CONCLUSION: Sal can promote proliferation of peritoneal macrophages stimulated by LPS and IFN-gamma, and it can inhibit apoptosis of peritoneal macrophages induced by CHX, Sal also can promote the phagocytosis of peritoneal macrophages which include un-activated and activated by LPS and IFN-gamma, Sal can reduce the production of ROS in activated peritoneal macrophages induced by LPS and IFN-gamma, while Sal can promote the production of NO in activated peritoneal macrophages induced by LPS and IFN-gamma.
Guo, Y., Y. Zhao, et al. (2010). "Synthesis, biological activity of salidroside and its analogues." Chem Pharm Bull (Tokyo) 58(12): 1627-1629.
Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 18 novel salidroside analogues were prepared through Koenigs-Knorr method, the effects of these compounds over PC12 was assessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The novel compounds differ in the substituents attached to the benzene ring or in the glycosyl donor. According to the data, compounds (3,5-dimethoxyphenyl)methyl beta-D-glucopyranoside and (3,5-dimethoxyphenyl)methyl beta-D-galactopyranoside with methoxy group at 3 and 5-positions of the benzene ring were the most viability at concentration of 300 micromol/l and 60 micromol/l, respectively.
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